Title: Part One / Pharmacopeia
Tags: pharmacopeia cvspham anaes analgesics neuropharm endopharm antimicro localanaes nmbd opioid autonomic volatile haemepharm pharm anticholinergic gitpharm renalpharm anes definition cvspharm haeme micro pharmacology respiratory resppharm obs cardiovascular cvpharm cvs antidote

Q: Local anaesthetic: Mechanism of Action
A: Use-dependent blockade of intracellular component of Na channel.

Q: Local Anaesthetics Onset: Drug and Patient factors
A: pKa: low pKa = faster onset as more unionised drug crosses membrane
Dose

Q: Local Anaesthetics Duration: Drug factors
A: Vasodilator properties
Use of additives
Lipid solubility
↑ Lipid solubility ↑ duration, as agent remains in the nerve for longer. Therefore ↑ potency ↑ duration of action. Duration of action is increased when pH increases, as the ionised portion falls.
Protein binding
↑ Binding ↑ duration. Binding ↓ as pH ↓, ↑ unbound drug fraction. LA bind to AAG, which is ↓ in pregancy.

Q: Local Anaesthetics Potency: Drug factors
A: Lipid solubility (higher = more potent)
Vasodilator action (more dilatation = less potent)

Q: Local Anaesthetics Systemic uptake: Drug and patient factors
A: Dose
- Fick's law
Use of vasoconstrictors
Site of entry (highest to lowest: intercost., caudal epidural, lumbar epidural, brachial plex., SC)

Q: Local Anaesthetics: Metabolism
A: Amides: Hepatic
Esters: Plasma esterases
Cocaine: both

Q: Local Anaesthetics: CNS toxicity potentiated by
A: Hypercarbia
Other CNS depressants

Q: Autocoid
A: Chemical messenger that acts on target cells close to the site of release, such as the cell itself and neighbouring cells

Q: Hormone
A: Chemical messenger produced by a ductless gland which has its action at a distant target cell via a specific protein receptor in this cell.

Q: TCA - Mechanism of Action
A: Competitive inhibition of NA and 5HT reuptake, antagonism of muscarinic, α, GABAa, histaminergic, and fast-Na channels

Q: TCA: CVS Toxicity
A: α-blockade (hypotension)
Fast-Na channel blockade (decreased myocardial impulse conduction)

Q: TCA OD - ECG findings
A: Wide QRS, right axis dev. of the terminal QRS, >3mm terminal R wave in aVR.
May also have: tachy, HB, ventricular arrhythmia

Q: Tricyclics: CNS toxicity
A: Predominantly anticholinergic: confusion, agitation, seziures, mydriasis

Q: Insulin synthesis and secretion
A: Rough ER of B cells in the Islets of Langerhans
Produced from proinsulin
Excreted via exocytosis

Q: Insulin pharmacokinetics
A: Minimally protein bound
Tiny Vd (0.075 L/kg), increased in diabetics.
Metabolised in liver, muscle, kidney by glutathione insulin transhydrogenase
Half-life 5 minutes
Renal elimination of inactive metabolites

Q: Actions of insulin that occur in seconds
A: Increased glucose, amino acid, ketone, and K+ uptake in muscle and fat

Q: Actions of insulin that occur in minutes
A: Increased muscle anabolism, decreased catabolism
Increased glycerol phosphate synthesis in fat
Decreased gluconeogenesis, ketogenesis and increased glycogen synthesis, protein synthesis, and lipid synthesis in liver

Q: Actions of insulin that occur over hours
A: Increased fatty acid synthesis in fat, increased cell growth

Q: Glucagon synthesis
A: Polypeptide hormone synthesised in pancreatic A cells

Q: Glucagon pharmacokinetics
A: Half-life 5 minutes
Hepatic metabolism. Secreted directly into the portal vein and so undergoes a high first pass metabolism

Q: Hepatic effects of glucagon
A: Glycogenolysis, gluconeogenesis, glucose release, ketone formation

Q: CVS effects of glucagon
A: Inotropy

Q: Metabolic effects of glucagon
A: Increased:
- Metabolic rate
- GH release
- Somatostatin release
- Lipolysis

Q: Stimulants to glucagon release
A: Hypoglycaemia & starvation
Amino acids
Physiological stress
β-agonists
Cortisol
ACh
Theophylline

Q: Somatostatin function
A: Polypeptide that inhibits secretion of glucagon, insulin, and other pancreatic peptides

Q: Compensatory mechanisms in long-term hypoglycaemia
A: SNS activation
Cortisol secretion
GH secretion

Q: BSL required to stimulate insulin release
A: 5.6

Q: Pattern of insulin secretion
A: Biphasic:
- Initial rapid release
- Prolonged, slow release

Q: Sensation of BGL by pancreas and method of insulin secretion
A: Glucose enters B cells via GLUT-2 transporter
Enters CAC and converted to pyruvate
Produced ATP inhibits ATP-sensitive K channels, reducing K efflux and depolarising membrane
Depolarisation increases Ca release, causing exocytosis of insulin granules (First release)
Glutamate produced during CAC stimulates maturation of other insulin granules, causing the second phase of insulin release

Q: BSL at which insulin secretion is inhibited
A: 4.6

Q: BSL at which glucagon secretion is stimulated
A: 3.8

Q: Effects of TSH
A: Increased iodine uptake
Increased iodination to form T4 and T3
Increased proteolysis of thyroglobulin

Q: Synthesis of thyroid hormone
A: Synthesised in follicles: single layer of cuboidal epithelium around a central lumen containing thyroglobulin.
Iodide transported into follicular cells, oxidised to iodine, and excreted into follicular cavity, where it iodinates thyroglobulin, which is then oxidised to T4 and T3.

Q: T4 halflife
A: 7 days

Q: T3 half-life
A: 24 hours

Q: Effects of thyroid hormone
A: Resp: ↑ MV due to ↑ CO2 production
CVS: ↑ HR, ↑ inotropy, ↑ CO, ↓ SVR, ↓ DBP
CNS: ↑ excitability
MSK: ↑ osteoblastic activity
GU: Impotence, oligomenhorrea
GIT:↑ GIT motility
Metabolic: ↑ BMR, ↑ carb, fat, and protein metabolism, ↑ thermogenesis,

Q: Acetazolamide: Class
A: Carbonic anhydrase inhibitor

Q: Acetazolamide: Indications (4)
A: Glaucoma, altitude sickness, epilepsy, diuresis

Q: Acetazolamide: Dosing
A: 250-1000mg in divided doses

Q: Acetazolamide: MoA
A: Noncompetive CA inhibitor in prox. tubule cells, reducing H+ prod. and subsequent Na reabsorption (via antiporter), causing alkaline diuresis.
Dec. aq. Humour production

Q: Acetazolamide: Absorption
A: 100% PO bioavailability

Q: Acetazolamide: Elimination
A: Urinary excretion (unchanged)

Q: Acetazolamide: Resp
A: Hyperventilation 2o to metabolic acidosis

Q: Acetazolamide: CNS
A: Decreased IOP
Decreased ICP 2o decreased CSF production

Q: Acetazolamide: GIT
A: Decreased gastric and pancreatic secretion

Q: Acetazolamide: GU
A: Diuresis
Urinary alkalinisation

Q: Adenosine: Class
A: Purine nuceloside

Q: Adenosine: Indications
A: - Reversion of AV nodal re-entry tachycardia
- Differentiation of SVT and VT

Q: Adenosine: Pharmaceutics
A: 3 mg.mL^–1 colourless solution

Q: Adenosine: MoA
A: Adenosine A_1 receptor agonist (G_i-coupled; located in AV node only), causing hyperpolarisation and reduction of Ca current, with subsequent blockade of AV nodal conduction

Q: Adenosine: Metabolism
A: Deaminated in plasma and absorbed by RBCs

Q: Adenosine: Elimination
A: Rapid deamination in plasma
T_½ <10 s

Q: Adenosine: CVS
A: ↓↓ AV nodal conduction, may cause AF/lutter
↓↓ inotropy (brief)
↓ SVR
Contraindicated in 2nd/3rd degree AV block and sick-sinus syndrome due to bradycardia (req. pacing) and VF

Q: Adenosine: Resp
A: Increased depth and rate of respiration. Potential bronchospasm (especially with concominant methylxanthines).

Q: Adenosine: CNS
A: Increased cerebral blood flow
Pain

Q: Adrenaline: Class
A: Naturally occurring catecholamine

Q: Adrenaline: Indications
A: HDx support
ACLS
Anaphylaxis
Vasoconstriction (Local anaesthetics)
Bronchoconstriction
Upper airway obstruction
Open angle glaucoma

Q: Adrenaline: Pharmaceutics
A: Naturally occurring catecholamine.
Clear acidic solution, 1:1000 or 1:10,000.
Light sensitive (brown glass).
Purged with nitrogen to prevent oxidation.

Q: Adrenaline: Dosing (Arrest)
A: 1mg

Q: Adrenaline: Dosing (Infusion)
A: 0.1-0.3mcg/kg/min (beta); >0.3mcg/kg/min (constrictive)

Q: Adrenaline: Distribution
A: Poor lipid solubility
Doesn't cross BBB

Q: Adrenaline: Metabolism
A: Metabolised by mitochondrial MAO and COMT within liver, kidney, and blood to VMA and metadrenaline (respectively).

Q: Adrenaline: Elimination
A: - t_½: 2 mins
- Urinary of inactive metabolites and their conjugates

Q: Adrenaline: Metabolic
A: ↑ BMR
↑ BSL
- Glycogenolysis in liver and muscle
- Gluconeogenesis
- Insulin variable (initially increaed with β_2 effect, decreased with α effect)
- Glucagon ↑
↑ FFA and ketones
- lipolysis activated (β3) and subsequent metabolism resulting in ketogenesis
Type B hyperlactataemia

Q: Adrenaline: Resp
A: Bronchodilation (potent)
↑ Minute ventillation (small)
↑ Secretion viscosity

Q: Adrenaline: CNS
A: ↑ Pain threshold
↑ MAC

Q: Adrenaline: GIT
A: Dec. intestinal tone and secretions

Q: Adrenaline: GU
A: ↓ RBF
Increased sodium reabsorbtion
- RAAS activation
Increased bladder sphincter tone
- Urinary retention

Q: Alfentanil: Class
A: Synthetic opioid

Q: Alfentanil: Pharmaceutics
A: Clear, colourless solution at 0.5/5 mg/ml. Low lipid solubility but pKa of 6.5 means a faster onset of action compared to fentanyl as most unionised at body pH

Q: Alfentanil: Mechanism of action
A: Highly selective MOP agonist.
GPCR, increases K conductance causing hyperpolarisation of cell membrane.

Q: Alfentanil: Onset
A: <90s

Q: Alfentanil: Duration
A: 5-10mins

Q: Alfentanil: Metabolism
A: Hepatic CYP3A3/4 to noralfentanil
Prolonged metabolism with midazolam due to CYP competition

Q: Gentamicin: Class
A: Aminoglycoside

Q: Aminoglycosides: Mechanism of action and spectrum
A: Block protein systhesis via binding to the 30S ribosomal subunit. Gram -ves. Limited Gram +ves. Nil anaerobic.

Q: Gentamicin: Dosing
A: 4-7mg/kg

Q: Gentamicin: Distribution
A: Vd 0.2L/kg, 70% protein bound, low lipid solubility. CSF penetration if meninges inflamed

Q: Gentamicin: Elimination
A: Excreted unchanged - prolonged elimination t0.5 1 up to 70/24 in renal impairment

Q: Gentamicin: Renal
A: Dose-dependent nephrotoxicity

Q: Gentamicin: CNS
A: Dose-dependent ototoxicity.
Increased risk with frusemide use.
Reduces ACh release, causing weakness.

Q: Gentamicin: Monitoring
A: Trough before dose. Peak 1/24 post dose.

Q: Amiodarone: Class
A: Class III antiarrythmic

Q: Amiodarone: Indications
A: Tachyarrythmias inappropriate for or resistant to treatment with other drugs

Q: Amiodarone: Pharmaceutics
A: 100/200mg tablets. Ampoule of 30/50 mg/ml, which should be reconstituted in dextrose.

Q: Amiodarone: Mechanism of Action
A: K+ channel blockade ↓ repolarisation (Class III)
β-blocker-like activity on SA and AV nodes, ↓ automaticity and nodal conduction (Class II)
Ca2+ channel blocker-like activity, ↓ inward Ca2+ current, ↑ depolarisation time and ↓ nodal conduction (Class IV)
α-blocker-like activity, ↓ SVR

Q: Amiodarone: Absorption
A: 50% PO bioavailability

Q: Amiodarone: Onset
A: 1/24 IV
Days to weeks PO

Q: Amiodarone: Distribution
A: Variable Vd, up to 70L/kg. 96% protein bound

Q: Amiodarone: Metabolism
A: Hepatic CYP3A4 to desethylamiodarone (weakly active)
Inhibits CYP3A4

Q: Amiodarone: Elimination
A: Biliary, skin and lacrimal glands
Amiodarone t_½ up to 55 days.
Desethylamiodarone t_½ 36 days (average)

Q: Amiodarone: CVS
A: ↓HR, ↓BP, ↓SVR; especially during rapid IV administration
↑QT without risk of TDP
Irritant to peripheral veins

Q: Amiodarone: GIT
A: Deranged LFTs, cirrosis, hepatitis (typically long-term use)

Q: Amiodarone: Endocrine
A: Hypothyroidism (6%), Hyperthyroidism (1%)

Q: Amiodarone: Resp
A: Pneumonitis, fibrosis or pleuritis in 10% at 3 years (10% mortality)

Q: Ampicillin: Class
A: Beta-lactam

Q: Ampicillin: Spectrum of activity
A: Gram +ve, Gram -ves inc. H. influenza, salmonella, E. coli, E. faecalis

Q: Ampicillin: MoA
A: Bacteriocidal. Prevents cell wall synthesis.

Q: Penicillins: Absorption
A: Good oral bioavailability

Q: Aspirin: Class
A: Non-selective NSAID

Q: Aspirin: Indications
A: Anti-platelet for TIA/MI/CABGs
Analgesia (including migraine)
Anti-inflammatory
Pre-eclampsia

Q: Aspirin: Pharmaceutics
A: White 100/300mg tablet of acetylsalicic acid

Q: Aspirin: MoA
A: Low dose
- Selective inhibition of platelet COX1 (irreversible; preventing thromboxane A2 production and aggregation) with sparing of endothelial COX1 (preserving PG I_2 production and resulting vasodilation)
High dose
- Non-selective inhibition of both COX isoforms

Q: Aspirin: Absorption
A: 70% bioavailability
Weak acid with a pKa of 3 - absorbed in stomach
Bulk absorption in small bowel despite alkaline environment

Q: Aspirin: Distribution
A: 85% protein bound
Weak acid with a pKa of 3, unionised in the stomach and unionised at physiological pH

Q: Aspirin: Metabolism
A: Hydrolyzed to salicylate (active) in GI mucosa, which is conjugated in liver to salicyluric acid
- Processes saturated in overdose

Q: Aspirin: Elimination
A: t_1/2 15-30 mins (unless zero order kinetics)
Urinary excretion (enhanced by alkaline urine)

Q: Aspirin: Haeme
A: Inhibited platelet aggregation, increased bleeding time

Q: Aspirin: Resp
A: Increased oxygen consumption and CO2 production due to uncoupled oxidative phosphorylation
Respiratory depression in overdose - may cause mixed respiratory and metabolic acidoses.
May induce asthma

Q: Aspirin: CNS
A: Antipyretic

Q: Aspirin: GIT
A: GI ulceration due to impaired mucous production

Q: Aspirin: GU
A: Proteinuria and casts

Q: Atropine: Class
A: Tertiary amine, antagonist of ACh at the muscarinic receptor

Q: Atropine: Indications
A: Bradycardia from vagal tone
Organophosphate poisoning
Counter muscarinic effects
Reversal of neuromuscular blockade

Q: Atropine: Pharmaceutics
A: Tertiary amine.
Clear, colourless solution at 0.6mg/ml. Racemic - action through L enantiomer.

Q: Atropine: MoA
A: Muscarinic antagonist

Q: Atropine: Duration
A: 1-2 hours

Q: Atropine: Distribution
A: Vd 1-2L/kg, rapidly distributed from central compartment. 50% protein bound

Q: Atropine: Metabolism
A: Hepatic esterases

Q: Atropine: Elimination
A: t0.5 2-3/24. Renal excretion of metabolites

Q: Atropine: CVS
A: Tachyardia (bradycardia at low doses through augmented vagal flow), peaks within 2-4 minutes

Q: Atropine: Resp
A: Bronchodilation
Decrease secretions
Increase RR

Q: Atropine: CNS
A: Central anticholinergic syndrome (less than hyoscine): Somnolence, confusion, amnesia, agitation, hallucinations, dysarthria, ataxia, delirium

Q: Atropine: GIT
A: Dec. salivation (less than hyoscine), gastric secretions, and tone

Q: Atropine: Renal
A: Urinary retention

Q: Benzylpenicillin: Class
A: Betalactam

Q: Benzylpenicillin: Spectrum
A: Gram+ve, gram-ve cocci, some gram -ve bacilli.

Q: Penicillins: Metabolism
A: Small portion hepatically metabolised

Q: Penicillins: Elimination
A: Majority eliminated as unchanged drug

Q: Benzylpenicillin: CNS
A: Lower seizure threshold

Q: Bupivicaine: Class
A: Amide local anaesthetic

Q: Bupivicaine: Pharmaceutics
A: Racemic mixture.
0.25-0.5% solutions ± 1:200 000 adrenaline OR 8% glucose.
R enantiomer has increased cardiotoxicity - some preparations have levobupivacaine only.

Q: Local anaesthetic: MoA
A: Block intracellular part of voltage gated Na channels in their inactive-closed stage

Q: Bupivicaine: Dosing
A: Up to 2mg/kg

Q: Bupivicaine: Onset
A: 1-15min

Q: Bupivicaine: Duration
A: Up to 9/24

Q: Bupivicaine: Distribution
A: 95% protein binding, high lipid solubility, pKa 8.1 - slower onset than lignocaine

Q: ACE-Is: Indications (4)
A: HTN
CCF
Diabetic Nephropathy
Post MI with LV dysfunction

Q: ACE-Is: MoA
A: Inhibit ACE, preventing conversion of angiotensin I to II.
May modualate sympathetic tone and kallikrein-kinin-prostaglandin system

Q: ACE-Is: Absorption
A: Generally good bioavailability (25-75%)

Q: ACE-Is: Distribution
A: Variable protein binding: 30-70%

Q: ACE-Is: CVS
A: ↓ SVR and preload, leading to ↓ BP.
Unaffected HR and baroreceptor response.

Q: ACE-Is: Renal
A: With a normal renal perfusion pressure: natriuresis
With low renal perfusion pressure: pre-renal failure (e.g. renal artery stenosis).
Increased renin production.

Q: ACE-Is: Resp
A: Bradykinin cough

Q: β-blockers: MoA
A: Decreased adenylcyclase and intracellular Ca, resulting in dec. HR, CO, and myocardial oxygen consumption

Q: Ceftriaxone: Class & generation
A: Cephalosporin, 3rd gen

Q: Ceftriaxone: Distribution
A: Vd 10L, 90% protein bound (displaces bilirubin from albumin causing hyperbilirubinaemia), crosses BBB

Q: Ceftriaxone: Elimination
A: t0.5 8/24. Predominant unchanged urinary excretion

Q: Ciprofloxacin: Class
A: Fluoroquinolone

Q: Ciprofloxacin: Mechanism and Spectrum
A: Bacteriocidal. Inhibit alpha subunit of DNA gyrase.
Gram+ve, Gram-ve, including anaerobes.

Q: Ciprofloxacin: Absorption
A: 80% bioavailability

Q: Ciprofloxacin: Distribution
A: 2L/kg, [tissue]>[serum], 40% protein bound, CSF penetration

Q: Ciprofloxacin: Metabolism
A: Hepatic, limited activity of metabolites

Q: Ciprofloxacin: Elimination
A: t0.5 4/24, active tubular secretion

Q: Ciprofloxacin: Interactions
A: Inc. risk of tendonopathy with concominant steroid use

Q: Ciprofloxacin: CNS/Other
A: Neuropsychiatric disturbances
Achilles tendon rupture

Q: Clonidine: Indications
A: HTN, pain, sedation, opiate and ETOH withdrawal

Q: Clonidine: MoA
A: Decreased central sympathetic outflow through central presynaptic α2 stimulation: analgesia, sedation, anti-HTN, anxiolytic

Q: Clonidine: CVS
A: Initial hypertension (peripheral stimulation) followed by hypotension and bradycardia
Decreased coronary resistance
Rebound HTN when ceased

Q: Clonidine: CNS
A: Sedation and anxiolysis (at low doses), analgesia without respiratory depression

Q: Clonidine: Metabolic
A: Increased BSL secondary to alpha-adrenergic stimulation

Q: Clonidine: Renal
A: Diuresis (likely ADH inhibition)

Q: Clonidine: Absorption
A: 100% PO bioavailability

Q: Clonidine: Distribution
A: Vd 2L/kg, highly lipid soluble (crosses BBB)

Q: Clonidine: Metabolism
A: Hepatic to inactive metabolites

Q: Clopidogrel: Class
A: Platelet ADP antagonist

Q: Clopidogrel: Dosing
A: Load: 300mg, Daily 75mg

Q: Clopidogrel: MoA
A: Irreversibly prevents ADP from binding to the receptor on platelet surface, preventing glycoprotein IIb/IIIa becoming active

Q: Clopidogrel: Duration
A: 5 days

Q: Clopidogrel: Distribution
A: 98% protein bound

Q: Clopidogrel: Metabolism
A: Prodrug, requires two-step oxidation via CYP 3A4/5, CYP2C19.
Small proportion to active drug and remainder to inactive metabolites

Q: Clopidogrel: Elimination
A: t0.5 6/24, active metabolite t0.5 30mins

Q: Clopidogrel: GIT
A: Mucosal irritation

Q: Dexmedetomidine: Class
A: Central ?2 agonist

Q: Dexmedetomidine: Pharmaceutics
A: D-stereoisomer of medetomidine

Q: Dexmedetomidine: MoA
A: Decreased central sympathetic outflow through central presynaptic ?2 stimulation, similar to clonidine but greater selectivity and potency. Greater sedation/analgesia

Q: Dexmedetomidine: Onset
A: 5-10min

Q: Dexmedetomidine: Distribution
A: Vd 1L/kg, 95% protein bound, lipid soluble

Q: Dexmedetomidine: Metabolism
A: Hepatic via N-glucuronidation, N-methylation, CYP2A6

Q: Dexmedetomidine: CVS effects
A: Dec. MAP and HR

Q: Dexmedetomidine: CNS
A: Sedation
Anxiolysis
Analgesia

Q: Dexmedetomidine: Interactions
A: Pharmacodynamic interaction with volatiles and analgesia

Q: Diazepam: Uses (6)
A: Anxiolysis, withdrawal, anticonvulsant, sedation, amnestic, muscle relaxation

Q: Benzodiazepines: MoA
A: Enhance receptor affinity for GABA, increasing inhibitory neurotransmisison by opening Cl- channels causing hyperpolarisation of the post-synaptic cell

Q: Diazepam: Absorption
A: PO 85% bioavailability, erratic IM absorption

Q: Diazepam: Distribution
A: Vd 1L/kg, 99% protein bound

Q: Diazepam: Metabolism
A: Hepatic to all active metabolites including oxazepam, tempazepam, and des-methyl-diazepam (has t_1/2β up to 100 hours)

Q: Diazepam: Elimination
A: t0.5 20-50 hours, active metabolite t0.5 100 hours

Q: Digoxin: Indications
A: AF, Aflutter, SVT, CCF

Q: Digoxin: Class
A: Cardiac glycoside

Q: Digoxin: Pharmaceutics
A: 62.5/125/250mcg tablets, a clear colourless solution containing 250mcg/ml. Narrow therapeutic window requring monitoring, usually 0.5-2mcg/L

Q: Digoxin: MoA
A: Inhibit Na/K ATPase -> inc. intracellular Na -> reducing Na/Ca pump action -> causing inc. intracellula Ca -> inc. inotropy. Inc Na causes dec. K, prolonging AV refractory period and slowing pacemakers. Also inc. vagal tone.

Q: Digoxin: Absorption
A: 70% PO bioavailability, varies with formulation

Q: Digoxin: Onset
A: PO 1-2/24, IV 5-60mins (peak 2/24)

Q: Digoxin: CVS
A: ↓ HR
↑ Inotropy
Arrhythmia (exacerbated by hypokalaemia, hypercalcaemia and acidosis)
- Bigemini
- PVCs
- 1st/2nd/3rd degree AV block
- SVT, VT

Q: Digoxin: Renal
A: Moderate diuretic effect
Hyperkalaemia in severe acute toxicity

Q: Digoxin: CNS
A: Deranged red-green colour perception, weakness, coma.
Headache, lethargy, confusion.

Q: Digoxin: Distribution
A: Vd 10L/kg - ↑ in hyperthyroidism, ↓ in hypothyroidism
30% protein bound

Q: Digoxin: Metabolism
A: Minimal hepatic metabolism, excreted unchanged

Q: Digoxin: Elimination
A: t0.5 30 hours. Elimination of unchanged drug - clearance dependent on renal function

Q: Digoxin: Interactions
A: ↑ Risk of dysrythmias with amiodarone, verapamil

Q: Digoxin: Toxicity
A: >2.5mcg/L leads to arrythmias and AV block, a change in red-green colour perception

Q: Diltiazem: Class
A: Benzothiazepine

Q: Diltiazem: Indications
A: Angina
HTN
SVT
Raynauds
Migraine
Oesophageal dysmotility

Q: Diltiazem: GIT
A: Decreased LOS tone

Q: Diltiazem: GU
A: Renal artery dilatation leading to diuresis
Tocolysis

Q: Diltiazem: Absorption
A: 40% bioavailability - high first pass metabolism

Q: Diltiazem: Metabolism
A: Hepatic active metabolites

Q: Diltiazem: Excretion
A: t0.5 4/24, of active drug and active metabolites

Q: Diltiazem: Interactions
A: Serious bradycardias when coadministered with β-blocker

Q: Dipyridamole: Class
A: Phosphodiesterase inhibitor

Q: Dipyridamole: Indication
A: CVA prevention

Q: Dipyridamole: MoA
A: Inhibits phosphodiesterase, increasing platelet cAMP, ↓ Ca2+, inhibiting platelet adhesion > aggregation
Also acts as a coronary vasodilator

Q: Dipyridamole: Dosing
A: 200mg BD for CVA prevention

Q: Dipyridamole: CVS
A: Potent vasodilator (via phosphodiesterase inhibition) - unsafe in recent MI and AS

Q: Dobutamine: Class
A: Synthetic catecholamine derivative (of isoprenaline)

Q: Dobutamine: Pharmaceutics
A: White powder for reconstitution, or clear fluid for injection. Should not be mixed with alkaline solutions.

Q: Dobutamine: Indications
A: Inotropic support in CCF/shock, pharmacological alternative to exercise stress-test

Q: Dobutamine: CVS
A: ↑ HR, CO, contractility, and automaticity.
Arrhythmogenic.
β2 effects may ↓ BP

Q: Dobutamine: Dosing
A: 2.5-40mcg/kg/min, low toxicity below 10mcg/kg/min

Q: Dobutamine: Metabolism
A: Hepatic by COMT (no MAO) to inactive metabolites

Q: Dobutamine: Elimination
A: Renal of unchanged drug and metabolites t _½ 2min

Q: Dopamine: Class
A: Natural catecholamine

Q: Dopamine: MoA
A: D1 (vasodilator) and D2 central receptor activation at low dose.
β>α at mid-dose.
α>β at high dose.

Q: Dopamine: Pharmaceutics
A: Adminster vial central line, not with an alkaline solution.

Q: Dopamine: Dosing
A: Low: 1-5mcg/kg/min
Mid: 5-15mcg/kg/min
High: >15mcg/kg/min

Q: Dopamine: CVS
A: Vasodilator at low dose
↑  chronotropy, ↑ inotropy at mid dose
↑ SVR and PVR at high dose

Q: Dopamine: CNS
A: Nausea due to effect on CTZ

Q: Dopamine: GIT
A: Splanchnic vasodilatation

Q: Dopamine: GU
A: Increased renal blood flow ith no effect on kidney function

Q: Dopamine: Distribution
A: Does not cross BBB

Q: Dopamine: Metabolism
A: Renal, hepatic, plasma by COMT and MAO. 25% of dose converted to norad

Q: Dopamine: Elimination
A: t0.5 2min, urinary excretion of metabolites

Q: Enoxaparin: Class
A: LMWH

Q: Enoxaparin: Pharmaceutics
A: Smaller fragments of heparin, prepared from UFH, with a mean molecular weight of 5000

Q: Enoxaparin: MoA
A: Inhibits Xa by potentiating action of ATIII inhibition of serine proteases

Q: Enoxaparin: Absorption
A: 90% bioavailability after SC injection

Q: Enoxaparin: Distribution
A: Vd 4.3L, does not bind to heparin binding proteins

Q: Enoxaparin: Metabolism
A: Hepatic to lower molecular weight fragments

Q: Enoxaparin: Elimination
A: t0.5 2-4x that of heparin, independent of dose. Renal excretion of active and inactive fragments

Q: Erythromycin: Class
A: Macrolide

Q: Erythromycin: MoA and Spectrum
A: Prevent bacterial protein synthesis by binding to 50S subunit.
Gram+ve, anerobes (including gram-ve), Neisseria & haemophilis

Q: Erythromycin: Absorption
A: 40% PO bioavailability

Q: Erythromycin: Distribution
A: 80% protein bound

Q: Erythromycin: Metabolism
A: Hepatic via demethylation

Q: Erythromycin: Elimination
A: t0.5 2/24, faecal excretion

Q: Erythromycin: CVS
A: QT prolongation

Q: Erythromycin: GIT
A: Prokinesis, nausa, vomiting

Q: Esmolol: Indications
A: Tachycardia, HTN, SVT termination

Q: Esmolol: Pharmaceutics
A: Clear solution at 10mg/ml. Irritant to veins

Q: Esmolol: Onset/Offset
A: Peak within 6-10 minutes, attenuation within 20 minutes

Q: Esmolol: Metabolism
A: Hydrolysis to RBC esterases to inactive metabolite
Half-life ~9 mins

Q: Fentanyl: Pharmaceutics
A: Clear colourless citrate solution at 50mcg/ml
Transdermal patches at 25-100mcg/hr

Q: Fentanyl: Absorption
A: No oral bioavailability due to first pass hepatic metabolism
50% bioavailability when buccal/SL
Rapid onset due to lipid solubility 600x that of morphine

Q: Fentanyl: Onset (IV/IM/TD)
A: IV: 30s
IM: 7-8min
Transdermal: 6/24

Q: Fentanyl: Metabolism
A: Significant first pass pulmonary metabolism
Hepatic demethylation to inactive norfentanyl

Q: Fentanyl: Elimination
A: Renal of inactive metabolites
IV t_1/2 190 mins
Prolonged context sensitive half-time following infusion

Q: Fentanyl: Unique CVS
A: Bradycardia but less hypotension than morphine

Q: Fentanyl: Resp
A: Respiratory depression
Bronchospasm RARE due to minimal histamine release.

Q: Flecainide: Class
A: Class Ic antiarrhythmic

Q: Flecainide: Indications
A: Paroxysmal AF/flutter, SVT, ventricular arrhythmias

Q: Flecainide: Pharmaceutics
A: IV 10mg/ml, PO 50-100mg.

Q: Flecainide: MoA
A: Class Ic antiarrhythmic. Local anaestheic agent which prolongs phase 0 of the AP by blocking fast sodium channels. No effect on AP duration or refraction.

Q: Flecainide: Absorption
A: 90% PO bioavailability

Q: Flecainide: Distribution
A: 50% protein bound

Q: Flecainide: Metabolism
A: Hepatic with active metabolites

Q: Flecainide: Dosing (Loading)
A: Bolus 2mg/kg over 10min, then 1.5mg/kg/hr for 1/24

Q: Flecainide: Dosing (PO)
A: 100-200mg BD

Q: Flecainide: CVS
A: ↓ Inotropy
Antiarhythmic except proarrythmogenic especially in the setting of LV dysfn/MI
↑ Pacing threshold

Q: Flecainide: CNS
A: Visual disturbances

Q: Flecainide: Interactions
A: Pharmacokinetic interactions with digoxin, propranolol, amiodarone

Q: Flucloxacillin: Class
A: Betalactam

Q: Penicillins: Mechanism of Action
A: Prevent peptidoglycan cross-linking, preventing cell-wall synthesis

Q: Flucloxacillin: Absorption
A: 70% PO bioavailability, well absorbed

Q: Flucloxacillin: Distribution
A: 95% protein bound, CSF penetration only with inflamed meninges

Q: Flumazenil: Class
A: Imidazobenzodiazepine. Competetive antagonist of BDZ

Q: Flumazenil: Indications
A: Reversal of BDZ sedation

Q: Flumazenil: MoA
A: Inverse agonist at GABAa.
Does not antagonise GABA-ergic neurons by non BDZ means (e.g. ETOH/barbs/GA)

Q: Flumazenil: Dosing (Bolus)
A: 0.1-0.3mg boluses up to 2mg

Q: Flumazenil: Onset
A: 1-3min

Q: Flumazenil: Duration
A: 1/24. Return to sedation is concerning given duration of action of BDZ

Q: Flumazenil: Distribution
A: Vd 0.5L/kg, 50% protein bound

Q: Flumazenil: Metabolism
A: Hepatic, high ER

Q: Flumazenil: Elimination
A: Biphasic t0.5, initially 10min, terminal 4080min

Q: Flumazenil: Precautions
A: Precipitation of withdrawal syndrome in dependent patient, convulsions

Q: Frusemide: Class
A: Loop diuretic

Q: Frusemide: Pharmaceutics
A: Clear solution, must be protected from light, at 10mg/ml

Q: Frusemide: MoA
A: Arteriolar vasodilation, reducing TPR. Blocks Na.K.2Cl symporter in the thick ascending limb

Q: Frusemide: Onset (PO/IV)
A: 30-60min PO onset, 5min IV onset

Q: Frusemide: Duration (PO/IV)
A: PO duration 6/24, IV duration 2/24

Q: Frusemide: Distribution
A: Vd 0.1L/kg, 99% protein bound

Q: Frusemide: Elimination
A: t0.5 0.5-2/24 (N renal fn), ESRD t0.5 9/24. 50% renal excretion as unchanged drug

Q: Frusemide: CVS
A: Pulmonary and systemic vasodilation
Diuresis causing decreased preload

Q: Frusemide: Renal
A: Diuresis and increased free water clearance. Increased RBF favouring corticomedullary flow. Reduced oxygen consumption in loop of henle

Q: Frusemide: Electrolyte & Metabolic
A: Hypokalaemia, hyponatraemia, hypomagnesaemia, hypochloraemic alkalosis.
Ototoxicity (usually transient), interstitial nephritis.

Q: GTN: Class
A: Organic nitrate

Q: GTN: Indications
A: Angina, APO, LVH, HTN

Q: GTN: Pharmaceutics
A: Tablets, patches, clear liquid at 5mg/ml. Presented in a glass vial as it absorbed into plastics:
- ~40-80% of the IV dose will be absorbed into giving set.

Q: GTN: MoA
A: NO donor, which stimulates guanylate cyclase to reduce intracellular Ca in smooth muscle cells, causing vasodilation (venous>arterial)

Q: GTN: Absorption
A: 5% bioavailability via oral route due to high first pass metabolism. Rapid absorption from sublingual muscosa

Q: GTN: Metabolism
A: Hepatic and within erythrocytes by nitrate reductase into active dinitrates/mononitrates/nitrites

Q: GTN: Elimination
A: t0.5 1-4mins. Urinary excretion

Q: GTN: CVS
A: Vasodilation of predominantly capacitance vessels: ↓ preload, ↓ VR, ↓ EDP, ↓ wall tension, ↓ myocardial O2 consumption (causing relief of angina)
- Arterial dilatation at high doses only (reflex tachycardia)
CO unchanged
Coronary vasodilation
- Coronary flow unchanged but redistributed subendocardial flow to ischaemic areas.

Q: GTN: Resp
A: Bronchodilatation
- May worsen V/Q mismatch

Q: GTN: CNS
A: ↑ CBF, which may cause HA

Q: Heparin: Indications
A: VTE, ACS, Haemodialysis, circuit prophylaxis (ECMO/Bypass)

Q: Heparin: Pharmaceutics
A: Derived from porcine intestinal mucosa rich in mast cells. Described in terms of IU rather than weight as collection of variable weight proteins with variable potencies

Q: Heparin: Absorption
A: Reduced bioavailability SC due to endothelial binding.

Q: Heparin: Distribution
A: Does not cross BBB or placenta, very high protein binding

Q: Heparin: Metabolism
A: Heparinases in liver, kidneys, and RAS

Q: Heparin: Elimination
A: t0.5: Variable. Binds to endothelial cells at low doses leading to short half-life, as dose is increased half-time is prolonged up to 150min

Q: Heparin: MSK
A: Osteoporosis (>1/12 use)

Q: Heparin: Reversal
A: Protamine, 1mg per 100 IU

Q: Hydralazine: Class
A: Antihypertensive/Direct vasodilator

Q: Hydralazine: Indications
A: HTN
Pre-eclampsia
CCF

Q: Hydralazine: Dosing
A: 25/50mg PO, 5-20mg IV

Q: Hydralazine: Pharmaceutics
A: 20mg ampoule or powder. Should not be reconstituted with dextrose.

Q: Hydralazine: MoA
A: Direct action on vascular smooth muscle:
- Activates guanylate cyclase, increasing cGMP levels, inhibiting calcium, causing relaxation

Q: Hydralazine: CVS
A: Arteriolar vasodilation with compensatory tachycardia and increased CO

Q: Hydralazine: CNS
A: Increased CBF

Q: Hydralazine: Renal
A: Increasd RBF but also sodium retention

Q: Hydralazine: Absorption
A: 30% bioavailability due to high first pass metabolism

Q: Hydralazine: Distribution
A: V_D 4L/kg, 90% protein bound

Q: Hydralazine: Metabolism
A: N-acetylated in gut and liver

Q: Hydralazine: Elimination
A: Dependent on acetylation rates

Q: Hydrochlorothiazide: Class
A: Thiazide diuretic

Q: Hydrochlorothiazide: MoA
A: Secreted into the PCT. Inhibits Na reabosption in DCT by blocking Na/Cl symporter. Also vasodilate and reduce TPR.

Q: Hydrochlorothiazide: Duration
A: 6-12/24

Q: Hydrochlorothiazide: Distribution
A: Vd 3L/kg, 70% protein bound

Q: Hydrochlorothiazide: Elimination
A: t0.5 6-12 hours as unchanged drug

Q: Hydrochlorothiazide: Fluid and Electrolyte
A: Hypokalaemia, hyponatraemia, hypochloraemic alkalosis, hypomagnesaemia

Q: Ibuprofen: Class
A: NSAID
Best safety profile of NSAIDs

Q: Ibuprofen: Pharmaceutics
A: White 200mg tablets

Q: Ibuprofen: Mechanism of Action
A: Reversible COX-1 & COX-2 inhibition, resulting in decreased formation of prostaglandin precursors.
Antipyretic, analgesic, anti-inflammatory properties

Q: Ibuprofen: Absorption
A: 85% bioavailability, rapid absorption.
pKa 4.5 - absorbed SB.

Q: Ibuprofen: Onset
A: 30-60mins

Q: Ibuprofen: Duration
A: 4-6/24

Q: Ibuprofen: Distribution
A: Vd 6.3L, 99% protein bound. May displace highly protein bound drugs e.g. warfarin.

Q: Ibuprofen: Metabolism
A: Hepatic to inactive metabolites

Q: Ibuprofen: Elimination
A: Renal of inactive metabolites

Q: Isoprenaline: Class
A: Synthetic catecholamine, predominantly ? agonist

Q: Isoprenaline: Indications
A: Heart block, unstable bradycardia, shock

Q: Isoprenaline: MoA
A: β1 and β2 agonist, activates andenyl cyclase, catalysing conversion of ATP to cAMP, inc. membrane permeability to Ca

Q: Isoprenaline: Dosing
A: 20mcg bolus or 0.5-10mcg/min

Q: Isoprenaline: Metabolism
A: Hepatic and pulmonary via COMT to inactive metabolites

Q: Isoprenaline: Elimination
A: t0.5 2.5-5 min

Q: Isoprenaline: CVS
A: ↑ HR, CO, contractility, and automaticity. Β2 effects may drop BP.

Q: Isoprenaline: Resp
A: Potent bronchodilator but worsens V/Q matching - increased mortality overall

Q: Ketamine: Class
A: Phencyclidine (PCP) derivative, which produces dissociative anaesthesia

Q: Ketamine: Indications
A: Induction
Procedural sedation
Analgesia
Asthma

Q: Ketamine: Pharmaceutics
A: Clear colourless solution at 10/50/100mg m/l of (usually) racemic ketamine hydrochloride.
pKa 7.5; solution pH 3.5-5.5 when reconstituted with water.
S enantiomer is 2-3x as potent, faster metabolised, and better SE profile.

Q: Ketamine: MoA
A: Non-competitive antagonist of NMDA and glutamate receptors in the CNS.
Some opioid, ACh, Na^+, and Ca^++ channel effect

Q: Ketamine: Dosing (Induction, IV/IM)
A: IV: 0.5-2mg/kg over 60s. IM: 4-10mg/kg

Q: Ketamine: Duration (IV/IM)
A: IV: 5-10min, IM: 10-20min

Q: Ketamine: Onset (IV/IM)
A: IV: 30s, IM: 2-8min

Q: Ketamine: Dosing (Analgesia)
A: 0.1-0.3mg/kg/hr

Q: Ketamine: Dosing (Anaesthesia, maint)
A: 0.6-3mg/kg/hr

Q: Ketamine: Dosing (Sedation, IV/IM)
A: IV: 0.2-0.75mg/kg IM: 2-4mg/kg. Maintenance of sedation is a 25% of the anesthesia maintenance dose, i.e. 0.15-0.75mg/kg/hr)

Q: Ketamine: CVS
A: ↑ HR, BP, CVP, CO due to ↑ sympathetic tone; R- > S-ketamine.
Myocardial depressant effect, beware pt with maximal sympathetic tone.

Q: Ketamine: Resp
A: Brief apnoea with rapid infusion.
Respiratory stimulant and bronchodilation.
Relative preservation of airway reflexes.
Maintained respiratory response to hypercapnoea.

Q: Ketamine: CNS
A: Dissociation, analgesia, emergence phenomena (hallucinations, delirium).
Dissociative anaesthesia by dissociating thalmaocortical and limbic systems on EEG.
Purposeful movements unrelated to stimulus may occur even during surgical anaesthesia.
↑ IOP.

Q: Ketamine: GIT
A: Increased secretions
Nausea, vomiting.

Q: Ketamine: Metabolic
A: Increased circulating catecholamines

Q: Ketamine: GU
A: Interstitial cystitis in chronic use

Q: Ketamine: Absorption
A: 16% oral bioavailability. Intranasal 50%.

Q: Ketamine: Distribution
A: Vd 3L/kg, 50% protein bound
High lipid solubility

Q: Ketamine: Metabolism
A: Hepatic, CYP450 to norketamine (30% as potent), which is metabolised to an inactive glucoronide

Q: Ketamine: Elimination
A: Bi-exponential
 - Rapid initial redistribution across lipid membranes
 - Slow hepatic metabolism, terminal elimination t_½ 1 hour
Urinary of inactive and active metabolites

Q: Labetalol: Class
A: β1 and non-selective α-blocker (β:α = 1:3 PO, 1:7 IV)

Q: Labetalol: Indications
A: HTN
Hypertensive emergencies (incl. pregnancy, alpha-agonist overdose, phaeochromocytoma)
Controlled hypotension
AMI

Q: Labetalol: Peak and Duration (IV)
A: Peaks at 10 min
Lasts 50min

Q: Levosimendan: Class
A: Ca sensitiser/Phosphodiesterase inhibitor

Q: Levosimendan: Indications
A: Short term management of severe acute heart failure

Q: Levosimendan: MoA
A: Binds to troponin C increasing myofilament Ca2+ sensitivity.
Also opens K+ channels causing vasodilation.
May have some PDE5 inhibition effect.

Q: Levosimendan: Dosing
A: IV. Loading dose 12-34mcg/kg over 10 min. Infusion rate 0.05-0.2 mcg/kg/min.

Q: Levosimendan: Duration (IV)
A: Half life of of parent drug levosimendan 1 hour. Half life of active metabolite 70-80 hours.

Q: Levosimendan: CVS
A: ↑ inotropy
Vasodilation
↑ in QTc, ↑ risk of arrhythmias

Q: Lignocaine: Class
A: Amide local anaesthetic, Class 1b antiarrhythmic

Q: Lignocaine: Indications
A: Ventricular arrhythmias, spinal, epidural, regional, local anaesthesia

Q: Lignocaine: Pharmaceutics
A: Solutions (0.5-2% ± adrenaline 1:80 000 - 200 000)
Gel (2%)
Ointment (5%)
Sprays (4%)
EMLA (2.5% with 2.5% prilocaine)

Q: Lignocaine: MoA
A: Blocks Na+ channels, rate of rise of phase 0 is ? action potential period is ?. In pacemaker cells phase 4 is prolonged reducing automacity.

Q: Lignocaine: Distribution
A: Protien bound, 60-80% to α1-acid glycoprotein
25% unionized at pH 7.4 (weak base with pKa of 7.9)
Highly lipid soluble

Q: Lignocaine: Metabolism
A: 90% hepatic with some active metabolites

Q: Lignocaine: Elimination
A: Biphasic half life, 7-30 min, 2 hours. (prolonged with CHF, liver disease, shock, RF). Excreted in urine (~90% as metabolites, 10% unchanged)

Q: Lignocaine: SE CNS
A: Active metabolites can accumulate causing CNS toxicity. Confusion, sedation, agitation, parathesia.

Q: Magnesium: Indications
A: Termination of VF/torsades, digitalis toxicity, pre-eclampsia/eclampsia, acute severe asthma, tocolysis, tetanus, hypoMg

Q: Magnesium: Mechanism of Action
A: Many:
- Antagonises entry of Ca2+
- Binds to cellular ATP acting as a cofactor for Na+/K+ ATPase, affecting cell membrane potential

Q: Magnesium: Distribution
A: 30% bound to albumin

Q: Mannitol: Class
A: Osmotic Diuretic

Q: Mannitol: Indications
A: Reduces intracranial and intraoccular pressure. Used to test airway hyperresponsiveness

Q: Mannitol: Pharmaceutics
A: 100g in 1000ml or 500ml (10 or 20%) solution

Q: Mannitol: MoA
A: Increases plasma osmolality drawing water out of CSF and vitreous body

Q: Mannitol: Onset
A: Diuresis 1-3 hours, ?ICP 15-30 min.

Q: Mannitol: Distribution
A: Confined to extracellular space, does not cross BBB

Q: Mannitol: Metabolism
A: Minimal hepatic metabolism to glycogen

Q: Mannitol: Elimination
A: Halflife 4.7 hours, excreted in urine 55-85% unchanged

Q: Meropenem: Class
A: Carbapenem, beta lactam

Q: Meropenem: Structure
A: Fused beta-lactam ring and an unsaturated five member ring with a carbon atom instead of a sulphur atom like penicillin

Q: Meropenem: Pharmaceutics
A: White crystal for reconstitution, 500mg or 1g

Q: Meropenem: MoA
A: Inhibits cell wall synthesis, binds penicillin-binding proteins, inhibiting final transpeptidation step of peptidoglycan synthesis.

Q: Meropenem: Distribution
A: ~0.3L/kg. 2% protein bound. Crosses the BBB with CSF conc equalling plasma.

Q: Meropenem: Metabolism
A: Partially hepatic

Q: Meropenem: Elimination
A: Half life 1-1.5 hours (renal impairment increases signif), excreted in urine ~70% as unchanged drug

Q: Meropenem: SE
A: Injection site irritation
Seizures with high doses
Caution in renal failure

Q: Metoprolol: Class
A: Beta Blocker, selective with no intrinsic sympathomimetic activity

Q: Metoprolol: Pharmaceutics
A: PO as IR or SR formulations.
IV formulation 1mg/ml.

Q: Metoprolol: Absorption
A: Extensive first pass metabolism with 50% PO bioavailability

Q: Metoprolol: Distribution
A: Volume of distribution 5.5L/kg, 10-20% protein bound, highly lipid soluble, crosses BBB

Q: Metoprolol: Metabolism
A: Hepatic via CYP2D6

Q: Metoprolol: Elimination
A: Half life 3-8 hours, exreted in urine 5-10% unchanged

Q: Midazolam: Class
A: Benzodiazapiene

Q: Midazolam: Structure
A: Imidazole ring structure which opens when pH < 4 - maintains water solubility

Q: Midazolam: Pharmaceutics
A: Clear solution at pH 3.5, water soluble with pKa 6.5.
Becomes 90% un-ionised at physiological pH, crossing lipid membranes

Q: Midazolam: Absorption
A: PO 50% bioavailability

Q: Midazolam: Distribution
A: V_D 1.5L/kg
95% protein bound

Q: Midazolam: Metabolism
A: Hepatic via CYP3A4 to active metabolites
>95% to active 1-alpha hydroxymidazolam: Conjugated and excreted in urine
<5% converted to oxazepam

Q: Midazolam: Elimination
A: t<_1/2β 2-4 hours, prolonged with cirrhosis, CHF, obesity and elderly.
Ereted in urine as glucuronide conjugated metabolites.

Q: Milrinone: Class
A: PDE inhibitor

Q: Milrinone: Pharmaceutics
A: Yellow solution, 1mg/ml, required dilution before use.
Incompatible with NaHCO3 and frusemide.

Q: Milrinone: MoA
A: PDE inhibition, preventing cAMP breakdown.
Targets cardiac and vascular tissue - vasodilation and ionotropic effect.

Q: Milrinone: Distribution
A: 70% protein bound

Q: Milrinone: Metabolism
A: Minimal hepatic

Q: Milrinone: Elimination
A: Half life ~2.5 hours, excreted in urine 85% as unchanged

Q: Milrinone: CVS
A: ↑ inotropy
↓ SVR and PVR

Q: Morphine: Class
A: Opiate, phenanthrene derivative

Q: Morphine: Absorption
A: 30% bioavailability oral, onset 30 min oral, IV 5-10 min.
Lower relative lipid solubility

Q: Morphine: pKa
A: pKa 8.0 (25% ionised at pH 7.4)

Q: Morphine: Metabolism
A: Metabolised by hepatic glucuronidation to:
- Inactive morphine-3-glucuronide (70%)
- Active morphine-6-glucuronide (10%)
M6G is 13x times as potent, may accumulate in renal failure

Q: Morphine: Elimination
A: Renal of active metabolites

Q: Morphine: Adverse Effects
A: ↓ Resp drive
- Intrathecal administration may result in delayed respiratory depression (rostral migration).
↓ Baroreceptor response (postural hypotension)
↓ BP
Dependence, addiction, tolerance, dysphoria, euphoria, confusion, psychomimetic effect.
↓ Small bowel secretions, CBD spasm.
Urinary retention.
Skin flushing, pruritis

Q: Nicorandil: Class
A: K+/ATP channel agonist + nitrate moiety

Q: Nicorandil: Uses
A: HTN, angina, CHF

Q: Nicorandil: CNS
A: Headaches, improves with ongoing use.

Q: Sodium Nitroprusside: Class
A: Inorganic nitrate prodrug

Q: Sodium Nitroprusside: Pharmaceutics
A: IV, light unstable

Q: Sodium Nitroprusside: MoA
A: Nitrous group forms NO in smooth muscle, ↑ guanylate cyclase, ↑ cGMP levels, ↓ intracellular calcium

Q: Sodium Nitroprusside: Metabolism
A: Reactions with OxyHb in RBC to form NO, CN, and MetHb.
CN metabolised in liver to SCN
CN may also react with VitB12 to form cyanocobalamin

Q: Sodium Nitroprusside: Elimination
A: Nitroprusside t½ <2 mins
Renal elimination of sodium thiocyanate (t½ 3 days, prolonged in renal impairment) and cyanocobalamin

Q: Sodium Nitroprusside: Toxicity
A: Methaemaglobinaemia
Cyanide poisoning

Q: Patient (NOT including electrolyte) factors that influence NMBs
A: Hepatic failure: Prolong aminosteroids and (in severe cases) suxamethonium
Renal failure: Prolongs aminosteroid duration
Pseudocholinesterase deficiency: Prolongs duration of suxamethonium
Age: Increased NMB sensitivity in neonates
Respiratory acidosis: Potentiates blockade
Hypothermia: Potentiates blockade
Hypovolaemia: Reduces rate of onset and enhances duration
Myasthenia gravis: Increased sensitivity to non-depolarising agents
Eaton-Lambert Syndrome: Increased sensitivy to all NMBs

Q: Electrolyte disorders affecting NMB
A: Hypokalaemia: Potentiate non-dep blockade, reduces depolarising blockade
Hyperkalaemia: Potentiate depolarising blockade, reduce non-depolarising blockade
Hypermagnesaemia: Potentiates blockade
Hypocalcaemia: Potentiates blockade

Q: Stimulators of ADH secretion
A: Increased plasma tonicity
Hypovolaemia
Hypotension
Angiotensin II
Stress response
Drugs

Q: Posterior Pituitary Hormones
A: ADH
Oxytocin

Q: Anterior Pituitary Hormones
A: ACTH
TSH
LH
FSH
GH
MSH
Prolactin

Q: ADH: Mechanism of Action
A: V1: Vasoconstriction of vascular smooth muscle
V2: Collecting ducts - increase aquaporin expression
      Endothelial cells - increase vWF and factor VIII release
V3: ACTH release

Q: Magnesium: CVS
A: ↓ SVR, hypotension
↓HR

Q: GABA A receptor
A: Post-synaptic ligand gated Cl- channel

Q: GABA B receptor
A: Pre- and post-synaptic GPCR which increases K conductance

Q: When inhaled, droplets less than [...] in diameter are likely to reach [...]
A: 1 micrometre; the alveolus

Q: Regarding drugs in the epidural space, vasocontrictors [...] the effect duration of other drugs by [...].
A: increase; reducing systemic absorption

Q: Classes of Ca channel blockers
A: Dihydropyridines
Phenylalkylamines
Benzothiazepines

Q: Paracetamol toxicity mechanism
A: Paracetamol partially metabolised to the toxic NAPQI (N-acetyl-p-amino-benzoquinone imine)
NAPQI normally conjugated with glutathione, which is exhausted in toxicity.
NAC is a glutathione precursor, which replenishes hepatic glutathione.

Q: Features of paracetamol overdose
A: Conscious
Nausea, vomiting, epigastric pain
Haemolytic anaemia
Distributive shock
Hypoglycaemia
Late (>48 hours) hepatic failure
Later (3-5 days) coagulopathy
Fulminant hepatic failure (3-7 days)

Q: Toxic dose of paracetamol: Single ingestion
A: 200mg/kg

Q: Toxic dose of paracetamol: Repeated
A: >150mg/kg/day for 2 days
>100mg/kg/day for 3 days

Q: Classification of ACE-Is
A: Active drug with active metabolites
Prodrug
Not metabolised and eliminated unchanged

Q: ACE-Is: Elimination
A: Typically renal of active drug and metabolites. Highly variable t0.5s

Q: [...] are preferentially excreted in [...] urine
A: Acidic drugs; alkaline

Q: Proportion of suxamethonium reaching NMJ without metabolism
A: 20%

Q: Mechanism of action of fibrinolytics
A: Cleave plasminogen to plasmin, which in turn breaks down fibrin into fibrin degadation products

Q: Oxycodone: Class
A: Semi-synthetic opioid

Q: Oxycodone: Pharmaceutics
A: White tablet in immediate or sustained releas formulation, colourless solution at 10mg/ml

Q: Oxycodone: MoA
A: mu receptor activity with weak kappa and delta activity.
Kappa action results in the negative effects (dysphoria, psychomimetic).

Q: Oxycodone: Absorption
A: 80% PO bioavailabilty

Q: Oxycodone: Distribution
A: 2.6L/kg
~45% protein bound

Q: Oxycodone: Metabolism
A: CYP3A to noroxycodone AND CYP2D6 to oxymorphone (active), both conjugated.

Q: Oxycodone: Elimination
A: Halflife 2-4 hours, exreted in urine.

Q: Phenytoin: Class
A: Anticonvulsant/Class Ib antiarrythmic

Q: Phenytoin: Pharmaceutics
A: Solution for injection
Dilution/infusion with normal saline only (strong acid, becomes gelatinous with dextrose)

Q: Phenytoin: Mechanism of Action
A: Binds and stabilises inactivated sodium channels (use-dependent blockade), preventing further generation of action potentials.
May also reduce Ca entry, blocking neurotransmitter release.

Q: Phenytoin: Absorption
A: Bioavailability 90% orally
Onset 30min-1 hour, duration is variable.

Q: Phenytoin: Distribution
A: Volume of distribution 0.6-0.7 L/kg, >90% protein bound.

Q: Phenytoin: Metabolism
A: Hepatic, hydroxylation and glucuronidation. Becomes zero order just above therepeutic range of 10-20 µg.kg^–1
Potent enzyme induction with interactions with BZDs, warfarin, others

Q: Phenytoin: Elimination
A: 6-24 hours depending on concentration, excreted in urine <5% unchanged drug remining as glucuronides

Q: Phenytoin: SE
A: Cardiac arrythmias
Hirsutism
Gingival hyperplasia
SIADH
Hepatic enzyme INDUCER
Tetatogenic
Aplastic anaemia
Significant interpatient variability

Q: Warfarin: Pharmaceutics
A: Racemic mixture of two enantomers R and S, with the S isomer more biologically active.

Q: Warfarin: MoA
A: Inhibits vitamin K epoxide reductase (VKOR), preventing gamma carboxylation of clotting factors II, VII, IX, X, protein C and S.
This prevents clotting factors binding to endothelium.

Q: Warfarin: Absorption
A: 100% PO bioavailability

Q: Warfarin: Distribution
A: Volume of distribution 0.12L/kg, 99% protein bound

Q: Warfarin: Metabolism
A: Hepatic via CYP2C9 oxidation, leading to interperson variability in dose requirement.

Q: Warfarin: Elimination
A: Half life ~ 40 hours. Excreted via urine 92% as metabolites.

Q: Warfarin: SE
A: Haemorrhage
Microthrombi and skin necrosis
Teratogenicity
Prothrombotic initially due to inital blockage of protein C and S

Q: Phenytoin: Uses
A: GTCS and Partial seizures
Atrial and ventricular arrhythmias, particually from digoxin
Trigeminal neuralgia

Q: Phenytoin: Dosing
A: 15-20mg/kg load
Maintenance 100mg BD/TDS

Q: Phenytoin: Therapeutic Range
A: 10-20mcg/mL

Front: Propofol pK_a and clinical implication
Back: pK_a = 11
A weak acid which is almost entirely unionized at pH 7.4
Reference: Peck & Hill

Q: Treatment of CN toxicity from SNP
A: Cease SNP
Hydroxycobalamin to chelate CN
Induce metHb with nitrites

Q: Methylene Blue: MoA
A: Methylene blue is reduced by NADPH-methaemoglobin reductase, which then reduces methaemglobin

Q: Classes of hormone
A: Lipid
- Steroid
- Eicosanoid
Peptide
- Short-chain
- Long-chain
- Glycopeptide
Monoamine derivatives
- Catecholamines
- Others

Q: Steroid hormone synthesis and release
A: Synthesised from cholesterol
Released immediately, not stored

Q: Steroid hormone examples
A: Aldosterone
Testosterone
Oestrogen
Cortisol

Q: Eicosanoid synthesis
A: From cell membrane phospholipid

Q: Eicosanoid examples
A: PGs
Thromboxanes
Leukotrienes

Q: Peptide hormone storage and release
A: Stored in granules, released by exocytosis

Q: Short-chain peptide hormone examples
A: Insulin
ADH
ACTH

Q: Long-chain peptide hormone examples
A: GH
Prolactin

Q: Glycopeptide hormone examples
A: LH
FSH
TSH

Q: Monoamine derivative examples
A: Catecholamines
- Adrenaline
- Noradrenaline
Serotonin
Thyroxine

Q: Hormones secreted by the hypothalamus
A: GnRH
CRH
GHRH
TRH
Somatostatin
Dopamine

Q: Classification of pituitary hormones
A: Anterior
- Simulating
- Direct-acting
Posterior

Q: Stimulating anterior pituitary hormones
A: ACTH
TSH
FSH
LH

Q: Direct acting anterior pituitary hormones
A: GH
Prolactin

Q: Posterior pituitary hormones
A: ADH
Oxytocin

Q: ACTH: Class and actions
A: Short chain peptide
Stimulates cortisol release from zona fasciculata

Q: ACTH: Stimulus and inhibition of release
A: Stimulated by CRH
Inhibited by cortisol

Q: TSH: Class and Actions
A: Glycoprotein hormone
Stimulates T4 and T3 synthesis and release

Q: TSH: Stimulation and inhibition of release
A: Stimulated by TRH
Inhibited by T3

Q: FSH: Class and Actions
A: Glycoprotein gonadotropin
Females: Stimulates oestrogen synthesis and follicle development
Males: Stimulates sperm maturation

Q: FSH: Stimulation and inhibition
A: Stimulated by GnRH
Inhibited by circulating sex steroids

Q: LH: Class and actions
A: Glycoprotein gonadotropin
Females: Stimulates ovulation and corpus luteum development
Males: Stimulates testosterone synthesis

Q: GH: Class and Actions
A: Long chain peptide
Lipolysis
IGF-1 release
- Cell growth

Q: GH: Stimulus and inhibition
A: Stimulated by GHRH. High with stress, hypoglycaemia, exercise.
Inhibited by somatostatin and IGF-1

Q: Prolactin: Class and Actions
A: Long-chain peptide
Promotes breast development and lactation

Q: Oxytocin: Class and Actions
A: Short-chain peptide (similar to ADH)
Uterine contraction
Let-down reflex (lacation)
Pair bonding

Q: Difference between hormone and cytokine
A: Hormones are produced by a gland and act distally
Cytokines are not produced by a speciaised gland, and tend to act locally (autocrine or paracrine)

Q: Contributors to the resting membrane potential
A: Imbalance between sodium and potassium chemical gradients, generating an electrical gradient (Nernst potentials).
Electrogenic nature of the 3Na/2K pump
Gibbs-Donnan effect (contribution from intracellular protein and phosphate)

Q: Monosynaptic stretch reflex process
A: Muscle stretch
Spindle fibre stretch with activation of Ia sensory axons
Ia axons stimulate α-motor neurons of innervated muscle
Contraction of muscle to maintain muscle length

Q: Cardiac effects of T3
A: ↑ β1-receptor expression, causing ↑ HR, ↑ contractility, and ↑ CO

Q: Define Colloid
A: Substance evenly dispersed throughout another solution in which it is insoluble

Q: Layers of adrenal gland
A: Zona Glomerulosa
Zona Fasciculata
Zona Reticularis
Medulla

Q: Zona Glomerulosa secretes
A: Aldosterone

Q: Zona Fasciculata secretes
A: Cortisol

Q: Zona reticularis secretes
A: Androgens

Q: Final product of catecholamine metabolism
A: VMA (vanillylmandelic acid)

Front: ECG changes associated with digoxin
Back: 1. Prolonged PR interval – delayed AV node conduction
2. ST segment depression (down sloping) – decreased slope of phase 3 in the action potential
3. T-waves – decreased amplitude or inversion
( 2+3. Gives characteristic "reverse tick" )
4. Shorter QT interval – more rapid ventricular repolarisation
Note:
these are not signs of toxicity (increased excitability due to increased intracellular Ca++ (typically resulting in atrial tachyarrhythmia) combined with profound AV block)
Reference: Peck & Hill, Cross & Plunkett

Front: Define the Overton-Meyer hypothesis
Back: The theory of anaesthetic action which proposes that the potency of an anaesthetic agent is related to its lipid solubility
Reference: Peck & Hill

Front: Which general anaesthetic agents act at the GABA_A receptor?
Back: Note: nitrous oxide also acts as a positve allosteric modulator at the GABA_A receptor
Reference: Peck & Hill

Front: Which general anaesthetic agents act at the glycine receptor?
Reference: Peck & Hill

Front: Which general anaesthetic agents act at the NMDA receptor?
Reference: Peck & Hill

Front: Which general anaesthetic agents act at the neuronal nicotinic acetylcholine receptor?
Reference: Peck & Hill

Front: Mechanism of R-etomidate
Back: Positive allosteric modulator at GABA_A receptor, binding at the beta-subunit general anaesthetic site
Reference: Peck & Hill

Front: What drugs bind at the β subunit of the GABA_A receptor
Back: Propofol
Etomidate
Barbiturates
Halogenated volatiles
All act as positive allosteric modulators.
Reference: Peck & Hill; Katzung

Front: Where do benzodiazepines bind on the GABA_A receptor
Back: modulatory site at the α/γ interface
Reference: Peck & Hill; Katzung

Front: Where does GABA bind at the GABA_A receptor?
Back: α subunit
Reference: Peck & Hill; Katzung

Front: Describe the GABA_A receptor
Back: Pentameric ligand-gated ion channel
Typically post-synaptic
Widespread throughout CNS
Chloride ionophore
Subunits:
- 2 α (with GABA binding sites)
- 2 β (with general anaesthetic/barbiturate site)
- 1 ɣ (with benzodiazepine site at α/ɣ interface)
Pharmacology determined by alpha-sub unit sub-type:
- BZ1 (anxiolysis): - cerebellum and spinal cord
- BZ2 (sedative): - cerebral cortex, hippocampus and spinal cord
Reference: Peck & Hill; Katzung

Front: Presentation of thiopentone
Back: Sodium salt as pale yellow powder
Ideally prepared as 2.5% (w/v) water solution with pH of 10.5.
Excipients (to promote enol form, which improves solubility):
- Na_2CO_3 (6% by weight)
- nitrogen gas (instead of CO_2 containing air)
Reference: Peck & Hill

Front: Thiopentone: CVS
Back: ↓ in venous compliance causing ↓ MSFP
↓ CO and SV
↓ SVR
Effects are potentiated in hypovolaemic, acidotic state as protein binding is reduced.
Effects are less marked when compared with equivalent doses of propofol.

Front: Drugs contraindicated in porphyria (relevant to anaesthesia)
Back: General anaesthetics:
- thiopentone and other barbiturates
- halothane
- etomidate
Local anaesthetics (bupivacaine is safe):
- cocaine
- lignocaine, prilocaine
Analgesics:
- Clonidine
- Diclofenac
Gastrointestinal drugs:
- Metoclopramide
- Hyoscine
- Ranitidine
Reference: Peck & Hill

Front: Adverse effects of thiopentone
Back: Resp: Depression, bronchospasm, laryngospasm
CVS: ↓ CO, ↓ SVR, compensatory ↑ HR
CNS: Antanalgesia (at low dose)
Anaphylaxis
Porphyric crisis
Reference: Peck & Hill

Front: Describe the effect of acidaemia on thiopentone pharmacokinetics
Back: Greater drug effect, due to:
- Greater fraction of unionized drug (weak acid with a pK_a of 7.6)
- reduced protein bound fraction

Q: Oxygen: Resp
A: ↓ Respiratory drive - beware hypoxic drive
Reduces PVR
Absorption atelectasis.
Pulmonary toxicity due to free radial formation when PiO2>0.6bar
- Bronchopulmonary dysplasia in neonates

Q: Oxygen: CVS
A: In hypoxia: Improve all CVS parameters
In hyperoxia: ↓ CO, ↓PVR, ↓PAP, coronary vasoconstriction

Q: Oxygen: CNS
A: CNS toxicity typically >1.6 bar

Q: Helium: Uses
A: Reduce specific gravity of inhaled gas mixtures, reducing Reynolds number and improving laminar flow

Q: Pharmacokinetics of helium
A: A: Diffuses across alveolar membrane proportionally to its pressure gradient
D: Distributes proportionally to pressure gradient
M: Nil
E: Respiratory, along gradients

Q: Respiratory effects of inhaled β-agonists
A: Bronchodilation
Reduced HPV (potential shunt)

Q: CVS effects of inhaled β-agonists
A: ↑ HR, ↓ BP

Q: GU effects of inhaled β-agonists
A: Uterine relaxation

Q: Metabolic effects of inhaled β-agonists
A: Hypokalaemia
Hyperglycaemia

Q: Salbutamol: Class
A: Synthetic sympathomimetic amine

Q: Salbutamol: Indications
A: Acute asthma
Hyperkalaemia

Q: Salbutamol: Distribution
A: Low protein binding

Q: Ipratropium - Class
A: Muscarinic antagonist

Q: Ipratropium: Metabolism
A: Hepatic to inactive metabolites

Q: Ipratropium: Elimination
A: Renal and faecal of inactive metabolites

Q: Respiratory effects of ipratropium
A: Bronchodilation

Q: GIT effects of ipratropium
A: Decreased secretions

Q: CNS effects of ipratropium
A: Mydriasis

Q: Ipratropium: Mechanism of Action
A: Antimuscarinic agents competitively antagonise ACh at M3 receptors in bronchial smooth muscle, preventing parasympathetic mediated bronchoconstriction.

Q: Theophylline: Absorption
A: High PO bioavailability

Q: Theophylline: Distribution
A: 40% protein bound

Q: Theophylline: Metabolism
A: CYP450 to active metabolites (caffeine, 3-methylxanthine)
Low hepatic extraction ratio

Q: Theophylline: Elimination
A: Highly variable:
- Renal disease
- Hepatic disease
- Age

Q: Theophylline: Respiratory
A: Bronchodilation
↑ Diaphragmatic contractility

Q: Theophylline: CVS
A: ↑ inotropy
↑ chronotropy
↑  arrhythmia

Q: Theophylline: CNS
A: ↓ Seizure threshold

Q: Theophylline: Renal
A: Natriuresis
Hypokalaemia

Q: Theophylline: Toxicity
A: Low TI
Tachyarrythmias - notably VF
Tremor, Seizures

Q: Steroids: Respiratory
A: ↑ bronchial smooth muscle response to catechols
↓ airway oedema

Q: Steroids: CVS
A: ↑ Inotropy
↑ Vascular smooth muscle response to catechols

Q: Steroids: CNS
A: Mood changes
Sleep disturbances

Q: Steroids: MSK
A: Atrophy
Thinning of skin

Q: Steroids: Renal
A: Glycosuria
Fluid retention

Q: Steroids: GIT
A: Gastric ulceration

Q: Steroids: Metabolic
A: ↑ Gluconeogenesis + DM
↑ Protein catabolism
Fat redistribution
Adrenosuppression

Q: Steroids - Immune
A: ↓ Transudate production
↓ Production of inflammatory mediators
↓ Macrophage and lymphocyte function
↓ Antibody production

Q: Corticosteroids - Metabolism
A: Hepatic

Q: Nitric Oxide: Mechanism of Action
A: Stimulates cGMP, reducing intracellular Ca

Q: Nitric Oxide: Metabolism
A: Metabolised to methaemoglobin and nitrite prior to reaching systemic circulation

Q: Nitric Oxide: Respiratory
A: Inhibits HPV, improves V/Q matching

Q: Nitric Oxide: CVS
A: ↓ Vascular resistance

Q: Nitric Oxide: CNS
A: ↑ CBF

Q: Nitric Oxide: Haeme
A: Inhibits platelet aggregation
MetHb

Q: Iloprost: MoA
A: Synthetic prostacyclin (PGI_2) analogue which also binds to prostaglandin receptors. Causes:
- Vasodilation
- Inhibition of platelet aggregation

Q: Iloprost: CVS
A: ↓ BP with compensatory ↑ HR

Q: Iloprost: Haeme
A: Inhibits platelet aggregation

Q: [...] is the only local anaesthetic which causes vasoconstriction at [...], all others cause [...]
A: Cocaine; low and high doses; vasodilation at low doses
Reference: Dr Podcast

Front: Factors increasing materno-fetal drug transfer in late pregnancy
Back: Increased unbound drug available for transport (relevant in highly albumin-bound drugs, alpha-1-acid glycoprotein is normal)
Increased uteroplacental blood flow
Increased placental surface area
Decreased thickness of semipermeable lipid membranes between placental capillaries
Greater physical disruption of placental membranes
More acidic fetal circulation to trap basic drugs
Reference: Varney's Midwifery

Front: MoA of α1-receptors
Back: G_q-coupled
Activate phospholipase C, ↑ inositol triphosphate (IP_3), ↑ Ca^2+ from SR

Front: MoA of α2-receptors
Back: G_i-coupled
Inhibit adenylate cyclase, ↓ cAMP

Front: MoA of β1-receptors
Back: G_s-coupled
Activate adenylate cyclase, ↑ cAMP

Front: MoA of β2-receptors
Back: G_s-coupled
Activate adenylate cyclase, ↑ cAMP levels, ↑ Na^+/K^+ ATPase activity, causing cellular hyperpolarisation

Front: Location, action and mechanisms of D_1 adrenoceptor activation
Back: CNS
- modulates extra-pyramidal activity
Splanchnic (renal and mesenteric) vessels
- vasodilatation
G_s-coupled adenylate cyclase activation, resulting in increased [cAMP]
Reference: Peck & Hill

Front: G_q class GPCR mechanism
Back: Alpha sub-unit promotes action of phospholipase C
Action is to convert phosphatidylinositol
4,5-bisphosphate (PIP_2; a membrane phospholipid), to form:
- inositol triphosphate (IP3)
- diacylglycerol (DAG)
Reference: Peck & Hill

Front: Why is MAC awake < MAC asleep
Back: 1. Hysteresis between alveolar and effect site concentrations of volatile agents, due to the concentration gradients on induction compared with emergence:
2. Neural inertia
- Neurons resist phase transition (difficult to get to sleep, difficult to wake up again)
Reference: Cross & Plunkett

Front: Ideal physical characteristics of an inhaled anaesthetic agent
Back: Long shelf-life
Light stable
Heat stable
Not flammable/explosive
Does not react with the components in the breathing circuit or in the bottle (rubber, metal, plastic, soda lime)
Liquid at room temperature
High SVP
Low specific heat capacity
Smells nice
Preservative free
Environmentally friendly
Cheap

Front: Ideal pharmacological properties of an inhaled anaesthetic agent
Back: Pharmacokinetic:
High oil:gas partition coefficient
Low MAC.
Low blood:gas partition coefficient
Rapid onset and offset.
Not metabolised
Non-toxic
Pharmacodynamic:
Does not cause laryngospasm or airway hyperreactivity
No effect on HDx parameters
Analgesic
Hypnotic
Amnestic
Anti-epileptic
No increase in ICP
Skeletal muscle relaxation
Anti-emetic
No tocolytic effects
Not teratogenic or otherwise toxic
Reference: Peck & Hill

Front: Define the concentration effect
Back: The phenomenon by which the rise in the alveolar partial pressure of an inhaled gas is disproportionately rapid when administered in high concentrations. (disproportionately refers to its oil:gas partition coefficient)
Pertains to any gas administered at high fractional concentrations; although in standard practice, nitrous oxide is the only relevant example.
(Note the two N_2O curves—the upper being at FiN_2O of 50%, and approaching 1 more rapidly than desflurane, even though desflurane has a higher oil:gas partition coefficient.)
Mechanism is due to greater solubility of N_2O compared with N_2 (20 times) and subsequent greater outward diffusion. This results in a reduction of alveolar volume in non-steady state conditions, concentrating the remaining alveolar gas. It also augments minute ventilation due to entrainment of dead space gas.
Reference: Cross & Plunkett; Peck & Hill
Other fields (not shown on cards):
Comment: chck if its blood to gas or oil to gas

Front: Define the second gas effect
Back: Disproportionately rapid increase in F_A/F_I ratio of a volatile anaesthetic when administered with nitrous oxide.
Due to the concentration effect, where the rise in alveolar concentration of a soluble gas is disproportionately rapid when administred at high concentrations, which leads to:
- Concentration of remaining alveolar as
- Entrainment of gas in the dead space

Front: Which IV anaesthetics produce active metabolites?
Back: Thiopentone (pentabarbitone), ketamine (norketamine)
Reference: Cross & Plunkett; Peck & Hill

Front: Order intravenous anaesthetics from high to low volume of distribution
Back: Propofol > ketamine = etomidate > thiopentone
Reference: Cross & Plunkett; Peck & Hill

Front: Order intravenous anaesthetics from high to low protein binding
Back: propofol > thiopentone > etomidate > ketamine
Propofol and thiopentone are the only agents with clinically significant binding
Reference: Cross & Plunkett; Peck & Hill

Front: Which intravenous induction agent is achiral?
Back: Propofol
Reference: Cross & Plunkett; Peck & Hill

Front: Which intravenous anaesthetic agents do not have active metabolites
Back: Propofol, etomidate
Reference: Cross & Plunkett; Peck & Hill

Front: Compare metabolism of intravenous anaesthetic agents
Back: Thiopentone (active metabolites): phase I (hepatic oxidation)
Propofol: phase I (hydroxylation) and phase II (glucuronidation)
Ketamine (active metabolites): demethylation, hydroxylation
Etomidate: esterases (plasma and hepatic)
Reference: Cross & Plunkett; Peck & Hill
Other fields (not shown on cards):
Comment: needs to be reworked

Front: Rank anaphylaxis risk of intravenous induction agents from high to low
Back: thiopentone > etomidate > ketamine (rash only) > propofol (no known reactions, despite containing purified egg and soya bean derivatives)
Reference: Cross & Plunkett; Peck & Hill

Front: Rank intravenous anaesthetics in terms of their effect on blood pressure, cardiac output (from high to low)
Back: Increases:
- Ketamine
Stable:
- Etomidate
Likely to reduce:
- Thiopentone < Propofol
Reference: Cross & Plunkett; Peck & Hill

Front: Compare intravenous anaesthetics in terms of their effect on heart rate (high to low)
Back: Causes tachycardia:
- ketamine (definitely)
- thiopentone (may cause reflex tachycardia)
Stable:
- etomidate
Bradycardia:
- propofol (may cause bradycardia through direct effect)
Reference: Peck & Hill

Front: Compare intravenous anaesthetic agents by their effect on systemic vascular resistance
Back: No change:
etomidate, ketamine (BP increased due to increased CO)
Variable:
thiopentone
Reduced:
propofol
Reference: Peck & Hill

Front: Which intravenous anaesthetics cause pain on injection?
Back: propofol, etomidate
Reference: Peck & Hill

Front: Which intravenous anaesthetics are not associated with nausea?
Back: Propofol (? anti-emetic), thiopentone
Reference: Peck & Hill

Front: Rank inhaled anaesthetics in order of percentage metabolized (high to low)
Back: Halothane > sevoflurane > enflurane > isoflurane > desflurane > nitrous oxide
Remember:
C-F bond is relatively stable
C-Cl, C-Br, C-I bonds are progressively  unstable and are metabolised by CYP2E1
Hence, halothane is the most unstable (C_2HClBrF_3) despite containing thymol as an excipient
Reference: Peck & Hill

Front: Describe the mechanism of diffusion hypoxia
Back: At the end of an N_2O/O_2 anaesthetic, inspired gas may be changed to N_2/O_2. The N_2O rapidly diffuses into the alveolus (as it now has a large concentration gradient), resulting in reduced alveolar O_2 partial pressure. It can be prevented by increasing the Fio_2 to 1.0
Reference: Peck & Hill

Regarding inhaled anaesthetics, Oil:gas partition coefficient is associated potency, while blood:gas partition coefficient is associated with speed of onset
Extra: B:G ∝ time to onset
O:G ∝ 1/potency
Reference: Peck & Hill

Q: Volatile agents reacting with [...] to produce [...] include:
[...]
A: soda lime; carbon monoxide; desflurane
enflurane
isoflurane
Extra: All are part of the ethyl-methy-ether series, containing R-CHF_2 moieties.
Effect is worse with dry soda lime:
- "Monday morning effect"
- high fresh gas flows
Reference: Peck & Hill

Front: Halothane: metabolism and toxicity
Back: CYP 2E1 (well perfused liver):
- trifluoroacetic acid, Br^– and Cl^–
Reductive metabolism (ischaemic liver):
- F^– and other toxic metabolites
Halothane hepatitis (not due to the above):
- reversible, subclinical transaminitis (hypoxic)
- fulminant necrotic (50-75% mortality)
Malignant hyperthermia
Reference: Peck & Hill

Front: Halothane hepatic necrosis: aetiology, incidence, risk factors and mortality
Back: Aetiology:
?trifluoroacetyl (oxidative metabolite)
Incidence:
1 in 2 500 - 35 000
Risk factors:
liver disease, past history of hepatotoxicity, multiple exposures (esp. within 3 months), female, middle age, obesity
Mortality:
50-75%
Reference: Peck & Hill

Front: Enflurane: Toxicity
Back: CO from reaction with absorbent
Generalized tonic-clonic-like EEG activity at high doses
MH
Nephrotoxicity (due to - F^– )
Hepatic necrosis (rarer but similar to halothane hepatic necrosis; i.e., high mortality)(CYP 2E1; 2%):
Reference: Peck & Hill

Front: Nitrous oxide: MoA
Back: - Stimulates dynorphin release (acts at KOP receptor)
- Positive allosteric modulator at GABA_A
- NMDA antagonist
Reference: doi: 10.2344/0003-3006(2007)54[9:AIUTAO]2.0.CO;2

Front: Rank inhaled anaesthetics by MAC (high to low)
Back: N2O > Xe > desflurane > sevoflurane > enflurane > isoflurane > halothane
Reference: Peck & Hill

Front: Rank inhaled anaesthetic agents by blood:gas partition coefficient (high to low)
Back: halothane > enflurane > isoflurane > sevoflurane > N_2O > desflurane > Xe
Reference: Peck & Hill

Front: Rank inhaled anesthetic agents by oil:gas partition coefficient (high to low)
Back: halothane > isoflurane = enflurane > sevoflurane > desflurane > Xe > N_2O
Reference: Peck & Hill

Front: Which inhaled anaesthetics have irritant properties
Back: isoflurane (pungent, causes coughing but is a bronchodilator)
desflurane (contra-indicated in non-intubated children due to risk of larygo-bronchospasm)
Reference: Peck & Hill

Front: Which inhaled anaesthetic has a sweet odour?
Back: Halothane
Reference: Peck & Hill

Front: Rank halogenated alkane anaesthetics by effect on minute ventilation (least to most)
Back: halothane, sevoflurane, desflurane, isoflurane, enflurane
Remember:
all produce increased respiratory rate and decreased tidal volume with only halothane having no effect on P_aco_2
Reference: Peck & Hill

Front: Rank the halogenated alkane anaesthetics by effect on cardiac contractility (best to worst)
Back: Minimal effect:
desflurane
Progressive depression:
sevoflurane, isoflurane, enflurane, halothane
Note:
although desflurane has least impact on contractility, sevoflurane is least likely to produce hypotension.
Reference: Peck & Hill

Front: Rank the halogenated alkane anaesthetics by chronotropic effect (most positive to negative)
Back: Marked tachycardia:
isoflurane > desflurane (esp. > 1.5 MAC) > enflurane
No effect:
sevoflurane
Bradycardia:
halothane
Reference: Peck & Hill

Front: Halogenated organic anaesthetic agent least likely to cause hypotension
Back: Sevoflurane (no effect on heart rate and least reduction in SVR)
Reference: Peck & Hill

Front: Halogenated alkane anaesthetic associated with coronary steal syndrome
Back: Isoflurane
Remember:
steal refers to reduction in flow of vessels not responsive to vasodilator effect (i.e., atherosclerotic) of agent due to diversion
Reference: Peck & Hill

Front: Rank halogenated alkane anaesthetics in order of sensitisation to catecholamines (worst to best)
Back: Halothane > enflurane
(no others are associated)
Reference: Peck & Hill

Front: Rank halogenated alkane anaesthetics by effect on cerebral blood flow (best to worst)
Back: isoflurane (nil if <1 MAC), all others, halothane (worst)
Remember:
- all reduce CMRO_2
- N2O increases cerebral blood flow
Reference: Peck & Hill
Other fields (not shown on cards):
Comment: conflicting reports in various texts

Front: Effect of inhaled anaesthetics on neuromuscular blockade
Back: Potentiates effect (halothane the least)
Reference: Peck & Hill

Classes of calcium channel blockers

Q: Dihydropyridine Examples
A: Amlodipine
Nimodipine
Nifedipine

Q: Benzothiazepine example
A: Diltiazem

Q: Phenylalkylamine example
A: Verapamil

Q: Verapamil: Uses
A: SVT, excluding AF with WPW
Angina prophylaxis
Hypertension (use is limited due to negative inotropic effect)

Q: Calcium channel blockers: Absorption
A: Well absorbed but high first pass metabolism decreases bioavailability

Q: Ca channel blockers: Distribution
A: Highly protein bound
Mostly lipid insoluble - nimodipine is an exception (crosses BBB - used in vasospasm)

Q: Verapamil: Metabolism
A: Hepatic to active norverapamil

Q: Verapamil: Elimination
A: Renal of active metabolites

Q: Verapamil: CVS
A: ↓ HR via ↓ SA and ↓ AV nodal conduction
↓ Inotropy
↓ SVR, ↓ BP
May precipitate arrhythmia including HB, and VF/VT in the presence of an accessory pathway

Q: Verapamil: CNS
A: ↓ Cerebral vascular resistance

Q: Non-dihydropyridine interactions
A: Concurrent β-blocker use may cause profound ↓ HR and ↓ inotropy

Q: Amlodipine: CVS
A: ↓ SVR, ↓ BP, with reflexive ↑ HR, ↑ CO

Q: Diltiazem: CVS
A: ↓ AV nodal conduction but typically stable HR
↓ SVR, ↑ CO
↓ CVR
↓ MVO2

Q: Adrenaline: CVS
A: Low-dose: β > α effect
- ↑ CO (inotropy + reduced afterload)
- ↑ HR
- ↑ myocardial oxygen consumption
- Coronary artery dilatation
- Arrhythmogenic
High dose: α > β effect
- Vasoconstriction (raised SVR, local tissue necrosis)
- ↑ BP

Q: Amiodarone: Interactions
A: Many due to CYP3A4 inhibition and high protein binding.
Include: Digoxin, statins, warfarin, phenytoin, and other antiarrhythmics.

Q: COX-1
A: Synthesises thromboxane and the prostaglandins which control RBF and mucosal barriers

Q: COX-2
A: Induced with tissue and endothelial damage (important in inflammation):
- In vascular endothelium where it synthesises prostacyclin (which opposes the action of thromboxanes)
- Inhibition may result in a relative abundance of thromboxane, causing platelet aggregation and vasoconstriction

Q: COX-3
A: COX-1 variant in the CNS, which mediates analgesic and antipyretic effects

Q: NSAIDS: SE
A: Asthma
Thrombotic events
- Greater with COX-2
Platelet dysfunction
Impaired GFR
Gastric erosion
Transaminitis

Q: Aspirin: Metabolic
A: Reye's syndrome:
- Mitochondrial damage
- Hepatic failure
- Cerebral oedema (and encephalopathy)
in children <12. Mortality 40%.

Q: β-blockers: Cardiac (not vascular) indications
A: Angina
Arrythmia
- AF
- SVT
- ST
CCF
MI (secondary prevention)

Q: β-blockers: Vascular indications
A: HTN
Hypotensive anaesthesia
- Laryngoscopy

Q: β-blockers: Non-CVS indications
A: Thyrotoxicosis
Glaucoma
Anxiety
Migraine prophylaxis

Q: Cardioselective β-blockers
A: BEAM:
- Bisoprolol
- Esmolol
- Atenolol
- Metoprolol

Q: Non-selective (β1 and β2) β-blockers
A: Propranolol
Sotalol
Timolol

Q: Non-selective (β & α) β-blockers
A: Carvedilol
Labetalol

Q: β-blockers: Respiratory
A: Bronchospasm

Q: β-blockers: CVS
A: ↓ Inotropy
↓HR
↓MVO2
↓ BP
↑SVR (β2 effect)
Arrhythmia

Q: β-blockers: CNS
A: Sleep disturbances
Nightmares
↓ IOP

Q: β-blockers: Metabolic
A: ↓ Insulin release

Q: β-blockers: Interactions
A: ↓ HR and inotropy with cardioselective Ca channel blockers

Q: Esmolol: Dosing
A: Load: 0.5mg/kg
Infuse at: 50-200μg.kg-1.min-1

Q: Dipyridamole: Metabolism
A: Partial hepatic to inactive metabolites

Q: Dobutamine: Resp
A: Potent bronchodilation

Q: Flecainide: Target plasma concentration
A: <0.9mg/ml

Q: Magnesium: CNS
A: CNS depression, anticonvulsant

Q: Magnesium: GU
A: ↓ Uterine tone and contractility

Q: Magnesium: Resp
A: Bronchodilation

Front: Define pain
Back: Unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage
Reference: IASP

Front: Define acute pain
Back: Defined as pain of:
- recent onset
- limited probable duration
- identifiable causal and temporal relationship to injury or disease
Reference: Acute Pain Management: Scientific Evidence; IASP

Front: Define chronic pain
Back: Pain that:
- persists beyond the time of tissue healing
- frequently has no clearly identifiable cause
Reference: Acute Pain Management: Scientific Evidence; IASP

Front: What is the difference between acute and chronic pain?
Back: Acute pain is:
- of recent onset
- associated temporally and causally with injury or disease
Chronic pain:
- persists beyond time of healing or disease
- frequently has no clearly identifiable cause
Remember:
- acute and chronic pain may overlap
- definitions involving time periods are arbitrary and do not reflect underlying pathophysiology
Reference: Acute Pain Management: Scientific Evidence; IASP

Front: Define local anaesthetic
Back: Drug which reversibly prevents the conduction of the nerve impulse in the region to which it is applied, without affecting consciousness.
Reference: Anaesthesia UK

Front: Categorise local anaesthetics
Back: Categorized by the linkage between thier hydrophilic and lipophilic functional groups into:
- amides
- esters
Remember, general structure of local anaesthetics:
Reference: Peck & Hill, ICU Adelaide

Front: Name the ester local anaesthetics
Back: Cocaine
Tetracaine
Procaine
Amethocaine
Mnemonic: CTPA

Front: Name the amide local anaesthetics in common use
Back: Pipecoloxylidides (or piperidine amides):
Mepivacaine
Ropivacaine
(Levo)bupivacaine
Amino amides:
Lignocaine
Prilocaine
Mnemonic:
all have an "i" before the "caine"
Reference: Peck & Hill

Front: What are the clinical implications of the differing structure of amide and ester local anaesthetics?
Back: Esters:
- unstable in solution (shorter shelf-life)
- metabolism produces para-aminobenzoate (allergenic)
Amides:
- stable in solution (longer shelf life)
- heat stable (can be autoclaved—sterile ampoules)
Reference: Peck & Hill

Front: Local anaesthetics: MoA
Back: Blockade of voltage gate sodium channels at the axon (highest density at the nodes of Ranvier, where these are present).
Local anaesthetics are weak bases, and must be in their unionized form to diffuse into the axon, where they become protonated.
Blockade occurs at the intracellular domain of the channel. Affinity is highest for the inactive receptor state, producing a use-dependence effect. When bound to the inactive channel, the refractory period of the channel is markedly prolonged.
Note:
membrane expansion theory has been largely discounted
Reference: http://www.frca.co.uk/article.aspx?articleid=220; ICU Adelaide

Front: What physical properties effect the pharmacology of local anaesthetics?
Back: Lipid solubility (determined by amine group):
- potency and protein binding
Protein binding:
- ∝ duration of action
- ∝ 1/effectiveness of intralipid rescue
pK_a (all are weak bases and must cross into the axoplasm to act):
- lower pKa  ∝ rapid onset
Vasoconstrictor properties:
- increases duration and potency
- most are vasodilators at low dose, and vasoconstrictors at high dose (except cocaine, which is always a vasoconstrictor)
Remember structural characteristics as well:
Ester vs. amide:
- amides more stable and slower to metabolize
Amine group length:
- increases potency, toxicity
- decreases rate of metabolism
Reference: http://www.frca.co.uk/article.aspx?articleid=220; ICU Adelaide

Front: What structural characteristics determine the pharmacological properties of local anaesthetics?
Back: Ester vs. amide:
- amides more stable and slower to metabolize, higher protein binding
- esters produce para-amino benzoate which is allergenic and are minimally protein bound
Amine group length:
- increases potency up to 10 carbons, toxicity continues to increase beyond 10 carbons
- decreases rate of metabolism
Tertiary amine:
- Determines lipid (3 bonds) vs. water (4 bonds) solubility
Lipophilic aromatic ring:
- Determines lipid solubility, and therefore potency
Remember these determine the physical characteristics:
Lipid solubility (determined by amine group):
- potency and protein binding
Protein binding (determined by amine group):
- ∝ duration of action
- ∝ 1/effectiveness of intralipid rescue
pK_a (all are weak bases and must cross into the axoplasm to act):
- lower pKa  ∝ rapid onset
Vasoconstrictor properties:
- increases duration and potency
- most are vasodilators at low dose, and vasoconstrictors at high dose (except cocaine, which is always a vasoconstrictor)

Front: Intralipid (20% solution): dosing in local anaesthetic systemic toxicity
Back: In a 70 kg patient, 100mL every five minutes as bolus plus infusion of 400mL over 20 minutes (i.e., 100mL/5 minutes)
Reference: AAGBI

Front: Rank commonly used local anaesthetics by lipid solubility
Back: bupiv > ropiv > ametho > ligno > prilo > cocaine
Remember:
this roughly correlates with many other properties (toxicity, potency, elimination half life)
Reference: Peck & Hill

Front: Rank commonly used local anaesthetics by pKa
Back: prilo < ligno < ropiv = bupiv < ametho < cocaine
Remember:
This correlates with speed of onset (except for cocaine).
Reference: Peck & Hill

Front: Define dependence, regarding pharmacology
Back: Occurrence of a characteristic withdrawl syndrome when a drug is withdrawn or antagonist administered

Q: Propofol t1/2ke0
A: 2.7min

Q: Thiopentone t1/2 ke0
A: 1.2 minutes

Q: Heparin: MoA
A: Potentiates the action of ATIII
Inhibits factor Xa, and (in higher concentrations) IXa, XIa, XIIa, vWF, and platelet aggregation

Q: Suxamethonium: Dose
A: 1-2mg/kg IV
3-4mg/kg IM

Q: Suxamethonium: Metabolism
A: Rapid hydrolysis by plasma cholinesterases
20% of dose reaches NMJ

Q: Suxamethonium: Elimination
A: <10% eliminated in urine due to rapid metabolism into choline and succinylmonocholine

Q: Suxamethonium: Resp
A: Apnoea
Masseter spasm
↑ Secretions

Q: Suxamethonium: CVS
A: Arrythmia (vagotonic and potassium related)
Bradycardia (vagotonic), may lead to junctional escape

Q: Suxamethonium: CNS
A: Increased ICP
Increased IOP (10mmHg, significant)

Q: Suxamethonium: MSK
A: MH
Myalgias

Q: Suxamethonium: Renal and Electrolyte
A: Hyperkalaemia (↑ by ~0.5mmol/L)

Q: Suxamethonium: Contraindicated populations
A: Burns >10%
Paraplegia
Neuromuscular disorders including critical illness myopathy
MH

Q: Suxamethonium: GIT
A: ↑ intragastric pressure (with ↑ in LoS tone)

Q: Suxamethonium: Immune
A: Anaphylaxis

Q: Non-depolarising NMBs: Distribution
A: Small Vd, confined to ECF

Q: Non-depolarising NMBs: MSK
A: Critical illness myopathy

Q: Rocuronium: Presentation
A: Clear colourless solution at 10mg/ml
Stable at room temperature

Q: Rocuronium: Dosing
A: 0.6-1.2mg/kg

Q: Rocuronium: Onset
A: 45-90s

Q: Rocuronium: Duration
A: 30 minutes, variable second dose

Q: Rocuronium: Metabolism
A: <5% hepatic deacetylation to inactive metabolites

Q: Rocuronium: CVS
A: ↑ HR at high doses due to muscarinic antagonism

Q: Rocuronium: Immune
A: Anaphylaxis

Q: Atracurium: Presentation
A: Colourless solution at 10mg/ml, stored at 4ºC
Chiral mixture of all ten extant diastereoisomers

Q: Atracurium: Dosing
A: 0.5mg/kg

Q: Atracurium: Onset
A: 90-120s

Q: Atracurium: Duration
A: 15-35 minutes

Q: Cisatracurium: Duration
A: 25-30 minutes

Q: Atracurium: Metabolism
A: - 60% hydrolysed by non-specific esterases (accelerated in acidosis)
- 40% Hofmann elimination (accelerated with high temp and alkalosis)
- Laudanosine (product of both processes) lowers seizure threshold as it is a glycine antagonist (theoretical issue)

Q: Cisatracurium: Metabolism
A: 80% Hofmann elimination (remainder eliminated unchanged)

Q: Atracurium: Resp/CVS
A: May potentiate histamine release: bronchospasm and hypotension

Q: Cisatracurium: Resp/CVS
A: May precipitate histamine release: bronchospasm and hypotension

Q: Equation for factors determining cerebral blood flow
A: Hagan-Poiseuille Equation:
- Driving pressure (CPP)
- Radius of vessels (CVR)
- Blood viscosity
- Length of the tube (a fixed quantity)

Q: ACE-I which is an active drug with active metabolites
A: Captopril

Q: ACE-I which is a prodrug
A: Ramipril, enalapril
Activated by hydrolysis by liver esterases

Q: ACE-I which is not metabolised and is excreted unchanged in urine
A: Lisinopril

Q: ACE-I: Interactions
A: Spironolactone: ↓ Aldosterone release, which ↑ the efficacy of spironolactone and may precipitate hyperkalaemia.
NSAIDs: PD interaction with fall in renal perfusion pressure

Q: ACE-Is: Endocrine
A: Hypoglycaemia

Q: ACE-Is: Haeme
A: Agranulocytosis
Thrombocytopenia

Q: ACE-Is: Immune
A: Angiooedema

Q: Classes of diuretic
A: Thiazides
Loop diuretics
Potassium sparing
Aldosterone antagonists
Osmotic (mannitol)
Carbonic anhydrase inhibitors

Q: Diuretics: Absorption
A: Poor bioavailability (acetazolamide is the exception)

Q: Frusemide: Absorption
A: 50% PO bioavailability

Q: Diuretics: Metabolism
A: Not metabolised

Q: Frusemide: Metabolism
A: Small amount renally metabolised to glucuronide

Q: Frusemide: CNS
A: Ototoxic (in large doses, or with aminoglycosides)

Q: Spironolactone: Endocrine effects
A: Gynaecomastia and irregular menses due to aldosterone antagonism

Q: Why does alfentanil have such a rapid onset
A: 90x more lipid soluble than morphine (less than fentanyl), but more rapid onset due to:
- low pKa (6.5)
- Less potent (greater doses used)

Q: Alfentanil: Key interactions
A: Midazolam
Prolonged duration of action of both drugs due to CYP competition

Q: NSAIDS: Resp
A: Induce asthma

Q: NSAIDs: Adverse CVS
A: May induce/exacerbate heart failure
All increase adverse cardiac events (e.g., additional 3 major adverse cardiac or vascular events (incl. 1 fatality) per 1000 person-years for celecoxib, ibuprofen, diclofenac) except:
- Naproxen (no change)
- Aspirin (reduces stroke and MI)

Q: NSAIDs: Renal
A: Prostacyclin and PGE2 are essential to maintain renal perfusion.
Inhibition causes afferent arteriolar constriction, decreasing renal NFP and GFR

Q: NSAIDs: GIT
A: All increase risk of gastric erosions due to inhibition of prostaglandin-dependent protective factors (esp. mucous production; COX_2 < ibuprofen < naproxen = diclofenac < ketorolac
Transaminitis

Q: Tramadol: MoA
A: Opioid agonits (particularly MOP)
5-HT reuptake inhibition
NA reuptake inhibition
NMDA receptor antagonist

Q: Tramadol: Class
A: Cyclohexanol derivative

Q: Tramadol: Pharmaceutics
A: Racemic mixture:
- (+)Tramadol (MOP and 5HT)
- (-)Tramadol, (NA reuptake inhibition)

Q: Tramadol: Absorption
A: 70% bioavailable

Q: Tramadol: Metabolism
A: Hepatic with active and inactive metabolites

Q: Tramadol: Elimination
A: Renal of metabolites with T_½β 300 minutes

Q: Tramadol: Respiratory
A: Minimal respiratory depression

Q: Tramadol: CVS
A: Avoid concominant MAO-I use due to NA reuptake inhibition effects

Q: Tramadol: CNS
A: Analgesia (equianalgesic doses produce less respiratory depression and constipation)
Lowers seizure threshold
- Avoid in epilepsy, SSRI/SNRI/TCA use

Q: Tramadol: GIT
A: N/V

Q: Paracetamol: Mechanisms of Action
A: Nonselective COX inhibition
- Central COX-3 inhibition gives antipyretic effects
Serotonergic inhibition
Endocannabinoid reuptake inhibition

Q: Paracetamol: Indications
A: Analgesia
Antipyretic

Q: Paracetamol: Dosing
A: 10-15mg/kg

Q: Paracetamol: Absorption
A: Bioavailability up to 90%, greater PR
Absorbed in small bowel - dependent on gastric emptying

Q: Paracetamol: Distribution
A: Minimally protein bond
Small Vd

Q: Paracetamol: Metabolism
A: Predominantly hepatic glucuronidation
10% is metabolised to the toxic NAPQI

Q: Paracetamol: Elimination
A: Actively secreted into renal tubules - may be retained in renal failure

Q: Penicillins: Mechanisms of resistance
A: Protect PBP
Alter PDP
Beta-lactamases

Q: Vancomycin: Class
A: Glycopeptide

Q: Glycopeptides: MoA
A: Inhibit cell wall synthesis

Q: Vancomycin: Indications
A: MRSA
C. difficile

Q: Vancomycin: Absorption
A: 0% PO bioavailability

Q: Vancomycin: Distribution
A: Poor CNS penetration - greater plasma level required for CNS infections

Q: Vancomycin: Metabolism
A: Minimal hepatic

Q: Vancomycin: Elimination
A: Renal of 90% unchanged drug

Q: Vancomycin: CVS
A: Phlebitis
Red man syndrome

Q: Vancomycin: CNS
A: Ototoxicity
- Typically permanent

Q: Vancomycin: Renal
A: Nephrotoxicity
- Typically temporary

Q: Vancomycin: Haeme
A: Thrombocytopenia

Q: Gentamicin: Metabolism
A: Not metabolised

Q: Metronidazole: Class
A: Imidazole

Q: Metronidazole: MoA
A: Preferential reduction
- Captures electrons, causing build up of intermediate metabolites and free radicals

Q: Metronidazole: Indications
A: Anaerobes
Protozoa

Q: Metronidazole: Absorption
A: 100% PO bioavailability

Q: Metronidazole: Metabolism
A: Hepatic with active metabolites

Q: Metronidazole: Adverse effects
A: Rash, headache, flushing, N/V

Q: Clindamycin: Class
A: Lincosamide

Q: Lincosamide: MoA
A: Inhibit protein synthesis by disrupting the 50S ribosomal subunit

Q: Clindamycin: Absorption
A: 90% PO bioavailability

Q: Clindamycin: Distribution
A: Excellent bony penetration

Q: Clindamycin: Metabolism
A: Hepatic with active and inactive metabolites

Q: Clindamycin: Elimination
A: Renal of all metabolites

Q: Clindamycin: MSK
A: May cause neuromuscular blockade

Q: Clindamycin: GIT
A: Pseudomembranous colitis
Deranged LFTs

Q: Clindamycin: Immune
A: Atopy
Eosinophilia
DRESS

Q: Types of Insulin with examples
A: Fast acting (Novorapid, Humalog)
Intermediate acting (NPH, protophane)
Long acting (Lantus, Levemir)

Q: Insulin: Uses
A: DM
Hyperglycaemia
Hyperkalaemia
β-blocker toxicity
Ca-blocker toxicity

Q: Insulins: Distribution
A: Minimal protein binding and minimal redistribution out of ECF - Vd 0.075L/kg

Q: Insulins: Metabolism
A: Glutathione insulin transhydrogenase

Q: Insulins: Elimination
A: Renal of inactive metabolites

Q: Metformin: Class
A: Biguanide

Q: Gliclazide: Class
A: Sulfonylurea

Q: Pioglitazone: Class
A: Glitazone

Q: Metformin: MoA
A: Delay glucose absorption
Increases peripheral insulin sensitivity
Inhibit hepatic gluconeogenesis

Q: Metformin: Dosing
A: 500mg - 2g BD

Q: Metformin: Absorption
A: PO bioavailability 60%

Q: Metformin: Distribution
A: Minimal protein binding

Q: Metformin: Metabolism
A: Not metabolised

Q: Metformin: Elimination
A: Renal elimination of active drug

Q: Metformin: Metabolic effects
A: Severe lactic acidosis

Q: Metformin: GIT
A: Diarrhoea

Q: Gliclazide: MoA
A: Increase insulin secretion from pancreatic β-cells
May increase insulin sensitivity

Q: Gliclazide: Absorption
A: 80% PO bioavailability

Q: Gliclazide: Dosing
A: 40-160mg BD

Q: Gliclazide: Distribution
A: Extensively bound to albumin by non-ionic forces - does not displace other highly bound drugs

Q: Gliclazide: Elimination
A: Renal elimination of active drug and inactive metabolites

Q: Gliclazide: Metabolic
A: Increased appetite
Weight gain

Q: Glitazones: MoA
A: Activates the intranucleic PPARγ receptor, affecting gene translation and increasing insulin sensitivity

Q: Pioglitazone: Dosing
A: 15-30mg daily

Q: Pioglitazone: Absorption
A: High absorption - delayed effect given MoA

Q: Glitazone: Metabolism
A: Hepatic with active and inactive metabolites

Q: Glitazone: CVS
A: Precipitate fluid retention

Q: Propofol: Class
A: Phenolic derivative

Q: Propofol: Uses
A: Induction
Sedation
TIVA
Anti-emetic

Q: Propofol: Presentation
A: White oil-in-water emulsion containing:
- 10mg/ml propofol
- 10% soybean oil
- 1.2% purified egg phosphatide
- NaOH (buffer)
Bacteriostatic agents
Risk of bacterial contamination limits shelf life
Energy content is 1.1kcal/ml

Q: Propofol: pKa
A: 11 (almost all unionised at physiologic pH)

Q: Propofol: Distribution
A: 98% protein bound
VD at 4L.kg-1
CSHT peaks at 50 minutes following a 9 hour infusion

Q: Propofol: Metabolism
A: Hepatic and extrahepatic sulfation to inactive metabolites
CO dependent

Q: Propofol: Elimination
A: - Tri-exponential elimination which can be described using a three-compartment model
- Terminal half-life of 5-12 hours, context-sensitive
- Urinary excretion of inactive phase II metabolites (gives it green colour)

Q: Propofol: Resp
A: Profound suppression of laryngeal reflexes
↓ Response to hypoxia and hypercapnoea.
Bronchodilation (may constrict if preparation contains sodium metabisulfite)
Apnoea

Q: Propofol: CVS
A: Arterial and venous dilation (via NO release) causing ↓  SVR, ↓  VR. ↓  Inotropy (and ↓  MVO2).
Causing: ↓ BP
Depresses baroreceptor reflex
Pain on injection due to lipid emulsion.

Q: Propofol: CNS
A: Hyponosis
Rapid LoC (within 1 arm-brain ciruclation time)
↓ CMRO_2, CBF, and ICP.
↓ IOP.
Anticonvulsant
Parodoxical excitatory effects in ~10% (dystonic movements of subcortical origin)
EEG may demonstrate seizure-like activity

Q: Propofol: MSK
A: Pain on injection

Q: Propofol: Renal
A: Green urine

Q: Propofol: Metabolic
A: Fat overload syndrome
Lipaemia with prolonged infusion

Q: Propofol: Toxic
A: Propofol infusion syndrome:
- Acidosis/bradycardia/MODS following prolonged infusion (>4mg/kg/hr)

Q: Lignocaine: Maximal dose
A: 3mg/kg without adrenaline
7mg/kg with adrenaline

Q: Bupivacaine: Maximal dose
A: 2mg/kg

Q: Cocaine: Maximal dose
A: 3mg/kg

Q: GABA receptor subtypes:
A: GABA A: Post-synaptic ligand-gated Cl ion channel. BDZ increase Cl conductance.
GABA B: Pre- and post-synaptic GPCR which increases K conductance.

Q: Benzodiazepines: Uses
A: Sedation
Anxiolysis
Hypnotic
Anticonvulsants
Amnestic
Muscle relaxation

Q: Benzodiazepines: Distribution
A: Highly protein bound, typically VD_SS between 0.75 and 1.5 L.kg^–1

Q: Benzodiazepines: Metabolism
A: Primary Hepatic metabolism
- 1,4 BZDs ("pams") metabolically related with common, active metabolites
- Heterocyclic BZDs ("lams") are metabolized to active alpha-hydroxylates and then conjugated
*=active metabolite

Q: Benzodiazepines: Respiratory
A: ↓ VT, ↑ RR
Loss of airway tone
Apnoea

Q: Benzodiazepines: CVS
A: ↓ SVR, ↓ SBP, ↓ DBP, ↑HR

Q: Benzodiazepines: CNS
A: Hypnosis
Sedation
Anterograde amnesia
Anticonvulsant
↓ MAC

Q: Benzodiazepines: Metabolic
A: ↓ Adrenergic stress response

Q: Classification of antipsychotics
A: Typical: High D2, less 5-HT. Greater effect on positive symptoms, more EPS.
Atypical: Less EPS

Q: Antipsychotics: Uses
A: Behavioural emergencies
Schizophrenia/psychosis

Q: Antipsychotics: CVS
A: QT prolongation

Q: Antipsychotics: CNS
A: Apathy, ↓ initiative, ↓ response to external stimuli, ↓ aggression
No loss of intellectual function

Q: Antipsychotics: Endocrine
A: ↑ Prolactin (typicals)

Q: Antipsychotics: Haeme
A: Leukopenia
Agranulocytosis

Q: Antipsychotics: Metabolic
A: Weight gain
DM
Hypercholesterolaemia
(all atypical > typical)

Q: Extrapyramidal side effects: Types
A: Acute dystonic reactions
Tardive dyskinesias

Q: Acute Dystonic Reaction
A: Involuntary movements and parkinsonian symptoms.
They are:
- More common with typical antipsychotic agents
- Decline with ongoing use
- Reversible with cessation of the agent

Q: Tardive dyskinesia:
A: - Pronounced and disabling involuntary movements
- Occur with long term use (10-20 years) of dopamine antagonists
Irreversible, and worsen when therapy is stopped

Q: Antipsychotics: Absorption
A: High PO bioavailability

Q: Antipsychotics: Distribution
A: Generally highly protein bound

Q: Antipsychotics: Metabolism
A: Typically hepatic to inactive metabolites

Q: Clozapine: Metabolism
A: Zero-order kinetics at upper limit of the dose range

Q: Antipsychotics: Elimination
A: Typically renal of inactive metabolites

Q: Anticonvulsants: Absorption
A: High PO bioavailability

Q: Anticonvulsants: Distribution
A: Highly protein bound

Q: Sodium valproate: MoA
A: Stabilises Na+ channels in their inactive state and GABAergic inhibition

Q: Carbamazepine: MoA
A: Stabilises Na+ channels in their inactive state and potentiates GABA

Q: Thiopentone: MoA
A: Positive allosteric modulator of GABA_A receptors (at a separate site to benzodiazepines) in the CNS, causing:
- ↓ Rate of GABA_A dissociation
- ↑ Duration of channel opening, causing effective hyperpolarisation due to increased Cl^- conductance.
May agonise channel at higher doses.

Q: Barbiturates: Uses
A: Induction of anaesthesia
Status epilepticus
ICP control

Q: Thiopentone: Dosing
A: 3-7mg.kg-1
Consider 75mg boluses, assessing haemodynamic and neuronal effects

Q: Thiopentone: Distribution
A: pKa 7.6 (60% unionised at physiological pH)
Rapid initial distribution gives a reliable, rapid offset
Slow redistribution and prolonged elimination half life contribute to long CSHT

Q: Thiopentone: Metabolism
A: Capacity dependent hepatic metabolism - saturatable at high doses (long CSHT with infusion)
Metabolised to (active) pentobarbital, which also increases the duration of its clinical effects due to its long duration of action

Q: Thiopentone: Resp
A: Dose dependent respiratory depression
Bronchospasm
Laryngospasm

Q: Thiopentone: CNS
A: Hyponosis and anaesthesia within 40 seconds of injection (duration: 5-10 minutes), with reliable loss of lash reflex with induction bolus dose (3-7 mg•kg^-1)
↓ CBF, ↓ ICP, ↓ CMRO2, anticonvulsant, progressive flattening of EEG leading to burst suppression at high doses
Antanalgesia in very low doses

Q: Thiopentone: Renal
A: ↓ RBF causing ↓ UO

Q: Thiopentone: GIT
A: Hepatic enzyme induction

Q: Thiopentone: Immune
A: Analphylaxis ~1;20,000

Q: Thiopentone: Metabolic
A: Porphyria

Q: Thiopentone: Other
A: Intraarterial injection causes microembolisation and ischaemia due to precipitation of thiopental crystals.
Due to change of thiopentone from the water-soluble enol tatomer to the insoluble keto tautomer.

Q: Respiratory effects of hypercapnoea
A: Increased respiratory drive

Q: CVS effects of hypercapnoea
A: Peripheral vasodilation
Pulmonary vasoconstriction
Myocardial depression
Arrythmogenic

Q: CNS effects of hypercapnoea
A: Increased CBF (and ICP)
SNS activation
CNS depression

Q: Respiratory effects of hypocapnoea
A: L shift of oxyhaemoglobin dissociation curve
Respiratory depression

Q: CNS effects of hypocapnoea
A: Decreased cerebral blood flow

Front: Rank the effects of the diuretic classes on sodium chloride excretion (high to low)
Back: loop + thiazide > loop > > thiazide > CAH = K^+-sparing
Reference: Katzung

Front: Rank the effect of the diuretic classes on NaHCO_3 excretion
Back: increase:
CAH >> thiazide = thiazide + loop >
no effect:
loop (no effect) = K^+-sparing (possible effect)
Reference: Katzung

Front: Rank the diuretic classes by K^+ excretion
Back: Reduce:
K^+-sparing
Increase:
loop + thiazide > loop = thiazide = CAH
Reference: Katzung

Front: Classify diuretics by effect on body pH
Back: Reduce (acidosis):
- CAH
- K+-sparing
Increase (alkalosis):
- loop
- thiazide
- loop+thiazide
Reference: Katzung

Front: Function of the proximal convoluted tubule
Back: Reabsorbtion of:
- 65%: Na, K, Ca and Mg
- 85%: NaHCO3
- 100%: glucose, amino acids
Iso-osmotic reabsorption of water
Reference: Katzung

Front: Function of the thin Descending limb of Loop of Henle
Back: Passive reabsorbtion of water
Reference: Katzung

Front: Function of thick ascending loop of Henle
Back: Active reabsorption of 15-25% of Na, K, Cl
Secondary active reabsorption of Ca, Mg
(this is how loop diuretics cause hypocalcaemia and magnasaemia)
Reference: Katzung

Front: Functions of cortical collecting duct/tubule
Back: Variable Na, Cl reabsorption driven by aldosterone (note: paracellular reabsorption of Cl due to electronegative lumen)
Variable K and H^+ excretion driven by aldosterone
Reference: Katzung

Front: Functions of medullary collecting duct
Back: Variable water reabsorption under ADH control (via V_2 receptor)
Reference: Katzung

Front: Drugs metabolized by CYP2C9
Back: propofol
parecoxib
losartan
wafarin
(note: nomenclature is CYP (family: 45% similarity)(subfamily: 55% similarity)(isoform)
Reference: Peck & Hill

Front: Define CC/CNS ratio. Compare lignocaine and bupivacaine. What is its utility?
Back: Ratio of local anaesthetic dose or concentration required to cause irreversible cardiovascular collapse to that required to cause seizures
Bupivacaine 2
Lignocaine 7
Earlier warning symptoms might avert cardiac arrest.

Front: How do you prepare sodium bicarbonate and lignocaine to form a physiological solution?
Back: 8.4% (1 M) NaCO3 1mL to 10mL of lignocaine solution gives approx 0.1 M NaCO3
This raises the pH of the solution to approximate physiological pH

Front: Hyaluronidase: mechanism of action
Back: Depolymerizes hyaluronic acid polysaccharide in extracellular matrix of connective tissue to aid diffusion of local anaesthetic when performing eye blocks

Front: How does excipient adrenaline affect the speed of onset of local anaesthetics?
Back: Sodium metabisulphate required to prevent oxidation of adrenaline lowers pH from approximately 6 to 3. This will increase the ionized fraction of local anaesthetic (as they are all weak bases with high pKa) reducing the speed of onset. This effect can be partly corrected by the addition of sodium bicarbonate.
Reference: David Olive

Front: Define nociception
Back: The neural process of encoding noxious stimulus

Front: Gabapentin and pregabalin: MoA
Back: Inhibit presentation of α_2δ subunit of voltage-gated calcium channels on the presynaptic membrane, preventing neurotransmission at the spinal cord level
↑ synaptic GABA concentration (gabapentin only)

Front: General actions of glucocorticoids
Back: In general: catabolic
Metabolic ("anti-insulin")
- ↑ BSL
- ↑ Gluconeogenesis and proteolysis
- ↓ Glucogenesis
Cardiovascular
- ↑ Response to catecholamines
Immunological
- ↓ Cellular, humoural immune responses
- ↓ Tissue healing
Haematological
- Neutrophilia
Renal
- Weak mineralocorticoid activity
Gastrointestinal
- Gastric erosions
Bones
- Osteopaenia
Reference: Adam Skinner

Front: List the main groups of drugs used to treat diabetes mellitus
Back: Exogenous insulin
Insulin secretagogues (block K^+ channel, depolarizing cell)
Sulphonylureas (2ng generation only; e.g., glibenclamide)
- displace insulin from beta-islet cells
Meglitinides (repaglinide)
Incretin mimetics (also inhibit release of glucagon; e.g., exenatide)
Insulin sensitizers
Biguanides (metformin)
- Enhance peripheral action of insulin, reduces glucose uptake from gut
Thiazolidinediones (pioglitazone)
- Nuclear PPAR-gamma (peroxisome proliferator-activated) receptor agonist
Inhibit glucose uptake
Alpha-glucosidase inhibitors (acarbose)
- Inhibits glucose uptake by inhibiting depolymerization of starches

Front: Methods of enhancing oxygenation prior to rapid sequence induction
Back: FiO2 1.0
CPAP
Vital capacity breaths
Apnoeic oxygenation
Positioning
Reference: Stan Tay

Front: Characterize the NMDA receptor
Back: Pentameric, ligand-gated cationic channel
- Fundamental NR1 subunit
- Modulatory R2A through R2D
Binds glutamate, requires co-stimulation with glycine or d-serine
Has Mg^2+ plug, which must be displaced (must reach intracellular [Ca^++] threshold)

Front: What is the Bristol TCI method
Back: Target blood propofol concentration of 3mcg/mL
Consists of blind dosing of:
1 mg/kg bolus
10 mins of 10mg/kg/min
10 mins of 8mg/kg/min
then 6mg/kg/min thereafter
with N2O
Without N2O (12/10/8...)

Front: Opioid structure/function relationships:
Back: Potency: 3 and 6 substitutions
Antagonist: substitutions on N17

Front: Prothrombinex: contents
Back: Note: contains heparin, and is contraindicated in HITTS
Reference: PI

Front: Define MAC_awake, MAC_BAR and MAC95. What are their values?
Back: MAC_awake:
Median alveolar volatile agent concentrations required to suppress purposeful responsiveness to verbal commands.
MAC_BAR:
Median alveolar concentration required to supress autonomic response to nociception.
MAC_95:
Median alveolar concentration required to suppress movement response to a standardized supramaximal painful stimulus in 95% of unpremedicated test subjects.
MAC_awake
0.3 for contemporary agents (except nitrous)
_
MAC_BAR
1.7 - 2.0
MAC_95
1.2

Front: Classify the hypersensitivity reactions
Back: Gell & Coombs classification
Type:
I - Immediate hypersensitivity, IgE mediated (local and systemic)
II - Cytotoxic, IgG or M mediated (local or systemic)
III - Immune complex mediated
IV - T-cell mediated
Reference: Kam & Power

Front: Compare the context sensitive half times of fentanyl and alfentanil
Back: At 2 hours:
- alfentanil > fentanyl
At steady state:
- alfentanil: 40 mins
- fentanyl: 290 mins
Remember:
Clearance: alfentanil < fentanyl (4 vs. 13 mL.kg^–1.min^–1), but Vd_ss: fentanyl >> alfentanil (4 vs. 0.6 L.kg^–1)
Reference: Stoelting

Front: How should a bolus dose of fentanyl calculated for intubation?
Back: Bolus dose = C_T x Vd, with desired C_T of 2 ng.mL^–1
Using V_DSS or V_1 for V_D are both inappropriate given the huge V_DSS and rapid distribution of the drug
The V_D at peak effect (Vd_pe, V_D calculated at equilibrium between effect site and plasma) is used
Remember:
V_D = dose/concentration
Therefore:
V_D_pe = dose/concentration (at peak effect)
For fentanyl:
V_D_pe = 75 L, thus bolus dose = 150 µg

Front: Factors affecting the speed of onset of local anaesthetic block to peripheral nerve
Back: Patient factors:
(factors altering the nerve's critical length)
- nerve diameter
- myelination (affected by disease, diabetes, ageing)
(factors affecting diffusion into the nerve)
- tissue pH
Drug factors:
- agent (lower pKa = faster onset)
(Fick's law factors:)
- dose and volume of injection
- proximity of injection
Reference: Examiner Reports

Front: Categorize α-adrenoceptor blockers
Back: Competitive:
Non-selective
- Phentolamine
α1:
- Prazocin
- Tamsulosin (alpha 1a selective)
α1 and non-selective β:
- Labetalol
- Carvedilol
α2
- Yohimbine
Non-competitive:
Irreversible
- Phenoxybenzamine
Reference: Stoelting

Front: Define inotrope
Back: A substance which alters the force generated by the myocardium during contraction

Front: Effect of ageing on pain perception
Back: 1. Higher pain threshold
- Multiple studies indicate increase pain threshold with ↑ age
- Different pain threshold for different types of pain
2. Difficulty with communication of pain
- Sensory & cognitive impairment may effect ability to convey quality, severity, location of pain
- Better data with visual descriptor scale than visual analogy scale (verbal skills remain intact)
3. High incidence of chronic pain
- Higher degree of disease burden from geriatric pain syndromes
- E.g. OA/RA/shingles/PVD/DM neuropathy
4. Large inter-individual variability
- Manifestation of pain in elederly is complex & multifactorial
    - Difference in pain perception, co-morbidities, access to treatment
- Often require multidisciplinary approach to pain assessment
Reference: Examiner Reports

Q: Dipyridamole: Indications
A: - Secondary prevention of stroke in combination with aspirin
- Prosthetic valves in combination with warfarin
- Persantin-thallium scans

Q: Dextran 70: Uses
A: DVT prophylaxis
Volume expander

Q: Dextran 70: MoA
A: - reduces platelet adhesiveness via vWF inhibition
- reduces red cell aggregation
- coats endothelium preventing aggregation
- dilutes coagulation factors

Q: Dextran 70: Adverse effects
A: - Fluid overload
- Hypersensitivity (incl. anaphylaxis)
- Renal failure

Q: Morphine: Receptors targed
A: MOP, KOP

Q: Fentanyl: Receptor Targeted
A: MOP

Q: Alfentanil: Receptor Targeted
A: MOP

Q: Remifentanil: Receptor targeted
A: MOP

Q: Oxycodone: Receptor Targeted
A: MOP, KOP, DOP

Q: Remifentanil: Dose
A: Bolus: 0.5-1mcg/kg
Infusion: 0.1-1mcg/kg/min

Q: Remifentanil: pKa
A: 7.1

Q: Fentanyl: pKa
A: 8.4

Q: Alfentanil: pKa
A: 6.5

Q: Oxycodone: pKa
A: 8.5

Q: Remifentanil: Absorption
A: 20x as lipid soluble as morphine

Q: Remifentanil: CSHT
A: CSHT constant at ~4min

Q: Remifentanil: Metabolism
A: Nonspecific plasma and tissue esterases

Q: Remifentanil: Elimination
A: Renal of inactive metabolites

Q: Remifentanil: Time to peak effect
A: 1-3 minutes

Q: Glycopyrrolate: Class
A: Quaternary amine, ACh antagonist at the muscarinic receptor

Q: Glycopyrrolate: Uses
A: Bradycardia, antisialagogue

Q: Glycopyrrolate: Dosing
A: 200-400μg

Q: Glycopyrrolate: Absorption
A: Minimal PO absorption

Q: Glycopyrrolate: Distribution
A: Crosses placenta but not BBB.
Vd 0.5L/kg

Q: Glycopyrrolate: Metabolism
A: Minimal hepatic hydrolysis

Q: Glycopyrrolate: Elimination
A: Renal of unchanged drug

Q: Glycopyrrolate: Resp
A: Bronchodilation
Antisialagogue

Q: Glycopyrrolate: CVS
A: Initail bradycardia (partial agonism)
Reverses vagal causes of bradycardia, may cause tachycardia.
HR peaks 3-9 miutes following use.

Q: Glycopyrrolate: MSK
A: Anhydrosis

Q: Glycopyrrolate: GIT
A: Reduced sections and motility

Q: Hyoscine: Class
A: Tertiary amine, muscarinic antagonist

Q: Hyoscine: Uses
A: Motion sickness, antisialagogue

Q: Hyoscine: Presentation
A: Racemic. Only L-isomer active

Q: Hyoscine: Dosing
A: 200-600μg

Q: Hyoscine: Absorption
A: <50% PO bioavailability

Q: Hyoscine: Distribution
A: Vd 2L/kg

Q: Hyoscine: Metabolism
A: Hepatic esterases

Q: Hyoscine: Elimination
A: Renal of metabolites

Q: Hyoscine: Resp
A: Bronchodilation. Greatest antisialagogue effect of any anticholinergic

Q: Hyoscine: CVS
A: Least likely anticholinergic to cause tachycardia

Q: Hyoscine: CNS
A: Most likely anticholinergic to cause central anticholiniergic syndrome

Q: Hyoscine: GIT
A: Reduced PO and gastric secretions, and gastric motility

Q: Warfarin: Interactions
A: Simple potentiation:
- Other anticoagulants/antiplatelets
Antagonism:
- Vit K
- FFP
Protein binding:
- NSAIDs
Inhibit metabolism:
- ETOH
- Allopurinol
- Erythromycin
- Ciprofloxacin
- Metronidazole
- TCAs

Q: Phase I vs Phase II block
A: Phase I
- No fade, no post-tetanic facilitation
- TOF ratio of 1.0
- Augmented with anticholinesterases
Phase II
- Fade, post-tetanic facilitation
- TOF ratio <1.0
- Inhibited with anticholinesterases

Q: Heparin: Adverse effects
A: Hypotension with bolus dosing
Osteoporosis with long duration therapy
Inhibition of aldosterone secretion, causing hyperkalaemia
HITTS

Q: Protamine: PD
A: Resp:
- PHTN
CVS:
- Hypotension and bradycardia (histamine release)
Haeme:
- Anticoagulant when given in excess

Q: Protamine: Dose
A: 1mg per 100 IU of heparin

Q: Dantrolene: MSK
A: Muscle relaxation
Significant prolongation of depolarising muscle blockade
No significant prolongation of non-depolarising muscle blockade

Q: Dantrolene: CVS
A: CVS collapse in conjunction with Ca channel blockers

Q: Remifentanil: Pharmaceutics
A: White crystalline powder with 1, 2, or 5mg remifentanil

Q: Ranitidine: Indications
A: - Zollinger-Ellison syndrome
- Reflux oesophagitis
- Gastric ulceration and H. pylori eradication (with antibiotics)
- High risk aspiration (preferred agent in pregnancy)

Q: Ranitidine: MoA
A: H_2 receptor antagonist; decreases H^+/K^+ ATP-ase activity by inhibiting adenylate cyclase in the parietal cells

Q: Ranitidine: GIT
A: - Raised gastric pH (by approx. 1)
- Reduced gastric secretions
- No change to motility or LOS tone

Q: Ranitidine: CVS
A: ↓ HR, ↓ BP and arryhythmogenic with rapid IV administration

Q: Ranitidine: Resp
A: Increase risk of microaspirations

Q: Ranitidine: Metabolic
A: Contraindicated in porphyria

Q: Ranitidine: Pharmacokinetics
A: - 50% oral bioavailability
- 15% protein binding
- CYP450 metabolism (partial)
- Urinary excretion

Q: Isoprenaline: GIT
A: - Splanchnic vasodilation and improved perfusion
- Raised blood glucose and free fatty acids

Q: Epoprostenol: Uses
A: ARDS rescue therapy (last line)
PHTN
Limb ischaemia
Raynauds
Haemodialysis circuits

Q: Epoprostenol: MoA
A: Prostacyclin receptor agonist (G_s-coupled)
- Inhibits platelet adhesion and aggregation by reducing intracellular Ca^++
- Vasodilation

Q: Epoprostenol: Respiratory
A: Bronchodilation
Reduced PVR

Q: Volatiles: Metabolism
A: Hepatic CYP2E1
Metabolises C-halogen (e.g. C-F) bonds, which can be nephro- and hepatotoxic.

Q: Volatiles: Resp
A: ↓ VT and ↑ RR; overall ↓ MV and ↑ PaCO2
Right-shift central CO2 response curve
Impaired HPV

Q: Volatiles: CVS
A: ↓ MAP (predominantly by ↓ in SVR)
↓ inotropy

Q: Volatiles: CNS
A: Hypnosis.
Analgesic (except halothane).
↓ CMRO2 but ↑ CBF. At < 1 MAC cause cerebral vasodilation but do not increase ICP. >1 MAC: uncoupling of the CBF-CMRO2 relationship, therefore ICP may ↑.
↓ EEG frequency such that θ- and δ-wave dominate the EEG as depth ↑. May cause burst suppression.

Q: Volatiles: MSK
A: Augment the effects of NMBD
MH

Q: Volatiles: Renal
A: Dose dependent ↓ in RBF, GFR, and UO secondary to ↓ in MAP
F- ions produced from hepatic metabolism of fluorinated ethers may produce high-output renal failure at serum concentrations >50μmol/L

Q: Volatiles: GIT
A: ↓ Hepatic blood flow

Q: Volatiles: GU
A: Tocolysis

Q: Volatiles: Toxic
A: Nephrotoxicity (F^- ions)
Hepatotoxicity (halothane)
Decreased fertility and increased risk of spontaneous abortion in operating theatre personnel.

Q: Sevoflurane: Pharmaceutics
A: Minimally soluble, light stable, not flammable.
Formulated with 300ppm of H2O to prevent formation of HF acid by Lewis acids in glass

Q: Sevoflurane: MW
A: 200.1

Q: Sevoflurane: BP
A: 58.5°C

Q: Sevoflurane: SVP (at 20°C)
A: 158mmHg

Q: Sevoflurane: blood:gas coefficient
A: 0.7

Q: Sevoflurane: MAC
A: 2%

Q: Sevoflurane: Metabolism
A: 3-5% CYP2E1 to hexafluoroisopropanol and inorganic F- (which may be nephrotoxic)

Q: Sevoflurane: Resp
A: Not irritant
Bronchodilation, ↓ MV
Smallest ↓ in VT and therefore smallest ↑ in PaCO2

Q: Sevoflurane: CVS
A: ↑ QT
↓ SVR causing ↓ MAP without a reflex ↑ HR.
Inotropy unchanged.
Smallest ↓ in BP of any inhalational agent.

Q: Sevoflurane: Unique CNS
A: ↑ Post-operative agitation in children compared to halothane

Q: Sevoflurane: Toxic
A: Sevoflurane interacts with alkaline components of baralyme > soda lime to produce Compound A (as well as B through E, which are unimportant), which is potentially nephrotoxic
F- ion production
Malignant hyperthermia

Q: Isoflurane: Pharmaceutics
A: Soluble in rubber, light stable, not flammable

Q: Isoflurane: MW
A: 184.5

Q: Isoflurane: BP
A: 48.5°C

Q: Isoflurane: SVP (at 20°C)
A: 239mmHg

Q: Isoflurane: Blood:gas partition coefficient
A: 1.4

Q: Isoflurane: Oil:gas partition coefficient
A: 98

Q: Isoflurane: MAC
A: 1.15

Q: Isoflurane: Metabolism
A: 0.2% hepatic to nontoxic metabolites

Q: Isoflurane: Resp
A: Bronchodilation, airway irritability.
↓ MV (greater than halothane) with ↑ in RR

Q: Isoflurane: CVS
A: Reflex ↑ HR due to ↓ MAP from ↓ SVR.
Small ↓ inotropy and CO, equivalent to sevoflurane but greater than desflurane.
May cause coronary steal.

Q: Isoflurane: Unique CNS
A: Best balance of ↓ CMRO2 for ↑ in CBF

Q: Isoflurane: Toxic
A: -CHF_2 group may react with dry soda lime to produce CO
CYP 2E1 (0.2%):
- no metabolites linked with toxicity
Malignant hyperthermia

Q: Desflurane: Pharmaceutics
A: Light sensitive, flammable at 17%

Q: Desflurane: MW
A: 168.0

Q: Desflurane: BP
A: 23.5°C

Q: Desflurane: SVP (at 20°C)
A: 669 mmHg

Q: Desflurane: Blood:gas partition coefficient
A: 0.42

Q: Desflurane: Oil:gas partition coefficient
A: 29

Q: Desflurane: MAC
A: 6.6

Q: Desflurane: Resp
A: Airway irritability: coughing and breath-holding
↑ Secretions

Q: Desflurane: CVS
A: Minimal ↓ inotropy (least of all inhalational agents), but greater ↓ in SVR and BP than sevoflurane.
↑ in HR, with a bigger increase at >1.5 MAC.

Q: Desflurane: Toxic
A: Desflurane has much greater greenhouse gas effects than sevoflurane or isoflurane
Some F^– but unlikely to be of significant toxicity
Produces carbon monoxide in reaction with soda lime
Malignant hyperthermia

Q: 4% Albumin: Pharmaceutics
A: Yellow-green colloid (~70 kDa) containing:
- Human Albumin 40 g/L
- Sodium 140 mmol/L
- Chloride 128 mmol/L
- Octanoate 6.4 mmol/L

Q: Ondansetron: Absorption
A: 60% PO bioavailability

Q: Ondansetron: Distribution
A: 75% protein bound

Q: Ondansetron: Metabolism
A: Hydroxylation by CYP2D6, then conjugated.
Dose reduce in hepatic failure.

Q: Ondansetron: Elimination
A: T_1/2 3 hours

Q: Ondansetron: MoA
A: Competitive 5HT_3 receptor antagonist
(centrally at CTZ, peripherally in gut)

Q: Ondansetron: GIT
A: Antiemetic
Constipation

Q: Ondansetron: CVS
A: - Bradycardia with rapid infusion
- Prolonged QTc and torsades

Q: Phenytoin: Interactions
A: CYP2C19 inducer. Increases metabolism of:
- BZD
- warfarin
- OCP
Metabolism inhibited by:
- Metronidazole
- Chloramphenicol
- Isoniazid
Metabolism induced by:
- Alcohol
- Carbamazepine

Q: Phenytoin: CVS
A: ↓ BP and heart block with rapid infusion
Antiarrhythmic (VW class Ib)

Q: Hydrochlorothiazide: Uses
A: HTN
Heart failure
Diabetes insipidus
Renal tubular acidosis

Q: Hydrochlorothiazide: Renal
A: - HyperCa due to increase calcium reabsorption in the DCT
- HypoCl
- HypoK
- Alkalosis

Q: Hydrochlorothiazide: Metabolic
A: ↑ BSL
↑ cholesterol and triglycerides
Competes with urate for excretion—may precipitate acute gout

Q: Hydrochlorothiazide: Haeme
A: Haemolysis
Agranulocytosis, leucopaenia, thrombocytopaenia

Q: Acid-suppressing drugs
A: Antacids:
- Aluminium-, sodium-, and magnesium-based physicochemical interaction with HCl
Mucosal protectors:
- e.g. Misoprostol stimulates mucous secretion
Anti-acid secretions:
- H2 antagonists
- PPIs

Q: Edrophonium: Uses
A: - Distinguishes between myasthenia gravis (increased strength), cholinergic crisis (decreased strength) or Lambert-Eaton myasthenic syndrome (may increase strength)
- Mivacurium reversal (as mivacurium is metabolized by butyrylcholinesterase which is relatively spared)

Q: Edrophonium: Class
A: Phenolic quaternary amine

Q: Edrophonium: MoA
A: - Competitive antagonism of acetylcholinesterase >> butyrylcholinesterase
- Increases acetylcholine release

Q: Edrophonium: Neuro
A: - Improves strength in presence of non-depolarizing agents and myasthenia gravis
- Potentiates depolarizing agents and cholinergic crisis

Q: Edrophonium: CVS
A: Bradycardia

Q: Edrophonium: Resp
A: Bronchospasm
Bronchorrhoea

Q: Pancuronium: Class
A: Bisquaternary aminosteroid

Q: Pancuronium: Presentation
A: 4 mg in 2 mL
Stored at 4ºC

Q: Pancuronium: Dosing
A: 0.1 mg.kg^-1

Q: Pancuronium: Onset
A: 90-150s

Q: Pancuronium: Duration
A: 60-100 minutes

Q: Pancuronium: CVS
A: Tachycardia due to muscarinic antagonism

Q: Pancuronium: Metabolism
A: 35% undergoes hepatic deacetylation
- 3-hydroxy-pancuronium (weakly active) and other inactive metabolites (3,17- and 17-(di)hydroxy-pancuronium

Q: Pancuronium: Elimination
A: 20% biliary of metabolites
80% unchanged drug in urine

Q: Vecuronium: Class
A: Monoquaternary aminosteroid

Q: Vecuronium: Pharmaceutics
A: 10mg freeze dried powder
Reconstituted with 5mL of water
Mannitol
NaOH

Q: Vecuronium: Dose
A: 0.1 mg.kg^-1

Q: Vecuronium: Onset
A: 90-120 seconds

Q: Vecuronium: Metabolism
A: 20% undergoes hepatic deacetylation
- 3-hydroxy-vecuronium (weakly active, short half-life) and other inactive metabolites (3,17- and 17-(di)hydroxy)

Q: Vecuronium: Elimination
A: 70% biliary
30% urinary

Q: Sugammadex: Class
A: γ cyclodextrin
(γ=8 sugar residues in ring)

Q: Sugammadex: Presentation
A: 100 mg/ml

Q: Rocuronium: Class
A: Monoquaternary aminosteroid

Q: Non-depolarising muscle relaxants: MSK
A: Muscular blockade, associated with:
- Fade
- Post-tetanic facilitation
Critical illness myopathy

Q: alpha-1 acid glycoprotein binds:
A: Basic drugs

Sevoflurane: Structure

Desflurane: Structure

Isoflurane: Structure

Q: Ropivacaine: Presentation
A: Enantiopure S-ropivacaine hydrochloride
0.2, 0.75 and 1% solutions

Q: Ropivacaine: Distribution
A: 15% unionized at pH 7.4 (pKa of 8.1)
94% protein binding
300 times the lipid solubility of cocaine

Q: Ropivacaine: Elimination
A: Terminal half-life of 120 mins
Urinary (~86%) and biliary (~14%)

Q: Ropivacaine: Metabolism
A: Metabolised to weakly-active hydroxyropivacaine

Structure of a variable bypass plenum vaporiser

Q: ACE-Is: Electrolyte
A: ↓ Aldosterone levels causing hyperkalaemia (should not be used with potassium sparing diuretics

Q: ACE-Is: Metabolism
A: - Prodrugs are hydrolyzed to "prilats" (e.g., enalaprilat, ramiprilat) by hepatic esterases
- Saturation kinetics may occur at high doses

Q: Amiodarone: CNS
A: Peripheral neuropathy and myopathy (rare)

Q: Amiodarone: MSK
A: Photosensitivity
Slate grey facies

Q: Propofol: Clearance
A: 30-60ml/kg/min

Q: Properties affecting topical use of drugs
A: Effects are largely determined by Fick's Law.
Pharmaceutic:
- Presentation
- Concentration of active drug
- Stability
- pH
- Additives (pH and vasoconstrictor)
Drug factors:
- Molecular weight
- pKa
- Lipid solubility
- Potency
- Vasoconstrictor/dilator action
Patient factors:
- Site
- Skin

Q: Nitrous Oxide: Manufacture
A: Heating ammonium nitrate to 250°C
Contaminants are actively removed, and include:
- NH3
- N2
- NO2
- HNO3

Q: Nitrous Oxide: Storage
A: Stored as a liquid
- Gauge pressure is only accurate when all remaining N_2O is gaseous
- Amount of N_2O in cylinder must be determined by weight

Q: Filling Ratio
A: Mass of N_2O in the cylinder compared ot the mass of water it could hold.
- 0.75 in temperate regions
- 0.67 in warm regions

Q: Poynting effect
A: When two gases dissolve each other, and so behave differently than would be expected from their individual properties

Q: Nitrous Oxide: Molecular Weight
A: 44

Q: Nitrous Oxide: Boiling Point
A: -88°C

Q: Nitrous Oxide: Critical Temperature and Pressure
A: 36.5°C / 72 bar

Q: Nitrous Oxide: Blood:gas coefficient
A: 0.47

Q: Nitrous Oxide: Oil:gas coefficient
A: 1.4

Q: Nitrous Oxide: MAC
A: 105

Q: Nitrous Oxide: Metabolism
A: <0.01% hepatic reduction

Q: Nitrous Oxide: Resp
A: Small ↓ in VT, ↑ in RR such that MV is unchanged.
Diffusion hypoxia due to second gas effect.

Q: Nitrous Oxide: CVS
A: ↑ SNS tone, mild myocardial depression.
↑ PVR

Q: Nitrous Oxide: CNS
A: Analgesic via endorphin and encephalin modulation, and on opioid receptors.
↑ CBF.

Q: Nitrous Oxide: GIT
A: PONV
Gaseous distension of bowel

Q: Nitrous Oxide: Toxic
A: High diffusing capacity:
- Dissolve 30x faster into air filled cavities than N2 will leave
- Increase volume of compliant cavities (bowel, PTHx)
- Increase pressure of non-compliant cavities (middle ear)
Oxidates cobalt ion in vit B12, preventing it's action as a cofactor for methionine synthetase, preventing DNA synthesis, causing:
- Megaloblastic bone marrow changes
- Agranulocytosis
- Peripheral neuropathy
- Teratogenicity - avoid 1st trimester.

Q: Theophylline: Dosing
A: 4-6mg/kg load
0.4mg/kg/hr thereafter

Q: Theophylline: Target concentration
A: 10mcg/ml

Q: Paracetamol toxicity: Risk factors
A: Glutathione deficient states
- Extremes of age
- Malnutrition
- Hepatic dysfunction
Enzyme inducers:
- Anti-epileptics
 - Phenytoin
 - Carbamazepine
 - Phenobarb
- Rifampicin
- ETOH
- OCP

Q: Morphine: V_D and protein binding
A: V_D 3.5 L/kg
35% protein bound

Q: Morphine: Clearance (ml/kg/min)
A: 15

Q: Fentanyl: Clearance (ml/kg/min)
A: 13

Q: Alfentanil: Clearance (ml/kg/min)
A: 6

Q: Remifentanil: Clearance (ml/kg/min)
A: 40

Q: Oxycodone: Clearance (ml/kg/min)
A: 13

Q: Equianalgesic doses (IV) of fentanyl, alfentanil, remifentanil, and oxycodone:
A: Fent: 150mcg
Alf: 1mg
Remi: 50mcg
Oxy: 10mg

Q: Morphine: MoA
A: - µ > δ = κ opioid receptor agonist

Q: Opioid: Resp
A: ↓ CO2 sensitivity, causing ↓ MV (↓ RR > ↓ V_T)
↑ Reliance on hypoxic drive
Cough suppression
Supression of airway reflexes
Histamine-mediated:
- Bronchospasm
- ↑ PVR
Chest rigidity ('wooden chest phenomenon'):
- Increased with high potency phenylpiperidines and high doses

Q: Opioid: CVS
A: ↓ HR
↓ BP due to histamine release (less with synthetic opioids)
↑ PVR
Suppression of CVS response to laryngoscopy

Q: Opioid: CNS
A: Analgesia
- Physical
- Emotional
↓ MAC up to 90%
Sedation.
Euphoria.
N/V due to CTZ stimulation.
Meiosis due to stimulation of the Edinger-Westphal nucleus.
Tolerance
Dependence

Q: Opioid: MSK
A: Muscle rigidity
Pruritis

Q: Opioid: Metabolic
A: Decreased secretion of:
- ACTH
- Prolactin
- Gonadotrophic hormone secretion
Increased secretion of:
- ADH

Q: Opioid: GIT
A: Decreased:
- Peristalsis
- GIT secretions
Causing subsequent constipation.

Q: Opioids: Immunological
A: Impaired:
- Chemotaxia
- Lymphocyte proliferation
- Antibody production

Q: Morphine: Time to peak effect
A: 10-30 minutes

Q: Fentanyl: Time to Peak Effect
A: 5 minutes

Q: Alfentanil: Time to peak effect
A: 90s

Q: Oxycodone: Time to peak effect
A: 5 minutes

Q: Pethidine: Unique CNS
A: Lower seizure threshold

Q: Fentanyl: Unique CNS
A: Lower seizure threshold in very high doses

Q: Opioid: Renal
A: - ↓ Renal plasma flow
- ↑ ADH
- ↑ Ureteric and sphincter tone - urinary retention

Q: Buprenorphine: MoA
A: Partial MOP agonist, KOP antagonist (antanalgesic effect)

Q: Opioids: Effects following intrathecal administration
A: Respiratory Depression
Analgesia (via MOP in the substantia gelatinosa)
- Synergistic with LA
- Dull pain > sharp pain
N/V
Pruritis
Urinary retention

Q: Drug factors affecting intrathecal administration of opioids
A: ↑ Lipid solubility:
- ↑ Diffusion to site of action (↑ onset)
- ↑ Uptake to systemic circulation
Receptor affinity:
↑ Affinity ↑ duration of action

Q: Intrathecal Morphine: Respiratory depression
A: Peak at 3-12 hours, up to 24 hours

Q: Intrathecal fentanyl: Respiratory depression
A: Peaks at 2 hours

Propofol: Structure

Q: Propofol: t_1/2α
A: Fast: 1-3 minutes
Slow: 30-70 minutes

Q: Propofol: t_1/2β
A: 2-12 hours

Q: Nitrous Oxide: Metabolic Effects
A: ↑ Homocysteine

Q: Propofol: GIT
A: Antiemetic
↓  HBF

Q: Intralipid: Mechanism of Action
A: Lipid sink:
- ILE binds unionised LA, causing it to distribute off receptor sites
Fatty acid metabolism
- Cardiac fatty acid metabolism is interrupted by LA
- ILE provides a source of fatty acids to allow metabolism to continue
Competitive antagonism
- ILE may directly inhibit LA binding

Q: Why is bupivacaine more cardiotoxic than lignocaine?
A: Takes 10x as long to dissociate from the cardiac Na+ channel as lignocaine.
Leads to
- Re-entrant arrhythmias
- VF
Risk increased in tachycardia, as it potentiates use-dependent blockade.

Q: Levosimendan: Non-CVS adverse
A: Headache
N/V

Q: Salbutamol: MoA
A: β_2 >> β_1 adrenoceptor agonist

Q: Salbutamol: Resp
A: Bronchodilation
Reversal of HPV
- May worsen V/Q inequality - give supplemental O_2

Q: Salbutamol: CVS
A: Low doses: β_2-mediated vasodilation (occasional)
High doses: β_1 activation
- arrhythmogenic (esp. with hypokalaemia)

Q: Salbutamol: Fluid/Electrolyte
A: Hypokalaemia due to Na^+/K^+ ATP-ase stimulation
Hyperglycaemia (esp. in diabetics and with steroids)

Q: Salbutamol: CNS
A: Tremor
- Due to effect on smooth muscle

Q: Salbutamol: Kinetics
A: A: High first pass metabolism by COMT leads to poor PO bioavailability
D: 10% protein bound
M: Hepatic COMT
E:  t_½ 4-6 hours
- Renal of metabolites and active drug

Ketamine: Structure

Adrenaline: Structure

Q: Adrenaline: Fluid/Electrolyte
A: Hypokalaemia
- β_2 effect
Increased sodium reabsorbtion
- RAAS activation

Q: Bupivacaine: Class
A: Pipecoloxylide (piperidine) amide local anaesthetic

Q: Bupivacaine: MoA
A: Use dependent voltage-gated sodium channel blockade
10x slower dissociation from inactive channel — arrhythmogenic

Q: Bupivacaine: CVS
A: Re-entry arrhythmias due to slow dissociation from myocardial channel
Produces direct cardiac depression:
- ↓ Phase 0 of the AP
- ↓ Conduction
- CVS collapse at high doses (via brady-asystole OR VT/VF)

Q: NSAIDS: Distribution
A: Most 99% protein bound, except:
- Paracetamol (10%)
- Aspirin (85%)
Small volumes of distribution

Q: NSAIDS: Metabolism
A: Typically hepatic metabolism to inactive metabolites and conjugates

Q: Mechanisms of aspirin overdose:
A: Gastric erosion due to inhibition of gastric protective and platelet functions
Stimulation of the CTZ: N/V
Activation of the respiratory center of the medulla results in hyperventilation and respiratory alkalosis
Metabolic acidosis due to interference with cellular metabolism:
- Krebs cycle
- Oxidative phosphorylation

Q: Features of aspirin overdose
A: Common
- Hyperventillation and respiratory alkalosis (early)
- Tachycardia
- Conscious (unless massive overdose), blurred vision, tinnitus
- Sweaty, febrile
- Nauseated
Critical
- Pulmonary oedema
- Encephalopathy
- Hypoglycaemia, hypokalaemia
- Coagulopathy, GI bleed

Q: NSAIDs: Absorption
A: All have high PO bioavailability

Q: NSAID: Classification
A: Non-selective COX inhibitors
Preferential COX_2 inhibitors
Specific COX_2 inhibitors

Q: NSAID: Haeme
A: Reduced platelet activation by thromboxane A_2 (except COX_2 agents; irreversible with aspirin)
May disturb balance between thromboxane and prostacyclin production, causing:
- Vasoconstriction
- Platelet aggregation (all, except naproxen and aspirin at low doses, which does not affect prostacyclin production)

Q: NSAIDs: MoA
A: Inhibition of COX which converts prostaglandin H2 into:
- Thromboxane
- Prostacyclin
- Prostaglandins
Two isoforms:
- COX_1 (constitutive; responsible for renal autoregulation, vascular endothelium gastric mucosa; also causes thromboxane A_2 production resulting in platelet aggregation)
- COX_2 (inducible in response to tissue damage; responsible for inflammatory processes)

Q: SNP: Dose
A: Infusion: 0.5-6 µg.kg^–1.min^–1

Q: Sodium Nitroprusside: CVS
A: Predominant arteriolar vasodilation:
- ↓ Afterload and may ↓ preload
Reflex ↑ HR
↓ Myocardial oxygen consumption
↓ PVR
Rebound hypotension when ceased.

Q: Sodium Nitroprusside: Resp
A: Impairs HPV and may ↑ V/Q inequality

Q: Sodium Nitroprusside: CNS
A: ↑ ICP due to vasodilation
May lead to headache.

Q: GTN: Uses
A: Angina (Rx and prophylaxis)
LVF associated with myocardial ischaemia
HTN
Oesophageal spasm

Q: Noradrenaline: Metabolism
A: Significant pulmonary 1st pass metabolism (up to 25%)
Remainder may be:
- Uptake into nerve and metabolised by MAO or recycled
- COMT by liver/lungs/spleen

Q: Noradrenaline: Excretion
A: t1/2 2 min
Renal of inactive metabolites

Q: Noradrenaline: Resp
A: Bronchodilation
↑ MV

Q: Noradrenaline: GU
A: ↓ Uterine blood flow

Q: Noradrenaline: GIT
A: ↓ HBF

Q: Noradrenaline: Renal
A: ↓ RBF

Q: Noradrenaline: Structure
A: Loss of -CH3 group on terminal amine results in loss of β activity

Q: Noradrenaline: Pharmaceutics
A: Clear, colourless, light-sensitive solution
Contains sodium metabisulfite

Q: Phenylephrine: Class
A: Sympathomimetic phenylethylamine derivative

Q: Phenylephrine: Kinetics
A: Hepatic metabolism by MAO
Renal elimination of metabolites

Q: Phenylephrine: CVS
A: ↑ SVR, potential reflex bradycardia.
Not arrythmogenic.

Q: Ephedrine: Class
A: Synthetic sympathomimetic

Q: Ephedrine: Indications
A: Anaesthesia-related bradycardia, hypotension
Nocturnal enuresis
Narcolepsy
Bronchospasm

Q: Ephedrine: MoA
A: Indirect and direct sympathomimetic
Inhibits MAO

Q: Ephedrine: Metabolism
A: Hepatic (not by MAO and COMT)
- Gives a longer (10-60 minute) duration of action, t_1/2β of 3-6 hours

Q: Ephedrine: CVS
A: Direct and indirect ↑ in HR, BP, and CO.
Arrhythmogenic.

Q: Ephedrine: CNS
A: ↑ MAC, mydriasis.

Q: Metaraminol: Kinetics
A: Some uptake into adrenergic nerve endings

Q: Xenon: Class
A: Noble gas
Inhalational Anaesthetic

Q: Xenon: MW
A: 131 g.mol^-1

Q: Xenon: BP
A: –108ºC

Q: Xenon: blood:gas partition coefficient
A: 0.14

Q: Xenon: oil:gas partition coefficient
A: 1.9

Q: Xenon: MoA
A: NMDA receptor antagonist

Q: Xenon: CVS
A: Slight ↓ HR
Stable inotropy and SVR

Q: Xenon: Resp
A: ↓ RR, ↑ V_T; overall stable MV
Dense and viscous gas.
Does not cause diffusion hypoxia.

Q: Xenon: CNS
A: ↑ CBF with concominant ↑ in ICP

Dopamine: Structure

Q: Dopamine: Resp
A: ↓ Response of carotid body to hypoxaemia

Q: Cocaine: Class
A: Ester local anaesthetic

Q: Cocaine: Uses
A: Topical local anaesthetic and vasoconstrictor

Q: Cocaine: Presentation
A: Hydrochloride Salt
- 10% solution
- 1 and 4% paste
- Moffat's solution (8% cocaine, 1% NaCO3, 1:2 000 adrenaline)

Q: Cocaine: Distribution
A: 95% protein bound
5% unionized at pH 7.4 (pKa 8.6)

Q: Cocaine: Metabolism
A: Hepatic esterases (unlike other ester local anaesthetics) and plasma esterases to inactive metabolites

Q: Cocaine: Elimination
A: Urinary of inactive metabolites

Q: Cocaine: CVS
A: ↑ Inotropy
↑ Chronotropy
↑ SVR
Arrhythmogenic
Cardiac ischaemia due to vasoconstriction

Q: Cocaine: CNS
A: Confusion, hallucinations
Seizures
Hyperthermia

Q: Local Anaesthetics: Distribution
A: All are weak bases with pKa > 7.4 and are therefore mostly ionized at physiological pH
Esters minimally bound, do not cross the placenta.
Amides (bupiv > ropiv > ligno > prilo) bind α_1-acid glycoprotein (high affinity) and albumin (low affinity, but high total binding)
- May cross placenta: dependent upon protein binding and fetal acidosis (ion trapping)

Q: Local anaesthetics: Metabolism
A: Esters:
- Rapidly hydrolysed by plasma cholinesterases and other esterases to produce metabolites including para-aminobenzoate (PABA; allergenic)
Amides:
- Slowly hydrolyzed by hepatic amidases (may be affected by protein binding, hepatic hypoperfusion and dysfunction)

Q: Intralipid: Uses
A: Local anaesthetic systemic toxicity
Parenteral nutrition
Rescue therapy for a variety of other toxidromes

Q: Intralipid: Presentation
A: 20% purified soybean oil-water emulsion
1.2% egg phospholipids (emulsifier)
2.25% glycerin
Trace NaOH (pH 8)

Draw the work of breathing graph (P_aw vs. V_T)

Q: Verapamil: MoA
A: L-verapamil:
- Competitive antagonism of L-type (slow) voltage-gated calcium channels in the SA and AV node >> antagonism of L-type channels in vascular smooth muscle
D-verapamil:
- Sodium channel blockade producing local anaesthetic effect

Q: Calcium Channel Blockers: MoA
A: Selective blockade of L-type voltage-gated calcium channels (does not antagonize T-, N- and P-types)
Variable selectivity for channel sub-types (i.e. cardiac myocytes, cardiac conduction system, vascular smooth muscle)

Q: Calcium Channel Blockers: Absorption
A: 20-60% PO bioavailability due to first pss metabolism

Q: Calcium Channel Blockers: Distribution
A: 75-90% protein bound

Q: Methadone: MoA
A: µ receptor agonist
NMDA receptor antagonist

Q: Methadone: Duration
A: 4-8 hours (analgesia)
Respiratory effects peak later than analgesic effects

Q: Methadone: CVS
A: Prolonged QT (risk of torsades de pointes)

Q: Methadone: Kinetics
A: 75% oral bioavailability (low first pass metabolism)
90% protein binding
Hepatic metabolism to inactive compounds
- Zero order kinetics at high doses
- T_½:18-36 hours—prolonged at higher doses
40% eliminated unchanged in urine

Q: Define PEEP
A: Supra-atmospheric airway pressure at the end of expiration

Lignocaine: Structure

Q: EMLA: Presentation
A: Emulsion of
- prilocaine 25 mg/mL
- lignocaine 25 mg/mL
Arlatone (emulsifier) 19 mg/mL
Carbapol (viscocity agent) 10 mg/mL
Water to 1g
NaOH (pH 9.4)

Q: EMLA: Peak effect
A: 3/24

Q: Digoxin: Therapeutic Range
A: 1-2 µg.L^–1
>2.5 µg.L^–1 (threshold)
>10 µg.L^–1 (severe toxicity)
>20 µg.L^–1 (indication for digoxin specific Fab)

Q: Digoxin: Toxidrome
A: Triad of:
- Gastrointestinal distress
- Hyperkalemia
- Life-threatening dysryhthmias

Q: Droperidol: Class
A: Neuroleptic

Q: Droperidol: Uses
A: Antipsychotic
Antiemetic
Neuroleptanalgesia (outdated practice of inducing sedation/amnesia with opioid and dopamine antagonist)

Q: Droperidol: CNS
A: Sedation
Extra-pyramidal side-effects (may develop up to 12 hours after administraion)
Anxiety (25% and for up to 48 hours)

Q: Droperidol: CVS
A: Hypotension via α-adrenoceptor blockade
Prolonged QT and VT in high doses

Q: Droperidol: Kinetics
A: 90% protein bound
Crosses BBB (compare with domperidone which does not)
Hepatic to inactive metabolites
Renal of inactive metabolites

Q: Prilocaine: Dosing
A: 6 mg.kg-1 (without adrenaline)
8 mg.kg-1 (with adrenaline)

Q: Labetalol: MoA
A: Selective α1 antagonist
Non-selective β antagonist (some β2 partial agonist effects)

Q: Labetalol: Dosing
A: 20-80mg IV bolus

Q: Labetalol: CVS
A: ↓ SVR without reflex tachycardia
CO unchanged
↑ Myocardial perfusion via β2 agonist effect

Q: EEG effect of volatile anaesthetics
A: All burst supress, except enflurane which is associated with epileptiform spike and wave activity at 3 Hz

Q: Determinants of GFR
A: [$]GFR = K_f(P_{GC}-P_{BC}-\pi_{GC})[/$]
Normal NFP = 13 mmHg
Kƒ:
- Function of SA x permeability
- Affected by foot processes of podocytes
P_GC
Increased (↑GFR)
- Renal arterial pressure
- Increased efferent areteriolar resistance
Decreased (↓GFR)
- increased afferent arteriolar resistance
P_BC
Increased (↓GFR)
- Obstructive uropathy
π_GC
Increased (↓GFR)
- High systemic plasma oncotic pressure
- Low renal blood flow (exaggerates reduction in NFP along the capillary)

Q: Etomidate: Dose
A: 0.3mg.kg^-1

Q: Etomidate: CVS
A: Most stable of intravenous agents
Slight reduction in SVR
Stable: myocardial oxygen consumption, contractility, BP

Q: Etomidate: Resp
A: Respiratory depression

Q: Etomidate: CNS
A: Sub-cortical excitation causing movement

Q: Etomidate: Metabolic
A: Adrenocortical suppression (mortality under maintenance conditions in sepsis and trauma)
Porphyric crisis

Q: Etomidate: Distribution
A: VD_SS 3.0 l.kg^-1
75% protein binding

Q: Etomidate: Metabolism
A: Hepatic esterases to ethyl alcohol and carboxylic acid of etomidate (inactive)

Q: Etomidate: Elimination
A: Bi-exponential elimination
- Terminal half life:1-4 hours
- Renal (85%) and biliary (15%) excretion

Q: Etomidate: MoA
A: Positive allosteric modulator at GABA_A

Q: Neostigmine: Distribution
A: Small VD_SS
Minimally protein bound

Q: Neostigmine: Absorption
A: Low PO bioavailability

Q: Neostigmine: Metabolism & Elimination
A: Plasma esterases to quaternary alcohol, with some hepatic metabolism
Renatl of unchanged drug and metabolites

Describe the EEG changes associated with REM sleep

Q: Dantrolene: Dosing
A: 2.5mg/kg up to 10mg/kg in acute scenario.
1mg/kg Q4-6H for the following 24/24

Q: Dantrolene: Kinetics
A: Irritant if extravasates
85% protein bound
Hepatic metabolism to active 5-hydroxy-dantrolene
Renal of metabolites

Q: Anaesthetic preconditioning describes
A: Decreased infarct and reperfusion injury seen in myocardium after they have been exposed to volatile agents

Q: Ketamine: t_1/2
A: α: 10-15 minutes
β: 2-4 hours

Q: Suxamethonium: Distribution
A: 30% protein bound
VD 0.25L/kg - very small due to minimal distribution due to rapid metabolism

Q: Rocuronium: ED_95
A: 0.3 mg/kg

Q: Vecuronium: ED_95
A: 0.05 mg/kg

Q: Pancuronium: ED_95
A: 0.07 mg/kg

Q: Atracurium: ED_95
A: 0.25 mg/kg

Q: Cisatracurium: ED_95
A: 0.05 mg/kg

Q: Define Eutectic
A: A mixture of substances with the lowest possible melting point than any other mixture of the same substances (and lower than that of either substance)

Q: Methyldopa: Class
A: Phenylalanine derivative

Q: Methyldopa: Dosing
A: 250-500mg PO BD-TDS

Q: Methyldopa: Kinetics
A: Highly variable PO bioavailability
50% protein bound, Vd 0.3L/kg
Intestinal and hepatic metabolism
40% renal elimination of unchanged drug

Q: Methyldopa: MoA
A: Metabolised to α-methyl-noradrenaline in the CNS, which agonises central α2 receptors.

Q: Methyldopa: CVS
A: ↓ SVR with unchanged HR or CO

Q: Hydralazine: MoA
A: Hydralazine has a multimodal mechanism of action, including:
- Opening K channels, hyperpolarising vascular smooth muscle
- Decreases intracellular Ca^2+ in vascular smooth muscle
- Activation of guanylate cyclase

Q: PPI: Kinetics
A: Absorbed in small bowel
Hepatically metabolised (CYP450)
Renal elimination of active drug and metabolites

Q: PPI: MoA
A: Irreversible antagonism of the parietal H+/K+ ATPase

Q: PPI: Resp
A: Pneumonitis/pneumonia due to microaspiration

Q: Key differences between particulate and non-particulate antacids
A: Non-particulate:
- Rapid absorption due to high water solubility
- Lower risk of pneumonitis if aspirated
- Potential metabolic alkalosis
- Taste bad
Particulate:
- Lower water solubility results in slower absorption and onset but no risk of alkalosis
- Higher risk of pneumonitis

Q: Non-particulate antacid example:
A: Sodium citrate

Q: Particulate antacid example:
A: Aluminium hydroxide/calcium carbonate

Q: Change in circulating volume with mannitol
A: 1-3ml/kg per 5g of mannitol

Q: Sevoflurane: oil:gas coefficient
A: 50

Q: List classes of antiemetics with examples
A: Serotonin antagonists
- Ondansetron
Corticosteroids
- Dexamethasone
Dopamine antagonists
- Phenothiazines (e.g.Chlorpromazine)
- Butyrophenones (e.g. Droperidol)
- Benzamides (e.g. Metoclopramide)
Anticholinergics
- Hyoscine
- Atropine
Antihistamines
- Cyclizine
NK1 antagonists
- Aprepitant
Others
- Benzodiazepines
- Cannabinoids
- Propofol

Q: Types of Additives
A: Preservatives
Antioxidants
Solvents
Emulsions
Buffers

Q: Types of preservatives
A: Benzyl alcohol
- Antimicrobial >2%
- Solvent >5%
- Toxin

Q: Antioxidant (additive) types:
A: Sulfites
- Hypersensitivity
- Neurotoxic

Q: Solvent types
A: Water
- For polar molecules
Non-aqueous solvents
- Propylene glycol (hypotension, arrhythmia)
- Mannitol (diuresis)
- Soybean oil (pain, allergy)

Q: Chemical properties of an emulsion
A: Unstable
Contamination
- Due to water content
Rancidity
- Oil

Q: Use of buffers in drug formulation
A: Maximises stability
- Prolongs shelf life
Maximises solubility
Preservative

Q: Antiseptic properties of isopropyl alcohol
A: Poor antiviral
Broad spectrum antibacterial

Q: Antiseptic properties of chlorhexidine
A: Poor antiviral
Broad spectrum antibacterial and antifungal

Q: Antiseptic effects of povidone iodine
A: Good antiviral
Broad spectrum including fungi, spores, TB

Q: Other properties (including toxic) of isopropyl alcohol
A: Irritant on wounds and mucous membranes

Q: Other properties (including toxic) of chlorhexidine
A: Hypersensitivity
Persistent antiseptic effect

Q: Other properties (including toxic) of povidone iodine
A: Hypersensitivity
Requires continual release of iodine to be effective.
Inactivated by organic substances.
Stains