Q51

How does frusemide exert its action?

  • Selectively inhibits Na+/K+/2Cl- transporter in thick ascending limb of loop of Henle thus preventing resorption of Na+ & Cl- 
  • Abolishes counter-current concentrating mechanism leading to dilute urine
  • Increased prostaglandin synthesis
    • -> inhibition of salt transport in thick ascending limb
    • -> increased renal blood flow, decreased pulmonary congestion, decreased LV filling pressures

Pass Criteria:

  • Bold to pass

What are the pharmacokinetic properties of frusemide?

  • Rapid absorption after oral administration
  • Oral bioavailability 50% (range 10-100%)
  • Highly protein-bound (>95%)
  • 50% conjugated in kidney & 50% excreted in urine unchanged (tubular secretion)
  • Elimination t1/2 1.5 – 2 hours
  • Peak effect 30 minutes IV / 1 hour oral

Pass Criteria:

  • List 3

What are the potential adverse effects of frusemide?

  • Electrolyte disturbances
    • Hypokalaemia
    • Hyponatraemia
    • Hypomagnesaemia
    • Hyperuricaemia
  • Postural hypotension and dizziness
  • Metabolic alkalosis
  • Allergy – rash, eosinophilia, interstitial nephritis
  • Increased LDL & triglycerides, decreased HDL
  • Hyperglycaemia
  • Ototoxicity (high dose IV)

Pass Criteria:

  • Bold + 2

Q52

What is the mechanism of action of captopril?

  • Angiotensin converting enzyme (kininase II) inhibitor: inhibits hydrolysis of A1 to A2
  • Hence, inhibits A2 effects (potent vasoconstrictor and increases aldosterone secretion – salt and H2O retention) and decreases pulmonary vascular resistance, blood pressure
  • Also, inhibits bradykinin inactivation to cause vasodilatation and decreased pulmonary vascular resistance, blood pressure

Pass Criteria:

  • Bold to pass

What are the adverse effects of captopril?

  • Hypotension, 1st dose especially if hypovolaemic, diuretics, salt restriction, GI loss
  • Acute renal failure especially with bilateral renal artery stenosis
  • Hyperkalaemia especially if renal insufficiency, Diabetes Mellitus
  • Cough, angioedema (bradykinin, substance P), wheeze
  • Fetal abnormalities
    • 2nd/3rd trimester – hypotension, anuria, renal failure
    • 1st trimester – teratogenesis
  • Aletered taste, allergic skin rash, drug fever (10%)

Pass Criteria:

  • 3 of bold to pass

What drugs interact with captopril?

  • K+ supplements, K+ sparing diuretics – increase hyperkalaemia
  • NSAIDs – impair blood pressure reduction (block bradykinin)
  • Other anti-hypertensives
  • Haemaccel

Pass Criteria:

  • Bold to pass

Q53

What are the indications for amiodarone?

  • Treatment of atrial and of ventricular tachyarrhythmias
  • Used both to revert VT & prevent recurrence
  • Used in VF/VT cardiac arrest (after 3 shocks & adrenaline)

Pass Criteria:

  • Bold to pass

Describe the mechanism of action of amiodarone.

  • Has Class I, II, III & IV effects
  • Prolongs the AP duration (hence QT interval) by K channel blockade

Pass Criteria:

  • Bold to pass

Can you describe the possible adverse effects of amiodarone associated with both its short and long term use?

  • Acute
    • Bradycardia & heartblock
    • Hypotension
  • Chronic
    • Pulmonary fibrosis
    • Abnormal liver function tests & hepatitis
    • Skin deposits -> photodermatitis & grey-blue disclouration in sun-exposed areas
    • Asymptomatic corneal microdeposits
    • Optic neuritis (rare)
    • Hypo/hyperthyroidism

Pass Criteria:

  • All bold + 1 other
  • Especially in those with pre-existing S/AVN disease
  • Due to peripheral vasodilation.

Q54

By what routes can GTN be administered?

  • Sublingual
  • Transdermal
  • IV
  • Oral
  • Buccal
  • Inhaled

Pass Criteria:

  • Bold 3/4

Why are parenteral routes favoured?

  • To avoid the hepatic first pass effect which significantly decreases bio-availability

Pass Criteria:

  • Bold 

What is meant by the term tachyphylaxis as it relates to Glyceryl Trinitrate?

  • Continuous exposure to nitrates – smooth muscle may develop tolerance
  • Particularly seen with continuous IV infusion or long acting preparations (oral, transdermal)

Pass Criteria:

  • Understand concept

What is the implication of this for the dosing and administration of GTN?

  • Concept of “drug-free” interval – at least 8h between doses

Pass Criteria:

  • Concept

What is the theoretical basis for this phenomenon?

  • Diminished release of nitric oxide resulting from reduced bioactivation secondary to depletion of tissue thiol compounds, decreased tissue sulphydryl groups, increased generation of O2 free radicals, decreased availability of CGRP
  • Systemic compensation – after > 1 day of therapy salt and water retention reverse favourable haemodynamic change

Pass Criteria:

  • For better candidates

When should GTN be used with caution?

  • Hypotension
  • Those on sildenafil
  • Inferior and posterior MI/RV infarct
  • Fixed cardiac output (AS, tamponade etc)
  • Raised ICP
  • Significant tachy/bradycardia
  • Allergy

Pass Criteria:

  • Bold + 2

 


Q55

What anti-arrhythmic class does amiodarone belong to?

  • Class 3: also class I, II, IV effects

Pass Criteria:

  • Bold to pass

What are the effects of amiodarone on the heart?

  • Increases action potential duration due to blockade of rapid component of delayed K+ current (Ikr). Chronic use also blocks slow K+ rectifier.
  • Prolongs QT (due to above effect). Blocks inactivated Na+ channels. Weak adrenergic and Ca++ channel blocker.

Pass Criteria:

  • Bold to pass

What other arrhythmias is amiodarone used for?

  • Atrial fibrillation
  • Ventricular tachycardia
  • Ventricular fibrillation
  • Supraventricular (re-entrant/accessory)

Pass Criteria:

  • 2 to pass

What arrhythmias may amiodarone cause?

  • Torsades de pointes (rare <1%)
  • Bradycardia
  • Heart block

Pass Criteria:

  • 1 to pass

 


Q56

What is the mechanism of action of Metaraminol?

  • Direct alpha 1 receptor agonist – some indirect effect through increased noradrenaline

Pass Criteria:

  • Bold to pass

What are its effects on the cardiovascular system?

  • Vaso and arterio – constriction in vascular beds.
  • Arterioconstriction –> increased blood pressure
  • Direct cardiac effects less important
  • Heart rate slows due to vagal feedback
  • Cardiac output unchanged or slight decrease as increased venous return and hence stroke volume

Pass Criteria:

  • Bold to pass

What role do sympathomimetics have in management of shock?

  • Temporising only
  • While other treatment instituted – fluids, etc
  • Efficacy not proven
  • Useful in ‘failure’ sympathetic nervous system (e.g. spinal injury or anaesthesia)

Pass Criteria:

  • Understanding of temporary only

 


Q57

What is the mechanism of action of GTN?

  • Nitrite -> NO -> increased cGMP -> Smooth muscle relaxation
  • Prostaglandins may be involved

Pass Criteria:

  • Bold to pass

What are its clinical effects?

  • Beneficial effects
    • Venodilation
    • Reduced venous return
    • Decreased ventiruclar pre-load
    • Reduced LVEDV
    • Reduced LV wall tension
    • Reduced myocardial oxygen consumption
    • Vasodilation of epicardial coronary arteries
    • Increased coronary collateral flow
    • Decrease systemic BP
  • Adverse effects
    • Hypotension
    • Tachycardia
    • Headache

Pass Criteria:

  • 2 of 3 bold
  • 2 adverse effects

What are the indications for GTN use in the ED?

  • Angina
  • Acute coronary syndrome
  • Hypertensive urgencies/emergencies
  • Acute pulmonary oedema
  • Aortic dissection (with beta-blockade)

Pass Criteria:

  • Bold + 2 others

Q58

What is digoxin's mechanism of action in heart failure

  • Ca accumulation in cells  (due to Na-/K+ ATP block, Na in cells drive Na/Ca exchange) leads to:
    • Increased contraction strength
    • > Stroke vol/CO per beat
      • Sith smaller EDSV
      • Small heart
      • Reduced right heart pressures/volume
    • Slower HR –> greater stroke volume (particularly if AF), via effects on parasympathetic fibres/AV node

Pass Criteria:

  • 2/3 Bold + one other

Why are patients in heart failure prone to digoxin toxicity?

  • Poor renal function from low CO
  • Potential dehydration and/or other drug interactions
    • ie: ACE/diuretics/spironolacton/ca channel blockers
  • Low K+ from other heart failure meds
    • especially diuretics (makes patients higher risk from dig/toxicity)
  • Poor cardiac reserve/output, altered digoxin handling during acute HF/fluid distribution changes/other major illnessess

Pass Criteria:

  • 2 including Bold to pass

What are the feature of digoxin toxicity?
Prompt: Any features from other organ systems

  • High K (associated strongly with mortality)
  • Yellow/green (or other) colour vision
  • GI
    • Diarrhea and vomiting
    • Nausea
    • Malaise
    • Anorexia
  • Arrhythmias from greater automaticity and also AV node block (particularly bradycardia but R on T as well)
  • Severe heart blocks, particularly if previous blocks, worsening failure, low BP
  • CNS
    • Tiredness
    • Lethargy
    • Headaches
    • Parasthesias
  • Candidate may differentiate acute vs. chronic

Pass Criteria:

  • Hyperkalaemia + at least 2 others from 2 different groups

Q59

Describe the mechanism of action of verapamil

  • Block voltage-gated L-type Ca channels (a1 subunit)
  • Reduced frequency of opening when depolarised
  • Resulting in decreased transmembrane Ca current and Ca influx:
    • Vascular smooth muscle relaxation (< dihydropyridines)
  • Cardiac – decrease AVN conduction, contractility, CO

Pass Criteria:

  • Bold to pass

What are the toxic effects of verapamil?

  • CVS:
    • Bradycardia
    • AV block
    • Cardiac arrest
    • Heart failure
    • Hypotension
  • Minor:
    • Flushing
    • Dizziness
    • Nausea
    • Constipation
    • Peripheral oedema

Pass Criteria:

  • 3 CVS + 1 Minor to pass

What antidotes can be use to treat verapimil toxicity?

  • IV Calcium
  • High-dose insulin (euglycaemia) therapy

Pass Criteria:

  • 1 of 2 to pass

Q60

What is the mechanism of action of atropine?

A competitive, reversible muscarinic ACh receptor antagonist. Binds to muscarinic receptors, preventing the release of IP3 (inositol triphosphate), DAG (diacylglycerol), and the inhibition of adenylyl cyclase caused by muscarinic agonists. It is equipotent at M1, M2, and M3 receptors.

Pass Criteria:

  • Bold to pass

Describe the organ effects of atropine.

  • Eye – mydriasis and cycloplegia
  • CNS – delirium, decreases tremor in Parkinson’s disease
  • CVS – tachycardia
  • Respiratory – bronchodilation and decreases secretions
  • GIT – decreases saliva production, decreases gastric acid secretion, decreases mucin production, decreases gastric emptying, decreases gut motility and intestinal transit time increases
  • GUT – relaxes ureteric and bladder wall smooth muscle, urinary retention
  • Skin – decreased sweating

Pass Criteria:

  • Need 3 organ systems with an example to pass.

What is atropine used for clinically?

  • Treating symptomatic bradyarrythmias/bradycardia
  • Opthalmology – as a mydriatic and cycloplegic
  • Ocassionally used in paediatric RSI utilising suxamethonium (not routine anymore) especially at 2nd doses
  • Drying of secretions (e.g. in cholinergic nerve agent/OP poisoning or in palliative care)
  • Traveller’s diarrhoea

Pass Criteria:

  • Bold plus 1 other to pass.

Extra question: Describe the pharmacokinetics of atropine.

  • Route of administration – IV, oral, nebulised, topical
  • Absorption – well absorbed orally
  • Distribution – wide Vd (including CNS)
  • Half life – 2 hours
  • Metabolism and Excretion:
    • 40% phase I and phase II metabolism and renally excreted
    • 60% excreted renally unchanged

Pass Criteria:

  • Extra question if time permits. No specific pass criteria.

 


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