Cardiac Pharmacology

Question 1

ACE-I

Answer 1

• Mechanism of action
  
  • Reduced aldosterone secretion - involved in volume regulation via Na and K excretion
  • Reduced ADH secretion - ADH acts on kidneys to increase reabsorption (independent of Na)
  • Reduced arterial vasoconstriction
  • Reduced sympathetic activity
• Contraindications
  
  • Hypotensive
  • Pregnancy (teratogenic)
  • Hx of angiooedema (hereditary idiopathic or ACE-I induced)
  • Renal artery stenosis
• Interactions
  
  • NSAIDs (renal impairment)
  • Diuretics (renal impairment)
• Side effects
  
  • Cough
  • Headache
  • Hypotension
  • Hyperkalaemia
  • Angiooedema
• Moniroting
  
  • BP (post)
  • U&Es (pre and post)

Question 2

CCBs

Answer 2

• Mechanism of action
  
  • Inhibiting L-type calcium channels
  • Reduce intracellular Ca
    
    • Vascular smooth muscle relaxation → vasodilation → ↓PVR →↓BP
    • ↓ Cardiac muscle contractility (negative inotropic action) → ↓CO → ↓BP
    • ↓ SAN rate (negative chronotropic action) → ↓HR → ↓CO→ ↓BP
    • ↓ AVN conduction (negative dromotropic action) → termination of supraventricular arrhythmias
• Contraindications
  • Hypotension/cardiogenic shock
  • AS (severe)
  • Cautious use in HF
  • Pregnancy risks unknown (avoid)
• Interactions
  
  • CYP3A4
• Side effects
  
  • Headache
  • Peripheral oedema
  • Constipation
  • Flushing
  • Dizziness
  • Gingival hyperplasia
• Monitoring
  
  • Nil

Question 3

Thiazide-like diuretics

Answer 3

• Mechanism of action
  
  • DCT of the nephron inhibiting the Na/Cl co-transported
  • Preventing Na and Cl entering the tubule cells and, therefore, water
  • Antihypertensive effects are due to vasodilation of peripheral vasculature
• Contraindications
  
  • Severe renal failure
  • Severe impairment of liver function (risk of hepatic encephalopathy)
  • Pregnancy
• Interactions
  
  • ACE-I or NASIDs (risk of renal failure)
  • Lithium (increases lithium concentration)
• Side effects
  
  • Maculopapular rash
  • Erectily dysfunction
  • Gout
  • Urinary frequency
• Monitoring
  
  • U&Es (Ca, Na, K)

Question 4

BBs

Answer 4

• Mechanism of action
  
  • Highly beta-1-selective-adrenoreceptor antagonist
  • Low affinity to the beta-2-receptor of the smooth muscles of bronchi and vessels
  • Reduced CO through nefative inotropic and negatice chronotropic effects
  • Reduced renin release through blockage of the sympathetic triggered release
  • Vasodilation due to blockade of beta-2-receptors in vascular smooth muscle
• Contraindications
  
  • Asthma
  • COPD (caution)
  • Cardiogenic shock (negatively inotropic)
  • Decompensated HF (negativly inotropic)
  • Bradycardia/2nd or 3rd degree HB
• Interactions
  
  • Rate-limiting CCBs
  • Amiodaone (risk of potentiated AV conduction time)
• Side effects
  
  • Bradycardia
  • Cold peripheries
  • Headache
  • Dizziness
  • Fatigue
  • Erectile dysfunciton
  • Hypoglycaemia (non-selective BBs)
• Monitoring
  
  • Careful monitoring in HF

Question 5

Loop diuretics

Answer 5

• Mechanism of action
  
  • Acts on Na/K/Cl symporter in the Loop of Henle
  • Prompt diuretic effect
  • Decreases ventricular filling pressures
  • Encourages hypocolaemia and lowers BP
• Contraindications
  
  • Hypovolaemia
  • Hyponatraemia/hypokalaemia
  • Hypotension
• Side effects
  
  • Acute gout
  • Electrolyte abnormalities (as above)
  • Urinary incontinence in elderly
  • Renal failure
• Monitoring
  
  • If on IV daily weights and U&Es
  • If on PO similar but less frequent

Question 6

Potassium sparing diuretics

Answer 6

• Mechanism of action
  
  • Inhibits action of mineralocorticoids - increased water excretion, lowers BP and prevents excretion of K
  • Potentiates action of ACE-I in HF - inhibits RAA system
  • Binds to androgen receptors of testosterone and reduces activity
• Contraindications
  
  • Addison’t disease
  • Hyperkalaemia
• Side effects
  
  • Hyperkalaemia
  • Renal dysfunction
  • Gynaecomastia
  • Hyperchloraemia, leg cramps
• Monitoring
  
  • Regular U&Es if titrating (pay close attention to K)