Drugs on the heart Flashcards
What are the determinants of myocardial oxygen supply?
Arterial oxygen content
Coronary blood flow
What are the determinents of myocardial oxygen demand?
Heart rate
Contractility
Preload
Afterload
What are the significant channels in the SA and AV nodes?
If – Hyperpolarization activated cyclic nucleotide-gated (HCN) Sodium channels (Stimulatory)
ICa – Transient (T-type) or Long Lasting (L-Type) Calcium channels (Stimulatory)
IK – Potassium channels (Inhibitory)
What channels are targeted by major drug groups?
B-blockers reduce sympathetic activity, reduce cAMP, decrease If and ICa
Calcium antagonists reduce ICa
Ivabradine reduces If
What are the two classes of calcium antagonists?
Rate slowing – Phenylalkylamine (E.G Verapamil) and Benzothiazepines (E.G. Diltiazem)
Non-rate slowing – Dihydropyridines (E.G amlodipine), Have no cardiac action but more potent smooth muscle action (Can causes reflex tachycardia)
What drugs are used to increase myocardial oxygen supply?
Organic nitrates – Produce NO, stimulates Guanylyl cyclase, causing dilation
Potassium channel openers – Hyperpolarizes tissue, prevents contraction
Also reduces afterload and preload via general vasodilation (Less resistance and less venous return) reducing need for oxygen.
How is angina treated?
Combination of drugs. Aim is to reduce heart O2 demand and increase heart O2 supply.
Beta blockers or Calcium antagonists as background treatments
Nitrate sprays to treat symptoms short term during an attack
Drugs such as potassium channel openers used if intolerant to other drugs. Also, Ivabradine is a new treatment and being tested for efficacy.
How is heart failure treated?
Beta blockers or Ivabradine. But beta blockers must be dosed carefully, if CO reduced from HR reduction then heart failure worsens. Also Beta 2 blockage can increase vascular resistance increasing afterload. (Try ones with ISA E.G pindolol or A1/B1 selective E.g Carvediol)
Nitrates to try and reduce afterload, reduce resistance against contraction
What are some common non-cardiogenic side-effects of beta-blockers?
Beta 2 blockage can cause bronchoconstriction and hypoglycaemia (masks the symptoms of hypos too?) Therefore, beta blockers contra-indicated for asthmatics, COPD sufferers and diabetics
Cold extremities – reduced vasodilatory capacity of peripheral vasculature
Fatigue, Impotence, Depression, CNS effects (RCTs question validity of these)
What are the side-effects of CCBs?
Rate-limiting (Verapamil) – Bradycardia and AV block. Constipation
Non-rate limiting (Dihydropyridines) – 10-20% patients experience ankle oedema, headache/flushing (due to profound vasodilation), palpation due to compensatory sympathetic response
What is a simple classification of arrythmias?
Supraventricular arrhythmias – Treated with drugs such as amiodarone, verapamil
Ventricular arrhythmias – Treated with drugs such as flecainide, lidocaine
Complex arrhythmias (both) – Treated with drugs such as disopyramide
What is the Vaughan Williams classification?
Classification of drugs based (badly) on where they target
I – Na+ channel blockade
II – Beta adrenergic blockade
III – Prolongation of repolarisation (mainly K+ channel blockade)
IV – Ca2+ channel blockade
What drugs don’t fit well?
Adenosine – effects smooth muscle and SA node, increases cAMP in vascular smooth muscle, decreases cAMP in SA node (Ventricular relaxation and reduction in heart rate)
Amiodarone – Can block all the channels (tends to be classed as III), good for treating re-entry arrhythmias. However also accumulates in body (half-life – 100 days!) and can cause photosensitive skin rashes, thyroid problems and pulmonary fibrosis.
Digoxin (cardiac glycoside) – Blocks the Na-K-ATPase. Causes sodium retention, more calcium exchanged into cell – increased contractility. Slows rate due to central vagal stimulation (increased refractory period and reduced AV conduction)
What are the side effects of digoxin?
Hypokalaemic people cannot compete well for digoxin (dose must be lower for same effects)
Can cause other dysrhythmias – AV block, ectopic pacemaker activity
