Pharmacology

Question 1

Basic electrophysiology of the heart:

Answer 1

SA action potential graph:
- If - Depolarisation (graph increases to threshold)
- Calcium channels open (graph increases from threshold to peak)
- Re-polarisation (potassium influx, graph decreases to negative value)

Ventricular AP graph:
- Vertical line increasing (rapid depolarisation) by an influx of Na
- Decreasing curve (potassium influx)
- Horizontal line (influx of Ca, equal K+ moving out)
- Graph decreases (K+ influx)

Question 2

Vaughn Williams classification of anti-arrhythmic drugs

Answer 2

Class I: Na Channel blockade
- Ia: Moderate
- Ib: Weak
- Ic: Strong

Class II: Beta adrenoreceptor blockade

Class III: K+ channel blockade

Class IV: Ca+ channel blockage

Question 3

state the primary molecular targets of class I, II, III and IV agents

Answer 3

Class I:
- Inhibits Na+ channel blocker
- Slows rapid depolarisation

Class II:
- Block beta adrenoreceptor
- Decreases rate of depolarisation by decreased cAMP resulting in decrease of Ca2+

Class III:
- Blocks K+ channels
- Increases AP duration
- Increases refractory period

Class IV:
- Ca2+ blocker
- Slows conduction at SA and AV nodes
- Decreases force of contraction

Question 4

Use-dependent block of voltage activated sodium channels by class I for ischaemic myocardium

Answer 4

Use dependent blocks: Bind preferentially to open and inactivate Na+ channels

Class I anti-arrhythmics manage ischaemia

Question 5

Examples of drugs used to treat supraventricular arrhythmias, ventricular arrhythmias, or both

Answer 5

Class I anti arrhythmic drugs:
- Flecainide, Lidocaine and Mexilitine

Class II: Beta blockers:
- Propranolol
- Atropine used to manage bradycardia onset by beta blockers

Class III: Amiodarone
- Very effective, but increased risk
- Prolong refractory period

Class IV:
- Verapamil, Diltiazem
- Treats high BP, angina, supra-ventricular arrhythmias

Question 6

How impulse conduction propagates through the myocardium:

Answer 6

1. L-type Ca channels open in response to change in membrane potential, Ca influx
2. Ryanodine receptor stimulated to open, releasing more Ca

Arrhythmias: Disturbances in electrophysiology of the heart as a result of
- Abnormal impulse formation
- Abnormal impulse conduction

Question 7

Mechanisms of action and indications for use of angiotensin-converting enzyme (ACE) inhibitors:

Answer 7

Examples:
- Ramipril
- Lisinopril

Used for:
- Hypertension
- Heart failure
- Secondary prevention after MI

Mechanism of Action:
- Inhibits angiotensin converting enzyme (ACE), reducing generation of angiotensin-II and aldosterone
- Reduces Na+ and water retention
- Reduced angiotensin-II (vasoconstrictor) leads to arterial and venous dilation

Question 8

Mechanisms of action and indications for use of angiotensin II receptors antagonists

Answer 8

Examples: Iosartan, valstaran

Given when:
- Hypertension
- Post-MI
- Heart failure when ACEi not tolerated

Mechanism of action:
- Inhibits binding of angiotensin II to AT1 in many tissue (vascular smooth muscle and adrenal glands)
- Causes vasodilation and blockage of aldosterone release

Question 9

Use of diuretics and calcium channel blockers in hypertension

Answer 9

Diuretics:
- Thiazide diurects
- Block Na+ re-absorption in kidneys

Ca2+ channel blockers:
- Dihydropydines (amlodipine)
- Rate limiting Ca antagonists
- Interfere influx of calcium ions through slow channels of cell membranes

Question 10

Describe the mechanism of action of cardiac glycosides and organic nitrates:

Answer 10

Cardiac glycosides: Digoxin
- Inhibits Na/K ATPase
- Increases [Ca2+]i
- Ca2+ extruded via Na+-Ca2+ exchanger
- Increasing Na+ in cell
- Decreases rate of Ca leaving cell
- Slows HR

Organic nitrates:
- Works on veins
- Triggers release of NO
- cGMP increases, lowering [Ca2+]i conc. and relaxing smooth muscle
- Causes vasodilation, reduces workload of heart and O2
- Also acts on minor coronary arteries to improve O2 delivery to myocardium