Objectives

Name the main classes of Anti anginal and anti

hypertensive drugs Describe the principles of drug action in the treatment of Angina and Hypertension Describe the mechanism of action of the above drugs Name the adverse effects of each of the drugs

Angina Pectoris

Main anti anginal drug classes

Organic Nitrates
Beta blockers Calcium Channel blockers (Antiplatelet drugs)

Angina Pectoris
SUPPLY DEMAND

Principals of drug Action in Angina

SUPPLY

Dilates Coronaries
Slows Heart Rate

DEMAND

Reduces Preload
Reduces Afterload Slows heart rate

Reduces contractility

The Nitrates
Cause Vasodilatation
Dilates Venules >> Arterioles Veno dilatation

Preload

O2 Demand

Coronary dilatation Coronary

Improves
Flow

Mechanism of action Releases NO intracellulary

Activates Guanylate cyclase cyclic GMP free intracellular Ca vascular smooth muscle relaxation

The Nitrates Oral / Sublingual / Transdermal / IV

GTN Sublingual spray usually

Short half life- few minutes Immediate relief of angina ISMN/ISDN Tablets Longer half life Continuous cover

The Nitrates
Nitrate Tolerance

Nitrate free period needed

Adverse Effects

Headache Hypotension Collapse

Calcium Channel blockers

Vasodilators,

arterioles >> venules Depress myocardium, slow cardiac conduction Varying selectivity to the above Arteriolar dilatation Afterload

cardiac conduction cardiac contractility

Heart rate

Mechanism of action
Block L type voltage gated Calcium channels in

arterioles Reduced Intracellular Calcium Smooth muscle relaxation Depress cardiac pacemaker cells Negative inotropic and chronotropic action

Calcium Channel blockers

Dihydropyridines Less effects on myocardium

nifedipine, amlodipine
Non- dihydropyridines More effects on

myocardium verapamil, diltiazem

Adverse effects of Ca ch. blockers

Ankle oedema

Flushing
Headache Hypotension

Palpitations

The Beta Adrenoreceptor blockers

Block cardiac 1 adrenoreceptor

Heart
rate

cardiac contractility

cardiac O2 demand

Also reduces renin secretion from the kidney

Beta Blockers
All betablockers have both 1 (cardiac) and 2

(peripheral) receptor blocking effects

Those which are more selective to 1 receptors

(cardioselective ) are more appropriate ie metoprolol, bisoprolol, atenolol Relatively non selectives may have more adverse effects ie propranolol

Adverse drug effects of Beta blockers

Bronchoconstriction

Caution in asthma Cold extremities Fatigue Bradycardia Hypoglycaemia Precipitation of cardiac failure Bad dreams

A bad dream..??

Drugs used in Hypertension

Principal Antihypertensive drugs

A -Angiotensin Converting Enzyme Inhibitors (ACE inhibitors) & Angiotensin II blockers

B -Beta adrenoreceptor blockers C - Calcium Channel blockers D Diuretics (thiazide diuretics)

Factors affecting blood pressure

BLOOD = CARDIAC PERIPHERAL PRESSURE OUTPUT RESISTANCE (vascular tone) Heart Rate Stroke Volume

Renin Angiotensin-Aldosterone System

Low renal bloof flow

renin Angiotensinogen ACE Angiotensin I Angiotensin II Angiotensin I

Angiotensin II is a powerful vasoconstrictor Stimulates Aldosterone release Na retension

ACE Inhibitors- mechanism

Inhibit synthesis of Angiotensin II

vascular resistance Blood Pressure Reduced aldosterone

Na/H2O retension

Stroke Vol
BP

ACE Inhibitors

ACE I s

captopril, ramipril, lisinopril Angiotensin Receptor blockers losartan, candesartan Particularly useful in diabetic nephropathy

Adverse effects?? find out!

Thiazide diuretics

Inhibits Na reabsorption in distal tubule of nephron Blood volume

Cardiac Output

Hydrochlorothiazide, Bendrofluazide

Adverse drug effects

Weakness Hypokalaemia Hyperuricaemia Skin rashes Glucose intolerance Increased cholesterol