CARDIOVASCULAR DISEASE

1. HYPERTENSION2. ISCHAEMIC HEART DISEASE3. THROMBO-EMBOLIC DISEASE Myocardial infarction Stroke

Medical Pharmacolgy & TherapeuticsWaller, Renwick & Hillier 2001W.B. Saunders

ARTERIAL BLOOD PRESSURE =

PERIPHERAL RESISTANCE X CARDIAC OUTPUT

CARDIAC OUTPUT = STROKE VOL. X H.R.

LOCAL CONTROL OF VASCULAR TONE

RISK FACTORS FOR CARDIOVASCULARDISEASE

1. SMOKING

2. HYPERLIPIDAEMIA

3. HIGH SALT INTAKE

4. HOMOCYSTEINAEMIA

5. LACK OF EXERCISE

6. OBESITY

7. DIABETES

8. ALCOHOL >4Pints Of Beer/Day

9. GENETIC

HYPERTENSION

Chronically elevated blood pressure:

Systolic > 140 mmHgDiastolic > 90 mmHg

90% of unknown cause – Essential Hypertension

Invariably associated with an increase inperipheral resistance

WHY IS HIGH B.P. HARMFUL ?

Hypertension is a risk factor for atherosclerosis:

High B.P. damages the endothelial cells liningblood vessels promoting formation of atherosclerotic plaque

Extra strain on heart as must pump blood against Increased peripheral resistance, LVH develops.

Eventually LV cannot meet work load - outputdeclines. If output from right side of heart remainsconstant - pulmonary oedema develops, oxygen exchange declines - less O2 for aerobic metabolism -heart further weakened Congestive Heart Failure

ARTERIAL BLOOD PRESSURE =

PERIPHERAL RESISTANCE X CARDIAC OUTPUT

Thus B.P. reduced by:

(a) Dilating resistance vessels(b) Reduce heart rate(c) Reduce blood volume

CARDIAC OUTPUT = STROKE VOL. X H.R.

ANTI-HYPERTENSIVE DRUGS

1. Drugs affecting the Sympathetic Nervous System

Centrally-acting

Clonidine } } α2 adrenoceptor agonistsα-Methyl-DOPA }

Moxonidine – Imidazoline receptor agonist

GANGLION BLOCKING DRUGS

Trimetaphan – obsolete except in some highly specialised surgical procedures (i.v.)

ADRENERGIC NEURONE BLOCKING DRUGS

Debrisoquine rarely used due to postural hypotension

α1 ADRENOCEPTOR ANTAGONISTS

Prazosin, Doxasocin

Blockade of post-synaptic α1- adrenoceptors lowers B.P. by:

(a)Reduces peripheral resistance(b) Dilates venous capacitance vessels > reduces venous return > reduces c.o.

No reflex tachycardia

β–Adrenoceptor Antagonists

Atenolol (β1), Propranolol (β1β2)

1. Reduction of heart rate & contractility

2. Blockade of juxtaglomerular β1 adrenoceptors which reduces renin secretion

PindololExhibits β1 antagonism when sympathetic activity High. Also partial agonist which dilates β1 receptorsIn skeletal muscle vessels

REDUCTION OF BLOOD VOLUME

THIAZIDE DIURETIC (Bendrofluazide)

This is first-line treatment of most GPs

DRUGS AFFECTING THE RENIN-ANGIOTENSIN SYSTEM

ACE INHIBITORS – Captopril, Enalapril

Competitively inhibit ACE – reduces Ang II generation (vascular wall) also circulating which reduces aldosterone output thus decreases Na+

reabsorption.

Prolongs half-life of Bradykinin (cough)

ANGIOTENSIN RECEPTOR ANTAGONISTS

Losartan, Telmisartan

Effects similar to ACE inhibitors.

No cough as no effect on BK

Potassium Channel Activators

Minoxidil

Promote K+ extrusion from VSMC

Used in severe hypertension (renal artery stenosis

Or Conns Syndrome)

N.B. Stimulates Hair Growth!

OTHER VASODILATOR AGENTS

Hydralazine

Mode of action uncertain may increase cGMPin VSMC

Diazoxide