CARDIOVASCULAR DISEASE 1.HYPERTENSION 2.ISCHAEMIC HEART DISEASE 3.THROMBO-EMBOLIC DISEASE Myocardial infarction Stroke Medical Pharmacolgy & Therapeutics Waller, Renwick & Hillier 2001 W.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 CARDIOVASCULAR DISEASE 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 mmHg Diastolic > 90 mmHg 90% of unknown cause – Essential Hypertension Invariably associated with an increase in peripheral resistance

WHY IS HIGH B.P. HARMFUL ? Hypertension is a risk factor for atherosclerosis: High B.P. damages the endothelial cells lining blood 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 - output declines. If output from right side of heart remains constant - pulmonary oedema develops, oxygen exchange declines - less O 2 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 } } α 2 adrenoceptor agonists α-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

α 1 ADRENOCEPTOR ANTAGONISTS Prazosin, Doxasocin Blockade of post-synaptic α 1 - 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 (β 1 ), Propranolol (β 1 β 2 ) 1. Reduction of heart rate & contractility 2. Blockade of juxtaglomerular β 1 adrenoceptors which reduces renin secretion Pindolol Exhibits β 1 antagonism when sympathetic activity High. Also partial agonist which dilates β 1 receptors In 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 cGMP in VSMC Diazoxide