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CARDIOVASCULAR DISEASE

CARDIOVASCULAR DISEASE. HYPERTENSION ISCHAEMIC HEART DISEASE THROMBO-EMBOLIC DISEASE Myocardial infarction Stroke. Medical Pharmacolgy & Therapeutics Waller, Renwick & Hillier 2001 W.B. Saunders. ARTERIAL BLOOD PRESSURE = PERIPHERAL RESISTANCE X CARDIAC OUTPUT.

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CARDIOVASCULAR DISEASE

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  1. CARDIOVASCULAR DISEASE • HYPERTENSION • ISCHAEMIC HEART DISEASE • THROMBO-EMBOLIC DISEASE • Myocardial infarction • Stroke Medical Pharmacolgy & Therapeutics Waller, Renwick & Hillier 2001 W.B. Saunders

  2. ARTERIAL BLOOD PRESSURE = PERIPHERAL RESISTANCE X CARDIAC OUTPUT CARDIAC OUTPUT = STROKE VOL. X H.R.

  3. LOCAL CONTROL OF VASCULAR TONE

  4. 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

  5. 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

  6. 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 O2 for aerobic metabolism - heart further weakened Congestive Heart Failure

  7. ARTERIAL BLOOD PRESSURE = PERIPHERAL RESISTANCE X CARDIAC OUTPUT CARDIAC OUTPUT = STROKE VOL. X H.R. • Thus B.P. reduced by: • Dilating resistance vessels • Reduce heart rate • Reduce blood volume

  8. ANTI-HYPERTENSIVE DRUGS • Drugs affecting the Sympathetic Nervous • System Centrally-acting Clonidine } } α2 adrenoceptor agonists α-Methyl-DOPA } Moxonidine – Imidazoline receptor agonist

  9. 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

  10. α1 ADRENOCEPTOR ANTAGONISTS Prazosin, Doxasocin • Blockade of post-synaptic α1- adrenoceptors • lowers B.P. by: • Reduces peripheral resistance • Dilates venous capacitance vessels > reduces • venous return > reduces c.o. No reflex tachycardia

  11. β–Adrenoceptor Antagonists Atenolol (β1), Propranolol (β1β2) 1. Reduction of heart rate & contractility 2. Blockade of juxtaglomerular β1 adrenoceptors which reduces renin secretion Pindolol Exhibits β1 antagonism when sympathetic activity High. Also partial agonist which dilates β1 receptors In skeletal muscle vessels

  12. REDUCTION OF BLOOD VOLUME THIAZIDE DIURETIC (Bendrofluazide) This is first-line treatment of most GPs

  13. 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)

  14. ANGIOTENSIN RECEPTOR ANTAGONISTS Losartan, Telmisartan Effects similar to ACE inhibitors. No cough as no effect on BK

  15. Potassium Channel Activators Minoxidil Promote K+ extrusion from VSMC Used in severe hypertension (renal artery stenosis Or Conns Syndrome) N.B. Stimulates Hair Growth!

  16. OTHER VASODILATOR AGENTS Hydralazine Mode of action uncertain may increase cGMP in VSMC Diazoxide

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