Transcript Document

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 O2 for aerobic metabolism heart further weakened Congestive Heart Failure
ARTERIAL BLOOD PRESSURE =
PERIPHERAL RESISTANCE X CARDIAC OUTPUT
CARDIAC OUTPUT = STROKE VOL. X H.R.
Thus B.P. reduced by:
(a) Dilating resistance vessels
(b) Reduce heart rate
(c) Reduce blood volume
ANTI-HYPERTENSIVE DRUGS
1. Drugs affecting the Sympathetic Nervous
System
Centrally-acting
Clonidine
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α-Methyl-DOPA }
α2 adrenoceptor agonists
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
Pindolol
Exhibits β1 antagonism when sympathetic activity
High. Also partial agonist which dilates β1 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