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Transcript
Anti Hypertensive
Agents.
Dr. Aisha AL-Ghamdi
Associate professor
Consultant internist
1
 Antihypertensives
are a class of drugs
that are used in medicine and
pharmacology to treat hypertension.
 Evidence
suggests that reduction of the
blood pressure by 5-6 mmHg can
decrease the risk of Stroke by 40%,
Coronary heart disease by15-20% and
reduces the likelihood of dementia, heart
failure, and mortality from cardiovascular
disease.
2
Antihypertensive groups









Diuretics.
Adrenergic receptor antagonists.
Adrenergic receptor agonist.
Calcium channel blockers.
Angiotensin-converting enzyme inhibitors.
Angiotensin II receptor antagonists.
Aldosterone antagonists.
Vasodilators.
Centrally acting adrenergic drugs.
3
DIURETICS
 help
the kidneys eliminate excess salt and
water from the body's tissues and blood.
 Loop diuretics:




bumetanide
ethacrynic acid
furosemide
torsemide
4
CONT.
Thiazide diuretics
 chlortalidone
 epitizide
 hydrochlorothiazide
and chlorothiazide
 bendroflumethiazide
5
CONT.
Thiazide-like diuretics:
 indapamide
 chlorthalidone
 metolazone
Potassium-sparing diuretics:
 amiloride
 triamterene
 spironolactone
6
CONT.
 Only
the thiazide and thiazide-like diuretics
have good evidence of beneficial effects
on important endpoints of hypertension,
and hence, should usually be the 1st
choice when selecting a diuretic to treat
hypertension
7
CONT.
The reason why thiazides-type diuretics are
better than the others is because of
1. Their vasodilating properties.
2. The diuretic effect of thiazides may be
apparent shortly after administration.
3. The full anti-hypertensive effect to
develop.takes longer (weeks of
treatment). {disadvantage !!}
8
Adverse effects of thiazides ;
1.
2.
3.
4.
5.
Hypokalemia → arrhythmias
Hyperuricaemia → acute gout.
increase serum LDL- cholesterol and TG.
Impair glucose tolerance and increase insulin
resistance. Reports of frank diabetes are rare.
Although thiazides probably should be avoided
as first-line drugs in patients with diabetes and
hyperlipidaemia.
Rarer side effects include nausea, headache,
rashes, photosensitivity and blood dyscrasias.
9
Adrenergic receptor antagonists
Beta blockers;
(no longer 1st line therapy in many countries)
atenolol, metoprolol, nadolol, oxprenolol,
pindolol, propranolol, timolol.
 Alpha blockers;
Doxazosin, phentolamine, indoramin,
phenoxybenzamine, prazosin ,terazosin,
tolazoline.
 Mixed Alpha + Beta blockers;
bucindolol, carvedilol, labetalol.

10
beta-receptor
Types →ß1 ß2 ß3
 Vasodilation (b2)
 Cardioacceleration (b1)
 Intestinal relaxation (b2)
 Uterus relaxation(b2)
 Bronchodilation (b2)
11
Adverse effects of b-blockers;
 slow
the rate of conduction at the atrioventricular node.
 Sinus bradycardia is common and is not a
reason to stop beta-blockers unless the
patient is symptomatic or the heart rate
falls below 40 beats/minute.
12
contraindicated in;
with 2ndand 3d degree heart block.
 Asthmatics
 rest ischaemia of the legs (Blockade of b
receptors in the peripheral circulation →
vasoconstriction)
 Diabetics (theoretically, reduce the
awareness of low blood glucose →mask
hypoglycemic symptoms).
 Patients
13
Adrenergic receptor agonist.
Alpha-2 agonists
Revise (α-receptors sites, function)


clonidine
methyldopa
14
alpha-receptor
Types → α1 (A,B,D) , α2 (A,B,C)
 Vasoconstriction
 iris dilation
 intestinal relaxation
 intestinal sphincter contraction
 bladder sphincter contraction
15
Calcium channel blockers
Block the entry of calcium into muscle cells in artery walls.
 Dihydropyridines;








amlodipine
felodipine
isradipine
lercanidipine »peripheral vasodilatation→ reflex tachycardia.
nifedipine(Adalat®)
nimodipine
nitrendipine
Non-dihydropyridines; diltiazem , verapamil.
»peripheral vasodilatation+ ↓ HR .
16
Adverse effects of CaCB;
Vasodilatation causes ankle oedema,
headache, flushing and palpitation. Some
of these side effects can be offset by
combining a calcium channel blocker with
a b-blocker.
Verapamil, Diltiazem can cause heart
block and reduces intestinal motility.
significant constipation may be occurred.
17
ACE inhibitors









captopril
enalapril
fosinopril
lisinopril
perindopril
quinapril
ramipril
trandopril
benzapril
18
Adverse effects of ACEI;

Cough commonest, more in females and older
patients.
 Angioedema more serious, but rare, which
occurs in about 0.1 to 0.2 per cent of patients.

Dramatic deterioration in renal function can
occur in patients with bilateral renal artery
stenosis. Serum urea and creatinine should,
therefore, be checked before and a few weeks
after starting an ACE inhibitor.
19
Angiotensin II receptor antagonists








Angiotensin II receptor antagonists work by antagonizing
the activation of angiotensin receptors.
candesartan
eprosartan
irbesartan
losartan
olmesartan
telmisartan
valsartan
20
Adverse effects of Angiot.II R.A.
 hyperkalaemia,
renal impairment and
hypotension. They are almost as well
tolerated as placebo. Nevertheless, cases
of angioedema have been reported with
some of these agents.
21
Aldosterone antagonists
 Eplerenone.
 Spironolactone.
Aldosterone antagonists are not
recommended as first-line agents for blood
pressure,but spironolactone and
eplerenone are both used in the treatment
of heart failure.
22
Vasodilators
Vasodilators act directly on arteries to relax
their walls so blood can move more easily
through them;used in
medical emergencies.
 sodium nitroprusside used in medical
emergencies.
 Hydralazine.
23
Centrally acting adrenergic drugs

Clonidine, Guanabenz, Methyldopa , Central
alpha agonists lower blood pressure by
stimulating alpha-receptors in the brain which
open peripheral arteries easing blood flow.
Central alpha agonists, such as clonidine, are
usually prescribed when all other antihypertensive medications have failed. For
treating hypertension, these drugs are usually
administered in combination with a diuretic.
24
CONT.
 Adverse
effects of this class of drugs
include sedation, postural hypotension,
drying of the nasal mucosa and rebound
hypertension.
 Some adrenergic neuron blockers are
used for the most resistant forms of
hypertension:
 Guanethidine
 Reserpine
25
CONT.
 These
drugs are old antihypertensive
agents but still have a role in some special
situations ex. Pregnancy, resistant HT.
 Considered cheap drugs.
26
Drugs used in treatment of HT in pregnancy
 Hydralazine.
 Methyldopa.
 Labetalol.
quiz. what is the group of each drug?
adverse effects?
27
The choice between the drugs;

Weighing side effects & cost and patient clinical
situation ! Examples:
asthmatics have been reported to have
worsening symptoms when using beta blockers.
sometimes the presence of other symptoms can
warrant the use of one particular
antihypertensive (such as beta blockers in case
of tremor and nervousness.
28