Anti Hypertensive Agents.

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Anti Hypertensive Agents.

• Dr. Aisha AL-Ghamdi
• Associate professor
• Consultant internist

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• 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.

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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.

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DIURETICS

• help the kidneys eliminate excess salt and water
  from the body's tissues and blood.
• Loop diuretics
• bumetanide
• ethacrynic acid
• furosemide
• torsemide

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CONT.

• Thiazide diuretics
• chlortalidone
• epitizide
• hydrochlorothiazide and chlorothiazide
• bendroflumethiazide

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CONT.

• Thiazide-like diuretics
• indapamide
• chlorthalidone
• metolazone
• Potassium-sparing diuretics
• amiloride
• triamterene
• spironolactone

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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

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CONT.

• The reason why thiazides-type diuretics are
  better than the others is because of
• Their vasodilating properties.
• The diuretic effect of thiazides may be apparent
  shortly after administration.
• The full anti-hypertensive effect to
  develop.takes longer (weeks of treatment).
  disadvantage !!

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Adverse effects of thiazides

1. Hypokalemia ? arrhythmias
2. Hyperuricaemia ? acute gout.
3. increase serum LDL- cholesterol and TG.
4. 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.
5. Rarer side effects include nausea, headache,
   rashes, photosensitivity and blood dyscrasias.

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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.

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beta-receptor

• Types ?ß1 ß2 ß3
• Vasodilation (b2)
•  Cardioacceleration (b1)
•  Intestinal relaxation (b2)
•  Uterus relaxation(b2)
•  Bronchodilation (b2)

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Adverse effects of b-blockers

• slow the rate of conduction at the
  atrio-ventricular 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.

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contraindicated in

• Patients 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).

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Adrenergic receptor agonist.

• Alpha-2 agonists
• Revise (a-receptors sites, function)
• clonidine
• methyldopa

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alpha-receptor

• Types ? a1 (A,B,D) , a2 (A,B,C)
•  Vasoconstriction
•  iris dilation
•  intestinal relaxation
•  intestinal sphincter contraction
•  bladder sphincter contraction

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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 .

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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.

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ACE inhibitors

• captopril
• enalapril
• fosinopril
• lisinopril
• perindopril
• quinapril
• ramipril
• trandopril
• benzapril

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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.

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Angiotensin II receptor antagonists

• Angiotensin II receptor antagonists work by
  antagonizing the activation of angiotensin
  receptors.
• candesartan
• eprosartan
• irbesartan
• losartan
• olmesartan
• telmisartan
• valsartan

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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.

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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.

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Vasodilators

• Vasodilators act directly on arteries to relax
  their walls so blood can move more easily through
  themused in
• medical emergencies.
• sodium nitroprusside used in medical emergencies.
• Hydralazine.

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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 anti-hypertensive
  medications have failed. For treating
  hypertension, these drugs are usually
  administered in combination with a diuretic.

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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

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CONT.

• These drugs are old antihypertensive agents but
  still have a role in some special situations ex.
  Pregnancy, resistant HT.
• Considered cheap drugs.

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Drugs used in treatment of HT in pregnancy

• Hydralazine.
• Methyldopa.
• Labetalol.
• quiz. what is the group of each drug?
• adverse effects?

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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.