8. hypotension & hypertension


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8. hypotension & hypertension

  1. 1. Drugs for the management of hypotension & hypertension
  2. 2. Introduction Hypotension: •BP below 100 / 60 mm Hg in women and less than 110 / 70 mm Hg in men. •orthostatic hypotension (orthostasis = standing upright), the blood rushes into the lower parts of the body when sitting down or standing up fast.
  3. 3. Diseases : •Severe hemorrhage •Heart diseases (cardiac insufficiency, arrhythmias, pericarditis) •Neurologic diseases •Addison’s disease Drugs •Antihypertensive drugs •Diuretics •Anti-anginal drugs •Vasodilators •Antiarrhythmic drugs •Antidepressants
  4. 4. Drugs used to treat hypotension If cerebral, renal, and cardiac perfusion is maintained, hypotension itself does not usually require vigorous direct treatment Sympathomimetic agents Used in a hypotensive emergency to preserve cerebral & coronary blood flow. The treatment is usually of short duration while the appropriate intravenous fluid or blood is being administered. Direct-acting α agonists • Norepinephrine, • Phenylephrine, & Methoxamine
  5. 5. Direct-acting α agonists Norepinephrine (Noradrenaline) is an agonist at •both α 1, α 2, & β 1 receptors. •↑peripheral resistance = ↑diastolic & systolic BP. Phenylephrine pure α 1 agonist. •longer duration of action than the catecholamines. •↑peripheral resistance = ↑diastolic & systolic BP. Methoxamine α 1 -receptor agonist. • prolonged duration of action •vagally mediated bradycardia.
  6. 6. Shock • Complex acute cardiovascular syndrome that results in a critical ↓ in perfusion of vital tissues & a wide range of systemic effects. • Usually associated with hypotension, an altered mental state, oliguria, & metabolic acidosis. • If untreated, it progresses to a refractory deteriorating state & death. Mechanisms responsible for shock : • Hypovolemia, cardiac insufficiency, & altered vascular resistance. Volume replacement & treatment of the underlying disease are the mainstays of the treatment of shock.
  7. 7. Shock Cardiogenic shock and acute heart failure, usually due to massive myocardial infarction, has a poor prognosis. •Dopamine or dobutamine : positive inotropic drugs •Dopamine acts on β1 receptors ( cardiac stimulation) dopaminergic receptors (renal & mesenteric vasodilation) α1 receptors (vasoconstriction) •Dobutamine acts on β1 ( cardiac stimulation)
  8. 8. Shock Anaphylactic shock : •Type I hypersensitivity reaction that affects both the respiratory & the cardiovascular systems causing •bronchospasm, mucous membrane congestion, angioedema, and severe hypotension •Inj Adrenaline, 0.3–0.5 mg IM •Activates α, β1, and β2 receptors, all of which may be important in reversing the pathophysiologic processes underlying anaphylaxis •Glucocorticoids and antihistamines (both H 1 - and H 2 -receptor antagonists) may be useful as secondary therapy in anaphylaxis.
  9. 9. Introduction Hypertension is the most common cardiovascular disease. Sustained hypertension damages blood vessels in kidney, heart, & brain and leads to an ↑incidence of renal failure, coronary disease, cardiac failure, and stroke. Normal Blood Pressure : Systolic 120 -129 mm Hg Diastolic 80 – 84 ,,,,,,,,,,, Mild Hypertension : 140 -159/90-99 ,,,,,,,,,,,, Moderate Hypertension 160 -179/100-109 ,,,,,,,,,, Severe Hypertension : >180/>110 ,,,,,,,,,,,
  10. 10. Introduction - III Etiology: • > 90% Unknown – Essential Hypertension ( so called because it was originally thought the raised BP was essential to maintain adequate tissue perfusion) • Secondary to known organic diseases such as Renovascular disease, Coarctation of aorta, Pheochromocytoma, Cushing’s disease, Hyperaldosteronism, etc. – The therapy is directed towards correction of underlying disease. Risk factors: • Smoking, Hyperlipidaemia, Diabetes mellitus, Obesity & history of any cardiovascular disease.
  11. 11. Antihypertensive agents 1. Centrally acting sympathoplegics 2. Adrenoceptor Antagonists α adrenergic receptor blockers β adrenergic receptor blockers 3. Angiotensin Inhibitors Angiotensin Converting Enzyme Inhibitors Angiotensin Receptor Blockers 4. Calcium channel Blockers 5. Diuretics 6. Vasodilators
  12. 12. Centrally Acting Sympathoplegic Drugs METHYLDOPA Stimulates α2 receptors in vasomotor center (VMC) thereby ↓sympathetic outflow from CNS & thus ↓ Peripheral vascular resistance, HR & CO. Uses : Hypertension in Pregnancy & Mild-moderate hypertension Adv effects: Sedation, Hyperprolactinemia, Hemolytic anemia, CLONIDINE Stimulates α2 receptors in VMC, ↓sympathetic outflow & thus ↓ Peripheral vascular resistance, HR & CO. Uses: Mild to moderate hypertension Adv effects: Sedation, dry mouth, mental depression
  13. 13. α Adrenergic Blockers PRAZOSIN: Doxazosin, Terazosin, Mechanism of Action • Blocks α1 receptors in arterioles & venules thereby produce vasodilation, ↓ peripheral vascular resistance. Uses : Mild to moderate hypertension, Benign Prostate Enlargement, Raynaud’s phenomenon, Pheochromocytoma (Nonselective α blocker Phenoxybenzamine) Adv effects: Postural hypotension - Ist dose phenomenon (Ist dose should be small & should be administered at bed time). Nasal stuffiness, dizziness, palpitation.
  14. 14. βAdrenergic Blockers Cardioselective (β1 Selective): Atenolol, Metoprolol, Bisoprolol, Nonselective (β1 & β2 ): Propranolol, Nadolol, Carteolol. α & β Blockers: Labetalol, Carvedilol Mechanism of Action: • Block β1 receptors in heart, ↓HR & CO • Inhibit β1 mediated Renin secretion from Juxtaglomerular cells (kidney) thereby depress the Renin-angiotensin- aldosterone system causing vasodilation & ↓ sodium & water retention. Adv effects: Bradycardia, bronchoconstriction (worsening of pre existing asthma), cold clammy skin, fatigue, impotency, mask the hypoglycemic symptoms in Type 1 DM
  15. 15. ACE inhibitors Captopril, Enalapril, Lisinopril • By inhibiting ACE they ↓formation of Angiotensin II, thereby causing vasodilation, ↓Na & water retention & inhibit Bradykinin metabolism thus ↑ vasodilation. Uses: Hypertension, Chronic Heart Failure & Diabetic nephropathy Adv effects: Dry cough, Angioedema, Hypotension Hyperkalemia, Teratogenicity ( Fetal hypotension, anuria & renal failure)
  16. 16. Angiotension receptor blockers (ARBs) Losartan, Valsartan, Olmisartan, Telmisartan,etc • Block the action of Angiotensin II on AT1 receptors => Vasodilation & • Inhibit Aldosterone secretion => ↓Na & water retention thus ↓ BP Advantages: Do not inhibit Bradykinin & hence no dry cough, angioedema & bronchospasm Contraindications of ACE-Inhibitors & ARBs: • Pregnancy • Patients with renal artery stenosis
  17. 17. Calcium channel blockers Amlodipine, Nifedipine, Nimodipine, Mech of action Block the L-type calcium channels in the arterial smooth muscles => Inhibition of calcium influx & Relaxation of smooth mucles => Vasodilation & ↓ BP Uses : Mild to Moderate Hypertension Subarachnoid hemorrhage (Nimodipine), Adv effects: Reflex tachycardia, Headache, Flushing, Constipation, Peripheral edema,
  18. 18. Thiazide Diuretics MOA: • Inhibit NaCl reabsorption by blocking Na+/Cl- tranporter in distal convulated tubules => Natriuresis => ↓ Blood volume & ↓ BP Uses: • Mild to Moderate Hypertension • Chronic Heart Failure Adverse effects • Hypokalemia, Hyperuricemia , Hyperglycemia , Hyperlipidemia • Hyponatremia
  19. 19. Loop Diuretics MOA: • Inhibit Na/K/2 Cl cotransporter in the Thick limb of ascending loop of Henle. => Natriuresis => ↓ Blood volume & ↓ BP Uses: • Moderate, Severe & Malignant Hypertension Adverse effects • Hypokalemia • Ototoxicity • Hyperuricemia • Hyponatremia
  20. 20. VASODILATORS Relax vascular smooth muscles => ↓Peripheral vascular resistance Oral : Hydralazine & Minoxidil Parenteral : Sodium Nitroprusside, Diazoxide HYDRALAZINE Arteriolar vasodilation, ↓Peripheral vascular resistance ↓BP Metabolized by Acetylation – genetically determined. Rapid acetylators have greater first pass metabolism, ↓ bioavailability & less antihypertensive benefit than do slow acetylators. Uses : Mild to Moderate hypertension Adv effects: Reflex tachycardia, Palpitation, Headache, Lupus erythematosus ( arthralgia, myalgia, skin rashes, & fever), Peripheral neuropathy.
  21. 21. VASODILATORS Uses of Sodium Nitroprusside: Hypertensive emergencies, Severe heart failure Adv effects: Accumulation of Cyanide ( metabolic acidosis, arrhythmias, excessive hypotension), Thiocyanate toxicity ( Weakness, Disorientation, Psychosis, & Convulsions), Hypothyroidism, Methemoglobinemia DIAZOXIDE Long acting parenteral arteriolar vasodilator, acts by opening potassium channels in vascular smooth muscles thereby ↓ peripheral vascular resistance & thus ↓BP Uses : Hypertensive emergencies Adverse effects; Excessive hypotension, Reflex tachycardia, Hyperglycemia