2. Hypertension Pathogenesis:
➢ Hypertension is the most common cardiovascular disease.
➢ Hypertension is a conventionally as a sustained increases in BP> 140/90 mm
Hg.
➢ The diagnosis of hypertension is based on repeated, reproducible
measurements of elevated blood pressure.
➢ The lethal effects of hypertension are caused mainly-
➢ Excess workload- heart failure- heart attack.
➢ High BP damages a major blood vessels in the brain- ‘Cerebral Stroke’.
➢ High BP injuries in kidneys – ‘Kidney Failure’.
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*Patients in whom no specific cause of hypertension can be found are said to have
ESSENTIAL Hypertension.
4. Pharmacotherapy of Hypertension:
Salt accumulation is the key factor of genesis of hypertension-
➢ Salt load in ECF- increase the osmolality of fluid- Thirst centre activate- ECF increase.
➢ Increase osmolality- stimulate the hypothalamus- Promote ADH- Reabsorption of water.
Pharmacological targets of Anti-hypertensive drugs:
➢ Diuretic- which lower blood pressure by depleting the body of sodium and
reducing blood volume and perhaps by other mechanisms.
➢ Sympathoplegic agents- which lower blood pressure by reducing peripheral
vascular resistance, inhibiting cardiac function, and increasing venous pooling in
capacitance vessels.
➢ Direct vasodilators- which reduce pressure by relaxing vascular smooth muscle,
thus dilating resistance vessels and—to varying degrees—increasing capacitance
as well.
➢ Drug inhibiting or modulating RAS system.
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5. Agra Public Pharmacy College, Artoni, Agra,
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*Source: Katzung; Page No-230
7. ➢ Other anti-hypertensive drugs:-
➢ Central Sympatholytics- Clonidine, Methyldopa
➢ Vasodilators- Arteriolar; Hydralazine; Minoxidil
- Arteriolar+ Venous; Sodium nitroprusside.
ACE- Inhibitors
➢ ACE (Angiotensin Converting Enzyme) distributed in many tissues.
➢ primarily endothelial cells
➢ blood vessels: major site for angiotensin II production
➢ Renin release from the kidney cortex is stimulated by reduced renal arterial
pressure, sympathetic neural stimulation, and reduced sodium delivery or
increased sodium concentration at the distal renal tubule
➢ Renin acts upon angiotensinogen to split off the inactive precursor decapeptide
Angiotensin I.
➢ Angiotensin I is then converted, primarily by endothelial ACE, to the arterial
vasoconstrictor octapeptide -Angiotensin II
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8. ➢ Angiotensin II has vasoconstrictor and sodium-retaining activity.
➢ ACE-inhibitors interference with the both short & long loop ‘Negative
feedback’ on renin release.
➢ Angiotensin II inhibitors lower blood pressure principally by decreasing
peripheral vascular resistance.
ADR’s:
– Hypotension (Diuretic withdrawn before beginning therapy).
– Cough (Dry cough- due to accumulation of bradykinin in the lungs).
– Hyperkalemia ( the conc. Of aldosterone- K+ retension (with K+ sparing
diuretcis).
– Acute renal failure
– Teratogenic toxic effects (first trimester)
– Skin rashes; Proteineuria; Angioedema
– Dysgeusia
– Neutropenia
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9. ➢ Drug Interactions:
➢ Antacids- reduce the bioavailability
➢ Aspirin- induced hyperkalemia- loss of anti-hypertensive effects
➢ Capsaicin- induced cough
Angiotensin Receptor Blocker’s
➢ Directly block Angiotensin II type-1 (AT1) receptor.
➢ Losartan and valsartan were the first marketed blockers of the angiotensin II
type 1.
➢ More recently- candesartan, eprosartan, irbesartan, and telmisartan have
been released.
➢ Do not block bradykinin breakdown.
➢ Do not block any receptors & ion channels, except for TXA2- receptor- some
‘Anti-aggregatory’ property.
➢ ADR’s:
➢ orthostatic hypotension
➢ renal insufficiency
➢ hyperkalemia
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10. Direct Renin Inhibitor (ALISKIREN):-
➢ Aliskiren is the first in a new class of potent, orally effective renin inhibitors.
➢ Whereas all of the other drugs act by inhibiting certain aspects of the ultimate step in the
reninangiotensin system (RAS), ie, angiotensin II, aliskiren targets the first and rate-limiting
step - namely, renin.
➢ ADR’s: Abdominal pain, loose motion cough, contraindicated in pregnacncy etc.
β-Blockers:
➢ Negative chronotropic & inotropic cardiac effects reduce CO
➢ β-blockers with intrinsic sympathomimetic activity (ISA)
➢ do not reduce CO
➢ lower BP
➢ decrease peripheral resistance
➢ Membrane-stabilizing action on cardiac cells at high enough doses
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11. ➢ ADR’S: bradycardia, abrupt discontinuation may cause rebound
hypertension or unstable angina etc.
➢ Greater affinity for β1 than β2 receptors.
➢ Cardioselective: atenolol; Nonselective: nadolol, propranolol
➢ Mixed α- and β-blockers: carvedilol, labetolol
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12. ➢ Calcium Channel Blockers:
➢ Inhibit influx of Ca2+ across cardiac & smooth muscle cell membranes
➢ CCBs block high-voltage (L-type) Ca2+ channels resulting in coronary & peripheral
vasodilation.
➢ They lower BP by decrease tpr. Without compromising CO
Centrally Acting Sympatholytics: (Methyldopa)
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13. ➢ Peripheral sympatholytic drugs such as alpha-adrenoceptor and beta-
adrenoceptor antagonists block the influence of norepinephrine at the
effector organ (heart or blood vessel)
➢ Ganglionic blockers that block impulse transmission at the sympathetic
ganglia
➢ Block sympathetic activity within the brain. These are called centrally acting
sympatholytic drugs.
➢ Methyldopa is a precursor of dopamine &NA
➢ It cause ‘FALSE NEUROTRANSMISSION’- ‘Methyl NA’- this mechanism
contribute to its anti-hypertensive action.
➢ ADR’s: Sedation, lethargy, hypersensitivity etc.
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