Anti Hypertensives

Anti Hypertensive drugs – 2
Centrally acting sympathoplegic drugs
• Once widely used in the treatment of hypertension.

• With the exception of methyldopa & clonidine, these drugs
are rarely used today.
• These agents reduce sympathetic outflow from vasomotor

centers in the brainstem
Alfa methyldopa: Mechanism of action
- methyl dopa (prodrug)


- methyldopamine

- methyl NE

Replaces NE in adrenergic nerve endings

Released in response to nerve stimulation

Stimulation of postsynaptic 2 receptors in the brain

 Sympathetic outflow from CNS

 PVR  CO & HR
 BLOOD PRESSURE
Alfa methyl dopa
• Cardiovascular reflexes remain intact

•  Renal vascular resistance
• Given OD
Use: Preferred antihypertensive during pregnancy
Side effects
• Sedation
• Hyperprolactinemia
 gynaecomastia in males & galactorrhea in females
• Hemolytic anemia
• Na & water retention
Clonidine
MOA:
• Stimulates α2 receptors in VMC
• ↓sympathetic outflow & thus
• ↓ peripheral vascular resistance, HR & CO.
Uses:
• Mild to moderate hypertension
• Diabetic diarrhea due to autonomic neuropathy
• Nicotine, alcohol & opioid withdrawal
Adv effects:
• Sedation, dry mouth, depression,
• Rebound hypertension on sudden withdrawal
 dose tapering is necessary
• Na & water retention
Βeta adrenergic blockers: mechanism of antihypotensive action
Βeta adrenergic blockers
Cardioselective (β1 Selective): Atenolol, Metoprolol, Bisoprolol,

Nebivolol (which also releases nitric oxide)
Esmolol (given IV has a short half-life (9–10 minutes).
Nonselective (β1 & β2 Blockers): Propranolol, Nadolol, Carteolol
α & β Blockers: Labetalol, Carvedilol
MOA:
• 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.
Uses:
• Mild to moderate hypertension

• Intraoperative and postoperative hypertension and
hypertensive emergencies (Esmolol)
• Pheochromocytoma and hypertensive emergencies (Labetalol)
• Heart failure and hypertension (Carvedilol)
• Angina pectoris
• Cardiac arrhythmias
Adv effects:
• Bradycardia
• Bronchoconstriction (worsening of pre existing asthma)
• Fatigue
• Impotency
• Depression, sedation, sleep problems (nightmares)
• Mask the hypoglycemic symptoms in Type 1 DM
Contraindications:
• Bronchial asthma & COPD
• Type 1 DM
• Heart block
Sudden withdrawal can cause arrhythmia, angina and rebound
hypertension (due to the up-regulation of β receptors).
• Therefore β-blockers must be tapered off gradually over a period of at
least a few weeks
α adrenergic blockers
Selective α1 receptor blockers: Prazosin, doxazosin, tamsulosin
Non selective (α1 & α2 receptor): Phenoxybenzamine, phentolamine
MOA:
• Blocks postsynaptic α1 receptors in arterioles & venules thereby
produce vasodilation, ↓ peripheral vascular resistance.
Adv effects:
• Postural hypotension – first dose phenomenon
• First dose should be small and administered at bed time
• Nasal stuffiness, dizziness, palpitation
• Reflex tachycardia (non-selective  blockers)
α blockers: Uses
Selective- a1 :
• Hypertension
• Benign prostatic hyperplasia (reduce urinary hesitancy and
prevent urinary retention)
Nonselective:
• Raynaud’s phenomenon
• Pre-surgical treatment of pheochromocytoma
• Severe hypertension due to overdose of
• Amphetamine
• Cocaine
11
Calcium channel blockers
Dihydropyridines: Amlodipine, Nifedipine, Nimodipine
Nondihydropyridines: Verapamil, Diltiazem
Dihydropyridines are more selective as vasodilators & have less

cardiac depressant effect on heart than Nondihydropyridines
MOA:
• Block the L-type calcium channels in the arterial smooth
muscles => inhibition of calcium influx & relaxation of smooth
muscles => Vasodilation & ↓ BP
• Dilate coronary, cerebral and peripheral arteries  reduce total

arterial resistance  preload / afterload
Calcium channel blockers
Adverse effects:
Common: Peripheral edema, constipation
Sinus node depression, atrioventricular blockade, bradycardia
(verapamil/diltiazem)
Reflex tachycardia & Flushing (dihydropyridines)
Gingival hyperplasia (Nifidepine)
Indications:
• Hypertension ( Amlodipine, Nifedipine)
• Supraventricular tachycardia & Cardiomyopathy (Verapamil)
• Stroke associated with subarachnoid hemorrhage (Nimodipine)
• Angina Pectoris (Diltiazem)
Contraindications:
Heart failure
β-blockers (with verapamil or diltiazem)
Vasodilators
Relax vascular smooth muscles => ↓peripheral vascular resistance
Oral : Hydralazine & Minoxidil
Parenteral : Sodium Nitroprusside, Diazoxide , Fenoldapam
HYDRALAZINE
• Arteriolar vasodilation, ↓PVR ↓BP
• Metabolized by Acetylation – genetically determined.
• Rapid acetylators have greater first pass metabolism, ↓
bioavailability & less antihypertensive benefit than do slow
acetylators.
Uses : Severe hypertension
Adv effects :
• Reflex tachycardia, Palpitation, sweating, and flushing
• Lupus erythematosus ( arthralgia, myalgia, skin rashes, & fever),
• Peripheral neuropathy.
Vasodilators
MINOXIDIL
• Arteriolar vasodilator ( opening of potassium channels in smooth muscle-- ↑
K+ conductance– Hyperpolarisation– relaxation of vascular smooth muscle)
thus causing ↓ BP
Adv effects:
• Reflex tachycardia, palpitations, edema
• Hirsutism, hypertrichosis
Uses: Severe hypertension & male type baldness topically
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, fluid retention
Sodium nitroprusside
 Powerful parenteral vasodilator (dilates both arteries & veins)

 Administered by infusion pump and BP continuously monitored
 IV infusion is sensitive to light and must therefore be made up
fresh before each administration and covered with opaque foil.
 Solutions should be changed after several hours
MOA:
• Releases nitric oxide which stimulates guanylyl cyclase => ↑
intracelluar cGMP which relaxes vascular smooth muscle,
resulting in ↓ peripheral vascular resistance & venous return.
Sodium nitroprusside
Uses: Hypertensive emergencies, severe heart failure

Adv effects:
• Accumulation of cyanide
• metabolic acidosis, arrhythmias, excessive hypotension
• Thiocyanate toxicity
• weakness, disorientation, psychosis, & convulsions
• Hypothyroidism
• Methemoglobinemia
Fenoldopam
• Peripheral arteriolar dilator used for hypertensive emergencies and

postoperative hypertension.
• Acts primarily as an agonist of dopamine D1 receptors, resulting in

dilation of peripheral arteries and natriuresis.
Side effects: Reflex tachycardia, headache, and flushing.

• ↑ intraocular pressure (should be avoided in glaucoma).
Hypertension: drug treatment
Hypertensive emergencies
Severe hypertension (BP >180/120 mm Hg) associated with rapidly

progressing damage to vessels and end organs (hypertensive
encephalopathy, acute left ventricular failure with pulmonary edema,
myocardial ischemia, acute aortic dissection, and renal failure).
• Hypertensive encephalopathy is a classic feature of malignant

hypertension.
• Characterized by severe headache, mental confusion, and

apprehension.
• Blurred vision, nausea and vomiting, and focal neurologic deficits are
common.
• If untreated, the syndrome may progress over a period of 12–48

hours to convulsions, stupor, coma, and even death.
Hypertensive emergencies: Treatment
Rapid normalization of BP may lead to cerebral hypoperfusion
& brain injury.
Aim is reduce the BP to a maximum of 25% within the first
hour; then, if the patient is clinically stable, lower the BP to
160/100 -110 mm Hg over the next 2-6 hours, and then
cautiously to normal over the following 24-48 hours.
• Subsequently, blood pressure can be reduced to normal
levels using oral medications over several weeks.
Powerful vasodilators (Nitroprusside, Nitroglycerine,

Hydralazine, Fenoldopam, or Diazoxide or Labetalol).
Esmolol is often used to manage intraoperative and
postoperative hypertension
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Anti Hypertensive drugs – 2

Centrally acting sympathoplegic drugs

• Once widely used in the treatment of hypertension.

• These agents reduce sympathetic outflow from vasomotor

- methyl dopa (prodrug)

• Cardiovascular reflexes remain intact

Cardioselective (β1 Selective): Atenolol, Metoprolol, Bisoprolol,

• Mild to moderate hypertension

Dihydropyridines are more selective as vasodilators & have less

• Dilate coronary, cerebral and peripheral arteries  reduce total

 Powerful parenteral vasodilator (dilates both arteries & veins)

Uses: Hypertensive emergencies, severe heart failure

• Peripheral arteriolar dilator used for hypertensive emergencies and

• Acts primarily as an agonist of dopamine D1 receptors, resulting in

Side effects: Reflex tachycardia, headache, and flushing.

Severe hypertension (BP >180/120 mm Hg) associated with rapidly

• Hypertensive encephalopathy is a classic feature of malignant

• Characterized by severe headache, mental confusion, and

• If untreated, the syndrome may progress over a period of 12–48

Powerful vasodilators (Nitroprusside, Nitroglycerine,

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