anti hypertensives

ANTI-HYPERTENSIVES

Dr. AMANULLA ABUL HASSANCHENNAI

BLOOD PRESSURE

• Measure of pressure exerted on the lateral wall of the blood vessels by a flowing column of blood

• Has two components – Systolic– Diastolic

• Normal- 120/80 mm of Hg

FACTORS INFLUENCING BP

• Blood pressure = Cardiac output (CO)* Total peripheral resistance(TPR)

• Cardiac output = Heart rate * Stroke volume• Stroke volume in turn depends upon the

venous return and blood volume• TPR depends upon the size of the blood

vessels mainly under the control of ANS• RAAS System

JNC – 8 ClassificationCategory Systolic Diastolic

Normal <120 <80

Prehypertensive 120-139 80-89

Stage 1 Hypertensive 140-159 90-99

Stage 2 Hypertensive >160 >100

Isolated Systolic Hypertension

>/=140 <80

How Anti Hypertensives work?

• By reducing blood volume and sodium concentration

• By abolition of the sympathetic activity• By dilating the blood vessels• By inhibiting the RAAS system

ANTIHYPERTENSIVES

DIURETICS SYMPATHOPLEGICS

VASODILATORS

RAAS INHIBITOR

DIURETICS• THIAZIDE-1st line drug in Management.

– Hydrochlorthiazide- 12.5 to 50 mg– Chlorthaidone- 12.5 to 25mg– Indapamide- 1.25 to 5 mg . Longer acting

• LOOP DIURETICS– Furosemide: 20 to 80 mg twice daily– Torsemide: 10 to 40 mg

• POTASSIUM SPARING– Amiloride: 5 to 10 mg– Spiranolactone: 25 to 50 mg– Triamterene : 100 mg

• Initial and prolonged effect?– Initailly: Both CO and TPR reduces– Later: CO comes to normal and TPR remains low

• ADR:– Hypokalemia* – Hyperglycemia* (What to do in diabetics?)– Hyperuricemia *(What to do in GOUT?)

ANTIHYPERTENSIVES

DIURETICS SYMPATHOPLEGICS

VASODILATORS

RAAS INHIBITOR

SYMPATHOPLEGICS

DRUGS DECREASING CENTRAL

SYMPATHETIC OUTFLOW

GANGLION BLOCKER

NEURON BLOCKERS

ALPHA BLOCKERS

BETA BLOCKERS

CENTRAL SYMPATHETIC OUTFLOW INHIBITORS

• CLONIDINE (0.1 to 0.2 mg twice daily) and ALPHA METHYL DOPA (250 to 500 mg twice daily)

• Alpha 2 receptor agonists in brain• ADR:

– Clonidine- Rebound Hypertension– Alpha Methyl Dopa- Hemolytic anemia

• Moxonidine and Rilmenidine- Imidazoline receptors that modulate the activity of alpha 2 recpetors in brain

• Better to add diuretics in prolonged use due to their sodium and water retention activity on prolonged use.

SYMPATHOPLEGICS

DRUGS DECREASING CENTRAL

SYMPATHETIC OUTFLOW

GANGLION BLOCKER

NEURON BLOCKERS

ALPHA BLOCKERS

BETA BLOCKERS

Ganglion Blockers

• Nn type receptor blockers in Ganglion• Both sympathetic and parasympathetic system

is blocked• Hence the side effects like Urinary retention

and dry mouth• Hexamethonium and Trimethopan• Not used nowadays except in Aortic dissection

SYMPATHOPLEGICS

DRUGS DECREASING CENTRAL

SYMPATHETIC OUTFLOW

GANGLION BLOCKER

NEURON BLOCKERS

ALPHA BLOCKERS

BETA BLOCKERS

ADRENERGIC NEURON BLOCKERS

• Reserpine, Guanethidine and Bretylium• Reserpine– Inhibits vesicular uptake of Adrenaline, Serotonin and

Dopamine.– Serotonin- Depression and Suicidal tendencies

• Guanethidine and Bretylium– Enters vesicles and displaces the Noradrenaline which in

turn is metabolised– Active orally– Orthostatic hypotension – Not a first dose phenomenon.

SYMPATHOPLEGICS

DRUGS DECREASING CENTRAL

SYMPATHETIC OUTFLOW

GANGLION BLOCKER

NEURON BLOCKERS

ALPHA BLOCKERS

BETA BLOCKERS

Alpha Blockers

• NON SELECTIVE:– Phenoxybenzamine: Pheochromocytoma– Phentolamine: Clonidine withdrawal– Tolazoline: Clonidine Withdrawal– Greater Tachycardia than selective

• SELECTIVE:– DOC in Hypertension with BPH– First dose hypotension– Do not impair metabolism: Can be used in Diabetics, CAD and Gout– Prazosin : 0.5 to 20 mg– Terazosin: 1 to 5 mg– Doxazosin: 1 to 4 mg– Usually bed time doses

SYMPATHOPLEGICS

DRUGS DECREASING CENTRAL

SYMPATHETIC OUTFLOW

GANGLION BLOCKER

NEURON BLOCKERS

ALPHA BLOCKERS

BETA BLOCKERS

BETA BLOCKERS

• Inhibition of Beta-1 receptors– Heart– JG apparatus– Brain

• Usually Cardioselective drugs are used• Celiprolol, Oxeprenalol, Pindolol, Alprenolol and

acebutalol• Esmolol, Atenolol, Nevibolol, Betaxolol and

bisoprolol.

• Metoprolol succinate 50-100mg and tartrate 50-100mg twice daily

• Nebivolol 5-10mg• Propranolol 40-120mg twice daily• Carvedilol 6.25-25mg twice daily• Bisoprolol 5-10mg• Labetalol 100-300mg twice daily• Carvedilol and Labetalol is both alpha and beta

blockers

• Not first line agents – reserve for post-MI/CHF• Cause fatigue and decreased heart rate • Adversely affect glucose metabolism• Mask hypoglycemic awareness• Non selective Beta blocker is contra-indiated

in Asthmatics

ANTIHYPERTENSIVES

DIURETICS SYMPATHOPLEGICS

VASODILATORS

RAAS INHIBITOR

Vasodilators

• May be – Arteriolar: Potassium Channel openers, CCB,

Dopamine agonist– Venodilator: Nitrates– Both arteriolar and Venous: Sodium

nitroprussides, ARB, ACE-i, Alpha blockers.

Vasodilators

Calcium Channel Blockers

Potassium Channel Openers

NO Releasers

Dopamine Agonist

Calcium Channel Blockers

Calcium Channel Blockers

Phenylalkylamines

Verapamil 80 to 120 mg thrice. ER-240 to 480 mg stat

Norverapamil

Benzothiazipines

Diltiazem180 to 360 mg

Dihydropyridines

Nifedipine, 30 to 90mg,Nicardipine,

Amlodipine 5-10mg etc

• Blocks L- type calcium Channels• Reducing the frequency of opening of the calcium channels and that

results in Smooth muscle relaxation and depression of heart.• Dihydropyridines are also called as peripheral CCBs- Reflex tachycardia

more common– Nifedipine– Amlodipine- Maximum Half life– Nicardipine- Longest acting

• Parentral• DOC of hypertensive emergency

– Nimodipine: Cerebroselective– Clevidipine: Ultrashort acting recently approved for Emergencies

• Verapamil> Diltiazem

VERAPAMIL-WHERE AND WHERE NOT?WHERE? WHERE NOT?

ANGINA SICK SINUS SYNDROME

PSVT CHF

HYPERTENSION ALONG WITH BETA BLOCKERS

HOCM

Vasodilators

Calcium Channel Blockers

Potassium Channel Openers

NO Releasers

Dopamine Agonist

POTASSIUM CHANNEL OPENERS• Releases potassium from smooth muscle leading to

hyperpolarisation and relaxation• Mainly Arteriolar• Hydralazine 25-100mg twice daily

– Drug induced lupus erythamatosis– Metabolised by acetylation*– Also a nitrate releaser- Needs intact endothelium

• Minoxidil 5-10mg– Prodrug activated to minoxidil sulphate by Phase 2 reaction– Safe in CKD– Hirsuitism

Vasodilators

Calcium Channel Blockers

Potassium Channel Openers

NO Releasers

Dopamine Agonist

NO releasers

Releases NO

Stimulate Guanalyl Cyclase

Increases cGMP

• Sodium nitroprusside– Short acting– Continous i.v infusion in hypertensive emergency– Accumulation of cyanide and produce toxicity– Lead to hypothyroidism due to accumulation of

Thiocyanate.

Vasodilators

Calcium Channel Blockers

Potassium Channel Openers

NO Releasers

Dopamine Agonist

DOPAMINE AGONIST

• FENOLDOPAM• D1 receptor agonist• Peripheral vasodilation• Suited for Patients with Renal diseases due to

improved renal perfusion• ADR:– Hypokalemia– Increased intraocular pressure

ANTIHYPERTENSIVES

DIURETICS SYMPATHOPLEGICS

VASODILATORS

RAAS INHIBITOR

RENIN INHIBITOR

• Aliskiren• Remikiren• Enalkiren• Can be used orally for Chronic hypertension• Not in protocol provided by JNC

ACE INHIBITORS

• Captopril• Lisinopril• Benazapril• Enalapril- 5 to 20mg• Fosinopril and quinapril 10-40mg• Ramipril 5-10mg• Trandolapril 2-8mg

Side effects

• Dry cough• Angioedema• Taste Disturbance• Orthostatic Hypotension• Renal Failure*• Contraindicated:– Pregnancy– Hyperkalemia– Renal artery Stenosis

Angiotensin Receptor Blockers.

• Candesartan 8-32mg• Valsartan 80-320mg• Losartan 50-100mg – Competetive antagonist of TXA2

• Olmesartan 20-40mg • Telmisartan 20-80mg• Side effects are all same as ACE-i Other than

Cough and Angioedema.

Initial Drugs of Choice for Hypertension

• ACE inhibitor (ACEI) • Angiotensin receptor blocker (ARB) • Thiazide diuretic • Calcium channel blocker (CCB)

• CKD irrespective of age and Race – ACEi and ARB

• Black people without CKD- Thiazide and CCB

JNC 8 Strategies

Goal BP

Lifestyle changes

• Smoking Cessation • Control blood glucose and lipids • Diet

Eat healthy (i.e., DASH diet) Moderate alcohol consumption Reduce sodium intake to no more than 2,400 mg/day

• Physical activity Moderate-to-vigorous activity 3-4 days a week averaging 40 min per session