Basic Hyper Tensive Drugs

8/6/2019 Basic Hyper Tensive Drugs

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The antihypertensives are a class of drugs that are used to

treat hypertension (high blood pressure). The therapy seeks to prevent

the complications of high blood pressure, such as stroke and myocardialinfarction.


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Based on mechanisms for controlling blood pressure:

Drugs affecting plasma and extra cellular volume i.e. diuretics.

Drugs affecting sympathetic discharge i.e.sympatholytics.

Drugs affecting renin angiotensin system.

Directly acting drugs like vasodilators.


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Diuretics have been the drug of choice for the past many years. They are

further divided into 3 groups:

Potassium SparingDiuretics

Loop DiureticsThiazide AndRelated

Drugs

Hydrochlorothiazide

Chlorothalidone

Indapamide

Chlorothiazide

Ethacrynic acid

Furosemide

Toresemide

Bumetanide

Amiloride

Triamterene

Spironolactone


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Hypokalaemia

Hyperuricaemia

Hypotension

Hyponatraemia

Hypercalcemia

Hypomagnesaemia


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Adrenergic antagonist

- B

lockers - Blockers

+ - Blockers

Calcium Channel Blockers

Centrally Acting drugs


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- Blockers - Blockers +

Blockers

Atenolol

Metoprolol

Timolol

Propanolol

Prazosin

Terazosin

Doxazosin

Phenoxybenzamine

Carvedilol

Labetalol


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CNS Effects

Alternation in Lipid metabolism

Renal function

Masking of hypoglycemia in

diabetes

Impotence

Drug withdrawal

Hypotension

Bradycardia

Fatigue

Insomnia

Sexual

dysfunction


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- Blockers Competitive block of -

receptors

Decreased peripheral

resistance

Fall in blood

pressure


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Dizziness

Drowziness

Lethargy

Headache

Palpitation

Nausea


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LabetalolActs faster than pure blockersFor treatment of hypertension and clonidine withdrawl.

CarvedilolNon selective and selective 1blocker.


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No Vasoconstriction

Reduces intracellular calcium.

Reduced vascular resistance

No excitation-contraction coupling

L- type Ca+ channels

CCBs

Fall in Blood Pressure


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Diphenylalkylamines: Verapamil

Benzothiazepines: Diltiazen

Dihydropyridines: Nifedipine, Amlodipine, Felodipine.

Peripheral and coronary artery dilation

Naturiuretic effect

Negative ionotropic effect

Nifedipine is the drug of choice in pregnancy related hypertension


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Constipation

Vertigo

Headache

Fatigue

Hypotension


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2

A

Receptors in VMC

Sympathetic Outflow

From VMC To

Blood vessels

Heart Rate And

Cardiac Output

Heart

peripheral vascularresistance

Decreased Blood Pressure

Clonidine

Sympathetic Outflow

Stimulates 2- VMC

-Methynoradrenaline

-Methyldopa

Heart Rate And Peripheral

Vascular Resistance

Decreased Blood Pressure


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Clonidine 0.10.6 mg

Clonidine patch 0.10.3 mg

Methyldopa 2501000 mg

Reserpine 0.050.25 mg

Guanfacine 0.52 mg

Sedation

DrowzinessRebound hypertension in case of clonidine


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Angiotensin II

Receptor

blockers

Renin

Inhibitors

Aldosterone

Inhibitors

ACE Inhibitors

Captopril

RamiprilLisinopril

Enalapril

Benazepril

Candesartan

LosartanValsartan

Telmisartan

Eprosartan

Eplerenone

Spironolactone

Aliskiren


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Kidney

Renin

Angiotensinogen

Angiotensin-converting enzyme

Angiotensin I

Angiotensin II

Vasodilation

Increased PG

synthesisBradykinin

Cardiac

hypertrophy and

remodelling

Aldosterone

release

Vasoconstriction

Na+ and H2O

retention

Increased PVR

Inactive

IncreasedB

.P.

ACE

Inhibitors

Renin

Inhibitors

AT II

antagonist

Aldosterone

antagonist


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C-Dry Cough

A- Angioedema

P- Potassium retention (Hyperkalemia)

T-Taste changes(dysgeusia)

O- Orthostatic hypotension(after first dose)

P- Proteinuria

R- Rashes

I- Itching

L- Loss of appetite,nausea, vomiting, diarrhoea


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Mainly venodilatation

Relaxation of vascular smooth muscles

Dephosphorylation of myosin light chains

Increased cGMP

Vasodilators

Arterial dilatationCoronary arterial

dilatation


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Nitrates: nitroglycerine, isosorbide dinitrate, erythryl tetranitrate.

Arterial dilators: hydralazine, minoxidil, diazoxide.

Headache

Postural hypertension

Tachycardia

Palpitations

Flushing

Syncope


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JNC7 recommends BP be reduced to < 140/90mmHg

For patients with diabetes or CKD: < 130/80mmHg

Consider initiating therapy with two drugs in patients whose BP is>20/10mmHg above goal (Stage 2 and Stage 1 patients at high risk)

thereby increasing the likelihood of achieving goal BP in a timely

manner.Multi-drug combinations often produce greater BP

reduction at lower doses of the component agents resulting in fewer

side effects. The use of fixed dose combinations may be more

convenient and simplify the treatment regimen.

More than2

/3 of patients will require two or more agents


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Low (therapeutic) dose of2 drugsmore effective than higher dose of single drugusually well toleratedadverse effects can be reduced

Economic benefits i.e. health care costs reduced.

Many combinations of agents with complementaryMOA available, e.g.RAS blocker/diuretic.RAS blocker/CCBs.


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BP may be controlled with 1 drug in some patients

However, majority of patients require 2 drugsCombination too potent causing hypotension

Benefit risk profile for each combination should be assessed in appropriatepatient population

Individualize therapy

Additive risk for dose independent adverse effects

However, mono components likely to be taken as part of a multi drugregimen

Balance against risk of dose dependent side effects with high dosemonotherapy and risk of inadequate BP control (stroke, heart failure and MI)

If adverse effects

must discontinue both drugs:

However components have well characterized safety profiles so causalcomponents usually identified easily


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Efficacy

Tolerability

Adherence


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Concomitant

Diseases

MyocardialInfarction

Diabetes

Angina

Pectoris

Heart

Failure

Renal

Diseases

DiureticsBeta

Blockers

ARBs

ARBs

ARBs

Diuretics

Diuretics

ACE

Inhibitors

Beta

Blockers

Beta

Blockers

B

etaBlockers

Beta

Blockers

ACE

Inhibitors

ACE

Inhibitors

ACE

Inhibitors

ACEInhibitors

Ca++ channel

blockers

Ca++ channel

blockers

Ca++ channel

blockers


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Situations possible:

Preexisting essential hypertension.

Pregnancy induced hypertension

preeclampsia.


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To Be Used:-Hydralazines

-Methyldopa

-Dihydropyridines

-

CardioselectiveB

etaB

lockers: Atenolol, Metaprolol.-Prazosin

To Be Avoided:

-Diuretics

-ACE Inhibitors-AT1 Antagonist

-Non Selective Beta Blockers

-Sodium Nitroprusside


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Systolic BP > 180 mm Hg or diastolic BP > 120 mm Hg

End organ damage present.

Control required within minutes

End organ damage present.

Control required within hours

Sodium nitroprusside

NifedipineGlyceryl trinitrate

Orally Active Agents: Labetalol

Furosemide


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Goodman gillmanLippincotts illustrated reviews on pharmacology 4th edition

Current medical diagnosis and treatment 2010

Essentials of medical pharmacology 6th edition

Seth

Textbook of obstetrics 6th edition

www.wikipedia.org

www.medspace.com

www.thepoint.lww.com


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Increased level ofBradykinin.

Angiotensin I

Angiotensin II

Increased retention of Sodium and Water.

Increased level ofBradykinin.

Decreased output of Sympathetic Nervous System.

Vasodilatation of Vascular Smooth Muscle.

ACE InhibitorACE Inhibitor

Fall in Blood

Pressure

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Basic Hyper Tensive Drugs