PHARMACOLOGY

ASSIGNMENT NO.02

Submitted by: Submitted to:

Nandraj Ma’am Areeba Shafiq
Roll No. 1817007

Date: 14-June-2020
OBJECTIVES
 1. What is hypertension?
 2. Classification of antihypertensive drugs.
 3. Explain each antihypertensive drug in detail.
 4. what is hypertensive crises and name the list of
drugs use to treat this condition
HYPERTENSION
Hypertension (HTN or HT) also known as high
blood pressure (HBP) is a long term medical
condition in which the blood pressure in the
arteries is persistently elevated.
It is defined as either..
 “a sustained systolic blood pressure of greater than
140 mm Hg or a sustained diastolic blood pressure
of greater than 90 mm Hg”.
CONT…
Causes:
1. Primary(essential) hypertension: The majority of patients (90-
95%) have essential hypertension, which is a form with no
identifiable underlying cause.
2. Secondary hypertension: A smaller number of patients (5-10%)
have secondary hypertension that is caused by an identifiable
underlying condition such as renal, vascular, endocrine
disorders, etc.

Hypertension is classified into four categories

Category Systolic Diastolic
mm Hg mm Hg
Normal <120 <80
Prehypertension 120-139 80-89
Stage I 140-159 90-99
Stage II ≥160 ≥100
CLASSIFICATION OF
ANTIHYPERTENSIVE DRUGS
 Diuretics
 Thiazides: hydrochloroquine, chlorthalidone, indapamide
 Loop diuretics: furosemide
 K+ sparing: spironolactone, amiloride, triamterene.

 ACE Inhibitor
 Captopril, enalapril, lisinopril, ramipril.
 Angiotensin II receptor antagonist
 Losartan,irbesartan,candesartan
 CALCIUM CHANNEL BLOCKERS
 Non- Dihydropyridine : Verapamil,diltiazam,
 Dihydropyridine : nifedipine,felodipine,amlodipine,lacidipine
CONT…
SYMPATHOLYTIC AGENTS
 ß - ADRENERGIC BLOCKERS
 Propranolol, metaprolol, atenolol.
 α+ß ADRENERGIC BLOCKERS
 Labetalol, carvedilol
 ADRENERGIC BLOCKERS
 Selective: prazosin, terazosin, doxazosin.
 Nonselective: Phenoxybenzamine, phentolamine

 CENTRAL SYMPATHOLYTIC
 Clonidine, methyldopa
VASODILATORS
 Hydralazine, minoxidil sodium
DIURETICS
 Diuretics are drugs that promote diuresis, or water
loss.
Diuretic drug classes:
 Loop diuretics – furosemide, bumetanide
 Thiazide and thiazide-like diuretics –
bendroflumethiazide, hydrochlorothiazide,
indapamide, metolazone
 Potassium-sparing diuretics – amiloride,
spironolactone
 The purpose of diuretics is to eliminate excess sodium
and water from the body. Some diuretic classes also
eliminate potassium, increasing the risk of
hypokalemia.
 DIURETICS
Drugs Mechanism of actions Adverse drug effects
•Thiziades & thiazide- most commonly used Hypotension
like diuretics: diuretic, inhibit the sodium- Photosensitivity
Hydrochlorothiazide chloride transporter in the Hypokalemia
distal tubule. (Thiazides,Loop)
Indapamide, Hyperglycemia
Metolazone (Thiazides,Loop)
inhibit the sodium- Dry mouth
•Loop diuretics –
Furosemide, potassium-chloride
Bumetanide cotransporter in the thick
ascending limb 
•Potassium-sparing Act at the cortical collecting
diuretics – duct
Amiloride,
Spironolactone
ACE INHIBITORS
Examples:
 Ramipril
 Lisinopril
 Perindopril

 Captopril

 Mechanism: ACE inhibitors block the conversion of angiotensin I into

angiotensin II.
 By blocking ACE, these drugs prevent aldosterone release from the
adrenal cortex and eliminate sodium ions (along with water) from the
kidneys. These two cumulative effects serve to reduce blood volume
and blood pressure.

 Side Effects:
 Hypotension – first-dose hypotension is prevalent with ACE inhibitors
 Persistent, dry cough – due to pulmonary kinin accumulation
 Hyperkalemia
ANGIOTENSIN II RECEPTOR
ANTAGONIST
 Also known as ARBs, or angiotensin receptor blockers. They are
sometimes used in place of ACE inhibitors, particularly where the
persistent, dry cough has become unbearable for the patient.
Adverse effect
Examples:
 Candesartan, Irbesartan, Losartan, Telmisartan

Mechanism:
ARBs work by blocking the action of angiotensin II at the
AT1 receptor. Because angiotensin II promotes aldosterone
secretion and acts as a vasoconstrictor, its blockage reduces
peripheral vascular resistance and, as a result, lowers blood
pressure.
Side Effects:
 Hypotension
 Hyperkalemia
 Renal failure (as with ACE inhibitors)
 Cough – though less likely than with an ACE inhibitor
ANGIOTENSIN II RECEPTOR
ANTAGONIST
Angiotensiogen

Renin

Angiotensiogen I

ACE

Angiotensiogen II

ARBS
AT1 AT2
receptor receptor
 CALCIUM CHANNEL BLOCKERS
 CLASSIFICATION
Diphenylalkylamine Verapamil

Benzothiazepines Dilitiazem

Calcium channel 1st

blocker Nifedipine
generation

Israpipine

2nd
Dihydropyridines Nicardipine
generation

Felodipine

3rd Amlodipine
generation
CALCIUM CHANNEL BLOCKERS
Mechanism of action:
 CCBs block the inward movement of calcium by binding to L type calcium
channels in the heart and in smooth muscle of the coronary and peripheral
vasculature.
 This causes vascular smooth muscle to relax and also reduce myocardial
contractility in the heart.
Side effect:
Because diltiazem and verapamil (the non-dihydropyridine CCBs) are used
as class III antiarrhythmic drugs, the side effect profile below focuses on
amlodipine and nifedipine.
 Flushing
 Headache
 Ankle swelling
 Palpitations
 Lightheadedness
 Cough
 Bradykinesia (Shortness of breath)
ALPHA ADRENERGIC BLOCKERS
Examples
 Prazosin
 Terazosin
 Doxazosin
 Phentolamine
 Phenoxybenzamine

Mechanism of action: These drugs produce a

competative block of alpha 1 adrenoceptors. They
decrease PVR and lowers arterial BP by causing
relaxation of both arterial and venous smooth
muscle. Therefore long term tachycardia does not
occur but salt and water retention does.
ΒETA-ADRENOCEPTOR–
BLOCKING AGENTS
Examples: Propranolol, metaprolol, atenolol.

Mechanism of action:
 The β-blockers reduce blood pressure primarily by
decreasing cardiac output. They may also decrease
sympathetic outflow from
the central nervous system (CNS) and inhibit the release of
renin from the kidneys, thus decreasing the formation of
angiotensin II and the secretion of aldosterone.
 Adverse effect
α-/β-ADRENOCEPTOR–BLOCKING AGENTS

 Labetalol and Carvedilol block α1, β1, and β2

receptors.
 Carvedilol, although an effective
antihypertensive, is mainly used in the treatment
of heart failure.
 Carvedilol, as well as metoprolol, a selective β1
antagonist, have been shown to reduce morbidity
and mortality associated with heart failure.
CENTRALLY ACTING
ADRENERGIC DRUGS
 Clonidine
This α2-agonist diminishes the central adrenergic
outflow, decreasing the firing rate of the sympathetic
nerves and the amount of norepinephrine release.
Clonidine is used primarily for the treatment of
hypertension that has not responded adequately to
treatment with two or more drugs.
 α-Methyldopa
This α2-agonist is converted to methylnorepinephrine
centrally to diminish adrenergic outflow from the
CNS. This leads to reduced total peripheral resistance
and decreased blood pressure. Cardiac output is
not decreased, and blood flow to vital organs is not
diminished.
VASODILATORS
 Arteriolar:
 Hydralazine, minoxidil, Diazoxide

 Arteriolar and venodilator:

 Sodium nitroprusside
CONT…
Hydralazine
 Used to treat hypertension, though it is more
often used to treat high blood pressure in
pregnancy – gestational hypertension.
Side effects with hydralazine include:
 Headache
 Tachycardia
 Palpitations
 Hypotension
 Aching / swelling joints
 Flushing
CONT…
Sodium Nitroprusside:
 used in cases of hypertensive emergency.
 It is administered via the intravenous route and, for this reason, has a
rapid onset of effect.
 Sodium nitroprusside deploys nitric oxide for its antihypertensive effect.
Nitric oxide works to reduce total peripheral resistance and venous
return. This reduces both preload and afterload.
Side effects associated with sodium nitroprusside include:
 Hypotension
 Cyanide poisoning

 Bradyarrhythmia
 Palpitations

 Tachyarrhythmia
 Confusion

 Dizziness
 Renal azotemia
HYPERTENSIVE CRISES
 Broadly covers both hypertensive emergency and
urgency.
 Hypertensive emergency:
 Defined as severe elevation in BP (>180/120 mm
Hg) complicated by evidence of impending or
progressive target organ dysfunction and
damage.
 They may require immediate BP reduction (not
necessarily to normal) to prevent or limit organ.
 Hypertensive urgency:
 When severe elevation in BP occurs without
acute target organ dysfunction or damage.
CONT…
The preferred drug to treat the condition
is
 sodium nitroprusside (i.v. infusion).

• The other drugs :

– nitroglycerin (i.v. infusion)
– hydralazine (i.v.)
– labetalol (i.v.)
REFERENCE
 Lippincott’s pharmacolgy 5th edition