ANTI HYPERTENSIVE

DRUGS
 Blood Pressure

Blood pressure is the force of blood pushing against the wall of

the arteries as your heart pumps out blood into the arteries. Its
level varies with age, sex, level of physical activity and
emotional changes.

Blood pressure is measured in millimeters of mercury (mmHg)

and is given as 2 figures:

systolic pressure – the pressure when your heart pushes blood

out
diastolic pressure – the pressure when your heart rests between
beats
 High Blood Pressure
(Hypertension)
Hypertension is when blood pressure is too high.

Hypertension is diagnosed if, when it is measured on two Blood pressure readings between
different days, the systolic blood pressure readings on both days 120/80mmHg and 140/90mmHg could mean
is ≥140 mmHg and/or the diastolic blood pressure readings on you're at risk of developing high blood
both days is ≥90 mmHg. (WHO). pressure if you do not take steps to keep your
blood pressure under control.
 HYPERTENSION
Blood pressure is determined by two things:

• the amount of blood the heart pumps (Cardiac Output).

• and how hard it is for the blood to move through the arteries.
(Peripheral Resistance).

The more blood the heart pumps and the narrower the arteries, the higher
the blood pressure.

Risk Factors:
Age Race Family History Too much salt
Obesity Lack of Exercise Tobacco use
Alcohol intake Stress Pregnancy
 Classification of HTN
 Primary/Essential Hypertension
 Most common
 mostly no identifiable cause
 tends to develop gradually over years.
 Secondary Hypertension
 A-Drug-induced hypertension:
● Steroids ● Estrogens ● NSAIDS
 B-Rebound hypertension:
occurs when blood pressure rises after you stop
taking or lower the dose of a drug (typically a
hypertension medication).
 C-Secondary to another disease.
 PATHOPHYSIOLOGY

Pathophysiology
Factors that play an important role in the pathogenesis of
hypertension include;
 genetics,
 activation of neuro hormonal systems such as the
sympathetic nervous system
 renin-angiotensin-aldosterone system,
 obesity,
 increased dietary salt intake.
Physiological Mechanism for Control of BP

 1. Renin Angiotensin Aldosterone system (RAAS)

 2. Baroreceptor Reflex
 MANAGEMENT OF HYPERTENSION

 Life Style Changes

 Pharmacological Treatment (Anti-Hypertensive Drugs)
 Classification of Anti Hypertensive Drugs

 1. Diuretics
 2. RAAS Inhibitors
 3. Ca Channel Blockers
 4. Sympatholytic Agents
 5. Vasodilators
 1. DIURETICS
(Na & H2O Loss)
Loop Diuretics Thiazide Diuretics K Sparing Diuretics
Decrease NaCl reabsorption Decrease NaCl reabsorption
but to less extent than loop Affects Na/K exchange in
kidney
in kidney
OR
Increase Diuresis Increase Diuresis Blocking action of Aldosterone

Less volume in vascular space

Initial decrease in intravascular space Decrease NaCl reabsorption
Less blood returns to heart in kidney

CO CO
CO

BP BP
BP
 Loop Diuretics Thiazide Diuretics K sparing
(Short Acting/Strong (Long Acting/Weak Diuretics
Action) Action)
Examples Furosemide Hydrochlorothiazide Spironolactone
• Severe HTN Mild to moderate HTN Often use in combination
• Renal particularly in patients with loop & Thiazide
Clinical Use insufficiency with volume based HTN diuretics to reduce loss of
• Cardiac failure and chronic kidney K++ that occurs with loop
• Cirrhosis disease & Thiazide

• Hypokalemia • Hepatic cirrhosis • Hyperkalemia

• Hypotension • Hypersensitivity to • Liver disease
Contraindications • Hypersensitivity thiazides or
to sulfonamides sulfonamides

• K+ depletion • Weakness • Hyperkalemia

• Allergic & other • Paresthesia • Allergic reactions
Toxicity reactions • K+ depletion • Mental confusion
• Ototoxicity • Hypersensitive • Headache
• Hypomagnesemia reactions
• Hyperglycemia
Precautions • Take the tablet in the morning.
• Hypokalaemia can occur with some diuretics
 2. CALCIUM CHANNEL BLOCKERS
(L-Type)
 Useful in all grades of Hypertension
 Effect is mainly due to peripheral vasodilation.
 Ca Channel Blockers
DIHYDROPYRIDINES
Non-DIHYDROPYRIDINES
(Amlodipine, Felodipine,
(Verapamil, Diltiazem)
Nicardipine, Nifedipine)
Ca+2

Reduced contraction

SVR

BP
 Dihydropyridines Non-Dihydropyridines
Examples • Amlodipine • Verapamil
• Felodipine • Diltiazem
• Nicardipine
• Nifedipine
Clinical Use • Treatment of chronic • Verapamil is more effective as cardiac
hypertension with oral depressant , therefore it is not used as
preparation (Nifedipine; antihypertensive agent & used as
Amlodipine) antiarrhythmic.
• Nicardipine can be given by I.V. • Diltiazem Used mainly for angina
route & used in hypertensive pictoris
emergency
Pharmacokinetics • Given orally and intravenous injection
• Well absorbed from G.I.T
• Verapamil and Nifedipine are highly bound to plasma protiens ( more than 90%),
while Diltiazem is less ( 70-80%).
• Onset of action within: 1-3 min after I.V.
• 30min - 2 h after oral dose
• Verapamil & Diltiazem have active metabolites,
• Nifedipine does not. Sustained-release preparations of Nifedipine can permit once-
daily dosing.
Adverse Effects Dizziness Bradycardia
Headache Cardiac conduction abnormality
Flushing Constipation
Periphral edema
Swelling of gums
Precautions Avoid drinking large quantities of grapefruit juice
Have high fibre diet and drink plenty of fluid to reduce the side effect of constipation
 3. ADRENERGIC
ANTAGONIST/SYMPATHOLYTICS

Adrenergic Antagonists Drugs Examples

Ganglion Blocker Trimethapan
Hexamethonium
Sympathetic Neuron Blocker Metyrosine
Reserpine
Guanethidine
Centrally acting Sympatholytic Clonidine
Alpha methyl Dopa
Alpha-1 Receptor Blocker Prazocin, Doxazocin, Trazocin
Beta-1 Receptor Blocker Propanolol, Metoprolol etc.
Ach
Nn Sympathetic
Neuron Blockers

Alpha Beta
Blocker Blocker
 CENTRALLY ACTING ADRENERGIC DRUGS
(Alpha-2 AGONISTS)

CLONIDINE METHYL DOPA

Stimulate Presynaptic Alpha-2
Methyl Dopa
Receptor in VMC & stimulates

Reduce Catecholamine/NA Methyl norepinephrine

production & release
(Active metabolite)

SVR & CO

Works with same mechanism

as Clonidine
BP
 Clonidine Methyldopa
Clinical Use Mild to moderate severe HTN Mild to moderate severe HTN

α -Methyldopa is the first line

treatment of hypertension in
pregnancy
Contraindications • Patients who are at risk of mental Acute Hepatic disease
depression
• Tricyclic antidepressants blocks the
activity of Clonidine
Toxicity • Sedation • Sedation
• Drowziness • Nightmares
• Rebound hypertensive crisis • Depression
• Headache & sweating • GIT disturbances
• Dry mouth

Precautions • Sudden stoppage of Clonidine after prolonged use may cause with
drawl symptoms.
• May cause drowsiness, if affected, patients should not drive or operate
machinery.
• Do not drink alcohol because this may worsen the side effects
 ALPHA-1 RECEPTOR BLOCKER

Alpha-1 Blockers
e.g. Prazocin
Doxazosin

Inhibition of Alpha 1 receptor Decrease In SVR

on smooth muscle BP
BP
 ALPHA-1 RECEPTOR BLOCKER

Examples Prazocin, Terazocin, Doxazocin

Clinical Use • Selective Alpha-1 receptor blocker
• Provide negative feedback to regulate NE production & release from synaptic
vesicles.
• More effective when used in combination with beta blocker (propranolol) or
Diuretics than alone
Pharmacokinetics • Prazocin is well absorbed but short acting (3-4 hours hours).
• Terazocin is extensively metabolized & has a half life of 12 hours.
• Doxazocin is preferred for its long half life (22 hours)
Adverse Effects • First dose hypotension
• Postural hypotension
• Dizziness
• Palpitations
• Headache
Precautions The first dose should be small & Take first dose at bedtime to avoid postural
hypotension
 Beta Receptor Blockers

 Selective Beta Blockers

 Non Selective Beta Blockers
 Beta Blockers

Selective Non-selective
Beta Blockers Beta Blockers
e.g. Atenolol, Metoprolol Labetalol, Carvedilol

Blocks Beta-1 + +
receptors on heart

CO SVR Renin
Decrease
Cardiac output Angiotensin II
Aldosterone
SVR

Reduction in
Blood Pressure
BP BP
Non cardio selective Propranolol
cardio selective • Bisoprolol
• Atenolol
• Metoprolol
Alpha & Beta • Labetalol
Adrenergic blocker • Carvedilol
Clinical Use • Mild to moderate HTN
• In combination with other agents in case of severe HTN
• therapeutic response may take up to two weeks
Adverse Effects • Tiredness
• cold hands and feet,
• slow heartbeat,
• diarrhea and nausea,
• sleep disturbances,
• nightmares
Contraindications • Non cardio selective (β1 & β2 ) drugs as propranolol are contraindicated in
patients with asthmatic patients
Precautions • May trigger asthmatic attack in patients with asthma or chronic bronchitis
• Symptoms of hypoglycemia may be masked in diabetic patients
 4. VASODILATORS

 Potassium Channel Openers

 NO Releasing Drugs
 VASODILATORS

K Channel Openers
NO Releasing Drugs
(Arteriodilators)

Minoxidil K+ Channels Vasodilation

Diazoxide Activation

Venodilator Arteriodilator
K+ Efflux
Pooling of
blood in veins SVR
Hyperpolarizati
on of vascular
smooth muscle Venous
Return
After Load

Vasodilation Pre Load

BP CO BP
MINOXIDIL
Effective Orally
Pro Drug
Topical Minoxidil is used to Promote HAIR GROWTH in male type of Baldness

DIAZOXIDE
Used in Treatment of Hypertensive emergencies (Administered IV)
Long duration of action
Also relaxes uterine smooth muscle
SODIUM NITROPRUSSIDE
Powerful Arteriodilator & Venodilator
Unstable: Rapidly decomposes on light exposure
Not given in Pregnancy
Can cause cyanide Poisoning (Must not be given more than 72 hours)

HYDRALAZINE
Directly acting Arteriodilator
Given orally

NITROGLYCERINE
Primarily a Venodilator
 5. Renin Angiotensin Aldosterone Blocker
System (RAAS)
 Renin Antagonist
 ACE Inhibitor
 Angiotensin II receptor Blocker
Renin Antagonist
e.g. Aliskiren

ACE Inhibitors
e.g. Captopril

Angiotensin II
Blocker e.g.
Losartan
 Direct Renin Antagonist

Class Drugs Pharmacology Profile

Direct Renin Aliskiren • Renin Antagonist
antagonist
• Aliskiren is an orally effective direct renin
inhibitor that blocks the generation of
angiotensin I from angiotensinogen, the
rate limiting step of RAAS activation.

• Aliskiren is currently indicated for the

treatment of hypertension, either alone or
in combination with other agents.
 ACE INHIBITORS

Drugs (-PRIL) Captopril, Lisinopril, Enalapril, Lisinipril

Clinical Use HTN
Heart failure
Diabetic Neuropathy
Contraindications Acute Renal failure
Pregnancy due to Teratogenicity
Toxicity Hyperkalemia
Cough ( due to inc. Bradykinin levels)
Angioedema ( due to inc. Bradykinin levels)
Interactions K sparing diuretics
NSAIDs
 ANGIOTENSIN II BLOCKERS

Drugs (- SARTAN) Candesartan, Irbesartan, Losartan, Valsartan

Clinical Use • First line agent for the treatment of HTN particularly in patients
with a compelling indication of Diabetes, HF, or CKD.
• No effect on Bradykinin so no cough and angioedema
• More potent than ACEI
Contraindications Acute Renal failure
Pregnancy due to Teratogenicity
Toxicity Hyperkalemia
Severe Hypotension in hypovolemic patients
Interactions K sparing diuretics
NSAIDs
 Anti Hypertensive Agents
safe in Pregnancy
Antihypertensive Class/action Dose Adverse effects
drug*
Labetalol Beta blocker 100 mg twice a day – 400 Bradycardia,
mg three times a day bronchospasm, headache
Nifedipine controlled Calcium channel 30 mg daily – 60 mg Headache (first-dose
release antagonist twice a day effect), flushing,
tachycardia, peripheral
oedema
Methyldopa Central action 250 mg twice a day – 750 Depression, dry mouth,
mg three times a day sedation, rarely
haemolysis and hepatitis
Hydralazine Vasodilator 25 mg three times a day – Flushing, headache,
50 mg three times a day lupus-like syndrome
Prazosin Alpha blocker 0.5 mg twice a day – 5 Orthostatic hypotension
mg three times a day
 Anti Hypertensive Agents
Contraindicated in Pregnancy
Antihypertensive Class/action Dose Adverse effects
drug*
Labetalol Beta blocker 100 mg twice a day – 400 Bradycardia,
mg three times a day bronchospasm, headache
Nifedipine controlled Calcium channel 30 mg daily – 60 mg Headache (first-dose
release antagonist twice a day effect), flushing,
tachycardia, peripheral
oedema
Methyldopa Central action 250 mg twice a day – 750 Depression, dry mouth,
mg three times a day sedation, rarely
haemolysis and hepatitis
Hydralazine Vasodilator 25 mg three times a day – Flushing, headache,
50 mg three times a day lupus-like syndrome
Prazosin Alpha blocker 0.5 mg twice a day – 5 Orthostatic hypotension
mg three times a day
 Anti Hypertensive Agents
In Hypertensive Crises
Hypertensive Emergency Hypertensive Urgency
Common sign severely elevated BP, usually defined as a diastolic pressure that exceeds 120 mm
Hg.
The elevated BP causes target organ There's little or no evidence of target
damage (brain, eyes, blood vessels, heart, organ damage.
and kidneys). 
Treatment • A first-line medical therapy in this • loop diuretics (bumetanide,
situation is labetalol, an adrenergic furosemide)
receptor blocker with both selective • beta-blockers (propranolol,
alpha1-adrenergic and nonselective metoprolol, nadolol)
beta-adrenergic receptor blocking • ACE inhibitors (benazepril,
actions. captopril, enalapril)
• calcium channel blockers
• Vasodilators such as nitroprusside and (amlodipine, verapamil)
nitroglycerin  • centrally acting alpha agonist such
as clonidine.
Route IV Oral (fast acting agents)