NO ATTENDANCE AFTER 5 MINUTES OF START OF CLASS

OBJECTIVES OF THIS
LECTURE:
Classify antihypertensive drugs.
Outline the mechanism of action of
antihypertensive drugs.
Describe the adverse effects of the
antihypertensive drugs.

BP= CO X PVD
CO- Cardiac out put,
PVD- Peripheral Vascular
Resistance

* Two mechanisms
which control CO &
PVD are
Baroreflexes (for
moment to moment regulation)

& Renin
Angiotensin
System

DIFFERENT CLASSES OF ANTI HYPERTENSIVE

AGENTS

Diuretics
Thiazide diuretics
First-line drug in mild
hypertension

Loop diuretics
Severe hypertension &
patient with poor renal
function

Potassium-sparing
Agents Especially in
patient with
failure

heart

SYMPATHOLYTIC (SYMPATHOPLEGIC) AGENTS

CENTRAL SYMPATHOLYTICS
Central Alpha2-selective agonists (clonidine, methyldopa)
Effects: reduces sympathetic out flow.
Uses
HT complicated by renal disease (no reduction in renal perfusion)
Methyldopa Drug of choice HT during pregnancy
Side effects
Rebound HT on abrupt withdrawal (Gradual tapering
recommended)
Methyldopa produces sedation and drowsiness

CLONIDINE

Imidazoline derivative

Partial agonist at 2A subtype receptors of brain stem

Stimulation of 2A subtype receptors decreases sympathetic outflow

Produces fall in BP and bradycardia

Moderately potent antihypertensive

Adverse effects:
Sedation, mental depression, dryness of mouth, impotence
Withdrawal hypertension

METHYL DOPA

- methyl analogue of dopa- precursor of dopamine and nor-adrenaline

Acts on central 2 receptors to decrease efferent sympathetic activity

Decreases total peripheral resistance more effectively

In large doses it inhibits dopa-decarboxylase enzyme and reduces the formation

of Nor-adrenaline and forms a false neurotransmitter in peripheral

It is a moderate efficacy antihypertensive

Widely used as antihypertensive especially along with diuretic agent

Preferred for he management of hypertension during pregnancy

-ADRENOCEPTORBLOCKING AGENTS

-ADRENOCEPTORBLOCKING AGENTS

The hypotensive response to blockers develop over 1-3 weeks and well sustained

Most blockers maintains antihypertensive effect over 24 hours

The blockers are classified in to

Non-selective blockers (propranolol)
Selective blockers (Atenolol, nebivolol)

The non-selective blockers carries risk for alteration in lipid profile of the patient- rise
LDL/HDL ratio

The contraindication for the use of blockers are

Cardiac disorders such as sick sinus syndrome, congestive cardiac failure
Pulmonary disorders (especially for non-selective blockers)
Peripheral vascular diseases (especially for non-selective blockers)

BETA -ADRENOCEPTORBLOCKING
AGENTS (PROPRANOLOL, ATENOLOL,
NEBIVOLOL)
Uses
Mild to moderate Hypertension used alone for stage
I hypertension
HT associated with cardiac disease.
Adverse effects
Common: bradycardia, exercise intolerance and
alteration

in

serum lipid profile

Rebound hypertension on Abrupt withdrawal

LPHA-ADRENOCEPTORBLOCKING
AGENTS
Alpha1-selective agents eg, prazosin
Pharmacological effect
reduce vascular resistance and venous return.
Uses:
mild to moderate hypertension
relax smooth muscle in the prostate, which is useful in
benign prostatic hyperplasia.
Side effects:
orthostatic hypotension, especially with the first few doses.
Ejaculation failure and impotency

PRAZOSIN

Selective 1 inhibitor

Dilates both resistance and capacitance vessels

Haemodynamic effects
Reduces t.p.r (total peripheral resistance)
Reduces mean BP
Minor reduction in venous return and cardiac output
Maintains renal perfusion and g.f.r

Prazosin does not impair CHO (carbohydrate) metabolism- suitable for diabetes (but not if
neuropathy is present)

It has favourable effect on lipid profile

Symptomatic improvement of co-existing benign prostatic hypertrophy

VASODILATORS
Hydralazine
Mechanism of action
Direct vasodilation of arteries and arterioles - reduces PVR
Uses
Moderately severe hypertension
Adverse effects:
compensatory responses (tachycardia, salt and water
retention)
Reversible lupus erythematosus

Minoxidil
Mechanism of action
Direct dilatation of arterioles.
Uses

Severe hypertension (refractory to other

antihypertensives)
Adverse effects
Reflex tachycardia and fluid retention may be severe

CALCIUM CHANNEL BLOCKERS

Mechanism of action
They block L-type Ca channels in various tissues
Verapamil: More selective on cardiac muscle
Deltiazem: Acts equally on both cardiac & smooth
muscles
Nifedipine: More selective on blood vessels
(-) SA Node Heart rate
(-) AV Node Conductivity
(-) Cardiac contractility

cardiac
output

Blood
Pressure

Vasodilatation peripheral resistance

uses
hypertensive patients who also have asthma,
diabetes, angina, and/or peripheral vascular disease
Adverse effects

verapamil
Constipation
should be avoided in patients with congestive
heart failure or with atrioventricular block due to its
negative inotropic and dromotropic

Nifedipine
Dizziness, headache, fatigue
gingival enlargement, dependent edema

All are contraindicated during pregnancy

Angiotensin converting
enzyme inhibitors (ACE
(Inhibitors (e.g.captopril)
Mechanism of
action

Uses of ACE inhibitors

slow the progression of diabetic
nephropathy and decrease albuminuria.
patients with chronic heart failure.
Adverse effects
1.Dry cough, angioedema (due to increased
bradykinin)
2.Rash
3.Fever
4.Altered taste

ANGIOTENSIN RECEPTOR
BLOCKERS (ARBS)
Losartan
Mechanism of action
Competitive inhibition angiotensin II at its AT1 receptor
site
uses
as ACE inhibitors
do not affect bradykinin metabolism

RENIN INHIBITOR
Aliskiren
Directly inhibits renin
lowers blood pressure about as effectively
as ARBs, A CE inhibitors, and thiazides.
can also cause cough and angioedema

ALGORITHM FOR ANTIHYPERTENSIVE THERAPY

ANTIHYPERTENSIVE
DRUG CHOICE
Diabetes

IN SPECIAL CONDITIONS
ACE inhibitors or ARBs are the first-line
treatment, since they reduce proteinuria and
slow down renal deterioration.
Coronary arterial disease
-blockers are the first-line choice

ANTIHYPERTENSIVE DRUG CHOICE

IN SPECIAL CONDITIONS
Heart failure
ACE inhibitors and diuretics are the first-line
treatment for hypertension

Pregnancy
- methyl dopa is the drug of first choice.
Other drugs that could be used include: labetalol,
hydralazine and nifedipine

DRUGS FOR HYPERTENSIVE

EMERGENCY

Nitroprusside
Parenteral vasodilator & short-acting agent
should be prepared freshly -light-sensitive
mechanism of action
release of nitric oxide (from the drug molecule itself), which
mediates vascular smooth muscle relaxation
Adverse effects
1.excessive hypotension
2.reflex tachycardia
3.if infusion is continued over several days, accumulation of
cyanide in the blood can be treated with an infusion of sodium
thiosulfate.

Labetalol
Blocks both an - and a -blocker
Does not cause reflex tachycardia
The major limitation is a longer half life

Nicardipine
A calcium-channel blocker, for intravenous
infusion.
Long half-life (approximately 8 hours)

Fenoldopam
Peripheral dopamine-1 receptor agonist that is
given as an intravenous infusion.
Relaxes mainly the renal (renal artery, afferent
and efferent arterioles) and mesenteric arterial
vessels
Diuretic action caused by the increase in renal
blood flow.
Beneficial in patients with renal insufficiency.