Antihypertensive

Drugs
Chapter 11
LEI-ANN JESSICA R. CABULAY

HYPERTENSION
Elevation
of
blood
pressure
from
the
normal range (varies
with age)
2 classifications:
PRIMARY/ESSENTIAL
HYPERTENSIONno
definite
cause,
idiopathic
SECONDARY
HYPERTENSION- with

BP
CARDIA
C
OUTPUT
STROKE
VOL.
PRELOA
D

AFTERLO
AD

TPR

HEART
RATE
CONTRACTILIT
Y

AFTERLOA
D

1. DIURETICS
lower blood pressure by
reduction of blood volume
thiazides (eg,
hydrochlorothiazide)- used in
mild hypertension
loop diuretics (eg,
furosemide)- used in moderate
and severe hypertension and
in hypertensive emergencies.

Side Effects:
Muscle weakness and cramps
Loss of sodium and potassium salts
Dizziness and nausea
Kidney problems
Heart damage
Minimal compensatory response

SYMPATHOLPLEGICS
A. Baroreceptor-Sensitizing Agents
A few natural products, such as veratrum
alkaloids, appear to increase sensitivity
of baroreceptor sensory nerves and
reduce SANS outflow while increasing
vagal tone to the heart.
These agents are toxic and no clinically
available drugs act at this site

SYMPATHOLPLEGICS
B. Central Nervous SystemActive Agents
Decrease sympathetic outflow
by activation of alpha 2
receptors in the CNS
Eg. Clonidine and methyldopa
Decrease cardiac output,
decrease vascular resistance
Side effects: rebound
hypertension (if stopped
abruptly) and sedation

SYMPATHOLPLEGICS
C. Ganglion-Blocking Drugs
Nicotinic blockers that act in the ganglia are very
efficacious, but because their adverse effects are
severe, they are now considered obsolete.
Hexamethonium and trimethaphan are extremely
powerful blood pressure-lowering drugs.

SYMPATHOLPLEGICS
D. Postganglionic
Blockers

Sympathetic

Nerve

Terminal

Reserpine- deplete adrenergic nerve terminals of its

norepinephrine stores
Guanethedine, Guanadrel-deplete and block release
of the stores of norepinephrine
MAOIs- form false transmitter (octopamine)
sympathetic post ganglionic neuron terminals
OBSOLETE

in

SYMPATHOLPLEGICS
E. Adrenoceptor Blockers
Alpha blockers- reduce vascular resistance and
decrease venous return
Non Selective alpha blockers- no value in chronic
hypertension because of its SE of excessive
tachycardia
Alpha 1 selective blockers- (prazosin, doxazosin,
terazosin)
Has SE of orthostatic hypotension (first few
doses)

SYMPATHOLPLEGICS
E. Adrenoceptor Blockers
Beta blockers- propanolol, atenolol, carvedilol,
metoprolol
Initially: reduce cardiac output
Later: decrease vascular resistance due to
reduced angiotensin levels

VASODILATORS
Drugs that dilate blood vessels by acting directly on
smooth
muscle
cells
through
nonautonomic
mechanisms, thereby decreasing blood pressure
Vasodilators act by four major mechanisms:
release of nitric oxide
opening of potassium
hyperpolarization)

channels

blockade of calcium channels, and

activation of D1 dopamine receptors

(which

leads

to

VASODILATORS
A. Hydralazine and Minoxidil
Hydralazine-acts through the release of nitric oxide from
endothelial cells
Hydalazine induced lupus erythematosus-reversible, dosage
must be < 200mg/dL
Minoxidil- systemic administration is reserved for severe
hypertension
Minoxidil minoxidil sulfate- potassium channel opener that
hyperpolarizes and relaxes vascular smooth muscle
SE: hirsutism- topical agent for baldness

VASODILATORS
B. Calcium Channel-Blocking Agents- effective
vasodilators
Nifedipine- prototype of dihydropyrimidine calcium
channel blocker
Verapamil- decreases cardiac output
Diltiazem- decreases cardiac output

VASODILATORS
C. Nitroprusside, Diazoxide, and Fenoldopam
Vasodilators used in hypertensive emergency
Nitroprusside
Light sensitive, short acting agent

Nitric oxide

Stimulation
of guanyl
cyclase

cGMP
concentratio
n in smooth
muscle

VASODILATORS
C. Nitroprusside, Diazoxide, and Fenoldopam
Diazoxide- thiazide derivative, (-) diuretic properties
Opens potassium channels, thus, hyperpolarizing and
relaxing smooth muscles
Decreases insulin release and can be used to treat
hypoglycemia caused by insulin producing tumors
Fenoldopam-activate dopamine D1 receptor prompt
marked arteriolar vasodilation
Used in hypertensive emergencies

ANGIOTENSIN ANTAGONISTS
ACE inhibitors (pril drugs)- inhibit enzyme
angiotensin converting enzyme, kinases II, peptidyl
dipeptidase leading to:
Reduction of angiotensin II and aldosterone
Increase in endogenous vasodilators of kinin family
(bradykinin)
Renal protective, useful in patients with diabetes &
heart failure
Toxicities: cough, renal and fetal toxicities
TERATOGEN

ANGIOTENSIN ANTAGONISTS
Angiotensin II Receptor Blockers (sartan drugs)
Competitively inhibit angiotensin II at its AT 1 receptor
site
Lower incidence of cough
Fetal and renal toxicities
TERATOGEN

RENIN
INHIBITO
R

RENIN INHIBITOR
Aliskiren
Toxicities: headache, diarrhea
TERATOGEN

CLINICAL USES OF
ANTIHYPERTENSIVE
DRUGS
A. Stepped Care (Polypharmacy)
overall toxicity can be reduced and compensatory
responses minimized by the use of multiple drugs at
lower dosages in patients with moderate or severe
hypertension
each additional agent is chosen from a different
subgroup until adequate blood pressure control has
been achieved.

CLINICAL USES OF
ANTIHYPERTENSIVE
DRUGS
The usual steps include:
(1)lifestyle measures
(2)diuretics (a thiazide)
(3) sympathoplegics (a blocker)
(4) ACE inhibitors, and
(5) vasodilators.
The vasodilator chosen first is usually a calcium channel blocker.
The ability of drugs in steps 2 and 3 to control the compensatory
responses induced by the others should be noted (eg, propranolol
reduces the tachycardia induced by hydralazine)

CLINICAL USES OF
ANTIHYPERTENSIVE
DRUGS

B. Monotherapy
This approach to treatment of mild and moderate
hypertension has become more popular than stepped
care because of its simplicity, better patient
compliance, andwith modern drugsa relatively low
incidence of toxicity.

CLINICAL USES OF
ANTIHYPERTENSIVE
DRUGS

C. Age and Ethnicity

Beta blockers- very effective to Whites and young
patients
Diuretics- very effective to Blacks and elderly

ACE
inhibitors

Whites and
young pts.

Beta
Blockers

Diuretics

Black
patients

Calcium
Channel
Blockers

Diuretics

Elder
ly
Calcium
Channel
Blockers

ACE
Inhibitors

CLINICAL USES OF
ANTIHYPERTENSIVE
DRUGS
D. Hypertensive Emergency
(formerly called malignant hypertension) accelerated
form of severe hypertension associated with rising blood
pressure and rapidly progressing damage to vessels and
end organs.
Management must be carried out on an urgent basis in
the hospital.
Powerful vasodilators (nitroprusside, fenoldopam, or
diazoxide) are combined with diuretics (furosemide) and
blockers to lower blood pressure to the 140160/90
110 mm Hg range promptly (within a few hours).