Anti-hypertensive agents
Hypertension is defined as a sustained diastolic blood pressure greater than 90 mm Hg accompanied by an elevated systolic blood pressure (>140 mm)
Classification:
1.
ACE
inhibitors
Captopril,
Enalapril, Lisinopril, Perindropil, Ramipril
2.
Angiotensin
(AT1) antagonist
Losartan,
Candesartan, Irbasertan
3.
Calcium
channel Blockers
Verapamil,
Diltiazem, Nifedipine, Felodipine, Amlodipine, Nitrendipine, Lacidipine
4.
Diuretics
I.
Thiazides :
Hydrochlorothiazides
II.
High ceiling :
Furosemide
III.
K+ sparing :
Spironolactone, Triamterene, Amiloride
5.
β-Adrenergic
Blockers
Propranolol,
Metoprolol, Atenolol.
6.
β
+ α Adrenergic Blockers
Labetalol,
Carvediol
7.
α
– Adrenergic Bockers
Prazocin,
Tarazocin, Doxazocin, Phentolamine, phenoxybenzamine
8.
Central
Sympatholytics
Clonidine,
Methyldopa
9.
Vasodilators
I.
Arteriolar :
Hydralazine, Minoxidil, Diazoxide
II.
Arteriolar + Venous :
Sodium nitroprusside
Non
pharmacological Therapy:
• Weight reduction
• Increases exercise
• Salt Restriction
• Relaxation and stress management
• Supplement of K+1, Ca+2 And Mg+2
• Cessation of
smoking and alcohol
ACE
Inhibitors
The angiotensin-converting enzyme (ACE) inhibitors lower blood pressure by reducing peripheral vascular resistance without reflexly increasing cardiac output,
rate, or contractility. These drugs block the angiotensin converting enzyme
that cleaves angiotensin I to form the potent vasoconstrictor, angiotensin II
Therapeutic uses:
Most effective in hypertensive patients who are white.
However, when used in combination with a diuretic, the effectiveness of ACE
inhibitors is similar in white and black hypertensive patients.
Adverse
effects
Common side effects include dry cough, rashes, fever,
altered taste, hypotension (in
hypovolemic states), and hyperkalemia.
Reversible renal failure can occur in patients with
severe renal artery stenosis.
Calcium
Channel Blockers
Actions:
Verapamil, diltiazem, nifdipine, and nicorandil decreases arterial pressure à decreases calcium influx into smooth muscle cells à decreases muscle tone and vascular resistance à vasodilators.
Therapeutic uses :
Calcium
channel blockers have an intrinsic natriuretic effect à therefore, they do not usually require the
addition of a diuretic. These agents are useful in the treatment of
hypertensive patients who also have asthma, diabetes, angina, and/or peripheral
vascular disease.
Pharmacokinetic:
short
half-lives (tl/2 = 3 to 8 hours) following an oral dose Ã
three times a day to maintain good control of hypertension. Verapmil and
diltiazem available in sustained release preparations
Adverse effect :
In
10% of patients, dizziness, headache, and a feeling of fatigue caused by a
decrease in blood pressure. Verapamil should be avoided in treating patients
with congestive heart failure due to its negative inotropic effects.
Diuretics
Thiazide diuretics
Spironolactone à ,
a potassium-sparing diuretic, is often used with thiazides.
Therapeutic uses:
Thiazide diuretics decrease blood in
both the supine and standing positions; postural hypotension is rarely
observed. Useful in the treatment
of black or elderly patients, and in those with chronic renal disease.
Adverse
effect:
Thiazide diuretics
induce hypokalemia and hyperuricemia in
70% of patients, and hyperglycemia in 10% of
patients. Serum potassium levels should be monitored closely in patients
who are predisposed to cardiac arrhythmias (particularly individuals with left ventricular
hypertrophy, ischemic heart disease, or chronic congestive heart failure) and
who are concurrently being treated with both thiazide diuretics and digitalis
glycosides. Diuretics should be avoided in the treatment of hypertensive
diabetics or patients with hyperlipidemia.
β-Adrenoceptor
Blocking Agents
ü The
β-blockers are more
effective for treating hypertension in white than in black patients, and in
young patients compared to the elderly.
ü Should
not used in severe chronic obstructive lung disease, chronic congestive heart
failure, severe symptomatic occlusive peripheral vascular disease and in
diabetics.
ü Should
be avoided in treating patients with asthma, congestive heart failure, and peripheral
vascular disease.
ü CNS
side effects such as fatigue, lethargy, insomnia, and hallucinations;
ü The
β-blockers may disturb
lipid metabolism, decreasing high-density lipoproteins (HDL) and increasing
plasma triacylglycerol.
Centrally acting adrenergic drugs:
Clonidine :
à This
α2-agonist diminishes central adrenergic outflow. is used primarily
for the treatment of mild to moderate hypertension that has not responded
adequately to treatment with diuretics alone.
à Useful
in the treatment of hypertension complicated by renal disease Ã
does not decrease renal blood flow or glomerular filtration .
à Absorbed
well after oral administration and is excreted by the kidney.
à Because
it causes sodium and water retention, clonidine is usually administered in combination
with a diuretic.
à It
can produce sedation and drying of nasal mucosa.
α –
Methyldopa:
This α2-agonist
is converted to methylnorepinephrine centrally to diminish the adrenergic
outflow from the CNS, è
leading to reduced total peripheral resistance and a decreased blood pressure.
Cardiac output is not decreased and blood flow to vital organs is not
diminished à especially valuable in treating
hypertensive patients with renal insufficiency.
The most common side effects of α – Methyldopa are
sedation and drowsiness.
Vasodilators
ü The
direct-acting smooth muscle relaxants, such as hydralazine and minoxidil Ã
act by producing relaxation of vascular smooth muscle, which decreases
resistance and therefore decreases blood pressure.
ü These
agents produce reflex stimulation of the heart, resulting in the competing
symptoms of increased myocardial contractility, heart rate, and oxygen
consumption. These actions may prompt angina pectoris, myocardial infarction,
or cardiac failure in predisposed individuals.
ü Vasodilators
also increase plasma renin concentration, resulting in sodium and water
retention. These undesirable side effects can be blocked by concomitant use of
a diuretic and a β-blocker.
Hydralazine:
Ã
causes direct vasodilation, acting primarily on arteries and arterioles Ã
decreased peripheral resistance Ã
reflex elevation in heart rate and cardiac output. Hydralazine Ã
used to treat moderately severe hypertension.
Adverse
effects of hydralazine Ã
headache, nausea, sweating, arrhythmia, and precipitation of angina. A
lupus-like syndrome can occur with high dosage, but it is reversible on
discontinuation of the drug.
Minoxidil:
ü It
causes dilation of resistance vessels (arterioles) but not of venules.
Administered orally for treatment of severe to malignant hypertension that is
refractory to other drugs.
ü Reflex
tachycardia may be severe and may require the concomitant use of a diuretic and
a β-blocker.
ü Minoxidil
causes serious sodium and water retentionÃ
volume overload, edema, and congestive heart failure. This drug is now used topically to treat male
pattern baldness - alopecia
[Note:
Minoxidil treatment also causes hypertrichosis (the growth of body hair).]
à Always
administered in combination with a β-blocker
such as propranolol (to balance the reflex tachycardia) and a diuretic (to
decrease sodium retention). Together, the three drugs decrease cardiac output,
plasma volume, and peripheral vascular resistance.
Sodium nitroprusside :
ü Nitroprusside
is metabolized rapidly (tl/2 of minutes) and requires continuous
infusion to maintain its hypotensive action. Sodium nitroprusside exerts few
ü Adverse
effects except for those of hypotension caused by overdose. Nitroprusside
metabolism results in cyanide ion production, although cyanide toxicity is rare
Ã
can be effectively treated with an infusion of sodium thiosulfate to produce
thiocyanate, which is less toxic and is eliminated by the kidneys.
ü Nitroprusside
is poisonous if given orally because of its hydrolysis to cyanide.
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