2. Clinical case scenario
Mr. Will a 45-year-old construction worker visits your OPD with
complaints of headaches, fatigue, and occasional dizziness. He
reported feeling stressed at work and stated that his blood
pressure was checked by a colleague at building site, who
reported readings of 150/95 mmHg.
He has a history of smoking a pack of cigarettes per day for
the past 15 years. His diet mainly consists of processed foods,
high in salt and fat. He has a family history of hypertension,
and his father had a stroke at the age of 60. His blood pressure
was measured to be 145/95 mmHg. How do you manage to
treat the patient?
3.
4. Hypertension
Hypertension is defined as a systolic blood pressure (SBP) of 140 mm Hg
or more, or a diastolic blood pressure (DBP) of 90 mm Hg or more, or
taking antihypertensive medication.
• It is a major risk factor for
– stroke,
– myocardial infarction,
– vascular disease, and
– chronic kidney disease.
5. Hypertension
Hypertension may be:
• Primary -develop as a result of environmental or
genetic causes, or
• Secondary -multiple etiologies, including renal,
vascular, and endocrine causes.
• Primary or essential hypertension accounts for
90-95% of adult cases, and secondary
hypertension accounts for 2-10% of cases.
6. Drugs and toxins that cause hypertension
• Alcohol
• Cocaine
• Cyclosporine, Tacrolimus
• NSAIDs
• Erythropoietin
• Adrenergic medications
• Decongestants containing ephedrine
• Herbal remedies containing licorice (including licorice
root) or ephedrine (and ephedra)
• Nicotine
7. Other causes include the following:
• Hyperthyroidism
• Hypercalcemia
• Hyperparathyroidism
• Acromegaly
• Obstructive sleep apnea
• Pregnancy-induced hypertension
8.
9. White coat hypertension (white coat
effect)
• The term “white coat” comes from references to the
white coats traditionally worn by doctors.
• The white coat effect means that the blood pressure is
higher when it is taken in a medical setting than it is
when taken at home.
• On average, when the blood pressure is taken at home
the systolic pressure can be around 10mmHg lower
than it would be if taken by a doctor and 5mmHg
lower on the diastolic pressure . For some people this
difference can be even greater.
10. Principles of
Antihypertensive Therapy
Non pharmacological therapy is a
mainstay in the treatment of all
types of HTN, esp. for Type I.
– Weight reduction in overweight
patients.
– Restriction to excessive sodium
intake.
– Increasing aerobic exercise.
– Moderate consumption of
alcohol.
Life style changes, however
difficult, may facilitate
pharmacological control of BP.
11.
12. Pharmacological Approach
1. DIURETICS
o Thiazides & Thiazide like Diuretics: Hydrochlorothiazide, Chlorthalidone, etc.
o Loop Diuretics: Furosemide, Bumetanide, etc.
o K+-sparing Diuretics: Spironolactone, Amiloride, etc.
2. ACE Inhibitors:
– Enalapril, Enalaprilat, Captopril, etc.
3. Angiotensin Receptor Blockers:
– Candesartan, Valsartan, etc.
4. Calcium Channel Blockers:
– Verapamil, Diltiazem, Amlodipine, etc.
13. Pharmacological Approach
5. Sympatholytic Agents:
o Beta Receptor Antagonists: Metoprolol, Atenolol, etc.
o Alpha Receptor Antagonists: Prazosin, Phentolamine,
Phenoxybenzamine, etc.
o Mixed Adrenergic Antagonists: Labetalol, Carvedilol, etc.
o Centrally Acting Agents: Methyldopa, Clonidine,
Guanabenz, etc.
o Adrenergic Neuron Blocking Agents: Reserpine,
Guanadrel, etc.
15. CENTRAL SYMPATHOLYTICS
• CLONIDINE :-
• Imidazoline derivative related to alpha adrenergic agonist
naphazoline.
• Major haemodynamic effects result from stimulation of
alpha 2a receptors.
• Decrease sympathetic outflow – fall in BP & bradycardia.
• On chronic administration , decrease in CO contributes
more to fall in BP than decrease in TPR.
• Moderately potent antihypertensive.
• Clonidine is frequently combined with a diuretic.
16. CLONIDINE
S/Es are common
• Sedation , mental depression , disturbed
sleep, dryness of mouth.
• Impotence , salt & water retention ,
bradycardia
Besides oral tablets it is also available as a
transdermal patch that allows weekly dosing.
17. Methyldopa
Methyldopa has an active metabolite, alpha-methyl-norepinephrine, a
potent false neurotransmitter.
Methyldopa activates presynaptic inhibitory alpha-adrenoceptors and
postsynaptic alpha2-receptors in the CNS and reduces sympathetic outflow.
It decreases total peripheral resistance.
Methyldopa reduces pressure in standing and supine positions.
Methyldopa is used to treat mild-to-moderate hypertension.
Methyldopa produces adverse effects drowsiness, dry mouth, and GI upset.
Sexual dysfunction may occur and reduce compliance.
18. Adrenergic neuronal blocking drugs
Reserpine
Reserpine eliminates norepinephrine release in response to nerve
impulse by preventing vesicular uptake.
It depletes norepinephrine from sympathetic nerve terminals in the
periphery and in the adrenal medulla.
Reserpine can be used in mild-to-moderate hypertension.
Reserpine most commonly produces GI disturbances. Mental
depression, sometimes severe, like Suicidal tendencies, may result,
especially with high doses; use of reserpine is contraindicated in
patients with a history of depression.
19. BETA BLOCKERS
• Mild antihypertensive
• Do not significantly lower BP in normotensive
patients
• Mild to moderate cases
20. Propranolol
• Propranolol antagonizes catecholamine action at both beta1- and beta2-
receptors. It produces sustained reduction in peripheral vascular resistance.
• Blockade of cardiac b1-adrenoceptors reduces heart rate and contractility.
• B2-Adrenoceptor blockade increases airway resistance and decreases
catecholamine induced glycogenolysis and peripheral vasodilation.
• Blockade of beta-adrenoceptors in the CNS decreases sympathetic activity.
• Propranolol also decreases renin release.
• Propranolol is used in mild-to-moderate hypertension.
21. Other Non-selective beta blockers
• Nadolol , timolol, carteolol, pindolol, penbutolol
• These drugs are similar in action to propranolol and block
both b1- and b2-adrenoceptors.
• Nadolol has an extended duration of action.
• Pindolol, carteolol, and penbutolol have partial agonist
activity (sympathomimetic).
22. Cardioselective beta blockers
Metoprolol, atenolol, acebutolol, bisprolol
These drugs are relatively selective for beta1-
adrenoceptors.
Acebutolol has partial agonist activity.
23. No abrupt discontinuation
Abrupt discontinuation of beta-adrenoceptor
blockers can worsen angina and increase risk
of MI.
Dose tapering
Dose should be gradually reduced over a
period of several weeks.
24. BETA & ALPHA BLOCKERS
• Labetalol is an alpha- and beta-adrenoceptor antagonist.
• Labetalol reduces heart rate and contractility, slows AV conduction, and
decreases peripheral resistance.
•
Labetalol is available for both oral and IV administration.
Labetalol is useful for treating hypertensive emergencies and in the
treatment of hypertension of pheochromocytoma.
• Labetalol does not cause reflex tachycardia.
• Carvedilol has a significantly greater ratio of beta to alpha antagonist activity
than labetalol.
25. BETA & ALPHA BLOCKERS
• LABETALOL :- reduces TPR & acts faster than pure beta blockers
• IV for rapid BP reduction
• Oral therapy is restricted to moderately severe HTN
• Is used for hypertension in pregnancy and hypertensive
emergencies.
• CARVEDILOL :- vasodilatation & has additional antioxidant/free
radical scavenging effect
26. Alpha Blockers
• Alpha-Adrenoceptor antagonists lower total peripheral
resistance by preventing stimulation (and consequent
vasoconstriction) of alpha-receptors, which are located
predominantly in resistance vessels of the skin, mucosa,
intestine, and kidney.
• These drugs reduce pressure by dilating resistance and
conductance vessels.
• The effectiveness of these drugs diminishes in some patients
because of tolerance.
27. Prazosin, terazosin, and doxazosin
These drugs are alpha1-selective antagonists.
These drugs are used in treating hypertension in patients
with symptoms of prostatic hyperplasia.
Prazosin, terazosin, and doxazosin are often administered
with a diuretic and a beta-adrenoceptor antagonist.
These drugs may produce initial orthostatic hypotension.
Other adverse effects are minimal.
28. Phentolamine and phenoxybenzamine
Phentolamine and phenoxybenzamine antagonize
alpha1- and alpha2-adrenoceptors.
These drugs are used primarily in treating
hypertension in the presence of pheochromocytoma.
Phentolamine is administered parenterally;
phenoxybenzamine is administered orally.
29. Vasodilators
• Vasodilators relax smooth muscle and lower
total peripheral resistance, thereby lowering
blood pressure.
• The use of vasodilators is declining as a result
of newer modalities, such as ACE inhibitors
and calcium channel-blocking agents, which
are more effective with fewer adverse effects.
30. Hydralazine
• Hydralazine reduces blood pressure directly by relaxing arteriolar
muscle. This effect is probably mediated by increasing K+ efflux and
decreasing Ca2+ influx, and
increasing the production of nitric oxide.
• Hydralazine elicits the baroreceptor reflex, necessitating co-
administration with a diuretic to counteract sodium and water
retention and a beta-blocker to prevent tachycardia.
It is used to treat chronic hypertension and in hypertensive crises
accompanying acute glomerular nephritis or eclampsia.
Hydralazine may cause a lupus like syndrome in slow acetylators
causing fever, arthralgia, malaise and hepatitis.
31. Minoxidil
Minoxidil has effects similar to hydralazine.
Minoxidil acts to increase K+ efflux, which hyperpolarizes cells and reduces the
activity of L-type (voltage-sensitive) calcium channels.
Minoxidil vasodilates predominantly arteriolar vessels.
Minoxidil also elicits the baroreceptor reflex, necessitating use of a beta-
adrenoceptor antagonist and a diuretic.
Minoxidil is useful for long-term therapy of refractory hypertension.
It is a potent vasodilator that causes severe fluid retention and edema.
Minoxidil produces hirsutism, an advantage in formulations that are now used
to reduce hair loss in both males and females.
32. Sodium nitroprusside
Sodium nitroprusside dilates both resistance and capacitance vessels; it
increases heart rate but not output.
It is used in hypertensive emergencies because of its rapid action.
Continuous infusion is necessary to maintain effects.
It is usually administered with furosemide.
On initial infusion, sodium nitroprusside may cause excessive vasodilation
and hypotension.
Sodium nitroprusside can be converted to cyanide and thiocyanate. The
accumulation of cyanide and risk of toxicity are minimized by concomitant
administration of sodium thiosulfate or hydroxocobalamin.
33. Diazoxide
Diazoxide is used intravenously to reduce blood
pressure rapidly, usually in an emergency situation.
Diazoxide is administered with furosemide to
prevent fluid overload.
This drug is declining in use because of its
unpredictable action and adverse effects.
34. Fenoldopam
• Fenoldopam (Corlopam) is a selective agonist
at dopamine DA1 receptors that increases
renal blood flow while reducing blood
pressure.
• Administered by infusion, it is a useful drug in
the
control of emergency hypertension.
35. Specialized vasodilators
• Drugs used to treat pulmonary hypertension
• Ambrisentan is a selective endothelin A receptor antagonist used to
treat pulmory hypertension. Plasma endothelin-1 is elevated in
patients with pulmonary hypertension. Ambrisentan is administered
orally. Peripheral edema is a common adverse effect of endothelin
receptor antagonists.
• Bosentan antagonizes both endothelin A and B receptors and reduces
pulmonary hypertension.
• Headache and edema are common side effects.
