Milk and Medications For Treatment of Hypertension

Hypertension
"A Silent Killer"

 

Definition:

Persistance elevation of arterial blood pressure above normal limit under normal basal condition.

Symptoms:

• Hypertension is called silent killer because it rarely causes symptoms.when blood pressure is very very high, these symptoms may occur:-

1. Headache.
2. Nosebleeds.
3. Palpitations.
4. Dizziness.
5. Numbness or tingling in the hands or feet.
6. Confusion.
7. Blurred vision.
8. Vomiting.

Management:

 STEP 1

The four main choices for initiating therapy of essential hypertension(HTN):
A)Diuretics.
B)Beta adrenergic blockers.
C)Calcium channels blockers.
D)Angiotention converting enzyme.

A)Diuretics:

• Effective alone or adjunct to other antihypertensives.
• Considered as(prefferd) starting agent for most patients, and an impotant part of multidrug HTN therapy.

>>>>The  diuretic chioces for HTN:
Thiazides(oral diuretics)used most _prototype is hydrochlorothiazide:

ACTION:-

1. Modest renal Na+ loss seems ti decrease vascular responsiveness to vasoconstrictors such as norepinephrine, peripheral vascular resistance falls.
2. Reduction of circulating fluid volume(diuresis) probably contributes to initial antihypertensive action in some patients, however the diuretic effect is usually short-lived but blood pressure control usually persists.
3. Flat dose-response curve : markedly insrease antihpertensive effect(but often does increase number, severity, of side effects).

Main side effects:-

1. Hypokalemia (Thiazides are potassium-wasting).
2. Risk of hyper uricemia, gout(Thiazides elevate serum urate).
3. Hyperlipidemias, hyperglycemia:
4. thiazides increase blood lipids and glucose, yet these drugs shouldn't  be absolutely avoided in patients with hyperlipidemias and/or frank diabetes mellitus.
5. Risk of hypovolemia(a particular concern in pregnancy: maternal volume depletion may>>> hyoperfusion of placenta)
6. Loop agents(e.g. furosemide__LASIX); NOT often a chioce for HTN , rarely chosen goal is to use diuretic for uncomplicated HTN.

B)Beta-blockers (e.g. propranolol; INDERAL)

• All orally effective B_blockers are approved for HTN.

Action:-

1. Reduce cardiac contractility.
2. Reduce renin release.

Uses:-

1. Effective alone or as adjunct(mainly to inhibit reflex tachycardia caused by some other antihypertensives).
2. May be preffered for patients who also have angina (not vasospastic),tachycardia, myocardial infarction,hyperthyroidism, migraines.
3. Reduction exercise tolerance may take these less than ideal chioce for some patients who are very physically active.

Contraindication:-

1. Asthma, emphysema.
2. Insulin-dependant diabetes mellitus.
3. Atrio-ventricular block or bradycardia.
4. Vasospastic angina.
5. Severe congestive heart failure.
6. Peripheral arterial disease.

N.B.

• B_blockers raise serum triglyceride levels and lower HDL.
• Discontinuing B_blockers Tx:

        never stop abruptly(to avoid risk of rebound increase heart rate).

C)Calcium channels blockers:

• Block slow voltage gated (L-type) Ca channels >>> decrease calcium influx to heart, blood vessels.

Types:-

1)Nondihydropyridines:Prototype verapamil(ISOPTIN):

Action:-

1. Reduce contractility.
2. Reduce vasoconstriction(i.e. cause vasodilatation).

Uses:-

• Mainly as alternative to B-blocker, antoanginal& antiarrhythmics as well.

Side effects:-

• Contipation is most common side effect.

Contraindication:-

• any situation in which depression of cardiac contractility, rate, automaticity, impulse conduction, would be dangerous(never combine with B-blocker).

 2)Dihydropyridines: prototype nifedipine(ADALAT):

• Selective vasodilator.
• No verapamil-like cardiac depression, thus...
• Might be chosen when cardiac depression from anondihydropyridine is to be avoided, or when the mild cardiac "stimulation" from dihydropyridine might be beneficial(e.g. concomitant bradycardia).
• Produces ankle edema.

D)ACE inhibitors (and other angiotensin"modifiers"):

• Propotype ACE inhibitor is captopril(CAPOTEN).

Actions:-

1. Inhibit Angiotension 2 synthesis(hence consequent vasoconstriction and aldosterone release).
2. Inhibit breakdown of bradykinin, avasodilator(ACE = bradykininase).

Uses:-

• Hypertention:

often cosidered suitable for hypertensive patient who also has congestive heart failure|(CHF) and/or diabetes mellitus w/o evidence of severe kidney diseases, and/or hyperlipidemia.

• Tx of CHF.
• Help delay progression of renal disease in patients with diabetic neuropathy.

Side effects:-

1. Most common : cough esp. with captopril(due to bradykinin)
2. Taste loss; allergic skin rash; drug fever.
3. Rare but serious: angioedema(to bradykinin).
4. May lead to excessive hypotention when used with diuretics(synergistic effects).
5. Aldosterone levels may indirectly>>> hyperkalemia, so K-sparing diuretics or oral K supplements cautiously.
6. Acute renal failure (in patients with bilateral renal artery stenosis).
7. Proteinuria with captopril.

Contraindications:-

• Bilateral renal artery stenosis >>>  acute renal failure.

• Angiotensin 2 receptors blockers (ARBs):

>>>prototype Losartan(COZAAR):

• Alternative to ACE inhibitor, fewer/no typical ACE inhibitor side efeeccts (e.g. cough&angiodema)
• Action:-
• only block A-11 receptors(>>>decrease mediated vasoconstriction and decrease aldosterone release.
• Lack effects on bradykinin metabolism.
• Share same pregnancy contraindication as ACE inhibitors.

STEP 2

• Alternative initial agents(sympathetic inhibitors)

A)selective peripheral alpha-blockers:

 Prazosin:

Actions:-

1. Block sympathomimetic-induced vasoconstriction in periphery via postsynaptic(alpha-1)blockade, with no effect on presynaptic alpha-receptors(alpha-2)
2. Usually 2nd line, but may be turned to as first choice in some cases e.g. patients with:
3. Hyperlipidemias.
4. Benign prostatic hypertrophy, as smooth muscle relaxing effect in GU tract(also due to alpha-blckade).

Side effects&Contraindication:-

1. Most important:Orthostatic hypotention(first dose faint effect)
2. Long term hypotention may trigger                     

• Reflex tachycardia(may need to add B-blocker to control it)
• Compensatory renal Na retention(may need diuretics).

• B)Centrally acting Alpha-Agonist: Clonidine(Catapress)

Actions:

• Central alpha-2 agonist reduces "sympathetic outflow" to periphery (e.g. to blood vessels& heart).

Side effect & Contraindications:-

1. Sedation, dry mouth and impotence(in men)common.
2. Little or no reflex tachycardia.
3. Danger: rebound increase blood pressure and heart rate with abrupt discontinuation; never stop abruptly

Related drugs:

• Methyldopa(ALDOMET)
• Preferred drug for managing HTN during pregnancy.
• Risk of hepatotoxicity.

C)Catecholamine Dopletor: Reserpine(Serpasil)

Actions:-

• Depletes peripheral neuronal norepinephrine>.>decrease vasoconstriction and heart rate.

Uses;-

• mainly when any of above drugs are ineffective (even in combination) or high cost is factor, otherwise this drug is seldom used.

Side effects&Contraindication:-

1. Bradycardia,possible CHF.
2. Peripheral autonomic: parasympathetic predominance,not used in peptic ulcer.
3. CNS: fatigue,drowsiness, suicidal depression,parkinsonism.

STEP3

Hydralazine:oral administration

Actions:

1. Direct acting vasodilator(dilate arteries& not veins)
2. Relatively rapid response.

Uses:-

1. For HTN when Step 1/2 drugs  ineffective
2. After load reduction for severe  CHF .

Side effects,need for adjuncts:

1. Reflex tachycardia(may necessitate B-blocker).
2. Renal Na retention(might have to add diuretic).
3. Lopus like syndrome(facial "rash"; joint pain, fever, characteristic blood tests)
4. Peripheral neuritis(hydralazine interferes with vitamin B6 metabolism).

Related drugs:

Minoxidil:-

• Seldom used because of side effects (only in life threatening severe hypertention),used topically in Tx of hair fall.

Side effects of Minoxidil:-

• Hirsutism
• Tachycardia
• Fluid&salt retention
• SO used with B-blocker and diuretic.

STEP4

Other oral antihypertensives:(RARLY USED)

• Mao inhibitors
• Guanethidine(acts like reseprine that also>>> mor complete NE depletion than reseprine).

Importance of MILK in Treatment of Hypertension:

• recent studies at the "American Heart Association's" and confirmed that addition of milk a few calories to the diet reduces the risk of developing high blood pressure, and proved that drinking milk for long periods of time decreases their systolic blood pressure, so decreasing the likelihood of hypertension in the future. In previous studies were detected multiple health benefits of eating yogurt repeated with regard to maintaining the body mass index (BMI) and body weight.

• Milk consists of a high concentration of calcium and other essential nutrients easily be affixed to the daily diet, is also a source of protein and imparts a feeling of fullness for a longer period of time.

• Underwent the study of nearly 2,000 volunteers proven safety diagnosed with high blood pressure at the beginning of the study, which lasted for 15 years during which fill a questionnaire to three times to check their consumption of milk, and the results confirmed the decreased likelihood of developing " high blood pressure" for approximately 31% of the volunteers were a daily consumption of milk for at least 2% of daily calories equivalent to 4.53 g of low-fat yogurt every three days as the rate of high systolic blood pressure decreases compared to those who did not rely milk part of their daily diet.

• Contribute to a diet with few calories and physical activity in reducing the incidence of chronic diseases such as high blood pressure, which causes delay in treatment in the damaged arteries and torn and works as a network picks up cholesterol and moves through the bloodstream to accumulate on the vascular wall.