Antihypertensive
drugs
I-Hypertension
a sustained diastolic blood pressure greater than 90 mm Hg accompanied by an elevated systolic blood pressure > 140 mm Hg
Chronic hypertension if not controlled can lead to
Congestive heart failure
Myocardial infarction
Renal damage
Cerebrovascular accidents
II- Etiology of hypertension
Secondary to other disease
Ninty percentage of patients from disorder of unknown origin affecting the blood pressure regulating mechanism
Family history of hypertension increases the liklihood of the disease
It occurs in blacks four times more than in whites
in middle aged males more than middle aged females
Predisposed factors
Stressful life style
High dietary intake of sodium
Obesity
Smooking
N.B NSAIDS interfere with the hypotensive action of many antihypertensives
III-Mechanisms for controlling blood pressure
Reducing the cardiac output
Deceasing the peripheral resistance
IV- Treatment sterategies
Mild hypertension can often be controlled with a single drug
More severe hypertension may require treatment with several drugs that are selected to minimize adverse effects of the combined regimen
Treatment is initiated with (a diuretic ,B blocker,ACE inhibitor or a Ca channel blocker ) depending on the individual patient
If not adequately controlled
B blocker is added if the initial was a diuretic or
a diuretic is added if the initial was a B blocker
A vasodilator can be added as a third step for those patients who still fail to response
A- Individual care
Black patients respond well to diuretics and Ca channel blockers
In elderly Ca channel .ACE inhibitors and diuretics are favored
N.B Hypertension may coexist with other disease that can be aggrevated by some of the antihypertensive drugs
ex
Diuretics and B blockers avoided in insulin dependant diabetes and in hyperlipidimia
B blockers avoided in asthma or chronic pulmonary disease
B-Patient compliance in antihypertensive therapy
ex B blockers can decrease libido and induce impotence in males particullary middle aged and elderly men
This this drug induced ***ual dysfunction may prompt the patient to discontinue therapy
Thus it is important to enhance compliance by carefully selecting a drug regimen that both
a) reduces advers effects
b) minimizes the number of doses required daily
V- Diuretics
Diuretics and/or B blockers are currently recommended as the first line drug therapy for hypertension
Recent data suggest that diuretics are superior to B blockers in older ******
A- Thiazide diuretics
ex: hydrochlorothiazide
the most widespread used diuretics
Therapeutic uses
Particularry useful in treatment of black or elderly patients
Can be used in those with chronic renal disease
Not effective in patients with inadequate kidney function i.e creatinine clearance less than 50 mls/min
N.B loop diuretics may be required in these patients
Adverse effects
Induce hypokalemia so serum ptassium level should be monitored closely in patients predisposed to cardiac arrythmia
Should be avoided in diabetes or hyperlipidemia
B-Loop diuretics
ex : bumetanide -furosemide
Act promptly even in patients who have poor renal function or have not respond to other diuretics
VI- B blockers
ex : atenolol - propranolol
Recommended as a first-line drug therapy for hypertension
Efficacious but have some contraindications
Propranolol : is the protoyype B blocker
acts on both B1 and B2 receptors so contraindicated in asthmatic patients
Atenolol : newer agents
selective for B1 receptors so commonly used in asthmatic patients
Therapeutic uses
Effective in white than in black
Effective in young than in elderly
Advers effects ... discussed
VII- ACE inhibitors
ex captopril - ramipril
Recommended when first- line agents are contraindicated or ineffective
Therapeutic uses
Most effective in white and young patients as B blockers
If used in combination with a diuretic the effectiveness will be similar in both white and black
Effective in patients with CHF ...unlike B blockers
A standard in care of patient following a myocardial infarction
Adverse effects
the most important are
Dry cough
Alterd taste
Hypokalemia :so K supplements and spironolactone are contraindicated
Fetotoxic : so must be avoided in pregnancy
VIII- Angiotensin
ex : losartan
Its phamacologic effects are similar to ACE inhibitors
Its adverse effects profile is improved over ACE inhibitors
Also fetotoxic
IX- Ca channel blockers
ex :Amlodipine - deltiazem - nifedipine - verpamil
Recommended when first line agents are contraindicated or ineffective
One study suggests that the use of short acting ones especially in high doses increase the risk of myocardial infarction
Deltiazem and Verpamil : discussed before
Amlodipine :a newer agent have the advantage that show little interaction with other cardiovascular drugs e.g : digoxin - warfarin
Therapeutic uses
Not usually require the addition of a diuretic
Can be used in asthmatic,diabetes,angina and/or peripheral vascular diseases
Adverse effects
The main ,is constipation in 10% of patients
X- Alpha adrenergic blocking agents
ex : prazosin - terazosin -oxazosin
May cause postural hypotension
Prazosin :Treat mild to moderate hypertension
prescribed in combination with propranolol or a diuretic for additive effect
XI- Centrally acting adrenergic drugs
A-Clonidine
Used for mild or moderate hypertension that has not responded adequately to diuretics alone
Useful in the treatment of hypertension complicated by renal diseases
As it causes sodium and water retention , it is usually administerd in combination with a diuretic
B- Alpha methyl dopa
Valuable in treating hypertensive patients with renal insufficiency
Can be used during pregnancy
XII- Vasodilators
ex :hydrazaline - minoxidil
Direct acting smooth muscle relaxants
Not used as hypotensives nowadays due to their serious adverse effects
Minoxidil : Nowadays used topically to treat
I-Hypertension
a sustained diastolic blood pressure greater than 90 mm Hg accompanied by an elevated systolic blood pressure > 140 mm Hg
Chronic hypertension if not controlled can lead to
Congestive heart failure
Myocardial infarction
Renal damage
Cerebrovascular accidents
II- Etiology of hypertension
Secondary to other disease
Ninty percentage of patients from disorder of unknown origin affecting the blood pressure regulating mechanism
Family history of hypertension increases the liklihood of the disease
It occurs in blacks four times more than in whites
in middle aged males more than middle aged females
Predisposed factors
Stressful life style
High dietary intake of sodium
Obesity
Smooking
N.B NSAIDS interfere with the hypotensive action of many antihypertensives
III-Mechanisms for controlling blood pressure
Reducing the cardiac output
Deceasing the peripheral resistance
IV- Treatment sterategies
Mild hypertension can often be controlled with a single drug
More severe hypertension may require treatment with several drugs that are selected to minimize adverse effects of the combined regimen
Treatment is initiated with (a diuretic ,B blocker,ACE inhibitor or a Ca channel blocker ) depending on the individual patient
If not adequately controlled
B blocker is added if the initial was a diuretic or
a diuretic is added if the initial was a B blocker
A vasodilator can be added as a third step for those patients who still fail to response
A- Individual care
Black patients respond well to diuretics and Ca channel blockers
In elderly Ca channel .ACE inhibitors and diuretics are favored
N.B Hypertension may coexist with other disease that can be aggrevated by some of the antihypertensive drugs
ex
Diuretics and B blockers avoided in insulin dependant diabetes and in hyperlipidimia
B blockers avoided in asthma or chronic pulmonary disease
B-Patient compliance in antihypertensive therapy
ex B blockers can decrease libido and induce impotence in males particullary middle aged and elderly men
This this drug induced ***ual dysfunction may prompt the patient to discontinue therapy
Thus it is important to enhance compliance by carefully selecting a drug regimen that both
a) reduces advers effects
b) minimizes the number of doses required daily
V- Diuretics
Diuretics and/or B blockers are currently recommended as the first line drug therapy for hypertension
Recent data suggest that diuretics are superior to B blockers in older ******
A- Thiazide diuretics
ex: hydrochlorothiazide
the most widespread used diuretics
Therapeutic uses
Particularry useful in treatment of black or elderly patients
Can be used in those with chronic renal disease
Not effective in patients with inadequate kidney function i.e creatinine clearance less than 50 mls/min
N.B loop diuretics may be required in these patients
Adverse effects
Induce hypokalemia so serum ptassium level should be monitored closely in patients predisposed to cardiac arrythmia
Should be avoided in diabetes or hyperlipidemia
B-Loop diuretics
ex : bumetanide -furosemide
Act promptly even in patients who have poor renal function or have not respond to other diuretics
VI- B blockers
ex : atenolol - propranolol
Recommended as a first-line drug therapy for hypertension
Efficacious but have some contraindications
Propranolol : is the protoyype B blocker
acts on both B1 and B2 receptors so contraindicated in asthmatic patients
Atenolol : newer agents
selective for B1 receptors so commonly used in asthmatic patients
Therapeutic uses
Effective in white than in black
Effective in young than in elderly
Advers effects ... discussed
VII- ACE inhibitors
ex captopril - ramipril
Recommended when first- line agents are contraindicated or ineffective
Therapeutic uses
Most effective in white and young patients as B blockers
If used in combination with a diuretic the effectiveness will be similar in both white and black
Effective in patients with CHF ...unlike B blockers
A standard in care of patient following a myocardial infarction
Adverse effects
the most important are
Dry cough
Alterd taste
Hypokalemia :so K supplements and spironolactone are contraindicated
Fetotoxic : so must be avoided in pregnancy
VIII- Angiotensin
ex : losartan
Its phamacologic effects are similar to ACE inhibitors
Its adverse effects profile is improved over ACE inhibitors
Also fetotoxic
IX- Ca channel blockers
ex :Amlodipine - deltiazem - nifedipine - verpamil
Recommended when first line agents are contraindicated or ineffective
One study suggests that the use of short acting ones especially in high doses increase the risk of myocardial infarction
Deltiazem and Verpamil : discussed before
Amlodipine :a newer agent have the advantage that show little interaction with other cardiovascular drugs e.g : digoxin - warfarin
Therapeutic uses
Not usually require the addition of a diuretic
Can be used in asthmatic,diabetes,angina and/or peripheral vascular diseases
Adverse effects
The main ,is constipation in 10% of patients
X- Alpha adrenergic blocking agents
ex : prazosin - terazosin -oxazosin
May cause postural hypotension
Prazosin :Treat mild to moderate hypertension
prescribed in combination with propranolol or a diuretic for additive effect
XI- Centrally acting adrenergic drugs
A-Clonidine
Used for mild or moderate hypertension that has not responded adequately to diuretics alone
Useful in the treatment of hypertension complicated by renal diseases
As it causes sodium and water retention , it is usually administerd in combination with a diuretic
B- Alpha methyl dopa
Valuable in treating hypertensive patients with renal insufficiency
Can be used during pregnancy
XII- Vasodilators
ex :hydrazaline - minoxidil
Direct acting smooth muscle relaxants
Not used as hypotensives nowadays due to their serious adverse effects
Minoxidil : Nowadays used topically to treat
male pattern baldness
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