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59-291 Section 3, Lecture 2
Diuretics:
-increase in Na+ excretion
(naturesis)
Thiazide and Related diuretics
-decreased PVR due to
decreases muscle contraction
-an economical and effective
treatment
-protect against osteoporosis
Loop diuretics
-used in patients with poor
kidney function where thiazide
derivatives will not be effective
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vasodilators
b-antagonists
a-antagonists
Angiotensin II
receptor antagonists
b-antagonists
CNS-directed
sympatholytics
b-antagonists
ACE inhibitors
Angiotensin II
receptor antagonists
diuretics
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Potassium-Sparing Diuretics
-mild diuretic and antihypertensive effect
-Minimize renal-K+ loss thus preventing hypokalemia
-If the patient can’t tolerate these drugs then use thiazide and take KCl
tablets
Drug Classification
Common Adverse Effects
Common Drug Interactions
Thiazide and loop
diuretics
Blood cell deficiencies,
hyperlipidemia, hyperuricemia,
hypokalemia, and other electrolyte
changes Aggravation of diabetes
Increase serum levels of
lithium. Hypotensive effect
decreased by NSAIDs and
augmented by ACE inhibitors
Potassium-sparing
diuretics
Hyperkalemia
Hyperkalemic effect
increased by ACE inhibitors
and potassium supplements
Diuretics
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Sympatholytics
Drug Classification
Common Adverse Effects
Common Drug
Interactions
Adrenergic receptor antagonists
α-Adrenergic receptor
antagonists
Dizziness, first-dose syncope, fluid
retention, and orthostatic
hypotension
Hypotensive effect increased
by β-adrenergic receptor
antagonists and diuretics
β-Adrenergic receptor
antagonists
Bradycardia, bronchoconstriction,
depression, fatigue, impaired
glycogenolysis, and vivid dreams
Cardiac depression increased
by diltiazem and verapamil.
Hypotensive effect decreased
by NSAIDs
Centrally acting drugs
Clonidine
Dry mouth, fatigue, rebound
hypertension, and sedation
Hypotensive effect decreased
by tricyclic antidepressants
Sedative effect increased by
CNS depressants
Guanabenz
Same as clonidine
Same as clonidine
Guanfacine
Same as clonidine but milder
Same as clonidine
Methyldopa
Autoimmune hemolytic anemia,
hepatitis, and lupuslike syndrome.
Other adverse effects same as
those of clonidine
Hypotensive effect increased
by levodopa. Other
interactions same as those of
clonidine
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vasodilators
b-antagonists
a-antagonists
Angiotensin II
receptor antagonists
b-antagonists
CNS-directed
sympatholytics
b-antagonists
ACE inhibitors
Angiotensin II
receptor antagonists
diuretics
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Angiotensin Inhibitors
Drug
Oral
Bioavailabili
ty
Absorption
Reduced by Food
Active
Metabolite
Duration of
Action
(Hours)
Angiotensin-converting enzyme inhibitors
Benazepril
37%
No
Benazeprilat
24
Captopril
75%
30-40%
None
Enalapril
60%
No
Enalaprilat*
24
Fosinopril
36%
No
Fosinoprilat
24
Lisinopril
25%
No
None
24
Quinapril
60%
25-30%
Quinaprilat
24
Ramipril
55%
No
Ramiprilat
24
Losartan
33%
10%
Carboxylic
acid
metabolite
24
Valsartan
25%
40%
None
24
Candesartan
15%
No
None
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12-Jun
Angiotensin receptor antagonists
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Angiotensin inhibitors
1. ACE inhibitors
2. Angiotensin
receptor inhibitors
Renin secretion induced by:
1-Symp. Outflow
2-reduction in BP and wall
tension in renal arterioles
3-reduced NaCl reabsorbtion
AT1
AT1
G-proteins
– IP3
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ACE inhibitors Adverse effects
• Increase fetal
morbidity and
mortality, especially
during 2nd and 3th
trimesters
• Renal failure in
patients with bilateral
renal artery stenosis
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Drug Classification
Common Adverse Effects
Common Drug Interactions
Angiotensin inhibitors
Angiotensin-converting
enzyme (ACE) inhibitors
Acute renal failure, angioedema,
cough, hyperkalemia, loss of
taste, neutropenia, and rash
Increase serum levels of
lithium. Hyperkalemic effect
increased by potassiumsparing diuretics and
potassium supplements.
Hypotensive effect
decreased by NSAIDs
Angiotensin receptor
antagonists
Hyperkalemia
Serum levels of drug
increased by cimetidine and
decreased by phenobarbital
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Vasodilators
• Organic nitrites and nitrates
– Amyl nitrites; (nitrites), administered by
inhalation
– Nitroglycerin (glyceryl trinitrate); sublingual,
oral or transdermal administration
• Calcium channel blockers
– Amlodipine, felodipine
– Diltiazem, verapamil
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Tolerance Aldehyde dehydrogenase releases
NO from nitroglycerin, and this process is
accompanied with formation of superoxide
anion free radical (O2-) that in turn, deactivate
aldehyde dehydrogenase
-to avoid periodically interrupt the
administration of the drugs
Pills –sublingual
Sustained release- patches,
skin ointments, IV
Adverse effects- headaches,
hypotension, dizziness, reflex
tachycardia, use b-blocker in
combination
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Ca2+- channel blockers (CCBs)
Suppress cardiac activity and
relax smooth muscles-in
combination increase coronary
blood flow
Side effects: fatigue, headache, dizziness,
flushing, peripheral edema
Occasionally cause gingival hyperplasia
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Selection of Antihypertensive Drugs for Patients with Specific
Traits or Concurrent Diseases
Patient Characteristic
Most Preferred
Drugs
Least Preferred
Drugs
Age over 65 years
Diuretic, ACEI, CCB
Centrally acting α2
agonist
African heritage
Diuretic, CCB
β-blocker
Pregnant
Methyldopa,
labetalol
ACEI, ARB
Angina pectoris
β-blocker, CCB
Hydralazine, minoxidil
Myocardial infarction
β-blocker, ACEI,
aldosterone
antagonist
Congestive heart failure
Diuretic, ACEI,
ARB, β-blocker
Recurrent stroke prevention
Diuretic, ACEI, ARB
Chronic kidney disease
ACEI, ARB
Diabetes
Diuretic, ACEI,
ARB, β-blocker,
CCB
Asthma
CCB, ACEI
Benign prostatic hyperplasia
α-blocker
Migraine headache
β-blocker, CCB
Osteoporosis
Diuretic
β-blocker
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