CLASSIFICATION OF ANTIHYPERTENSIVE AGENTS
Drug MOA Indications Pharmaco- Adverse effects Drug Interactions
Kinetics
I. DRUGS THAT ALTER SODIUM AND WATER BALANCE (DIURETICS)
Overall MOA: decrease body Na stores by:
Increase Na excretion -> Decrease blood volume -> decrease CO
Effect on vascular resistance (vessel stiffness and neural reactivity)
Decrease Na of vessel wall -> Decrease Na-Ca exchange -> Decrease intracellular Ca and concentration
a. Thiazide Diuretics -blocks the NaCl cotransporter in distal Initial monotherapy -Hypokalemia (except K K-sparing plus ACE
• Chlorothiazide convoluted tubules or in combination w/ other drugs sparing) inhibitors/renal
• Hydrochlothiazide -Hypomagnesemia insufficiency:
-Impaired glucose tolerance HYPERKALEMIA
-Hyperlipidemia
*these two contains -Reduced uric acid excretion
Benzothiadiazine Spironolactone:
gynecomastia,
menstrual
b. Loop Diuretics -blocks Na-K-2Cl transporter in Thick Ascending irregularities, GIT
• Furosemide Limp of Loop of Henle problems (diarrhea)
• Bumetamide
• Ethacrynic acid
c. K Sparing Diuretics
Aldosterone Receptor Agonist
(dependent on circulating
aldosterone)
• Spirolonactone
Epithelium Na Channel Blocker
(ENAC) – NON steroidal
• Triamterene
• Amiloride
d. Others -blocks the structure but contain unsubstituted
• Indapamide sulfonamide
• Metolazone
• Xipamide
II. DRUGS THAT ALTER SYMPATHETIC NERVOUS SYSTEM FUNCTION
a. Central- acting Reduce sympathetic outflow from vasopressor
sympathoplegic drugs centers in brainstem with increased sensitivity to
baroreceptor control
, L-dopa analog converted to alpha- -Treatment of hypertension, either alone or Peak of action: Overt Sedation Other
methyldopamine and then alpha- with other agents 4-6 hours Long term: mental lassitude, hypertensive drugs
methylnorepinephrine. Duration of action: impaired concentrartion, Lithium Ferrous
METHYLDOPA Either STIMULATES central alpha-2 24 hrs nightmares, depression, sulfate/gluconate
adrenoreceptors -Usually used after other agents have failed
(L-a-methyl-3,4- vertigo, extrapyramidal MAO inhibitors
due to side effects
dihydroxyphenylalanine) signs, lactation, (+) Phenylpropanolamine
Half – life: COOMB’S TEST, hepatitis, B-blocker (Propanolol
Safe in Pregnancy Reduce PVR, variable effect on HR and CO,
-Also may be used for treatment of severe 2 hours drug fever and tolbutamide)
reduce RVR
dysmenorrhea, menopausal flushing,
glaucoma Dose response Postural hypotension:
curve: NO volume depleted patients
-Clonidine is useful in the management of
withdrawal symptoms in opioid- or Route: Oral,
nicotinedependent persons Parenteral
Alpha-2 agonist decreases sympathetic outflow Dry mouth, sedation (less TCA
from CNS and increase parasympathetic tone for transdermal), depression Alcohol, barbiturates,
Binds to an imidazoline receptor other sedatives
Duration of action: Hypertensive crisis upon Digitalis, Calcium
Reduction of CO due to decreased HR and 7 days withdrawal: nervousness, channel blockers
CLONIDINE
(2. imidazoline derivative) relaxation of capacitance vessels as well as tachycardia, headache
reduction PVR and decreased Rena Half-life: sweating
Vascular Resistance 8-12 hours
GUANABENZ
DISCONTINUE
GUANFACINE
GRADUALLY
Dose response
curve: YES
Rare: Postural hypotension
Route: Transdermal,
oral
b. Ganglion – blocking Competitively block nicotinic cholinoreceptors on Sympathoplegia (excessive
agent postganglionic neurons in both sympathetic orthostatic hypotension and
and parasympathetic ganglia sexual dysfunction)
• Trimethapan
• Mecamylamine Parasympathoplegia
(constipation, urinary
retention, precipitation of
glaucoma, blurred vision, dry
mouth, etc)
Drug MOA Indications Pharmaco- Adverse effects Drug Interactions
Kinetics
I. DRUGS THAT ALTER SODIUM AND WATER BALANCE (DIURETICS)
Overall MOA: decrease body Na stores by:
Increase Na excretion -> Decrease blood volume -> decrease CO
Effect on vascular resistance (vessel stiffness and neural reactivity)
Decrease Na of vessel wall -> Decrease Na-Ca exchange -> Decrease intracellular Ca and concentration
a. Thiazide Diuretics -blocks the NaCl cotransporter in distal Initial monotherapy -Hypokalemia (except K K-sparing plus ACE
• Chlorothiazide convoluted tubules or in combination w/ other drugs sparing) inhibitors/renal
• Hydrochlothiazide -Hypomagnesemia insufficiency:
-Impaired glucose tolerance HYPERKALEMIA
-Hyperlipidemia
*these two contains -Reduced uric acid excretion
Benzothiadiazine Spironolactone:
gynecomastia,
menstrual
b. Loop Diuretics -blocks Na-K-2Cl transporter in Thick Ascending irregularities, GIT
• Furosemide Limp of Loop of Henle problems (diarrhea)
• Bumetamide
• Ethacrynic acid
c. K Sparing Diuretics
Aldosterone Receptor Agonist
(dependent on circulating
aldosterone)
• Spirolonactone
Epithelium Na Channel Blocker
(ENAC) – NON steroidal
• Triamterene
• Amiloride
d. Others -blocks the structure but contain unsubstituted
• Indapamide sulfonamide
• Metolazone
• Xipamide
II. DRUGS THAT ALTER SYMPATHETIC NERVOUS SYSTEM FUNCTION
a. Central- acting Reduce sympathetic outflow from vasopressor
sympathoplegic drugs centers in brainstem with increased sensitivity to
baroreceptor control
, L-dopa analog converted to alpha- -Treatment of hypertension, either alone or Peak of action: Overt Sedation Other
methyldopamine and then alpha- with other agents 4-6 hours Long term: mental lassitude, hypertensive drugs
methylnorepinephrine. Duration of action: impaired concentrartion, Lithium Ferrous
METHYLDOPA Either STIMULATES central alpha-2 24 hrs nightmares, depression, sulfate/gluconate
adrenoreceptors -Usually used after other agents have failed
(L-a-methyl-3,4- vertigo, extrapyramidal MAO inhibitors
due to side effects
dihydroxyphenylalanine) signs, lactation, (+) Phenylpropanolamine
Half – life: COOMB’S TEST, hepatitis, B-blocker (Propanolol
Safe in Pregnancy Reduce PVR, variable effect on HR and CO,
-Also may be used for treatment of severe 2 hours drug fever and tolbutamide)
reduce RVR
dysmenorrhea, menopausal flushing,
glaucoma Dose response Postural hypotension:
curve: NO volume depleted patients
-Clonidine is useful in the management of
withdrawal symptoms in opioid- or Route: Oral,
nicotinedependent persons Parenteral
Alpha-2 agonist decreases sympathetic outflow Dry mouth, sedation (less TCA
from CNS and increase parasympathetic tone for transdermal), depression Alcohol, barbiturates,
Binds to an imidazoline receptor other sedatives
Duration of action: Hypertensive crisis upon Digitalis, Calcium
Reduction of CO due to decreased HR and 7 days withdrawal: nervousness, channel blockers
CLONIDINE
(2. imidazoline derivative) relaxation of capacitance vessels as well as tachycardia, headache
reduction PVR and decreased Rena Half-life: sweating
Vascular Resistance 8-12 hours
GUANABENZ
DISCONTINUE
GUANFACINE
GRADUALLY
Dose response
curve: YES
Rare: Postural hypotension
Route: Transdermal,
oral
b. Ganglion – blocking Competitively block nicotinic cholinoreceptors on Sympathoplegia (excessive
agent postganglionic neurons in both sympathetic orthostatic hypotension and
and parasympathetic ganglia sexual dysfunction)
• Trimethapan
• Mecamylamine Parasympathoplegia
(constipation, urinary
retention, precipitation of
glaucoma, blurred vision, dry
mouth, etc)
