ACE Inhibitors

ACE Inhibitors

• Captopril (CAPOTEN). Captopril, the first ACE inhibitor to be

marketed
• Enalapril (VASOTEC). Enalapril maleate, the second ACE inhibitor
approved in the United States
• Lisinopril (PRINIVIL, ZESTRIL).
• Benazepril (LOTENSIN).
• Fosinopril (MONOPRIL).
• Quinapril (ACCUPRIL).
• Ramipril (ALTACE).
 Therapeutic uses
• Hypertension

• ACE inhibitors slow the progression of diabetic

nephropathy and decrease albuminuria

• Chronic heart failure

 Adverse effects
• Dry cough due to accumulation in the lungs of bradykinin .
• Rash, fever, altered taste, hypotension
• hyperkalemia
• Acute Renal Failure
• ACE inhibitors are fetotoxic and should not be used by women
who are pregnant.
 ANGIOTENSION II RECEPTOR ANTAGONIST
• Losartan
• Valsartan
• Candesartan
• Eprosartan
• Irbesartan
• Telmisartan
 ANGIOTENSION II RECEPTOR ANTAGONIST
• They block angiotension II receptor type 1 (AT1).
• They don’t cause dry cough associated with ACEIS, since these
agents act on angiotension receptors and have no effect on
bradykinin
• These drugs ↓ aldosterone levels and cause hyperkalemia
especially in patients receiving potassium sparing diuretic.
 Adverse Effects
• Hypotension
• Hyperkalemia
 Therapeutic Uses

Hypertension
 RENIN INHIBITOR
• Aliskiren
• It lowers blood pressure about as effectively as ARBs, ACE
inhibitors, and thiazides.
• Aliskiren can cause diarrhea, especially at higher doses, and
can also cause cough and angioedema.
• Aliskiren is contraindicated during pregnancy.
 Central alpha 2 agonists and other centrally acting
drugs
• Clonidine
• Activation of α 2 receptors in CNS causing inhibition of NA
release
• ↓ cardiac output and peripheral resistance
•
• Effective in management of sever hypertension or renin
dependent hypertension
 Adverse effects
• Dry mouth, bradycardia,
• withdrawal syndrome (tachycardia, ↑BP and headache)
 α methyl dopa
• is an analog of L-dopa and is converted to α-methyldopamine and
α–methylnorepinephrine.
• Alpha-methylnorepinephrine is stored in adrenergic nerve vesicles
and is released by nerve stimulation to interact with postsynaptic
adrenoceptors.
• α-methylnorepinephrine bind more tightly to α2- than to α1-
adrenoceptors. This leads to reduced total peripheral resistance
and a decreased blood pressure.
• The most common side effects of α-methyldopa are sedation and
drowsiness.
• It has been used in hypertensive pregnant patients.
 Hydralazine
• This drug causes direct vasodilation, acting primarily on
arteries and arterioles. This results in a decreased peripheral
resistance.
• Is used to treat moderately severe hypertension.
• It is almost always administered in combination with a β-
blocker, such as propranolol (to balance the reflex tachycardia.
 Minoxidil
• This drug causes dilation of resistance vessels (arterioles) .
• Is administered orally for treatment of severe to malignant
hypertension.
• causes serious sodium and water retention, leading to volume
overload, edema, and congestive heart failure.
• Minoxidil treatment also causes hypertrichosis (the growth of
body hair).
 Reserpine
• Reserpine
• At very low concentration, blocks the transport
of noradrenaline and other amines into synaptic
vesicles by binding to the transport protein.
• Noradrenaline accumulates instead in the
cytoplasm, where it is degraded by MAO.
 Reserpine
• Reserpine also causes depletion of 5-HT and dopamine.
• Reserpine is now only used experimentally, but was at one
time used as an antihypertensive drug
• Its central effects, especially depression, which probably
result from impairment of noradrenergic and 5-HT-mediated
transmission in the brain .
 Guanethidine
• Guanethidine blocks the release of stored norepinephrine as

well as displaces norepinephrine from storage vesicles (thus

producing a transient increase in blood pressure)

 Therapeutic Uses
• Hypertension especially in patients with Psychic depression or

Parkinsonism

• Eye drops in Glaucoma

 Alpha Adrenoceptor Blockers
• Prazosin
• Terazosin
• Doxazosin
 Alpha Adrenoceptor Blockers
• Prazosin was the first α1-selective antagonist

• Prazosin is short-acting

• Similar drugs with longer half-lives (e.g. doxazosin, terazosin)

 Therapeutic Uses:
• Essential hypertension
• Benign Prostatic Hyperplasia (BPH)
• Congestive heart failure
 Adverse Effects
• Severe postural hypotension
• Start by small dose (1mg) at bed time then increase the dose
gradually.
• Flush and nasal congestion
• COP → ↓ RBF → ↓ Urine formation → Fluid retention (Add
Diuretic)
• Failure of ejaculation
• Postural hypotension
 Sodium Nitroprusside
• Sodium nitroprusside is a powerful parenterally administered
vasodilator that is used in treating hypertensive emergencies
as well as severe heart failure
• The action occurs as a result of release of nitric oxide.
 Sodium Nitroprusside
• Nitroprusside metabolism results in cyanide ion production.
Although cyanide toxicity is rare, it can be effectively treated
with an infusion of sodium thiosulfate to produce thiocyanate,
which is less toxic and is eliminated by the kidneys.