Review of Pharmacology - 9E (2015)

Review of Pharmacology
RENIN INHIBITORS
Aliskiren, remikiren and enalkiren are the drugs that inhibit the enzyme renin. So these drugs
will decrease the activity of RAAS causing fall in blood pressure. These drugs can be used
orally for the treatment of chronic hypertension.
Cardiovascular System
N
Aliskiren, remikiren and enalkiren
are oral renin inhibitors
All ACEI are prodrugs except
captopril and lisinopril.
C - Cough
A - Angioedema
P - Prodrugs (except captopril
and Lisinopril)
T - Taste disturbances
O - Orthostatic hypotension
(when combined with
diuretics)
P - Pregnancy (contraindicated)
R - bilateral Renal artery
stenosis (contra-indicated)
I
- Increased K + (contraindicated)
L - Lower the formation of Ang
II (Mechanism)
ANGIOTENSIN CONVERTING ENZYME INHIBITORS (ACEI)
This group of drugs inhibits the enzyme kininase II or ACE. So, these drugs decrease the
activity of RAAS and also potentiate the vasodilatory action of bradykinin. Because these are
preventing the conversion of angiotensin I to angiotensin II, so these can decrease the action of the
former but not the latter.
• Captopril, enalapril, lisinopril, ramipril, perindopril, trandolapril, fosinopril and moexipril
etc are the compounds in this group.
• Important differences between captopril and other ACEIs is that captopril is less
potent, has fast onset and short duration of action and less absorption in presence of food in
GIT. Because of short and fast action, it can cause postural hypotension which is not
seen with other ACEI.
• All ACEI are prodrugs except captopril and lisinopril. Other drugs like enalapril
are converted to its active metabolite (enalaprilat) and thus are slow acting.
• Enalaprilat is available as a separate drug meant for use in hypertensive emergencies
by i.v. route.
• ACEI are used for the treatment of hypertension, CHF, evolving MI, diabetic nephropathy,
diabetic retinopathy, non-diabetic renal disease and also in scleroderma crisis. These drugs
reduce proteinuria in diabetic as well as non-diabetic renal disease and also prevent
the manifestations of scleroderma crisis which are mediated by angiotensin II.
• Most frequent adverse effect associated with these agents is dry cough. It can be
reduced by iron supplements and asprin. ACEI can also cause angioedema. Both
cough and angioedema is due to elevated levels of bradykinin.
• These can cause hyperkalemia if used along with other agents causing elevation of
serum potassium (like potassium sparing diuretics).
• Other adverse effects include rashes, dysguesia (altered taste sensation), and acute renal
failure (if used in bilateral renal artery stenosis). It is important to distinguish between
acute renal failure and a normal predictable rise in serum creatinine secondary to
ACE inhibitor therapy. An increase in serum creatinine upto 30% within 2-5 days can
be expected in most patients started on ACE inhibitors. It stabilizes in 2-3 weeks and
is reversible on stopping drug therapy. These drugs are contra-indicated in pregnancy
(teratogenic in second half of pregnancy) and when serum creatinine is more than 3.5
mg/dl.
ARBs do not increase bradykinin
and thus have less chances
of causing cough and angioedema
as compared to ACE
inhibitors.
ANGIOTENSIN RECEPTOR BLOCKERS (ARBs)
Losartan, valsartan, irbesartan, candesartan, telmisartan and eprosartan act by antagonizing the
action of angiotensin II at AT 1
receptors. These drugs do not increase bradykinin and thus
have less chances of causing cough and angioedema. ARB act at a distal site, so these will
inhibit the activity of RAAS even when angiotensin II is generated by non-ACE pathway.
Due to this reason, ARB can be combined with ACEI for various indications. Losartan results
in the production of active metabolites in the liver. Losartan is also a competitive antagonist
of TXA 2
and attenuates platelet aggregation. All indications, adverse effects and contraindications
of ACEI also apply to ARB except that incidence of cough and angioedema is less
with ARB.
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