Review of Pharmacology - 9E (2015)

Review of Pharmacology
N
Istaroxime is an investigational
steroid (in Phase II trials) that acts
by inhibiting Na + - K + - ATPase.
But in addition, it also increases
the entry of Ca 2+ in sarcoplasmic
reticulum. This action may render
the drug less arrhythmogenic
than digoxin.
Contra-indications and interactions
• Hypokalemia, hypomagnesemia and hypercalcemia increases the risk of digitalis
toxicity.
• Diuretics like thiazides and furosemide (cause hypokalemia and hypomagnesemia)
should be used cautiously.
• Quinidine and calcium channel blockers (verapamil, diltiazem) decreases the renal
clearance and thus increases the toxicity by pharmacokinetic mechanisms.
• Antacids, metoclopramide and sulfasalazine decrease the absorption of digitalis
from GIT.
• Digitalis can convert partial AV block to complete block, so should not be used in such
patients.
• Elderly, hypothyroid and patients with renal or hepatic disease are pre-disposed to
digitalis toxicity.
• In thyrotoxicosis and acute myocarditis, the chances of developing digitalis induced
arrhythmias are high.
• It should be used in MI only when it is accompanied by heart failure and atrial
fibrillation.
• Reason for contra-indication in WPW syndrome has been discussed above.
• Digitalis is of no value in patients with HF, sinus rhythm and the following co-existings
conditions; HOCM, myocarditis, mitral stenosis and chronic constrictive pericarditis.
Cardiovascular System
Contraindications of digitalis
Contraindicated
- Carditis (Myocarditis)
In - Increased Ca 2+
(Hypercalcemia)
Weak - WPW Syndrome
H - Hypokalemia
and Hypomagnesemia
E - Elderly
A - AV Block (Partial)
R - Renal failure
(Digoxin)
T - Thyroid (hyper or
hypothyroidism)
D. Inodilators
Drugs in this group include inamrinone (previously known as amrinone), milrinone and
vesnarinone. The name inodilators is obtained from their action as ionotropic agents as well
as their vasodilatory actions. These drugs inhibit the enzyme phosphodiesterase III and thus
increase cAMP in heart and blood vessels. cAMP increases transmembrane influx of Ca ++
in myocardial cells and thus increases contractility whereas it results in the relaxation of
vascular smooth muscle (vasodilation). These drugs are indicated for short term i.v. use in
severe and refractory CHF. Thrombocytopenia is the major adverse effect of inamrinone and
is rare with milrinone (so, latter is preferred). Both of these drugs can result in arrhythmias.
Levosimendan is another agent that sensitizes the myocardium to Ca ++ apart from inhibiting
phosphodiesterase.
Nesiritide is a recombinant
BNP
NESIRITIDE
BNP is particularly valuable in differentiating cardiac from pulmonary causes of dyspnoea.
Nesiritide is a recombinant BNP (brain derived natriuretic peptide, normally secreted by
ventricles). Like ANP, it also increases cGMP and thus causes vasodilation. As the name
suggests, it increases the excretion of sodium through the kidney. It has a short half life and has been
used i.v. for acute CHF associated with dyspnoea at rest. The limiting factor is its breakdown
by the enzyme, neutral endopeptidase (NEP) in the body. Inhibitors of this enzyme (ecadotril)
are being tested for use in CHF.
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