Review of Pharmacology - 9E (2015)

Review of Pharmacology
Ticlopidine, clopidogrel and
pra sugrel act as irreversible
antagonists of P 2
Y 12
receptor of
ADP whereas Ticagrelor and
cangrelor are direct-acting
reversible P 2
Y 12
receptor antagonists..
Feature Abciximab Eptifibatide Tirofiban
Specificity for Gp IIb/IIIa No Yes Yes
Plasma t 1/2
Short (min) Long (2.5 hr) Long (2 hr)
Platelet bound t 1/2
Long (days) Short (s) Short (s)
Renal clearance No Yes Yes
• Cilastazole is a phosphodiesterase-3 inhibitors and results in elevated cAMP levels. It
reduces platelet aggregation and also possess peripheral vasodilatory action. It can
be used for the treatment of intermittent claudication.
• Bleeding is the main problem with all antiplatelet drugs.
• Antiplatelet drugs are used for prophylaxis of MI (aspirin is used most commonly),
cerebrovascular disease and in artificial heart valves (dipyridamole + warfarin is
preferred).
New Antiplatelet Agents
Hematology
• Two groups of newer antiplatelet agents are in advanced stages of development.
• Ticagrelor and cangrelor are direct-acting reversible P 2
Y 12
receptor antagonists.
Ticagrelor is orally effective. As compared to clopidogrel, it produces greater and
more predictable antiplatelet action. It also has more rapid onset and offset of action
as compared to clopidogrel. It is the first new antiplatelet drug to demonstrate
a greater reduction in cardiovascular death than clopidogrel in patients with
acute coronary syndromes. It has recently been approved by FDA. Cangrelor is
intravenous reversible P 2
Y 12
receptor antagonist in late stages of development.
• Vorapaxar is an orally active inhibitor of thrombin receptors on platelets called
protease-activated receptor 1 (PAR-1). It has recently been approved as antiplatelet
drug in patients with history of MI or peripheral artery disease.
COAGULANTS
Vitamin K is involved in the
activation of various clotting
factors (like II, VII, IX and X) as
well as anti-clotting proteins (like
protein C and S)
Main coagulant in the body is vitamin K. It is of three types; K 1
(phytonadione), K 2
(menaquinone) and K 3
(menadione). Vitamin K is involved in the activation of various clotting
factors (like II, VII, IX and X) as well as anti-clotting proteins (like protein C and S). It carries out
the final step in activation of these factors, i.e. gamma carboxylation of glutamate residues.
Main indications of using vitamin K are
• Deficiency states like dietary deficiency, prolonged antimicrobial therapy, liver
disease etc.
• Newborns (because usually they have deficiency of this vitamin).
• Overdose of oral anticoagulants like warfarin.
For most of these indications, vitamin K 1
is used. Menadione (K 3
) is contra-indicated
in patient with G-6-PD deficiency (causes hemolysis) and in newborn (more chances of
kernicterus due to competitive inhibition of glucuronidation of bilirubin and its displacement
from plasma protein binding sites).
Anticoagulants
Three major groups of anticoagulants are used; warfarin group, indirect thrombin inhibitors
(heparin group) and direct thrombin inhibitors. Heparin can be used both in vivo as well as
in vitro.
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