Pharmacology 8: Clotting therapy and Anaesthetics Flashcards
Examples of anticoagulant drugs and when are they used?
warfarin
heparin
tment and prophylaxis of disorders resulting from intravascular clotting- thromboembolisms.
synthesis of what factors related to clotting is promoted by Vit K?
prothrombin (II), VII, IX and X
also proteins C and S
what derivatives competitively antagonise
Vit K?
coumarin derivatives e.g. Warfarin.
how is warfarin therapy reversed?
give parenteral Vit K- slow- pro-coagulant affects re-warfarinisation for 6 weeks
fresh frozen plasma- replace activated clotting factors straight away-fast
ADRs of warfarin?
haemorrhage pupura excessive bruising nausea hepatic dysfunction pancreatitis skin necrosis- more at risk if protein C or S deficient in pregnancy- teratogen
active site of heparin?
pentasaccharide sequence- binds to Antithrombin
what factors does heparin inhibit?
thrombin, Xa (also IXa, XIa and XIIa)
why is heparin given IV/SC?
poor GI absorption- large molecular weight
what is dose of warfarin monitored by?
INR- international normalised ratio
what is dose of heparin monitored by?
APTT- activated partial thromboplastin time
ADRs of heparin?
bleeding
bruising
thrombocytopenia
osteoporosis- if LT administration
how can heparin therapy be reversed?
protamine sulphate- causes dissociation of heparin/antithrombin III complex, and binds irreversibly to heparin. Give it patient actively bleeding.
use of antiplatelet agents?
tment and prophylaxis in patients with vascular disease (mainly arterial) e.g. IHD, cerebrovascular disease.
examples of 2 agents which inhibit thromboxane A2?
aspirin
dipyridamole
actions of thromboxane A2?
platelet aggregation
vasoconstriction
action of dipyridamole?
inhibits platelet phosphodiesterase- increases cAMP which activates PKA and DECREASES intracellular Ca2+ necessary for platelet aggregation.
Positive Ionotrope and vasodilatory (flushes & headaches)
Secondary Prevention of Stroke
how do clopidogrel and ticlopidine inhibit platelets?
platelet ADP receptor antagonists- irreversibly inhibit ADP dependent pathway of platelet activation
why are fibrinolytic drigs which generate plasmin themselves e.g. tPA, described as clot-specific?
work preferentially in the presence of fibrin, in contrast to streptokinase= binds to and activates endogenous plasminogen, producing plasmin by altering its conformation, causes degree of fibrinolytic activity in general circulation.
why can streptokinase NOT be used twice in a patient?
bacterial protein (from beta-haemolytic streptococci) so antigenic, therefore on 1st use it generates blocking antibodies which persist for many yrs in patient, so would cause anaphylaxis if given again.
what might streptokinase cause transiently when being infused?
hypotension
contraindications for starting fibrinolytic tment after MI or PE?
active peptic ulcer recent trauma or surgery history of cerebral haemorrhage or stroke of uncertain aetiology uncontrolled hypertension coagulation defect
when are thrombolytic/fibrinolytic drigs used?
STEMI- but NOT 1st line
massive PE
acute ischaemic stroke- must ensure haemorrhagic stroke eliminated as cause via CT/MRI scan*
symptoms and signs of acute coronary syndrome (unstable angina, STEMI/non-STEMI)?
chest pain dyspnoea nausea sweating palpitations pallor narrow pulse pressure
where is plasminogen produced?
liver
what stimulate tissue plasminogen activator release in body?
endothelial injury
streptokinase t1/2?
15mins
t1/2 of alteplase (recombinat tPA)?
3mins
compare and contrast streptokinase and recombinant tPA for use in thrombolytic therapy e.g. 1st line tment in STEMI
-No significant difference between efficacy
-rtPAs have slightly better survival rates but higher
incidence of intracranial bleeding
-Streptokinase can only be used once (immunogenic)
-rtPAs can be used repeatedly
-rtPAs are easier to administer- rapid IV bolus injection
-rtPAs are expensive
how does tranexamic acid work to stop bleeding induced by thrombolytic therapy?
lysine analogue
binds to lysine binding sites on plasminogen and inhibits binding to fibrin and streptokinase.
what predicts potency for virtually all anaesthetic agents?
lipid solubility- to gain access to their target sites in lipid membranes
which anaesthetics appear to exert their primary pharmacologic action on NMDA receptors?
ketamine and nitrous oxide
NMDA= responsive to glutamate excitatory neurotransmitter, so inhibiton of this.
molecular sites of action of anaesthetics?
inhibitory and excitatory ligand-gated ion channels
how do anaesthetics affect inhibitory ligand-gated ion channels?
increase sensitivity of GABA and glycine activated Cl- iion channnels to hyperpolarise neurones and decrease their excitability.
Propofol- acts on GABA channels