IC3a (standard drugs) Flashcards

1
Q

what is the mechanism of action of dipyridamole?

A

adenosine binds to A2 receptor = acitvated = ATP converted to CAMP by AC then to AMP by PDE3. CAMP also reduces calcium ion concentration.

Dipyridamole inhibits reuptake of adenosine, increasing plasma adenosine levels and activation of the A2 receptor.

Dipyridamole inhibits PDE3 reducing CAMP degradation

both lead to increased CAMP levels resulting in decreased ca2+

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2
Q

what is the other effect of dipyridamole

A

will inhibit adenosine reuptake and pde in vascular smooth muscle causing vasodilation.

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3
Q

in view of the effect, what is the other indication for dipyridamole

A

vasodilator properties used to stimulate exercise for myocardial perfusion imaging (induce reflex tachycardia and increase cardiac perfusion)

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4
Q

what is the onset and peak effect of oral dipyridamole

A

onset 20-30min
peak 2-2.5 hours

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5
Q

what is DOA of dipyridamole

A

3 hours

need to be modified release/

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6
Q

ADR dipyridamole and caution

A

headache, hypotension, dizzy, flush, GI distrubance (diarrhoea, N/V)

caution bleeding with other anticoauglants/platelets, esp heparin

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7
Q

c/i of dipyridamole

A

1)hypersx
2) hypotension or severe CAD
- reflex tachycardia = mi, angina, ecg…

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8
Q

ddi of dipyridamole

A

adenosine = increase cardiac adenosine levels

cholinersterase inhibitors (eg donepezil, rivastigmine: aggravate myasthenia gravis

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9
Q

what is the moa of aspirin (description of the drug class also) AND DOSING

A

it is a reversible cox inhibitor with selectivity for cox 1 over cox 2
inhibition of cox 1 = inhibits txa2 production. txa2 promotes platelet aggregation and vasoconstriction. (7-10 days for new platelet to form)

however, cox 2 inhibition inhibits pgi2 formation. pgi2 inhibits platelet aggregation as well.

therefore low dose OD dosing preferred over TDS-QDS to allow cox 2 enzyme synthesis (3-4 hours)
- 75-325mg loading, 40-160mg daily

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10
Q

ADR of aspirin (and reason)

A

upper gi events like gastric ulcer, bleeding due to inhibition of cox1 causing inhibition of production of protective prostaglandin in the stomach.

increased bleeding

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11
Q

c/i and caution for aspirn

A

caution in platelet and bleeding disorders

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12
Q

role of adp in platelet aggregation

A

adp binds to p2y12 receptors on platelet = promote the adp mediated increase in cell surface expression of gp2b-3a receptors = inhibit platelet aggregation via fibrinogen and activation of platelet (for release of agonists)

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13
Q

ddi of aspirin

A

caution bleeidng iwth other antiplatelets and anticoagulants

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14
Q

clopidogrel vs ticagrelor vs prasugrel
- moa and binding
- onset
- reversibility

A

clopidogrel is a product with active metabolite binding irreversibly to the adp binding site of p2y12
- delayed onset 6-8 hours and interindividual variability due to cyp2c19 mediated metabolism
- duration of action 7-10 days (lifetime of platelt)

VS

ticagrelor (not a prodrug) with reversible inhibtion (NOT at the same binding site) to inhibit g protein action and signalling
- faster onset
- recovery depends on serum conc of parent and active metabolite = 2-3days

vs

prasugrel is a prodrug with irreversible inhibition of p2y12
- more ptoent
- depend on 3a4, 2b6 metabolism

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15
Q

adr clopidogrel and ticagrelor

A

bleeding, haemorrhage (esp intracranial)., dyspepsia, rash

bronchospasm, dyspnoea, hypotension (due to p2y12 receptors of lungs and heart)

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16
Q

c/i and caution of clopidogrel

A

1) hypersx
2) active apatholoigical bleeeding

caution: at risk of bleeding, cyp2c19 variants

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17
Q

ddi clopidogrel

A

warfarin, nsaid, salicylates = increase risk of bleeding

macrolide = reduce effect

strong 2c19 inhibitors eg ppi, fluoxetine, ketonazole) = reduce effect (cannot convert to active metabolite)

rifamycin - increase effect

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18
Q

ddi tiacgrelor

A

1) anticoagulants, fibrinolytics, & long-term NSAIDs may ↑bleeding risk

2) Aspirin doses >100 mg/day decrease ticagrelor effect but ↑bleeding risk

3) CYP3A inducers (e.g., dexamethasone, phenytoin, etc) may decrease ticagrelor level and antiplatelet effect

4) CYP3A strong inhibitors (e.g., clarithromycin, ketoconazole, etc) may
↑ticagrelor level and risk of adverse reactions

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19
Q

c.i and caution for ticagrelor

A

c/i hypersx, severe hepatic impairment, breast feeding
c/i hx of intracranial haemorrhage, active pathological bleeding (e.g. PUD)

caution: risk of bleeding, elderly, moderate hepatic failrue

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20
Q

moa of vit k antagonist warfarin

A

acts on all 3 pathways

warfarin inhibits vit k reductase enzyme (vkorc1) that reactivates oxidised vit k (epoxide) to the active form (hydroquinone)

prevents the carboxylation and activation of factor 2, 7, 9, 10. (which also converts active vit k to oxidised inactive form)

21
Q

warfarin onset, time to peak, full therapeutic effect, DOA, absorption speed

A

24-72 hours onset
peak 2-8h oral
full effect 5-7 days
duration 2-5 days
rapid and compleete oral absorption

22
Q

warfarin metabolism, t1/2, polymorphism

A

hepatic, 2c9 primarily
with 20-60 t1/2

polymorphism in 2c9 and vkorc1

23
Q

warfarin excretion

A

urine and faeces

24
Q

warfarin adr

A

haemorrhage/bleeding

hepatitis (increased with >60y, male, on warfarin<1month)

cutaneous necrosis and breast/butt/extremeties infarction (3-5days after initiation, due to reduced blood supply to adipose tissue)

25
c/I warfarin
hypers bleeding: active bleeding, risk of pathological bleeding, after recent major surgery HTN: severe/malignant hypertension renal/hepatic: several renal or hepatic disease infection: severe bacterial endocarditis, pericarditis, pericardial effusion pregnancy (teratogenic) = haemorrahgic disorder of foetus
26
caution warfarin
breastfeeding diverticulitis/colitis mid-mod HTN mid-mod hepatic or renal disease drainage tubes in any orifice
27
ddi warfarin
paracetamol long-term therapy (> 2 weeks) at high doses (> 2g/day) **may increase bleeding** 2c9 inhibitor Numerous drugs (including allopurinol, NSAIDs, salicylates, proton pump inhibitors, metronidazole, etc) **may ↑risk of bleeding** Numerous traditional medicines, herbs, supplements, and foods (including gingko, ginseng, reishi mushrooms, cranberry juice, etc) **may ↑risk of bleeding** Numerous drugs (including barbiturates, rifampin corticosteroids, spironolactone, thiazide diuretics, etc) *- diuretic increase concentration of clotting factors. * *- rest are 2c9 inducers* ** may DECREASE efficacy of warfarin ** Numerous traditional medicines, herbs, and supplements (including supplements containing vitamin K, green tea, vitamin K-rich foods, etc) **may DECREASE efficacy of warfarin**
28
is warfarin used in pregnancy?
does not cross placental, not associated with fatal malformations
29
what are the properties of dabigatran etexilate
prodrug to dabigatran dabigatran and acyl glucuronide metabolites are competitive, reversible non-peptide antagonists of thrombin (2a)
30
what are the properties of rivaroxaban
competitive reversible antagonist of activate factor x (xa)
31
what reverses dabigatran
idarucizumab - humanised monoclonal atb = binds to dabs and metabolites with higher affinity than they have for thrombin. emergency or urgent surgery; life threatening bleeiding
32
what reverses rivaroxaban
andexanet alfa recombinant modified human factor xa decoy protein
33
pk dabigatran (ba, peak, metabolism, t1/2, excretion)
BA: 3-7% peak: 3h metabolism: excreted unchanged t1/2: 12-17 excretion: urine
34
pk Rivaroxaban (ba, peak, metabolism, t1/2, excretion)
BA: 80-100% peak: 2.5-4h metabolism: hepatic t1/2: 5-9h excretion: urine 66, faeces 28
35
ddi dabigatran
↑risk of bleeding: antiplatelets, anticoagulants, fibrinolytics, NSAIDs, ketoconazole DECREASE dabigatran level: rifampin
36
ddi Rivaroxaban
↑risk of bleeding: anitplatelets, anticoagulants, NSAIDs, P-glyco- protein (P-gp) & CYP3A4 inhibitors DECREASE rivaroxaban level: P-gp)& CYP3A4 inducers
37
difference in pk of heparin vs lmwh
BA: 30 vs 86-98 t1/2: 1 vs 4 renal excretion: no vs yes thrombocytopenia risk: <5 vs <1% lmwh preferred due to longer half life, higher BA
38
moa heparin and lmwh
potentiate antithrombin iii through binding + conformational change = inactivate thrombin heparin: 2a, 10a, (9a, 11a, 12a). lmwh: 10a (and lesser extent, 2a)
39
ADR of heparin and lmwh
bleeding epidural /spinal hematoma and paralysis in those receiving epidural/spinal anesthesias/spinal puncture heparin induced thrombocytopenia - bind to pf4 on activated platelet surface = heparin-pf4 complex = ing antibody.
40
what reverses heparin
protamine sulfate IV infusion - highly basic peptide binds to negatively charged heparin neutralising it (only partial in lmwh)
41
heparin and lmwh c/i
hypersx pork products or heparin active major bleeding thrombocytopenia or antiplatelet antibodies
42
caution for heparin / lmwh
elderly, risk of bleeding: prosthetic heart valve, major surgery, regional or lumbar block anaesthesia, blood dyscrasia, recent childbirth, pericarditis, pericardial effusion, renal insufficiency (for lmwh)
43
ddi heparin/lmwh
↑risk of bleeding: anitplatelets, anticoagulants, fibrinolytics, NSAIDs, SSRIs ↑risk of bleeding: with various herbs/foods, including chamomile, fenugreek, garlic, ginger, ginkgo, ginseng.
44
what are r-tpa drugs and special properties
recombinant tissue plasminogen activator drugs ie alteplase. (ends with -teplase) - the drugs have longer plasma t1/2 vs native tPA - bind preferentially to clot associated plasminogen (compared to urokinase, streptokinase)
45
ADR of alteplase
1) BLEEDING: haemorrhage/bleeding 2) CARDIAC: Ventricular arrhythmias, hypotension, oedema 3) EMBOLISM: Cholesterol embolization, venous thromboembolism 4) Hypersensitivity and anaphylaxis
46
reversal agents for alteplase
trenaxamic acid OR aminocaproic acid - compete for binding at lysine on plasminogen and plasmin
47
c/I of alteplase
active bleeding, prior intracranial haemorrhage, recent intracranial/spinal surgery (<3months), serious head injury, stroke
48
caution of alteplase
Caution in patients with major surgery within 10 days, risk of bleeding (e.g., peptic ulcer), cerebrovascular disease, mitral stenosis, atrial fibrillation, acute pericarditis or subacute bacterial endocarditis
49
ddi of alteplase
increase bleeding risk with antiplatelets esp dipyridamole, aspirin) and anticoags (esp warfarin and heparin) decrease alteplase level: nitroglycerin