Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

PR3154 Haematology & Musculoskeletal > Haematology - Pharmacology > Flashcards

Haematology - Pharmacology Flashcards

(66 cards)

Start Studying
1
Q

What are the classes of drugs in haematology?

A

Antiplatelets, Anticoagulants, Fibrinolytics (thrombolytics)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the common antiplatelets?

A

Dipyridamole, Aspirin, Clopidogrel, Ticagrelor, Prasugrel, Ticlopidine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the common anticoagulants?

A

Warfarin, Direct thrombin inhibitors (Dabigatran), Anti-Xa inhibitors (Rivaroxaban, Apixaban, Edoxaban), Heparin (UFH, LMWH)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the common fibrinolytics?

A

r-TPA (Alteplase), Tenecteplase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the MOA of dipyridamole?

A

Inhib adenosine reuptake into inactivated platelets & rbc. Increased plasma adenosine activation of A2 rece on inactivated platelets. Adenosine inhib platelet activation & aggreg.

Additionally inhib PDE-3 in inactivated platelets (which break down cAMP–> AMP). More surviving cAMP to further inhib platelet activation & aggreg/

Inhib of adenosine reuptake & PDE-3 in vascular SM –> vasodil

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the indications for dipyridamole?

A

Adjunct antiplatelet in combi w other antithrombotics.
IV infusion as alt to exercise for myocardial perfusion imaging

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe the PK of dipyridamole.

A

A:
- Onset fast after PO admin (20-30min).
- Peak effect: 2-2.5h

E:
- Duration of action: ~3h (usually a MR preparation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the S/E associated w dipyridamole?

A

Dose limiting vasodilation
Headache
Hypotension
Dizziness
Flushing
GI disturbances
Diarrhoea
NV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the DDI associated w dipyridamole?

A

Increases adenosine
Decreases cholinesterase inhib (may aggrevate myasthenia gravis)
Heparin, and other antithrombotics: Increased bleeding risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the CI w dipyridamole?

A

Hypersensitivity to drug
Hypotension
Severe CAD (induction of acute hypotension, reflex tachycardia, angina pectoris, ECG abnormalities MI)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the MOA of aspirin?

A

Irreversible COX-1 inhib > COX-2 inhib
Inhib of COX-1 in platelets:
- Decrease pdtn of TXA2 which promotes platelet aggreg –> Decreased platelet aggreg
- Takes 7-10d to reverse

Inhib of COX-2 in endothelial cells:
- Decreased pdtn of PGI2 which inhib platelet aggreg –> increased platelet aggreg
- Restoration within 3-4h w clearance of low dose aspirin

Effect dep on ratio of COX-1: COX-2 inhib

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Why is low dose aspirin favoured over high dose aspirin in antiplatelet indications?

A

Low dose aspirin favours inhibition of platelet aggregation by action of COX-1 inhib prevailing over COX-2 inhib of endothelial cell PGI2 pdtn

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe the PK of aspirin.

A

A:
- Clinically sig antiplatelet effect onset: 3-4h
- Max antiplatelet effect onset: 2-3d (cont admin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the S/E associated with aspirin?

A

Upper GI events (ulcer, bleeding): inhib of COX-1 pdtn of PG in stomach, low dose aspirin cardioprotective prop assox w 2-4x increase in UGI

Bleeding (when combi w other antithrombotics)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the DDI associated with aspirin?

A

Other antithrombotics: bleeding risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the special considerations or CI with aspirin?

A

CI in bleeding or platelet disorders

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Describe the MOA of the P2Y12i? (Clopidogrel, Ticagrelor, Prasugrel)

A

Binds to the ADP P2Y12 rece on platelets. Prevents release of ADP from platelets, prevents xp of GpIIb/IIIa rece complex on platelets. Decrease platelet activation and aggregation.

Clopidogrel: irreversible, competitive
Ticagrelor: reversible, non-competitive (recovery 2-3d upon discontinuation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Describe the PK of Clopidogrel vs Ticagrelor

A

M:
- Clopi: CYP2C19 (polymorphism) but most activated by CYP3A4, 2B6, 1A2 > 2C9, 2C19
- Tica: CYP3A4 substrate, P-gp transporter inhib

E:
- Clopi: t1/2 -1.9h, 50% urinary, 46% faecal
- Tica: t1/2 - 7h (tica), 9h(active metabolite), 26% urinary, 58% faecal

Onset:
- Tica faster than clopi

Tmax:
- Clopi: 1h vs Tica: 1.5h(tica), 2.5h(active metabolite)

Time to platelet aggreg SS (no LD):
- Clopi: 5-6d vs Tica: 2d

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the S/E associated w P2Y12i?

A

Common: Epistaxis, gum bleeding, easy bruising, dyspnoea, dizziness, syncope, hypotension, bradycardia, diarrhoea, nausea, cough

Severe: Melena, fresh blood with stools, haemoptysis, haematemesis, haematuria, sudden severe headache, bleeding lasting >15min, ICH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the DDI associated w Clopidogrel?

A

Warfarin, NSAIDs, salicylates: Increased bleeding risk
Strong to moderate CYP2C19 inhib (PPI, fluoxetine, ketoconazole): Decreased antiplatelet effect

CYP3A4 inducers: ASMs, Rifampin
CYP3A4 inhib: itraconazole, fluconazole, ketoconazole, voriconazole, ritonavir, clarithromycin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Describe the transporters and enzyme implications w P2Y12i.

A

Clopi:
- Meta by CYP3A4, 2B6, 1A2 > 2C9, 2C19
- P-gp inhibitor

Tica:
- Meta by CYP3A4
- P-gp inhibitor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the drug disease interaction with ticagrelor?

A

Gout: raises uric acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the DDI associated w Ticagrelor?

A

Antithrombotics, fibrinolytics, long term NSAIDs: Increased bleeding risk

CYP3A inducers
- ASMs, ritonavir

CYP3A inhib
- Itraconazole, ketoconazole, fluconazole, posaconazole, ritonavir, clarithromycin

P-gp substrates
- Digoxin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the special considerations w P2Y12i?

A

PGx
Loss of fn mutation 2/3 alleles for CYP2C19 precludes the use of clopidogrel in ACS as they are assoc w increased risk of MACE. Ticagrelor and prasugrel preferred for those with loss of fn mutation.

Aspirin doses >100mg/day: Decrease ticagrelor effect but increase bleeding risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
What are the CI w P2Y12i?
Severe: Lacation Severe hepatic impairment Hypersensitivity to drug Hx of ICH Active pathological bleeding Caution: Mild-mod hepatic impairment Risk of bleeding Elderly
26
Describe the time to .. for P2Y12i.
Time to recovery: - Clopi: 7-10d - Tica: 2-3d Time to surgery: - Clopi: 5d - Tica: 3d
27
Describe the MOA of warfarin.
Inhib vitamin K reductase (VKORC1). Reduced reactivation of vit K, reduced activation of clotting factor II, VII, IX, X.
28
What are the S/E assoc w warfarin.
Common: Epistaxis, gum bleeding Severe: Melena, fresh blood with stools, haemoptysis, sudden severe headache, bleeding lasting >15min Hepatitis - greatest risk in older males durg early treatment >60y, on warfarin <1mo Cutaneous necrosis (~ 1 in 10 000), infarction of breast, buttocks & extremities - 3-5d after ini treatment Low BMD
29
Describe the PK of warfarin.
A: - PO rapid & complete M: - Hepatically metabolised. S-enantiomer by CYP2C9 (affected by polymorphisms), R-enantiomer by CYP3A4, 1A1, 1A2 E: - t1/2: 20-60h (high inter pt var) - Urine & faeces - 92% renally cleared as metabolites Onset: - Action (PO): 24-72h(lag for endogenous reserves of active vit K depleted) - Time to peak, plasma (PO): 2-8h - Full thera effect: 5-7d Duration of action: 2-5d (long t1/2 of some coag factors)
30
What are the special considerations w Warfarin?
CYP2C9 loss of fn mut, polymorphism: Reduced clearance of warfarin, reduced dosage requirements VKORC1 polymorphism: increased sensitivity to warfarin, reduced dosage requirement CANNOT interchange brands If miss dose and rmb within 6-8h, take missed dose. Otherwise miss the dose and take as per normal the next day. Do not double dose. Look out for illness, particularly if close to next blood draw Keep diet consistent (vit K) Avoid smoking: CYP450 induction Avoid alc: - Binge: CYP450 inhib - Chronic alcoholism: CYP450 indution
31
What are the benefits of genotyping for warfarin initiation?
Faster time to therapeutic range Req fewer dose titration durg first two weeks, fewer follow up Assoc w INR stability in >=70y.o. absence of chronic disease Assoc w INR stability in CHF, DM and target range for INR >=3.0
32
How to predict maintenance dose for warfarin?
BSA, Age, Target INR, race, current thrombosis, amiodarone use, smoking status PGx - Limited use since time lag/turnaround of gene testing, pt already sent home. Beneficial for those req - <=21mg/week or 8mg/day - >=49mg/week or 7mg/day Local maintenance dose: 3-4mg vs Indians/Caucasians: 8-10mg
33
How can the effects of warfarin be reversed?
Fresh Frozen Plasma Prothrombin Complex Concentrates Vit K
34
What are the DDI w warfarin?
Other antithrombotics: Increased bleeding risk CYP2C9 inhib (amiodarone, fluconazole, voriconazole, cotrimoxazole, metronidazole, PPI): Increase warfarin levels, increase bleeding risk - Amiodarone: pre-emptively adjust maintenance dose by 30-50% - In PUD, pre-emptively adjust maintenance dose of warfarin by 35% CYP2C9 inducers (CBZ, PB, rifampin): Decrease warfarin level, therapeutic efficacy Abx: Decreased bacterial pdtn of menadione (vit K), increase warfarin effect. If unadjusted increases INR. Pre-emptively adjust dose of warfarin for bactrim (by 25-50%) and ciprofloxacin (by 20-30%). No adjustment needed macrolides, augmentin, doxycycline. Paracetamol: long term thera (>2 weeks) @ high doses (>2g/day) increased bleeding Traditional meds: gingko biloba, ginseng, reishi mushroom, cranberry - increase risk of bleeding Food - CYP2C9, 3A4 inhib (cranberry juice, pomegranate juice, grapefruit juice, tumeric
35
What are the CI w warfarin?
Hypersensitivity to drug Severe renal or hepatic disease Subacutre bact endocarditis, pericarditis, pericardial effusion Pregnancy Active pathological bleeding, risk of pathological bleeding Severe or malignant HTN After recent major surgery Caution: Breastfeeding Diverticulitis, colitis Mild - mod HTN Mild - mod renal or hepatic disease Drainage tubes in any orifice
36
Describe the MOA of direct thrombin inhibitors (dabigatran).
Competitive reversible non-peptide antagonist of thrombin (factor IIa) Dabigatran etexilate is a prodrug of dabigatran
37
What are the S/E assoc w DTI?
Common: Epistaxis, gum bleeding Severe: Melena, fresh blood with stools, haemoptysis, sudden severe headache, bleeding lasting >15min Dyspepsia, abdo discomfort
38
Describe the PK of DTI.
A: - F 3-7% (v low compared to rivarox) To enhance absorption in small intestine, admin as enteric coated prep M: - Largely xcre unchanged E: - Urine - t1/2: 12-17h Revesal on discontinuation 3-5d Onset: - Rapid - Peak action: 3h
39
What are the special considerations of DTI?
Must control HTN - otherwise high risk of ICH
40
What are the DDI assoc w DTI?
Anticoag, fibrinolytics, antiplatelets: ↑ bleeding risk Long term NSAIDs: ↑ bleeding risk P-gp & CYP3A4 inducers:↓ rivarox levels, ↓ anticoag effect (subtherapeutic) - CBZ, PHT, PB, Valproic acid (1st gen ASMs) - [CI] Rifampin, rifampicin: ↓ dabigatran level by 1/2, anticoag effect - Consider alt PPI: ↓ absorption of dabigatran St John's wort: P-gp/BCRP, CYP3A4 induction. -Shld be avoided Garlic: Mild CYP3A4 inhib Ginger, ginseng: Anticoagulation/antiplatelet Gingko biloba, Green tea: P-gp inhib, anticoagulation/antiplatelet effect
41
What are the CI w DTI?
Active pathological bleeding ICH
42
How can the effects of DTI (dabigatran) be reversed?
Withhold 1-2d if renal fn normal, non life-threatening bleed Idarucizumab - Humanised mab fragment - Binds dabigatran & its acyl glucuronide metabolites w higher affin than binding affin of dabigatran to thrombin - Indicated in reversal for emergency surgery/urgent procedures, lifethreatening or uncontrolled bleeding - Reverses effects in min but cos $2000, only avail in certain hospitals Dialysis - Likely dialysable, highly renal CL dep - Will take time, req catheter
43
Describe the MOA of factor Xa inhibitors?
Direct, competitive, selective reversible antagonist of factor Xa. Inhib conversion of prothrombin to thrombin Inhib conversion of fibrinogen into fibrin --> inhib fibrin clot formation
44
What are the S/E assoc w Xa inhibitors?
* Common: - Nose bleeding - Gum bleeding - Easy bruising - Bleeding from small cuts for 10-15min even w P - Heavier menstrual bleeding - NV - Abdo pain * Rare, but serious: - Hematuria - Hemoptysis - Hematemesis - Melena - Fresh red blood w stools - ICH - Sudden, severe headache - Spinal or epidural hematomas
45
Describe the PK of rivaroxban.
A: - F: 80-100% - Tmax: 2-4h (adult) D: - High protein binding (>90%) M: - Hepatic, CYP3A, 2J2 - 18% CYP3A4 substrate - Substrate of P-gp & BCRP E: - Urine (66%) & faeces (28%) - Active metabolite dep on kidney for CL --> renal impairment some impact on dosing - t1/2: 5-9h Shorter than dabi. Reversal on discontinuation 1-2d Onset: - Rapid - Peak action: 2.5-4h
46
Describe the PK of apixaban.
A: - F: 50% - Tmax: 3-4h D: - High protein binding (87%) M: - Hepatic, CYP3A>CYP1A2, 2C8, 2C9, 2C19, 2J2 - 25% CYP3A4 substrate - Substrate of P-gp & BCRP E: - Renal 25% (unlikely dialysable) - t1/2: 12h (8-15)
47
Which of the DOACs are cleared renally?
Dabigatran (80%), Rivaroxaban (66%), Apixaban (25%) Edoxaban not reliant on either renal or hepatic CL.
48
Which of the DOACs are cleared hepatically?
Dabigatran largely excre unchanged Rivaroxaban, Apixaban (75%) Edoxaban not reliant on either renal of hepatic CL.
49
What are the enzyme/transporter concerns assoc w the DOACs?
Dabigatran: Plasma esterases, P-gp Rivaroxaban: CYP3A4, P-gp, BCRP Apixaban: CYP3A4, P-gp, BCRP Edoxaban: Minimally CYP3A, P-gp
50
What are DDI assoc w Xa inhib?
P-gp & CYP3A4 inhib: ↑ antiXa levels, ↑ bleeding risk Strong: Ketoconazole, Itraconazole, voriconazole, posaconazole, ritonavir - Pre-emptively reduce dose Apix 5mg BD --> 2.5mg BD, 2.5mg BD --> avoid use Weak: Clarithromycin, erythromycin - Consider alt P-gp & CYP3A4 inducer: ↓ antiXa levels, ↑ clotting risk Strong: DVT/PE treatment - X use, SPAF/VTET - no dose adj, monitor - ASM: PHT, CBZ, PB - Rifampicin[CI] : ↓ antiXa level by 1/2, anticoag effect St John's wort: Use w caution Garlic: Mild CYP3A4 inhib Ginger, ginseng: Anticoagulation/antiplatelet Gingko biloba, Green tea: P-gp inhib, anticoagulation/antiplatelet effect
51
What are the CI w Xa inhib?
Active pathological bleeding, PUD, Hepatic disease w coagulopathy, Mod-severe mitral stenosis, mechanical heart valve
52
How can the effects of Xa inhibitors be reversed?
Withhold 1-2d if renal fn normal, non-life threatening bleed Prothrombin complex concentrates - Caution in fluid restriction since low [ ] may req large loading to ensure suff clotting factors admin Andexanet alfa - Recombinant modified human factor Xa decoy protein
53
How can swapping bet DOAC and warfarin for TB pts be done?
- TB agents induce liver fn, takes min 4 weeks for full induction effects - Start at 1.5-2x est maintenance dose of warfarin - Perform LFT, PT, INR - Repeat TCU over first 4-8weeks
54
Describe the MOA of r-TPA.
Recombinant variants of tPA Longer t1/2 than native (endogenous) tPA Advantage > urokinase, streptokinase - Bind preferentially to clot assoc plasminogen, activating plasmin at clot Plasmin mediates fibrinolysis = depolymerise, breakg down fibrin meshwork that stabilises the thrombus Cells & platelets trapped in clot to be slowly released back into bloodstream
55
Describe the MOA of UFH.
* UFH int w AT via the pentasaccharide seq of the drug * Binding triggers a conformational change at the active centre of AT --> accel int w factor Xa * Thereby catalyse inactivation of factor Xa * Req formation of ternary heparin antithrombin-thrombin complex - At least 18 saccharides units
56
Describe the MOA of LMWH
Same as UFH heparin BUT selective blocking of the common pathway (factor Xa & to a lesser xtent IIa) - Less inhib activity than thrombin
57
What are the S/E assoc w heparin?
Haemorrhage (1-5% pts treated w IV heparin) - Anticoag effect disappears within h of discontinuation ↑ risk of epidural or spinal haematoma & paralysis in pts receiving epidural or spinal anaesthesia or spinal puncture Heparin induced thrombocytopenia (HIT) = low platelet count - Heparin binds to platelet factor 4 (PF4) on activated platelet surface - Trigger IgG against heparin-PF4 complex - Lower risk w LMWH (1% vs heparin 5%)
58
Describe the PK of heparin.
A : - F: 86-89% (greater F than heparin) E: - t1/2: 4h - Renal xcre * MW: ~5000 Da Note: Longer t1/2 & higher F favours
59
What are the DDI assoc w heparin.
Antiplatelets, anticoagulants, fibrinolytics: ↑ bleeding risk NSAIDs: ↑ bleeding risk SSRIs: ↑ bleeding risk Var herbs/foods incl chamomile fenugreek, garlic, ginger, ginkgo, ginseng: ↑ bleeding risk
60
How can the effects of heparin be reversed?
Protamine sulfate IV infusion to reverse effects of heparin - 5kDa cationic polypeptide derived from salmon sperm - Highly basic peptide stably binds -vely charged heparin & neutralises anticoag prop of heparin - Only partial reversal for LMWH Andexanet alfa - Off label use for reversal - Recombinant modified human factor Xa decoy protein
61
What are the CI w heparin.
Hypersensitvity to heparins Active major bleeding Thrombocytopenia or presence of antiplatelet Ig Caution: Prosthetic heart valves Elderly Risk of bleeding or hematoma incl major surgery, regional or lumbar block anaesthesia, blood dyscrasias, recent childbirth, pericarditis or pericardial effusion, renal insuff (for LMWH) Pregnancy - UFH & LMWH do not cross placenta & hv not been assoc w fetal malformations
62
What are the S/E assoc w r-TPA?
Haemorrhage Ventricular arrhythmias Hypotension Oedema Cholesterol embolisation VTE Hypersensitivity and anaphylaxis
63
Describe the PK of r-TPA.
DOA: 20-30min
64
What are the DDI assoc w r-TPA?
Antiplatelets (esp dipyridamole, aspirin), anticoagulants (esp warfarin, heparin), fibrinolytics: ↑ bleeding risk Nitroglycerin: may ↓ alteplase level
65
What are the CI w r-TPA?
Active bleeding Prior intracranial haemorrhage Recent (3mo) intracranial or intraspinal surgery Recent srs head injury Recent stroke Caution - Presence of stable clots that cld cause embolism if rapidly fragmented & mobilised - Major surgery within 10d - Risk of bleeding - Cerebrovascular disease - Mitral tenosis - AF - Acute pericarditis - Subacute bact endocarditis
66
How can the effects of r-TPA be reversed?
Tranxemic acid & aminocaproic acid - Compete for lysine binding sites on plasminogen & plasmin - Block int w fibrin

PR3154 Haematology & Musculoskeletal (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions