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PR3153 > CA Pharmacology > Flashcards

CA Pharmacology Flashcards

1
Q

What is the MoA of phenytoin and carbamazepine?

A

Block voltage-dependent Na+ channels → ↓excitability

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2
Q

Phenytoin has a ________ therapeutic range, ________ kinetics, and ____________ PK r/s.
This causes phenytoin to have ____________ clearance, where clearance ________ with ________ concentration

A

Phenytoin has a narrow therapeutic range, saturable kinetics, and non-linear PK r/s (zero order kinetics).
This causes phenytoin to have capacity-limited clearance, where clearance decreases with increasing concentration

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3
Q

Can phenytoin be used in pregnancy?

A

No! Contraindicated!

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4
Q

Phenytoin has ________ bioavailability, and absorption is ________ but _______

A

Phenytoin has high bioavailability (95%), and absorption is complete but slow

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5
Q

Can phenytoin be taken together with enteral feeds? Why or why not?

A

No
↓bioavailability when taken together with enteral feeds (space apart by 2hrs)

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6
Q

True or false?

Taking a lower dose of phenytoin is more effective as compared to taking a higher dose

A

True
Lower bioavailability is observed at high doses >400mg/dose

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7
Q

Does phenytoin require dose adjustment in renal impariment? Why or why not?

A

True
Phenytoin is highly protein bound (90%).
Renal impairment may lead to uremia/ hypoalbuminuria → displace phenytoin and ↓protein binding → ↑free phenytoin and more toxic ADRs

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8
Q

True or false?

Phenytoin dominantly undergoes linear hepatic metabolism

A

False
Though phenytoin does undergo hepatic metabolism (100%), it is non-linear (capacity limited clearance)

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9
Q

Does phenytoin induce or inhibit metabolising enzymes? What enzymes does phenytoin affect?

A

Induce CYP2C9, CYP2C19, CYP3A, UGT

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10
Q

True or false

Carbamazepine is highly protein bound and hepatically eliminated

A

True
75-85% protein binding, 100% hepatic elimination (autoinduction)

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11
Q

Does carbamazepine induce or inhibit metabolising enzymes? What enzymes does phenytoin affect?

A

Induce CYP450, CYP1A2, CYP2C9, CYP2C19, CYP3A, UGT

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12
Q

Carbamazepine undergoes ________. This causes ________ clearance and ________ half-life of carbamazepine with repeated doses → ________ metabolism of other drugs

Maximal effect of the above occurs ________ after initiation.
Hence do not start with desired maintenance dose (risk of dose-dependent SEs), but instead gradually ________ dose over initial few weeks

A

Carbamazepine undergoes autoinduction. This causes increased clearance and shorter half-life of carbamazepine with repeated doses → increases metabolism of other drugs

Maximal effect of the above occurs 2-3 weeks after initiation.
Hence do not start with desired maintenance dose (risk of dose-dependent SEs), but instead gradually increase dose over initial few weeks

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13
Q

What is the MoA of sodium valproate?

A

Block voltage-dependent Na+ and Ca+ channels → ↓excitability
Also inhibits GABA transaminase → ↑GABA → ↑inhibition

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14
Q

HLA alleles associated with carbamazepine are:____________.
These alleles can cause ____ and _____

A

HLA-B1502 and HLA-A3101
Causes SJS and TEN

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15
Q

True or false

Phenytoin, carbamazepine, and sodium valproate can be used in all types of seizures

A

False
Phenytoin and carbamazepine cannot be used in absence seizures.

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16
Q

Sodium valproate experiences ____________. This causes ________ protein binding at ________ concentration.

A

um valproate experiences saturable protein binding. This causes decreased protein binding at increasing concentration.

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17
Q

True or false?

Sodium valproate has ____high/low____ protein binding.

A

High (75-95%)

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18
Q

Does sodium valproate induce or inhibit metabolising enzymes? What enzymes does valproate affect?

A

Inhibit CYP2C9, UGT, epoxide hydrolase

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19
Q

What is the MoA of diazepam?

A

Binding of GABA is ↑by benzodiazepine → ↑binding of GABA on GABA receptors on Cl- channels → Cl- channels open → ↑influx of Cl- ions → hyperpolarization → ↑inhibition

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20
Q

What happens during acute toxicity/ overdose of diazepam? What is used to treat it?

A

SEs: severe respiratory depression, esp when w alcohol
Tx: flumazenil (benzodiazepine antagonist)

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21
Q

True or false?

Diazepam and barbituates are associated with withdrawal symptoms/ tolerance and dependence

A

True

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22
Q

True or false

Benzodiazepines have higher dose-dependent depression of CNS as compared to barbiturates

A

False
Opposite!

Benzodiazepines reaches a peak. Whereas barbiturates just keeps increasing linearly so more dangerous, hence not used often nowadays

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23
Q

Tolerance and dependence occurs due to ______________.
Withdrawal effects involve:____________ (4)
Is important to withdraw ___________

A

Frequency of use
Disturbed sleep, rebound anxiety, tremor, and convulsions
Gradually

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24
Q

Diazepam is a ________ benzodiazepine.

A

Long-acting

Lasts around 1-2 days

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25
Q

What is the MoA of Phenobarbital?

A

Same MoA as benzodiazepines, but at a site distinct from them

Binding of GABA is ↑by benzodiazepine → ↑binding of GABA on GABA receptors on Cl- channels → Cl- channels open → ↑influx of Cl- ions → hyperpolarization → ↑inhibition

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26
Q

True or false?

Indication of diazepam is all seizures?

A

True

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27
Q

What are the indications of phenobarbital?

A
  1. Sedative-hypnotic
  2. AED for paediatric/ neonatal pts (IV loading dose f/b IV/PO maintenance dose)
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28
Q

True or false?

Flumazenil is effective for treating barbiturate overdose

A

False
Flumazenil only blocks benzodiazepine sites, not effective for treating barbiturate overdose

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29
Q

What are the indications of levetiracetam? State which are monotherapy and which are adjunct.

A

Monotherapy: partial onset seizures in newly diagnosed epilepsy
Adjunct: partial onset, myoclonic, and primary generalised tonic-clonic seizures

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30
Q

What is the MoA of lamotrigine?

A

Block voltage-gated Na+ channels → inhibit release of glutamate → prevents sustained repetitive neuronal depolarization

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31
Q

What are the indications of lamotrigine? State which are monotherapy, adjunct, and initial.

A

Adjunct/ monotherapy: partial and generalised seizures
Adjunct/ initial: Lennox-Gastaut syndrome
Monotherapy: typical absence seizures

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32
Q

What are the DDIs of lamotrigine? Which anti-epileptic drug increases or decreases t1/2?

A

↓t1/2: carbamazepine and phenytoin
↑t1/2: valproate

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33
Q

What are the indications of topiramate? State which are monotherapy, adjunct, and prophylaxis.

A

Monotherapy: partial and generalised seizures
Adjunct: Lennox-Gastaut syndrome
Prophylaxis: migraine headaches in adults (not for acute tx!)

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34
Q

True or false?

Topiramate is predominantly cleared renally

A

True

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35
Q

True or false?

Topiramate is a potent inducer of drug-metabolising enzymes

A

False

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36
Q

True or false

All ASM may result in an increase in suicidal ideation and behvaiour. Should discontinue drug when patient experiences/ exhibits such symptoms

A

False!
Risk of stopping ASM is greater than the benefit of discontinuing it to reduce SEs
Close monitoring done instead

37
Q

List 3 antiepileptic drugs

A
  1. Phenytoin
  2. Carbamazepine
  3. Sodium valproate
  4. Diazepam
  5. Phenobarbital
  6. Levetiracetam
  7. Lamotrigine
  8. Topiramate
38
Q

What is the MoA of cafergot?

A

Ergotamine:
Alpha-adrenergic and 5-HT receptors (5-HT1B/1D) agonists on intracranial vessels → vasoconstriction
Inhibit norepinephrine uptake and adrenoreceptors → prolonged vasoconstriction

Caffeine:
Adenosine A1, A2A and A2B receptor antagonists → vasoconstrict cerebral vasculature
May ↑GI absorption of ergotamine by ↑solubility of ergotamine and ↓ gastric pH

39
Q

Cafergot is a combination of ________ and ________

A

Caffeine and ergotamine

40
Q

What is the indication of cafergot?

A

Acute tx of migraine (given at 1st symptom of attack)

41
Q

What are the ADRs of cafergot?

A

Common: N/V, cramps, insomnia, transient lower limb muscle pain
Rare: hypersensitivity, MI, ergotism (vascular ischaemia)

42
Q

Where is cafergot contraindicated in?

A

Pre-existing conditions:
* Stroke/ TIA
* Ischemic coronary artery disease
* Coronary artery vasospasm
* Uncontrolled HTN
* Peripheral vascular disease
* Gastrointestinal ischemia
* Hx of hemiplegic/ basilar migraine

Concomitant use of triptans within 24hrs
Potent CYP3A4 inhibitors (proteases inhibitors, macrolides)

(similar to triptans, vasoconstriction)

43
Q

Fill in the blanks, regarding the PK of cafergot:
Routes: ________
F = _______
_______ absorbed, max plasma concentrations reached in _______
_______ protein bound
CYP_____ __________

A

Routes: Oral, rectal
F = 2-5% (low)
Rapidly absorbed, max plasma concentrations reached in 1.5-2hrs
Highly protein bound
CYP3A4 inhibitor

44
Q

What are the DDIs of cafergot?

A

CYP3A4 inhibitors (causes increased ergot toxicity → vasospasm and tissue ischaemia)
Vasoconstrictor agents: ergot alkaloids, sumatriptan, other 5HT1 agonists

45
Q

True or false?

Triptans have a more potent vasoconstriction effect than ergotamine.

A

False!
Ergotamine and dihydroergotamine have more potent vasoconstriction effect (hit more receptors than triptans), hence its place in practice have been mostly replaced by triptans

46
Q

What is the MoA of sumatriptan?

A

Selective serotonin (5-HT1B and 5-HT1D) receptor agonist →:
* Vasoconstriction of intracranial extracerebral blood vessels
* Inhibition of vasoactive peptide release by trigeminal neurons
* Inhibition of nociception neurotransmission within trigeminocervical complex

↓ neurogenic inflammation/ inhibits trigeminal nerve activity, but does not alter cerebral blood flow)

47
Q

What is the indication of sumatriptan?

A

Acute tx of migraine, should be taken early when pain intensity is mild

48
Q

What are the ADRs of sumatriptan?

A

Common: dysgeusia, chills, pressure, tightness, serotonin syndrome (transient ↑BP, flushing)
Rare: minor disturbances in LFTs

49
Q

Where is sumatriptan contraindicated in?

A

Pre-existing conditions:
* Stroke/ TIA
* Ischemic coronary artery disease
* Coronary artery vasospasm
* Uncontrolled HTN
* Peripheral vascular disease
* Gastrointestinal ischemia
* Hx of hemiplegic/ basilar migraine

Concomitant use of MAOi or within 2w of discontinuation of MAOi therapy
Concomitant use of ergotamine-containing/ ergot-type medication within 24hrs

(similar to ergotamines, vasoconstriction)

50
Q

What are the routes of administration for sumatriptan?

A

Oral, nasal, IV

51
Q

Sumatriptan is eliminated by ________ mediated by ______

A

Oxidative metabolism, MAO

52
Q

True or false?

If sumatriptan is not effective in treating patient’s medication, should change drug class.

A

False
Lack of response to one triptan does not predict response to other triptans -> trial of another triptan

53
Q

True or false?

Triptans can cause recurrence of migraine, and so an additional dose should be taken to alleviate this.

A

True
20-50% of pts experience recurrence of migraine 48hrs after 1st dose → take additional dose of triptan

54
Q

What is the MoA of CGRP mABs?

A

Monoclonal Ab CGRP (receptor) inhibitor → prevent signalling

CGPR: calcitonin gene-related peptide, is a nociceptive neuropeptide at trigeminal ganglion and causes vasodilation → trigger migraine-like headaches

55
Q

List 2 CGRP mABs. State where do they exert their effect on.

A

Block CGRP receptor on trigeminal nerve: erenumab
Block CGRP: eptinezumab, fremanezumab, galcanezumab

56
Q

CGRP stands for:

A

Calcitonin gene-related peptide

57
Q

What is the indication of CGRP mABs?

A

Prophylaxis of migraine in adults

58
Q

What are the ADRs of CGRP mABs?

A

Hypersensitivity, injection site reactions, constipation, nausea, pruritus, raynaud, HTN, joint pain, nasopharyngitis ?

Raynaud: a disorder that causes decreased blood flow to the fingers. In some cases, it also causes less blood flow to the ears, toes, nipples, knees, or nose.

59
Q

Clinical benefits of CGRP mABs can be seen within ________

A

3 months, but note that long-term partial blockade effect is unknown

60
Q

What is the route of administration of CGRP mABs? How often is the dosing frequency?

A

SC, monthly

61
Q

Erenumab has ________ kinetrics at therapeutic doses, as CGRP receptor binding is ______

A

Linear, saturated

62
Q

What is the MoA of NSAIDs?

A

Inhibit prostaglandin synthesis → prevent neurologically mediated inflammation in the trigeminovascular system

63
Q

What is the indication of NSAIDs?

A

Mild to moderate migraine attacks

64
Q

What are the ADRs of NSAIDs? When should NSAIDs be used with caution/ avoided?

A

GI discomfort (dyspepsia, N/V, diarrhoea), CNS (somnolence, dizziness)
Caution/ avoid: prev PUD, renal disease, severe cardiovascular disease, hypersensitivity to aspirin

65
Q

What are some CNS dose-dependent common adverse effects of ASMs?

A

Headache, drowsiness, fatigue, dizziness, confusion, nystagmus, ataxia, visual disturbances, mental changes

can anyhow whack and be correct ~ ML

66
Q

What are some GI dose-dependent common adverse effects of ASMs?

A

N/V

can anyhow whack and be correct ~ ML

67
Q

What are some psychiatric & cognitive dose-dependent common adverse effects of ASMs?

A

unusual behaviour (behavioural changes), slurred speech

can anyhow whack and be correct ~ ML

68
Q

What are some strategies to mitigate ASM dose-dependent A/E?

  • Initiate at ____ dose and slowly ____ dose
  • Avoid ____ ____ ____
  • Restrict therapy to ____ drug only
  • Administer largest dose at ____ (for bothersome symptoms)
  • Give in ____ ____
  • ____ ____ formulations
  • Reduce ____ ____ dose
A
  • Initiate at low dose and slowly uptitrate dose
  • Avoid large dosage changes
  • Restrict therapy to one drug only
  • Administer largest dose at bedtime (for bothersome symptoms)
  • Give in divided doses
  • Sustained release formulations
  • Reduce total daily dose
69
Q

What are some idiocyncratic adverse effects of ASM?

A
  • Blood dyscrasia (aplastic anaemia, agranulocytosis),
  • Hepatotoxicity (1st Gen ASMs)
  • Pancreatitis (SV)
  • Lupus-like rxn
  • Exfoliative dermatitis
  • Hypersensitivity (SJS, TEN), rash
70
Q

What PGx testing can be conducted for CBZ-induced SJS/TEN?

A

HLA-B*1502
if positive: avoid carbamazepine and phenytoin

71
Q

Do you know the lamotrigine dosing guidelines?

If a patient taking valproate is initiated on lamotrigine, how do you uptitrate his dose?

A

Week 1-2: Take 25mg EOD
Week 3-4: Take 25mg OD
Week 5 until maintenance: Increase by 25-50mg per day every 1-2 weeks

Usual Maintenance dose (in 1-2 divided doses):
With Valproate only: 100-200mg OD
With Valproate and other meds (induce glucuronidation): 100-400mg OD

im so sorry

72
Q

Do you know the lamotrigine dosing guidelines?

If a patient is initiated on lamotrigine, how do you uptitrate his dose?

A

Week 1-2: Take 25mg OD
Week 3-4: Take 50mg OD
Week 5 until maintenance: Increase by 50mg per day every 1-2 weeks

Usual Maintenance dose (in 1-2 divided doses):
225-375mg per day

im so sorry

73
Q

Do you know the lamotrigine dosing guidelines?

If a patient taking phenytoin is initiated on lamotrigine, how do you uptitrate his dose?

or carbamazepine/phenobarbital/primidone

A

Week 1-2: Take 50mg OD
Week 3-4: Take 100mg OD (2 divided doses)
Week 5 until maintenance: Increase by 100mg per day every 1-2 weeks

Usual Maintenance dose (in 2 divided doses):
300-500mg per day

im so sorry

74
Q

List at least 3 common ASMs with aromatic rings

A

Carbamazepine, Lamotrigine, Oxcarbazepine, Phenytoin, Phenobarbital

75
Q

What component of aromatic ASMs causes immunogenecity through interactions with proteins or cellular macromolecules?

A

Arene-oxide intermediate

76
Q

Which ASM can cause Gingival Hyperplasia?

A

Phenytoin

77
Q

Which ASM can cause Hirsutism?

A

Chronic Phenytoin Therapy

78
Q

Which ASM can cause Alopecia?

A

Valproate

79
Q

Which ASM can cause Peripheral Neuropathy?

A

(long term) Phenytoin, Carbamazepine, Phenobarbitone

can try folate supplementation

80
Q

Which ASM can cause Osteomalacia?** How?**

A

Phenytoin, Carbamazepine, Phenobarbitone

increased Vit D clearance, leading to secondary hypoparathyroidism, increased bone turnover and decreased bone density

81
Q

Which ASM can cause Increased Weight Gain?

A

Valproate

gradually reversible with discontinuation

82
Q

Which ASM can cause Anorexia / Weight Loss?

A

Topiramate / Felbamate

Reversible with discontinuation

83
Q

Which ASM can cause Suicidal Ideation?

A

ALL ASMs.
Just start ASMs though.

84
Q

Which ASM can cause Tolerance/ Dependence?

A

Benzodiazapems / Barbiturates

85
Q

What are the associated withdrawal effects of Benzodiazepams / Barbiturates?

A

Disturbed sleep, rebound anxiety, tremor, convulsions

86
Q

Choose the most appropriate answer regarding gabapentin and pregabalin:
* hepatic/renal elimination
* low/high protein binding
* no/have DDIs

A
  • Renal elimination
  • Low (0%) protein binding
  • No DDIs
87
Q

Choose the most appropriate answer regarding clozabam:
* hepatic/renal elimination
* low/high protein binding
* no/have DDIs

A
  • Renal elimination
  • High (80-90%) protein binding
  • Have DDIs
88
Q

What are the 4 pharmacological classes to look out for DDIs w ASM?

A
  • Antidepressants and antipsychotics
  • Immunosuppressive therapy
  • Antiretroviral therapy
  • Chemotherapeutic agents
89
Q

What is the active component of Carbamazepine?

A

its active metabolite: Carbamazepine-10,11-epoxide (CYP3A4)

PR3153 (10 decks)

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