Pharmacology

Question 1

MOA of phenytoin

Answer 1

Block voltage-gated Na+ channels

Question 2

Cautions for phenytoin

Answer 2

• Narrow therapeutic range
• Teratogenic

Question 3

MOA of carbamazepine

Answer 3

Block voltage-gated Na+ channels

Question 4

Metabolism of carbamazepine

Answer 4

• Liver metabolism
• CYP inducer
• t1/2 reduces on repeated doses
• Promotes its own degradation

Question 5

Cautions for carbamazepine

Answer 5

SJS / TEN

Question 6

MOA of valproate

Answer 6

• Block voltage-gated Na+ & Ca2+ channels
• Inhibit GABA transaminase

Question 7

Valproate distribution

Answer 7

• Highly bound to plasma proteins
• Can displace plasma protein binding of other AED –> increase toxicity
• Demonstrates saturable protein binding even within therapeutic range

Question 8

MOA of benzodiazepines

Answer 8

• Allosteric regulator for GABA-A receptors on Cl- channels
• Enhances GABA binding and Cl- influx, increasing the inhibitory effect of GABA on postsynaptic neurons

Question 9

Absorption of diazepam

Answer 9

• Onset: 0.5 hours
• Half-life: 43 hours
• Duration of action: 1-3 days

Question 10

Absorption of lorazepam

Answer 10

• Onset: 2 hours
• Half life: 12 hours
• Duration of action: 10-20 hours

Question 11

Cautions for benzediazepines

Answer 11

• Avoid alcohol
• Frequent use builds tolerance
• Gradual withdrawal needed

Question 12

Treatment for benzodiazepine overdose

Answer 12

Flumazenil

Question 13

MOA of barbiturates

Answer 13

Bind to a separare site from benzodiazepines and potentiate GABA-A-mediated Cl- influx

Question 14

Barbiturates duration of action

Answer 14

Long-acting:
- 1-2 days
- anticonvulsants e.g. phenobarbital

Short-acting:
- 3-8 hours
- Sedative & hypnotics e.g. pentobarbital, amobarbitak

Ultrashort-acting:
- 20 mins
- Anesthesia e.g. thiopental

Question 15

PK properties of levetiracetam

Answer 15

• Linear PK
• Route: oral or IV
• High solubility & permeability
• Low intra & interindividual variability

Question 16

MOA of lamotrigine

Answer 16

• Block voltage-gated Na+ channels
• Inhibit glutamate release
• Impede sustained repetitive neuronal depolarization

Question 17

PK of lamotrigine

Answer 17

• Linear
• PO administration
• Shorter half-life in children
• Half-life decreased with carbamazepine & phenytoin, increased with valproate

Question 18

Indication of topiramate

Answer 18

• Monotherapy for partial & generalised seizure (including tonic-clonic)
• Adjunct for lennox-gastaut syndrome
• Prophylaxis of migraine in adults

Question 19

PK of topiramate

Answer 19

• Linear
• Oral administration
• Long half-life
• Primarily eliminated by renal clearance

Question 20

MOA of cafergot

Answer 20

Vasoconstriction of the external carotid network by stimulating alpha-adrenergic and 5HT receptors (1B & 1D)

Question 21

PK of cafergot

Answer 21

• Oral / rectal administration
• Peak concentration in 1.5-2 hours
• High plasma protein binding
• Low bioavailability

Question 22

DDI of cafergot

Answer 22

• Inhibits CYP3A
• Interacts with CYP3A inhibitors (results in ergotism: vasospasm, tissue ischemia)

Question 23

ADR of cafergot

Answer 23

Common:
- Nausea, vomiting

Rare:
- Hypersensi
- Myocardial infarct
- Ergotism

Question 24

Caution for cafergot

Answer 24

Not to be used with other vasoconstrictors e.g. ergot alkaloids, sumatriptan, 5HT1 agonists

Question 25

MOA of sumatriptan

Answer 25

- Selective vascular 5HT1D receptor agonist - Selectively constricts carotid arterial circulation, but does not affect cerebral blood flow - Inhibits trigeminal nerve activity

Question 26

PK of sumatriptan

Answer 26

- Oral / nasal / IV administration - Rapid absorption - Low plasma protein binding - Eliminated by monoamine oxidase A

Question 27

Caution for sumatriptan

Answer 27

Contraindications: - Hypersensi - Concurrent administration with MAO inhibitors - History of MI

Question 28

ADR of sumatriptan

Answer 28

Common: - Dysgeusia (unpleasant taste) - Transient BP rise - Flushing - Sensation of cold - Feeling of pressure, tightness Rare: - LFT derangements

Question 29

MOA of Erenumab

Answer 29

- Inhibits binding of calcitonin gene-related peptide to CGRP receptors which acts as nocireceptive neuropeptides at trigeminal ganglion - Prevents CGRP from causing vasodilation and stimulating trigeminal nerves

Question 30

Indication of erenumab

Answer 30

Migraine prophylaxis in adults with at least 4 days of migraine per month

Question 31

PK of erenumab

Answer 31

- S/C administration mostly - Clinical effect reached in 3 months - Linear PK at standard doses

Question 32

ADR of erenumab

Answer 32

- Hypersensi - Injection site reactions - Pruritus - Constipation

Question 33

DDI of carbamazepine

Answer 33

1A2, 2C, 3A4, UGT inducer

Question 34

DDI of phenytoin

Answer 34

2C, 3A, UGT inducer

Question 35

DDI of phenobarbital

Answer 35

1A, 2A6, 2B, 3A, UGT inducer

Question 36

DDI of levetiracetam

Answer 36

Nil

Question 37

DDI of gabapentin

Answer 37

Nil

Question 38

DDI of pregabalin

Answer 38

Nil

Question 39

DDI of topiramate

Answer 39

Moderate 3A inducer at high dose Weak CYP inhibitor

Question 40

DDI of perampenel

Answer 40

Weak 2B6, 3A4/5 inducer Weak 2C8, UGT inhibitor

Question 41

Absorption of phenytoin

Answer 41

- Slow but complete absorption - Reduced absorption at doses higher than 400 mg - Reduced with enteral feeds (space >2 hours apart)