IC4 - Pharmacology Flashcards
What are the first line drugs for newly diagnosed partial and generalised tonic clonic seizures?
Phenytoin, carbamzepine, sodium valproate
What is the mechanism of action of phenytoin and carbamazepime?
Block voltage dependent Na+ channels
Phenytoin and carbamazepine are suitable for all seizures except ______.
Absence seizures
Phenytoin should be avoided in _____.
Pregnancy (teratogenic)
Why does phenytoin requires monitoring and titration?
- Narrow therapeutic range
- Saturation kinetics
- Non linear relationship between dose and plasma concentration
Carbamazepine is a CYP450 _____.
Inducer
Why does carbamazepine quicken elimination of other drugs?
It is a CYP inducer. The T1/2 of other drugs are shortened with repeated doses.
What is the gene that causes Carbamazepine to have effect on Asians with SJS or TEN?
(HLA)-B*1502 allele
What is the MOA of sodium valproate?
Block voltage dependent Na+ and Ca2+ channels and inhibits GABA transaminase to increase GABA
Valproate displaces other antiepileptics due to it _____ affinity with plasma proteins.
high
How does Benzodiazepines exert their effects?
Enhances binding of GABA by acting on GABA(A) receptors Cl- channels and increase influx of Cl- ions leading to hyperpolarization. Therefore, neurons cannot fire.
What is an example of benzodiazepine?
Diazepam
How is benzodiapine overdose treated?
Flumazenil (benzodiazepine antagonist)
Benzodiazepines can cause acute toxicity such as __________.
severe respiratory depression
Name one barbiturate.
Phenobarbital
How does barbiturate works?
Potentiate GABA(A) mediated Cl- currents at a different site
How is phenobarbital administered?
IV loading followed by IV/oral maintenance dose
Which population group is phenobarbital used in?
Pediatrics or neonatal
Flumazenil is _______ for barbiturate overdose.
not effective
Which group of antiepileptic has a linear dose dependent side effect for depression of CNS?
Barbiturates
Levetiracetam is a _____ derivative?
pyrrolidone
What is Levetiracetam used for?
Adjuctive for Partial Onset seizures, myoclonic, primary generalized tonic clonic seizures
How can Levetiracetam be given?
Oral/ IV
Mr Tan has been diagnosed with Epilepsy at the A&E today due to partial onset seizures What is the drug of choice as monotherapy?
Levetiracetam
How does lamotrigine works?
Block voltage gated sodium channels, inhibit release of glutamate and impedes sustained repetitive neuronal depolarization
What is the indication for lamotrigine and topiramate?
Partial seizures
General seizures including tonic clonic seizures
Monotherapy of lamotrigine is indicated for _________ seizures.
typical absence
Patient A has Lennox-Gastaut syndrome. What can he be given for treatment?
Lamotrigine (adjunctive or initial)
Topiramate (adjunctive)
Lamotrigene half life decreases if co-adminstered _______ and _______.
carbamazepine, phenytoin
____ when given with lamotrigine increases the half life of lamotrigine.
Valproate
What class of drug is topiramate?
Sulfate substituted monosacaride
Topiramate can be given as _____ for migrane in adults.
Prophylaxis
How is topiramate cleared?
Renal
How does cafergot works?
Tonic action on vascular smooth muscles in the external carotid network. Leads to vasoconstriction by stimulating alpha-adrenergic and 5-
HT receptors (especially 5-HT1B and 5-HT1D receptors)
What is the indication of cafergot?
Acute treatment of migraine (given at first symptom of attack)
How can cafergot be administered?
Oral or rectal
Cafergot reaches plasma concentration in ______.
1.5-2 hr
Cafergot has _____ plasma protein binding
high
Cafergot has _____ absolute bioavailability.
low ( 2 to 5%)
Cafergot is a _____ inhbitor.
CYP3A
Why should CYP3A inhibitors such as cafergot not be given together with macrolide antibitoics?
Elevated exposure to ergot toxicity (vasospasm and tissue ischaemia)
______ agents such as ergot alkaloids, sumatriptan and other 5HT1 agonists should not be given to patients on cafergot.
Vasoconstrictor
What are the side effects of cafergot?
N/V
What are the rare side effects of cafergot?
Hypersensitivity, myocardial infarct, ergotism (vascular ischaemia)
How does Sumatriptan works?
Selective vascular serotonin (5-HT1d) receptor agonist.
Selectively constricts the carotid arterial circulation, but does not
alter cerebral blood flow. Inhibits trigeminal nerve activity
What is sumatriptan indicated for?
Acute migraine with or wo aura
How can sumatriptan be administered?
Oral, nasal, IV
How is sumatriptan eliminated?
By oxidative metabolism mediated by
monoamine oxidase A (MAO).
Sumatriptan has _____ plasma protein binding.
low
Who should not be given sumatriptan?
Known hypersensitivity to triptans,
concurrent administration with MAO inhibitors, myocardial infarct
What is the undesirable effects of sumatriptan?
Dysgeusia (unpleasant taste),
transient BP increase, flushing, sensation of cold, pressure, tightness
What are the rare side effects of sumatriptan?
Minor disturbances in liver function
tests
How does Erenumab works?
Block CGRP receptors
What is the clinical indication of erenumab?
Prophylaxis of migraine in adults (at least 4 days per months)
How can erenumab be given?
SC , monthly
What are the side effects of Erenumab?
Hypersensitivity reactions, injection site reactions, constipation, puritis
