Pharmacology Flashcards
State the 2 general MOA of Antiepileptics
1) Decrease membrane excitability by altering Na+ and Ca2+ conductance during action potentials.
2) Enhance effects of inhibitory GABA neurotransmitters.
State the MOA of Phenytoin
Blockade of voltage depedent Na+ channels -> prevents influx of Na+ and action potential
State which of the 1st line anti-epileptics can be used for all types of seizures except absence seizures.
Phenytoin, Carbamazepine
State which of the 1st line anti-epileptics can be used for all types of seizures including absence seizures.
Valproic acid
Lamotrigine (not 1st line but still can use)
State the characteristics of Phenytoin that necessitates dose titration and monitoring
1) Narrow therapeutic range (plasma concentration 40-100 μM)
2) Saturation kinetics and consequent non-linear relationship between dose and plasma concentration
Is Phenytoin teratogenic?
Yes
State MOA of Carbamazepine
Blockade of voltage depedent Na+ channels
State the quirks of Carbamazepine (2)
- Hepatic enzyme (CYP450) inducer, T½ shortens with repeated doses -> accelerates elimination of other drugs
- Pharmacogenomics effects in Stevens Johnson Syndrome/ Toxic Epidermal Necrolysis ((HLA)-B* 1502)
State the MOA of Valproate
- Blockade of voltage dependent Na+ and Ca2+ channels AND
- Inhibits GABA transaminase -> increased GABA
State the potential DDI mechanism of Valproate (applies to other 1st gen ASM also)
- Strongly bound to plasma proteins, displaces other antiepileptics -> increase bioavailability of other antiepileptic
State the dose related side effects of antiepileptics (9)
CNS effects
* Drowsiness, confusion, nystagmus (eyes become non-aligned), ataxia, slurred speech, nausea, unusual behaviour, mental changes, coma
State the non-dose related side effects of antiepileptics (6)
1) Hirsutism,
2) Acne,
3) Gingival hyperplasia (increased growth of gums),
4) Folate deficiency,
5) Osteomalacia (softening of bone),
6) Hypersensitivity reactions (including Stevens Johnson syndrome)
State the MOA of Benzodiazepines
- Enhance inhibitory effects of GABA by binding to allosteric site of GABA receptor and -> increased Cl- influx -> hyperpolarization and decreased neuron firing
What is the reversal agent for Benzodiazepines?
Flumazenil (Benzodiazepine site inhibitor)
State the ADRs of Benzodiazepines/ Phenobarbital (3 main)
1) Acute toxicity/ overdose
o Can cause severe respiratory depression (e.g CV collapse, lung collapse), especially used concurrently with alcohol
o Treatment is by flumazenil, a benzodiazepine site antagonist
2) Side effects during use:
o Drowsiness, confusion, amnesia
o Impaired muscle coordination (impairs manual skills)
3) Tolerance and dependence
o Tolerance depends on frequency of use. Therefore, tolerance develops faster for epilepsy than for use to induce sleep
o Dependence can develop. Withdrawal effects include disturbed sleep, rebound anxiety, tremor and convulsions
o Important to withdraw gradually
o Has abuse potential
State the MOA of Barbiturates
Also potentiate GABAA mediated Cl- currents, but at a site distinct from benzodiazepines -> Flumazenil will not work if overdosed on Phenobarbital
State the indication for Barbiturates in Epilepsy (2)
- Use as a sedative hypnotic has largely been replaced by benzodiazepines due to barbiturates’ tendency to develop tolerance and dependence
- Use as AED mainly for pediatric or neonatal patients (IV loading dose followed by IV or oral maintenance doses) -> highly limited use as AED
State the duration of actions for the different Barbiturates (Long-acting, Short, Ultrashort) and what are their uses
o Long acting (1-2 days) -> Anticonvulsant
E.g Phenobarbital
Preferred so no need to dose so often
o Short (3-8hrs) -> Sedative & Hypnotic
E.g pentobarbital and amobarbital
o Ultrashort (20 min) -> I.V induction of anesthesia
E.g Thiopental
MOA of Lamotrigine
- Blocks voltage gated sodium channels, inhibits release of glutamate, impedes sustained repetitive neuronal depolarization
State the indications of Lamotrigine (2)
- Indicated for adjunctive or monotherapy treatment of partial seizures and generalised seizures, including tonic clonic seizures
- Monotherapy of typical absence seizures
- Adjunctive or initial AED for Lennox-Gastaut syndrome (severe childhood epilepsy)
MOA of Cafergot
- 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 -> agonist on these receptors)
Which of the antimigraine drugs are indicated for acute treatment?
Cafergot, Sumatriptan
Which of the antimigraine drugs are indicated for prophyalaxis treatment?
Erenumab
ADR of Cafergot (4)
- Common:
o Nausea and vomiting - Rare:
o Hypersensitivity , myocardial infarct, ergotism (vascular ischaemia)
What are the DDI of Cafergot?
- Substrate of CYP3A. Should not be used with other CYP3A inihibitors like macrolide antibiotics -> elevated exposure to ergot toxicity (vasospasm and tissue ischaemia + other vasoconstrictive effects)
- Should NOT be used with other vasoconstrictor agents (including ergot alkaloids, sumatriptan and other 5HT1 agonists).
State the PK characteristics of Cafergot (AD)
- Oral (also rectal).
- Rapidly absorbed (maximum plasma concentrations reached in 1.5-2 hr).
- High plasma protein binding -> stuck in plasma = low absolute bioavailability (2-5%)
MOA of Sumatriptan
- Selective vascular serotonin (5-HT1B and 5-HT1D) receptor agonist -> constricts cerebral vessels +
- Inhibits trigeminal nerve activity and inhibits vasoactive peptides released by trigeminal neurons -> inhibition of nociception (inhibition of central pain amplification)
ADR of Sumatriptan (~12)
- Common
o Dysgeusia (unpleasant taste), transient BP increase, flushing, sensation of cold, pressure, tightness
o Sleepy, tired, dizzy
o Pain or tightness in throat/jaw
o Vertigo - Rare
o Minor disturbances in liver function tests
o Heart attack
o Seretonin syndrome
State the PK characteristics of Sumatriptan (ADM)
- Oral, nasal, IV.
- Rapidly absorbed, low plasma protein binding.
- Eliminated primarily by oxidative metabolism mediated by monoamine oxidase A (MAO).
MOA of Erenumab
- Monoclonal antibody calcitonin gene related peptide (CGRP) inhibitor. Blocks CGRP receptors.
What are the PK characteristics of Erenumab? (Administration, onset of effect, kinetic type)
- Subcutaneous injection (monthly).
- Clinical benefit typically within 3 months. Linear kinetics at therapeutic doses (as CGRP receptor binding is saturated).
ADR of Erenumab (4)
- Hypersensitivity reactions, injection site reactions, constipation, pruritis
