25 Antiepileptic drugs Flashcards by Emma :)

Q

25.01 SODIUM CHANNEL INHIBITORS

Carbamazepine, oxcarbazepine, phenytoin - actions

A

anticonvulsant
relieves neuropathic pain

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Q

25.01 SODIUM CHANNEL INHIBITORS

Carbamazepine, oxcarbazepine, phenytoin - MOA

A

blocks Na+ channels to inhibit action potential initiation and propagation
use-dependence of block means that action is preferentially on rapidly firing neurons in the epileptic focus

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Q

25.01 SODIUM CHANNEL INHIBITORS

Carbamazepine, oxcarbazepine, phenytoin - abs/distrib/elim

A

these drugs are metabolised by P450 and are potent enzyme inducers, thus associated with many serious drug interactions
phenytoin half-life 20h, but increases with dose due to saturation kinetics
monitoring of plasma concentrations required due to narrow therapeutic range

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Q

25.01 SODIUM CHANNEL INHIBITORS

Carbamazepine, oxcarbazepine, phenytoin - clinical use

A

partial and generalised (tonic-clonic) seizures
also neuropathic pain and bipolar disorder
phenytoin use is decreasing due to poor pharmacokinetic and toxicity profile, although still used in status epilepticus

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Q

25.01 SODIUM CHANNEL INHIBITORS

Carbamazepine, oxcarbazepine, phenytoin - adverse effects

A

drowsiness, dizziness, ataxia, mental disorientation
rare, but serious skin reactions with carbamazepine
phenytoin may cause thickening of the gums and hirsutism

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Q

25.02 T-TYPE CALCIUM CHANNEL BLOCKERS

Ethosuximide - actions

A

anticonvulsant with specific action on absence seizures

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Q

25.02 T-TYPE CALCIUM CHANNEL BLOCKERS

Ethosuximide - MOA

A

blocks T-type Ca2+ channels in thalamic neurons to counteract the slow (3 Hz), spike-and-wave firing pattern thought to be important in absence epilepsy

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Q

25.02 T-TYPE CALCIUM CHANNEL BLOCKERS

Ethosuximide - abs/distrib/elim

A

given orally
oxidised by cytochrome P450 system
half-life 60h

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Q

25.02 T-TYPE CALCIUM CHANNEL BLOCKERS

Ethosuximide - clinical use

A

drug of choice for absence seizures (not effective against partial or tonic-clonic seizures)

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Q

25.02 T-TYPE CALCIUM CHANNEL BLOCKERS

Ethosuximide - adverse effects

A

anorexia, GIT upset, pancytopaenia
rash, drowsiness, fatigue
overdose can cause coma and respiratory depression

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Q

25.03 BROAD-SPECTRUM ANTIEPILEPTIC

Valproate - actions

A

anticonvulsant
mood stabiliser

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Q

25.03 BROAD-SPECTRUM ANTIEPILEPTIC

Valproate - MOA

A

several actions may contribute to the antiepileptic action
blocks voltage-gated Na+ channels to inhibit action potential initiation and propagation
inhibits GABA transaminase to reduce GABA breakdown
may also affect T-type calcium channels

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Q

25.03 BROAD-SPECTRUM ANTIEPILEPTIC

Valproate - abs/distrib/elim

A

given orally
subject to glucuronidation and mitochondrial oxidation
half-life 9-16h

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Q

25.03 BROAD-SPECTRUM ANTIEPILEPTIC

Valproate - clinical use

A

broad coverage of most forms of epilepsy, but appears particularly useful in generalised seizures and absence seizures
manic phase of bipolar disorder
migraine
contraindicated in women of reproductive age due to risk of teratogenicity

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Q

25.03 BROAD-SPECTRUM ANTIEPILEPTIC

Valproate - adverse effects

A

nausea and vomiting
tremor
weight gain
reproductive dysfunction
hepatotoxicity
teratogenic effects (e.g. neural tube defects, including spina bifida)

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Q

25.04 BENZODIAZEPINES

Lorazepam, midazolam, diazepam, clonazepam, clobazam - actions

A

anticonvulsant
also hypnotic and anxiolytic

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Q

25.04 BENZODIAZEPINES

Lorazepam, midazolam, diazepam, clonazepam, clobazam - MOA

A

bind to benzodiazepine binding site on GABAA receptor to enhance channel opening by GABA
increased Cl− permeability reduces electrical excitability
clonazepam and clobazam are said to be more selective anticonvulsants with less sedation

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Q

25.04 BENZODIAZEPINES

Lorazepam, midazolam, diazepam, clonazepam, clobazam - abs/distrib/elim

A

given orally for chronic use (IV for status epilepticus)
if no IV access, IM/buccal midazolam or rectal diazepam
metabolised by P450 system and glucuronide conjugation

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Q

25.04 BENZODIAZEPINES

Lorazepam, midazolam, diazepam, clonazepam, clobazam - clinical use

A

lorazepam, diazepam or clonazepam can be given IV for status epilepticus
oral clonazepam is used for tonic-clonic and absence seizures
clobazam is used as an add-on anticonvulsant to existing therapy

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Q

25.04 BENZODIAZEPINES

Lorazepam, midazolam, diazepam, clonazepam, clobazam - adverse effects

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A

unwanted effect in treating epilepsy is sedation
severe respiratory depression when used IV or in combination with other CNS depressants (e.g. ethanol)

Q

25.05 BARBITURATES

Phenobarbital - actions

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A

anticonvulsant
hypnotic (at higher doses)

Q

25.05 BARBITURATES

Phenobarbital - MOA

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A

binds to barbiturate binding site on GABAA receptor to enhance Cl− channel opening by GABA
this reduces neuronal excitability and action potential frequency at the epileptic focus
effects on Na+ and Ca2+ channels may contribute to the anticonvulsant activity

Q

25.05 BARBITURATES

Phenobarbital - abs/distrib/elim

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A

given orally
some drug is excreted unchanged, but the majority is oxidised in the liver
half-life 50-100h

Q

25.05 BARBITURATES

Phenobarbital - clinical use

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A

tonic-clonic and simple partial seizures, but less frequently used in clinical practice nowadays due to toxicity and unfavourable pharmacokinetics related to liver enzyme induction

25.05 BARBITURATES Phenobarbital - adverse effects

highly sedative megaloblastic anaemia, hypersensitivity reactions in overdose - coma, respiratory and circulatory failure induces dependence

25.06 BROAD-SPECTRUM ANTIEPILEPTIC Gabapentin (similar: pregabalin) - actions

anticonvulsant, analgesic, anxiolytic

25.06 BROAD-SPECTRUM ANTIEPILEPTIC Gabapentin (similar: pregabalin) - MOA

action is attributed to binding to the α2-δ-1 and α2-δ-2 subunits of voltage-activated Ca2+ channels (P/Q or N-type) to block Ca2+ entry and exocytosis of transmitter (glutamate) from nerve endings (enhanced release of GABA has also been suggested)

25.06 BROAD-SPECTRUM ANTIEPILEPTIC Gabapentin (similar: pregabalin) - abs/distrib/elim

given orally excreted unchanged half-life 6h (longer with renal impairment)

25.06 BROAD-SPECTRUM ANTIEPILEPTIC Gabapentin (similar: pregabalin) - clinical use

adjunctive treatment for partial seizures widely used to treat neuropathic pain anxiolytic used in generalised anxiety disorders

25.06 BROAD-SPECTRUM ANTIEPILEPTIC Gabapentin (similar: pregabalin) - adverse effects

sedation, dizziness and unsteadiness both gabapentin and pregabalin have become drugs of abuse because they potentiate the effects of opioids

25.07 BROAD-SPECTRUM ANTIEPILEPTIC Lamotrigine - actions

anticonvulsant reduces frequency of mood episodes in bipolar disorder

25.07 BROAD-SPECTRUM ANTIEPILEPTIC Lamotrigine - MOA

inhibition of glutamate release decreases postsynaptic neuronal excitation this may be due to Na+ (and perhaps Ca2+) channel inhibition in the nerve ending

25.07 BROAD-SPECTRUM ANTIEPILEPTIC Lamotrigine - abs/distrib/elim

given orally subject to hepatic glucuronidation half-life 24-36h

25.07 BROAD-SPECTRUM ANTIEPILEPTIC Lamotrigine - clinical use

broad-spectrum anticonvulsant, covering partial and generalised seizures, including absence bipolar disorder

25.07 BROAD-SPECTRUM ANTIEPILEPTIC Lamotrigine - adverse effects

dizziness, headache, double vision, sedation serious skin rashes may occur in a small percentage of patients, particularly children

25.08 AMPA RECEPTOR BLOCKERS Topiramate (similar: perampanel) - actions

anticonvulsant

25.08 AMPA RECEPTOR BLOCKERS Topiramate (similar: perampanel) - MOA

topiramate most likely blocks AMPA/kainate receptors for glutamate, but also blocks voltage-dependent Na+ channels and potentiates GABA action on GABAA receptors perampanel is a non-competitive blocker of the AMPA receptor on postsynaptic neurons

25.08 AMPA RECEPTOR BLOCKERS Topiramate (similar: perampanel) - abs/distrib/elim

given orally

25.08 AMPA RECEPTOR BLOCKERS Topiramate (similar: perampanel) - clinical use

generalised tonic-clonic and partial seizures (usually as adjuncts) also used for migraine prophylaxis

25.08 AMPA RECEPTOR BLOCKERS Topiramate (similar: perampanel) - adverse effects

psychomotor slowing, motor incoordination, memory impairment, paraesthesia, sedation, fatigue, confusion visual disturbances

25.09 BROAD-SPECTRUM ANTIEPILEPTIC Levetiracetam (similar: brivaracetam) - actions

anticonvulsant

25.09 BROAD-SPECTRUM ANTIEPILEPTIC Levetiracetam (similar: brivaracetam) - MOA

activity is thought to be due to binding to synaptic vesicle protein SV2A - how this modifies the release of neurotransmitter (e.g. glutamate) is not established

25.09 BROAD-SPECTRUM ANTIEPILEPTIC Levetiracetam (similar: brivaracetam) - abs/distrib/elim

given orally or IV mostly excreted unchanged half-life 7h

25.09 BROAD-SPECTRUM ANTIEPILEPTIC Levetiracetam (similar: brivaracetam) - clinical use

broad-spectrum anticonvulsant monotherapy for partial seizures in newly diagnosed epilepsy as an adjunct to other anticonvulsants in the treatment of partial, generalised or myoclonic seizures

25.09 BROAD-SPECTRUM ANTIEPILEPTIC Levetiracetam (similar: brivaracetam) - adverse effects

dizziness, headache, fatigue, sedation few drug interactions

25.10 OTHER ANTIEPILEPTIC AND ANTI-SPASTICITY DRUGS Vigabatrin

irreversible inhibition of GABA transaminase in GABAergic nerves increases the GABA concentration restricted clinical use because vigabatrin causes visual field defects

25.10 OTHER ANTIEPILEPTIC AND ANTI-SPASTICITY DRUGS Tiagabine

inhibits GABA reuptake (by GAT-1) into GABAergic nerve endings and glia, thus raising synaptic GABA concentration and inhibiting neuronal activity adjunct use in partial seizures

25.10 OTHER ANTIEPILEPTIC AND ANTI-SPASTICITY DRUGS Zonisamide, lacosamide

act on Na+ channels mainly used in partial seizures

25.10 OTHER ANTIEPILEPTIC AND ANTI-SPASTICITY DRUGS Baclofen

selective agonist at GABA receptor acts mainly on spinal cord for muscle spasticity from multiple sclerosis or spine trauma not used in epilepsy