Antiepileptics ✔️ Flashcards
(108 cards)
1
Q
What are the main mechanisms of action of antiepileptic drugs?
A
• Sodium (Na) channel block
• Calcium (Ca) channel block
• Enhancement of GABA-mediated synaptic inhibition
• Modulation of glutamate levels and NMDA receptor activity
• Cannabidiol (newer mechanism)
2
Q
Which drugs block sodium (Na) channels as their mechanism of action?
A
Phenytoin, carbamazepine, valproate (to a certain degree), and lamotrigine.
3
Q
Which drugs block calcium (Ca) channels?
A
Ethosuximide and pregabalin
4
Q
Which drugs enhance GABA-mediated synaptic inhibition?
A
Benzodiazepines (BZDs), vigabatrin, and tiagabin.
5
Q
Which drugs affect glutamate levels and the NMDA receptor?
A
Lamotrigine and valproate
6
Q
What is a newer antiepileptic drug that acts by a different mechanism than traditional drugs?
A
Cannabidiol
7
Q
How well are most antiseizure drugs absorbed?
A
They are well absorbed, with 80–100% of the dose reaching circulation
8
Q
Do antiseizure drugs bind strongly to plasma proteins?
A
Most do not, except phenytoin and valproic acid.
9
Q
How are most antiseizure drugs cleared from the body?
A
They are mainly cleared by hepatic mechanisms and converted to active metabolites.
10
Q
What is the plasma clearance profile of most antiseizure drugs?
A
Relatively slow; most are medium- to long-acting with some half-lives >12 hours
11
Q
What effect do older antiseizure drugs have on liver enzymes?
A
They are potent inducers of hepatic microsomal enzymes.
12
Q
How do extended-release antiseizure formulations benefit patients?
A
They allow for once- or twice-daily dosing, improving compliance.
13
Q
What are the three functional states of sodium channels?
A
Resting, open, and inactivated.
14
Q
What causes sodium channels to cycle through open and inactivated states?
A
A train of action potentials (AP).
15
Q
When is drug binding strongest in sodium channels?
A
When the channel is in the inactivated state, followed by the open state.
16
Q
What does ‘use-dependence’ mean in sodium channel blockers?
A
The depth of block increases with action potential frequency.
17
Q
Which types of drugs show use-dependence?
A
Antiepileptic and antidysrhythmic drugs.
18
Q
How is phenytoin administered in status epilepticus?
A
Intravenously (I.V)
19
Q
What types of seizures is phenytoin used to treat?
A
• All partial seizures (simple and complex)
• Tonic clonic seizures
• Status epilepticus (I.V)
20
Q
Is phenytoin effective in absence seizures?
A
No, and it may worsen them
21
Q
Despite what issues is phenytoin still widely used?
A
Side-effects and unpredictable pharmacokinetics.
22
Q
What is the mechanism of action of phenytoin?
A
Na⁺ channel block
23
Q
What are the side effects of phenytoin?
A
• Nystagmus
• Ataxia
• Gingival hyperplasia (especially in children)
• Fetal malformations (e.g., cleft palate)
• Teratogenicity
24
Q
Which drug class can competitively inhibit phenytoin’s plasma albumin binding?
A
Salicylates
25
True or False:
Phenytoin and carbamazepine induce hepatic enzymes.
True
26
What is the effect of enzyme induction by phenytoin on other drugs?
Increases metabolism of other antiepileptics, anticoagulants, and oral contraceptives
( hint: seizures, clots, and pregnancy )
27
What is the route of administration for carbamazepine?
Orally
28
How is carbamazepine treatment typically initiated?
With a low dose and gradual build-up to avoid dose-related toxicity.
29
What is the drug of choice for all partial seizures?
Carbamazepine
30
Besides partial seizures, what other seizure type is carbamazepine used to treat?
Tonic-clonic seizures.
31
What are the therapeutic uses of carbamazepine?
• Tonic-clonic seizures
• All partial seizures
32
True or False:
Carbamazepine is one of the most widely used antiepileptic drugs.
True
33
What is the mechanism of action of carbamazepine?
Sodium (Na) channel block
34
What are the side effects of chronic carbamazepine use?
• Stupor
• Coma
• Respiratory depression
• Serious liver toxicity (requires frequent liver tests)
35
True or False:
Liver function tests are necessary during chronic carbamazepine therapy.
True
36
How is valproate administered?
Orally
37
Is the mechanism of action of valproate fully understood?
No, it involves several mechanisms, but is not fully known because antiepileptic activity doesn’t correlate well with blood/tissue levels.
38
What are the known mechanisms of action of valproate?
Block of voltage-gated Na+ channels, block of NMDA receptor-mediated excitation, and GABA potentiation.
39
True or False:
Valproate is effective in many kinds of epilepsy.
True
40
Is valproate effective in some types of infantile epilepsy?
Yes
41
Why is valproate useful in adolescents with both grand and petit mal seizures?
Because it is effective against both types, unlike most antiepileptics.
42
Is valproate effective in myoclonic seizures?
Yes
43
Can valproate be used in absence seizures with generalized tonic-clonic attacks?
Yes
44
Does valproate reduce the incidence and severity of tonic-clonic seizures?
Yes
45
Is valproate used in manic depressive illness and migraine prophylaxis?
Yes
46
What are the major side effects of valproate?
• Ataxia & Tremors
• Liver failure → idiosyncratic but may be fatal (frequent monitoring required when starting the drug)
• Teratogenic (e.g., spina bifida)
47
What are the effects of increased intracellular calcium ([Ca²⁺]i) through Ca channels?
• Neurotransmitter (NM) release
• Phosphorylation/activation of many excitatory channels, receptors, and enzymes
48
What are the subtypes of calcium channels?
L, N, P, R, T subtypes
49
Which calcium channel subtype is involved in absence seizures?
T-type calcium channel
(due to its role in rhythmic discharge in thalamic relay neurons)
50
What is the first choice drug for absence seizures?
Ethosuximide
51
What is the mechanism of action of ethosuximide?
Inhibition of T-type calcium channels
52
What are the side effects of ethosuximide?
• Nausea & Anorexia (MAINLY)
• Leukopenia & Aplastic anemia (in sensitive individuals)
53
What serious adverse effect can ethosuximide cause in susceptible individuals?
It may precipitate tonic-clonic seizures
54
How is GABA-mediated synaptic inhibition improved?
By 3 ways:
• Potentiating GABA effects via GABA-A receptor (e.g. BZDs)
• Inhibiting GABA uptake (e.g. tiagabine)
• Inhibiting GABA transaminase (e.g. vigabatrin)
55
Which drug potentiates the effects of GABA by binding to a modulatory site on the GABA-A receptor?
Benzodiazepines (BZDs)
56
Which drug improves GABA-mediated synaptic inhibition by inhibiting GABA uptake?
Tiagabine
57
Which drug inhibits GABA transaminase to enhance GABA action?
Vigabatrin
58
What is the effect of GABA potentiators on absence seizures?
They worsen absence seizures
59
What are examples of drugs that potentiate GABA-mediated synaptic inhibition?
• Benzodiazepines (BZDs)
• Tiagabine
• Vigabatrin
60
What is the mechanism of action of phenobarbital?
Enhances the activation of GABA-A receptors, facilitating GABA-mediated opening of Cl⁻ channels.
61
What are the therapeutic uses of phenobarbital?
• Simple partial seizures
• Tonic-clonic seizures
(especially if unresponsive to diazepam or phenytoin)
• Recurrent seizures in children, including febrile seizures
(caution: may depress cognitive performance in children)
62
In what case is phenobarbital used for tonic-clonic seizures?
When patients are unresponsive to diazepam or phenytoin
63
How is phenobarbital used in children?
It is used to treat recurrent seizures, including febrile seizures (with caution due to possible cognitive performance depression)
64
Why must caution be taken when using phenobarbital in children?
Because it can depress cognitive performance in children.
65
What are the common side effects of phenobarbital?
• Sedation
• Ataxia
• Nystagmus
• Rebound seizures on discontinuance
66
In which condition is phenobarbital contraindicated?
Porphyria
67
What can happen in phenobarbital overdose?
Coma, respiratory and circulatory failure
68
How commonly is phenobarbital used nowadays?
Rarely used today
69
What is the mechanism of action of benzodiazepines (BZDs)?
Enhance activation of GABA-A receptors, facilitating GABA-mediated opening of Cl⁻ channels.
70
What is diazepam used for in epilepsy?
Status epilepticus (administered I.V. or rectally in acute cases).
71
What are the side effects of BZDs like diazepam?
• Drowsiness
• Ataxia
• Respiratory and cardiac depression (when given I.V., acutely)
72
Why are most benzodiazepines (BZDs) not used for maintenance therapy in epilepsy?
Because they are too sedating
73
Which BZDs are used in chronic epilepsy treatment due to being more anti-epileptic and less sedating?
Clonazepam and clobazam
74
What is a major risk of abruptly stopping clonazepam or clobazam?
Withdrawal syndrome, which can worsen seizures.
75
What is the mechanism of action of vigabatrin?
• Irreversible inhibitor of GABA transaminase (GABA-T)
• May inhibit vesicular GABA transporter
= Leads to sustained increase in extracellular GABA concentration in the brain
76
What are the therapeutic uses of vigabatrin?
• Adjunct therapy in refractory complex partial seizures
• West’s syndrome (infantile spasms)
77
What is the first ‘designer drug’ in epilepsy?
Vigabatrin
78
True or false
Vigabatrin is used in the treatment of West’s syndrome (infantile spasms).
True
79
What are common side effects of Vigabatrin?
• Drowsiness
• Dizziness
• Weight gain
80
What serious side effect is Vigabatrin associated with in infants?
Intramyelinic edema
81
What long-term side effect is associated with Vigabatrin therapy?
Irreversible visual field defects in up to 1/3 of patients
82
Why is Vigabatrin typically reserved for refractory cases (e.g., infantile spasms)?
Due to its risk of serious side effects like visual field defects and intramyelinic edema in infants
83
What is the mechanism of action of Tiagabine?
GABA uptake inhibitor in neurons and glia
84
What does Tiagabine increase in the brain?
Extracellular GABA levels in the forebrain and hippocampus
85
What effect does Tiagabine have on synaptic inhibition?
Potentiates tonic inhibition and prolongs the action of synaptically released GABA
86
Which GABA transporter does Tiagabine preferentially inhibit?
GAT-1 (rather than GAT-2 or GAT-3)
87
What is the therapeutic use of Tiagabine?
Adjunct treatment of partial seizures
88
What are common side effects of Tiagabine?
• Nervousness
• Dizziness
• Tremor & Ataxia
• Excessive confusion
89
What side effect requires discontinuation of Tiagabine?
Excessive confusion or ataxia
90
True or False:
Tiagabine may cause seizures in some patients taking other medications.
True
91
How is Lamotrigine administered?
Orally
92
In which treatment settings can Lamotrigine be used?
As both add-on and monotherapy
93
What is the mechanism of action of Lamotrigine?
• Produces voltage- and use-dependent inactivation of Na⁺ channels
• Decreases synaptic release of glutamate
94
What are the therapeutic uses of Lamotrigine?
• Primary generalised seizures in childhood (including absence and myoclonic seizures)
• Partial seizures
• Manic-depression
95
What are the side effects of Lamotrigine?
• Dizziness, headache, diplopia
• SKIN RASH (hypersensitivity)
96
What precautions and risks are associated with Lamotrigine-induced hypersensitivity skin rash?
• Risk reduced by slow dose introduction
• High risk in pediatric patients (1–2% may develop life-threatening dermatitis)
97
How do gabapentin and pregabalin exert their antiepileptic effect?
(mechanism of action)
• Bind to α2δ subunit on Ca²⁺ channels
• Inhibit the release of neurotransmitters and neuromodulators
• Decrease synaptic release of glutamate
98
What are the side effects of gabapentin?
• Dizziness
• Unsteadiness
• Memory loss
• Viral infections
• Double vision
• Unusual eye movements
99
What are the side effects of pregabalin?
• Dizziness
• Ataxia
• Tremor
• Weight gain
• Edema
• Blurred vision
100
True or false
Gabapentin and pregabalin can be used alone or as add-on therapy.
True
101
What does pregabalin convert into in the body?
Pregabalin turns into gabapentin.
102
What are the therapeutic uses of Gabapentin and Pregabalin?
Used for:
• Partial seizures, with or without secondary generalisation
• Neuropathic pain
103
What is the proposed mechanism by which Gabapentin (GBP) may reduce neuropathic pain, and is it the same as its antiepileptic mechanism?
• The α2δ subunit is found in all VDCCs (voltage dependent calcium channels)
• The α2δ1 subunit forms a complex with presynaptic NMDA receptors (upregulated on PAFs), which may contribute to neuropathic pain
• Gabapentin may reduce neuropathic pain by binding to this α2δ1–NMDA receptor complex
• However, it is still uncertain whether this is the same mechanism responsible for its antiepileptic effect
104
Why is felbamate considered a third-line drug?
Due to its high incidence of aplastic anemia and severe hepatitis.
105
What is the mechanism of action of felbamate?
• Multiple, use-dependent block of NMDA receptors
• Potentiation of GABA-A receptor responses
106
What is cannabidiol approved for in pediatric epilepsy?
Intractable childhood seizures in patients 2 years or older with Dravet syndrome or Lennox-Gastaut syndrome.
107
Why is the mechanism of action (M.O.A) of cannabidiol considered complex?
• CB-1 receptors couple to different G proteins.
• Different ligands (exogenous or endogenous) prefer different signaling pathways.
108
What are some downstream effects of CB-1 receptor activation by cannabidiol?
• Inhibition of adenylyl cyclase (AC)
• Activation of potassium conductance
• Inhibition of calcium conductance
• Overall inhibition of synaptic transmission, possibly via direct or indirect action after CB-1 activation.
