Antiepileptic Drugs Flashcards
Epilepsy definition?
Is a polymorphic chronic disease,
Caused by CNS dysfunction.
Manifested by repeated seizures.
Seizures are result of what?
)Result of the epieptogenic area activity.
#)Neurons of this area - pathologically increased excitability, spread of action potential.
#)Involves some part of the brain or the whole brain.
Types of seizures?
Generalized & Partial
Features of Generalized seizures?
)The whole brain is involved in pathological impulsation.
#)Patient is unconscious.
Features of partial seizures?
)Characterized by the origin of the pathological impulsation.
#)Specific clinical manifestations.
#)Without complete loss of consciousness.
What are the principles of pharmacotherapy of epilepsy?
■ It’s a chronic disease, treated for longtime. (Months-Years)
■ Used orally to prevent seizures & parenterally in case of the status epileptic or tonic-clonic seizures.
■ Necessary to establish an exact form of epilepsy because different forms of it are treated by different drugs.
■ Drug combinations are used to,
- Decrease side effects
- Increase efficiency of treatment
■ Cancellation of drug therapy is possible - in the absence of seizures within 3-4 years.
Antiepileptic drugs (Mechanism of action)
Inhibit a generation of the action potentials in neurons and (or) their spread in the brain by,
1) Influence on the ion channels (Na, K, or Ca).
2) Enhancing of inhibitory (GABA-ergic), or
3) Weakening of excitatory (glutamatergic) processes in the CNS.
What are the 2 groups of antiepileptic drugs?
● Main (first generation) drugs
● Second generation drugs
List out main (primary) antiepileptic drugs?
● phenytoin
● carbamazepine
● valproic acid
● ethosuximide
● clonazepam
● phenobarbital
primidone
● diazepam
trimethadione
acetazomilade
List out second generation drugs.
● Lamotrigine
● gabapentin
● topiramate
vigabatrin
● levetiracetum
tiagabine
zonisamide
clabazam
Reasons for using second generation antiepileptic drugs?
■ Adjuncts to the treatment of epilepsy.
■ Used in case of previous group insufficiency or poor tolerability.
Special features of second generation antiepileptic drugs?
● No need to control a plasma level of drugs, cz they have not recommended a therapeutic range of concentrations.
● Rarely cause changes in the blood formula and the liver.
● The safety of the drugs from the 2nd generation in pregnancy is poorly understood.
What are the types of generalised forms of seizures?
■Tonic-clonic seizures
■Absence seizures
■Myoclonic seizures
■Atonic seizures
What are the features of Tonic-clonic seizure (grand mal) / Drugs used?
》Tonic spasm & clonic jerking.
》Occurs in 30% cases
●carbamazepine
●Phenytoin
●Valproic acid
●Phenobarbital
●Primidone
What are the features of Absence seizure (petit mal) / Drugs used,
》patient freezes, stares at one point
(Eyes are wide open)
》Common in children, Lasts for about 30 seconds. / Occurs in 10% of cases.
●Ethosuximide
●Clonazepam
●Valproic acid
What are the features of Myoclonic seizures / Drugs used,
》Short term muscle contractions of one limb or whole body (seconds)
》Occurs in 4% cases.
● Clonazepam
● Valproic acid
What are the features Atonic seizures? / Drugs used,
》Develops sudden muscle relaxation > patient falls.
》Patients are advised to wear helmets to prevent head injuries.
● Valproic acid
● Lamotrigine
What are features of simple partial seizures/ Drugs used,
》Last 30 secs to 1 min
》Involves a group of muscles
▪︎clonic convulsions of the right
thumb.
》Occurs in 10% cases.
●Phenytoin
●Carbamazepine
●Phenobarbital
●Lamotrigine
●Felbamate
●Primidone
What are the features of complex partial seizures / Drugs used,
》Lasts 30 seconds to 2 minutes.
》Express - meaningless movements like lip licking or wringling hands.
》Impairment of consciousness.
》Occurs in 35% cases.
●Phenytoin
●Carbamazepine
●Lamotrigine
●Phenobarbital
●Valproic acid
●Primidone
What are the features of status epilepticus? Drugs used?
》A series of tonic-clonic seizures > without return of consciousness.
●All drugs administered Intravenously.
▪︎diazepam
▪︎lorazepam
▪︎fosphenytoin
▪︎Phenobarbital sodium
▪︎lidocaine
Or
▪︎general anesthetics (in severe cases only)
About phenytoin & mechanism of action?
● One of the best antiepileptic drugs.
Without a pronounced sedative
action.
● MOA - Blocks Na+ channels of neurons.
Pharmacokinetics of phenytoin?
●Slowly absorbed in the intestine.
●Undergoes intensive metabolism in the liver.
●Penetrates well through the blood-brain barrier and produces high concentrations in the brain.
●It can be given orally or intravenously
in an emergency (status epilepticus).
● Inductor of microsomal enzymes.
Application & side effects of Phenytoin?
App:
●Drug of choice for the prevention of partial and tonic-clonic seizures.
●Status epilepticus can be treated with it or
its prodrug-fosphenytoin.
SE:
●Gingival hyperplasia.
●Depresses the CNS
▪︎sedative or hypnotic effect,
▪︎mental confusion,
▪︎nystagmus,
▪︎ataxia
●causes gastrointestinal disorders. (nausea, vomiting)
●Phenytoin inhibits insulin secretion and causes hyperglycemia and
glycosuria.
●It blocks the action of vitamin B12 which can lead to megaloblastic anemia. ●Phenytoin is a teratogenic drug
(cleft lip, cleft palate, and congenital heart defects).
Carbamazepine,
MOA, pharmacokinetics, clinical applications.
Side effects?
●Has a similar structure to tricyclic antidepressants.
●The mechanism of the action, pharmacokinetics, and clinical applications are similar to phenytoin (except use in status epilepticus). besides,
●Also widely used as a mood stabilizer in the treatment of
the bipolar disorders and is highly effective in the
trigeminal neuralgia.
Side effects,
●CNS and gastrointestinal tract disorders, which are caused
by carbamazepine, are similar to phenytoin.
●This drug can cause the development of coma and respiratory depression in toxic doses.
●Hepatotoxic
(change the activity of the liver enzymes)
●Gematotoxic
(anemia, thrombocytopenia, and leucopenia).
Valproic acid (valproate) & MOA?
●One of the best among the drugs for the treatment of
absence and myoclonic seizures.
●It can also be used in
tonic-clonic and partial seizures.
MOA -
●Increases the GABA level.
●Blocks NMDA-receptors, Na channels and T-type of Ca2+ channels in thalamic neurons.
●This complex action mechanism explains the effectiveness of valproic acid in different forms of epilepsy.
Pharmacokinetics of Valproic acid?
●Well absorbed in the gastrointestinal
tract, intensive (90%) binds with plasma proteins.
●Metabolized in the liver and does not induce microsomal enzymes in the live. but can slow down the metabolism of phenytoin,
carbamazepine,
phenobarbital.
●Metabolites are excreted in the urine.
What are the side effects of Valproic acid?
●Gastrointestinal disorders
(nausea,
vomiting,
heartburn
abdominal pain).
●A rare, but potentially fatal, effect is idiosyncratic hepatotoxicity.
●It develops in the children under 2 years, who receive a combination of antiepileptic drugs.
●Valproic acid possesses teratogenicity (spina bifida).
Phenobarbital MOA & Side effects?
●Applied mainly for the treatment of febrile seizures in the children due to the strong hypnotic action.
MOA,
●Enhances an inhibitory process (stimulates GABA-receptors) and weakens excitatory effects.
●In high concentration,
phenobarbital blocks Na and Ca channels.
Side effects:
●CNS disorders (especially dependence).
Facts about Primidone?
●Converted into phenobarbital & phenylethylmalonamide.
●All three are - anticonvulsant.
MOA - Almost similar to phenytoin.
Side effects - similar to phenobarbital
What benzodiazepines are used for epilepsy?
●Clonazepam
▪︎Effective in treatment of absences.
▪︎Myoclonic seizures.
▪︎Infantile spasms.
●Diazepam & Lorazepam
▪︎Drugs of choice in case of the status epilepticus (IV)
Side effects,
●Cause drowsiness
●Clobazam is least sedative.
●& dependence
Facts Ethosuximide, MOA, Pharmacokinetics, Side effects?
●Used for the treatment of absence.
MOA:
●Blocks Ca channels
(T-type in thalamic neurons).
Pharmacokinetics:
●Has a long half-life (for about 3 days).
Side effects:
●CNS (headache, drowsiness) ●gastrointestinal disorders
(the irritated mucous membrane)
●Often develop;
allergic skin rashes,
leukopenia,
thrombocytopenia,
aplastic anemia are less common.
Lamotrigine MOA & Side effects?
●Blocks Na channels and reduces glutamate release.
●It causese,
dangerous allergic skin reactions, drowsiness,
dizziness,
diplopia,
and nausea.
●Lamotrigine is used for the monotherapy of partial seizures, for the children with absence and myoclonic seizures.
Gabapentin & Pregabalin MOA & Side effects?
●They are structural analogs of GABA. ●They increase its concentration in the CNS,
which modifies the activity of the Ca channels, and, as a result,
reduce the synaptic glutamate excretion.
Application:
●partial and tonic-clonic seizures.
●They are highly effective for the treatment of chronic neuropathic pain (in diabetes and herpes).
Side effects:
●drowsiness,
●headache,
●tremor,
●ataxia.
