ANTIEPILEPTIC DRUGS

Seizure is associated with the episodic high frequency discharge of impulses by a group of
neurons in the brain.
Seizure may be partial or generalized depending on the location and the spread of the
abnormal neuronal discharge. The attack mainly involves motor, sensory or behavioral
phenomena.
Partial seizures are often associated with damage to the brain, whereas generalized seizure
occurs without obvious cause. Two common forms of generalized seizures are grand mal and
petit mal.
Mechanism of action
Anticonvulsant drugs act by two mechanisms: by reducing electrical excitability of cell
membrane and by enhancing GABA mediated synaptic transmission.
The main drugs used in the treatment of epilepsy are phenytoin, carbamazepine, valproate,
ethosuximide and phenobarbitone.
Phenytoin
It is commonly used antiepileptic drug. It is effective against different forms of partial and
generalized seizures; however it is not effective in absence seizures.
Well absorbed when given orally. It is metabolised by the liver. It is liver enzyme inducer and
therefore, increases the rate of metabolism of other drugs.

Main side effects are sedation, confusion, gum hyperplasia, skin rash, anaemia, nystagmus,
and diplopia.
Carbamazepine
It is derived from tricyclic antidepressant. Its pharmacological action resembles those of
phenytoin, however, it is chiefly effective in the treatment of partial seizure. It is also used in the
treatment of trigeminal neuralgia and manic-depressive illness.
It is powerful inducer of liver microsomal enzymes, thus accelerates the metabolism of
phenytoin, warfarin, oral contraceptives and corticosteroids.
Carbamazepine causes sedation, mental disturbances and water retention.
Valproate
Valproate is chemically unrelated to the other antiepileptic drugs. The mechanism of action is
unknown. It is used in grand mal, partial, petit mal and myoclonic seizure.
Relatively has few side effects, however, it is potentially hepatotoxic. It is non sedating.
Ethosuximide
Has fewer side effects and used in the treatment of absence seizures.
Phenobarbitone
It is well absorbed after oral administration and widely distributed. Renal excretion is enhanced
by acidification of the urine. Phenobarbitone is liver enzyme inducer and hence accelerates the
metabolism of many drugs like oral contraceptives and warfarin.
The clinical use of phenobarbitone is nearly the same as that of phenytoin. The most important
unwanted effect is sedation.
Benzodiazepines: Clonazepam and related compounds, clobazam are claimed to be relatively
selective as antiepileptic drugs. Sedation is the main side effect of these compounds, and an
added problem may be the withdrawal syndrome, which results in an exacerbation of seizures if
the drug is stopped.
MANAGEMENT OF PARKINSONISM
Parkinsonism: Parkinsonism is characterized by a combination of rigidity, bradykinesia, tremor,
and postural instability. It is due to the imbalance between the cholinergic and dopaminergic
influences on the basal ganglia. Thus, the aim of the treatment is either to increase

dopaminergic activity (by dopamine agonist) or to decrease cholinegic (antimuscarinic drugs)
influence on the basal ganglia.
Levodopa
Levodopa, the immediate metabolic precursor of dopamine, does penetrate the blood brain
barrier, where it is decarboxylated to dopamine. Levodopa is rapidly absorbed from the small
intestine. Food will delay the appearance of levodopa in the plasma. It is extensively
metabolized by peripheral dopa decarboxylase, hence given in combination with carbidopa, a
peripheral dopa decarboxylase inhibitor.
When levodopa is given without carbidopa it causes vomiting (which is due to stimulation of
emetic center to dopamine) and CVS disorder (tachycardia, ventricular extrasystoles, atrial
fibrillation and due to increased catecholamine formation peripherally).
Dopamine agonists
The enzymes responsible for synthesizing dopamine are depleted in the brains of Parkinsonism
patients, and drugs acting directly on dopamine receptors may therefore have a beneficial effect
additional to that of levodopa. There are a number of dopamine agonists with antiparkinsonism
activity.
e.g: Bromocryptine
Monoamine Oxidase Inhibitors: Selegiline (deprenyl), a selective inhibitor of monoamine
oxidase B, hinders the breakdown of dopamine; as a result, it prolongs the antiparkinsonism
effect of levodopa. Selegiline has only a minor therapeutic effect on parkinsonism when given
alone. It may reduce disease progression.
Amantadine
Amantadine, an antiviral agent, was by chance found to have antiparkinsonism properties. Its
mode of action in parkinsonism is unclear, but it may potentiate dopaminergic function by
influencing the synthesis, release, or reuptake of dopamine.
Acetylcholine Blocking Drugs (Benztropine, Trihexyphenidyl)
A number of centrally acting antimuscarinic preparations are available that differ in their potency
and in their efficacy in different patients. Treatment is started with a low dose of one of the
drugs in this category, the level of medication gradually being increased until benefit occurs or
adverse effects limit further increments. Antimuscarinic drugs may improve the tremor and
rigidity of Parkinsonism but have little effect on bradykinesia.

Adverse Effects
Antimuscarinic drugs have a number of central nervous system effects, including drowsiness,
mental slowness, inattention, restlessness, and confusion, agitation, delusions, hallucinations,
and mood changes. Other common effects include dryness of the mouth, blurring of vision,
mydriasis, urinary retention, nausea and vomiting, constipation, tachycardia, tachypnea,
increased intraocular pressure, palpitations, and cardiac arrhythmias.
Contraindications: Acetylcholine-blocking drugs should be avoided in patients with prostatic
hyperplasia, obstructive gastrointestinal disease, or angle-closure glaucoma.
ANTIPSYCHOTIC AGENTS
Psychotic illness is characterized by delusion, hallucinations, thought disorder, social
withdrawal and flattering of emotional response. Antipsychotics are a group of drugs used
mainly for treating schizophrenia.
Antipsychotic agents are classified into typical neuroleptics (chlorpromazine, thioridazine,
haloperidol, flupenthixol) and atypical neurolopitics (clozapine, sulpiride).
Most antipsychotic drugs are readily but incompletely absorbed. Many of these drugs undergo
significant first-pass metabolism. Very little of any of these drugs is excreted unchanged, as
they are almost completely metabolized to more polar substances.
The phenothiazine antipsychotic drugs, with chlorpromazine as the prototype, have a wide
variety of central nervous system, autonomic, and endocrine effects. It blocks receptors
including; dopamine and alpha-adrenoceptor, muscarinic, H1 histaminic, and serotonin (5-HT2)
receptors. Of these, the dopamine receptor effects quickly became the major focus of interest.
Clinical uses

• Schizophrenia
• Mania
• Vomiting
  Adverse Reactions
• Extrapyramidal reactions
• Seizures
• Autonomic nervous system effects (antimuscarinic effects, orthostatic hypotension)
• Metabolic and Endocrine Effects (weight gain, hyperprolactinemia, infertility, loss of
  libido and impotence)