Gujarat Forensic Sciences University

YEAR :- 2019-2020
PAPER 1- Pharmacology And Pharmaceutical Analysis.
Assignment Topic :- Drugs of convulsive disorder.

Presented To:- Presented by:-

Miss. Akanksha Mam Ananya karmakar &
Shalini Singh
Forensic Chem. & Toxi.
Specialization
• Seizure:-
 transient episodes associated with abnormal
excessive electrical discharges.
 from CNS neurons.
 due to epilepsy or due to a systemic disorder
like hypoglycemia or hypocalcaemia, or an
intracranial / severe systemic infection.
 Drugs can also induce seizures.
• Epilepsy:-
characterised by recurrent seizures.
 associated with disturbance of consciousness
or characteristic body movement (convulsion).
sometimes autonomic hyperactivity.
Drugs use in treatment of seizure:-

• Anticonvulsants: drugs which are used to abolish

convulsive seizures (antiseizure) and
• Antiepileptic: drugs which are administered
prophylactically to prevent seizures.
 Anti seizure drugs can also classified as:-

• Centrally acting:- e.g. General anaesthetics,

Diazepam, Paraldehyde, Barbiturates and specific
antiepileptics.

• Acting on spinal cord :- e.g. Mephenesin.

• Peripheral skeletal muscle relaxants:-

e.g. d-Tubocurarine and Succinylcholine.
 Commonly used drugs for treatment
of epilepsy:-
Drug Steady Serum half life Dose (mgs/day) Therapeutic
state (hr) plasma conc.
(days) (mgc/ml)

Adult child
Phenytoin sodium 7-8 24 20 100-400 10-20

Phenobarbitone >21 120- 72-96 60-180 10-40

140
Carbamazepine 3-4 12 8 200-1500 4-12

Ethosuximide 7-10 55 30 500-1500 40-100

Valproate 1-4 15 11 500-2000 50-100

 AED (Antiepileptic drugs):-
• act by preventing the generation and spread
of the seizure.
• Drugs for focal-seizure inhibit mainly the
voltage-activated Na+ channels.
• while absence seizure drugs inhibit voltage-
activated Ca++ channels.
• The agents modulating GABA transmission are
effective against partial and tonic- clonic
seizures.
Mechanism of action of AEDS:-
Hydantoin derivatives: DIPHENYLHYDANTOIN
Also called as Phenytoin sodium.
introduced by Merritt and Putnam in 1938.
still an important drug in the treatment of epilepsy
(with exception of absence and myoclonic seizures).
It is structurally related to barbiturates.

Structure of Diphenylhydantoin.
 Pharmacodynamic:-
• Mechanism of action.
• Pharmacological action.
Mechanism of action:-

Na + channel closed

Na + channel active

Na + channel inactive
 Reduction in neuronal Na + concentration causes:
Inhibits the spread of seizure discharges in the brain
and shortens the duration of after discharge.
**High concentrations of Phenytoin also augment
brain level of GABA, 5-HT and homovanillic acid.
This may contribute to its toxicity.
 Pharmacological action:-
• CNS actions:
It exerts a selective anti-epileptic action
without causing drowsiness.
The onset of action is slow even on IV
injection but the action persists for a
considerable time after cessation of therapy.
• Cardiovascular actions:
 cell membrane stabilizing effect on the
myocardium.
 Pharmacokinetics (ADME):-
• Route of administration:-
 Well absorbed when given orally.
 Also available as IV in emergency (50mg/min ).
• Absorption:-
 From guts.
 plasma peak level at 3-12 hours after ingestion.
• Distribution :-
 Vd (70 kg) – 45L
 In plasma, it is 70-95% albumin bound.
 Concentration in cerebrospinal fluid is equal to the
unbound plasma concentration.
• Bioavailability :-
On oral ingestion = 90%
• Metabolism (biotransformation):-

Biotransformation rate is low.

98% done by liver, metabolized mainly by
parahydroxylation in the liver.
drug is concentrated in bile and is reabsorbed from
the intestine as parahydroxyphenol.
**In individuals deficient in the liver parahydroxylase,
toxicity can occur even with small doses.
• Excretion or elimination:-

elimination is exponential and the plasma t½

is about 24 hours.
About 94% of a single dose is excreted in
urine within 48 hours as glucuronide
conjugate.
***On chronic medication, the drug disappears
from the plasma within 3 days after stopping
the treatment because it induces hepatic
microsomal enzymes.