Notesale: Turn your study into money

Document Preview

Extracts from the notes are below, to see the PDF you'll receive please use the links above

---

Drugs acting on CNS

Epilepsy

• It is a condition due to too many brain cells over excited in a given time
• Group of disorder characterized by paroxysmal cerebral dysrhythmia
manifesting as brief episodes of seizures
• Types :
• Generalized – neuronal overactivity widespread
•
•
•
•
•

Generalised tonic clonic seizures (GTCS) – grand mal
Absence seizures – petit mal
Atonic seizures
Myoclonic seiures
Infantile spasms

• Partial – neuronal overactivity in one part of brain
• Simple partial – without loss of consciousness
• Complex partial –with loss of consciousness

Let’s read this scenario
• A 12 year old boy was a known case of epilepsy who is currently
receiving treatment with sodium valproate
...
There he was given Diazepam per rectally which caused
his seizure to be arrested
...
Enhancement of GABA action – Cl- channel opening
• Barbitrates, benzodiazepines – facilitate GABA function
• Gabapentin – GABA analogue
• Vigabatrin, valproate – inhibit GABA breakdown by GAA transaminase

2
...
Inhibition of Ca2+ channel function
• Ethosuximide, trimethadione

Carbamazepine
• MoA
• Chemically related to tricyclic antidepressant ; pharmacologically to phenytoin
• Clinical benefit in treatment of
• Partial seizures
• Mania and manic depression, bipolar disorder
• Trigeminal neuralgias

• Properties of carbamazepine
• Given orally
• It is a strong inducer of hepatic enzymes
• Some metabolites also have antiepileptic properties

• What are the unwanted effects with their use?
•
•
•
•
•

Drowsiness, dizziness and ataxia, vertigo
Severe mental and motor disturbances
Water retention – hyponatraemia
Gastrointestinal and cardiovascular side effects
Bone marrow depression (neutropenia), hypersensitivity (rashes,
photosensitivity, hepatitis)
• Acute intoxication – coma, convulsion, collapse
• Hepatic enzyme induction
• accelerates the metabolism of many drugs – phenytoin, oral contraceptives, warfarin and
corticosteroids

Phenytoin
• MoA
• Stabilization of neuronal membrane – prolong inactive state of Na+ channels
• Prevents repetitive detonation of normal brain cells
• High frequency discharges are reduced

• Properties
• Given orally, >80% plasma protein bound
• Metabolized in liver – excreted as glucoronide
• Variable plasma concentration – use with other drugs affects its plasma protein
binding as well as hepatic clearance
• Complex pharmacology and many side effects has limited its use today

• What are the problems with phenytoin use?
• In therapeutic use
•
•
•
•
•

Gum hypertrophy
Hirsuitism, acne, hypersensitivity reactions
Megaloblastic anemia
Osteomalacia, hyperglycemia
Teratogenesis – fetal hydantoin syndrome

• At high plasma levels
• Cerebellar and vestibular manifestation – ataxia, vertigo, diplopia, nystagmus
• Drowsiness, behavioral alteration, confusion
• Cardiac arrhythmias, hypotension

Valproate
• MoA
• Frequency dependent Na+ channel inactivation
• GABAergic inhibition – by increasing GABA levels and inhibiting catabolism by GABA
transaminase
• Inhibit T type Ca2+ channels

• Properties and uses
• Broad spectrum anticonvulsant action effective in all types of seizures – main se in
generalized seizures
• Also in
• Partial seizures
• Myoclonic and atonic seizures
• Mania and bipolar disorder

• What are the side effects with valproate use?
•
•
•
•
•
•

They have relatively low toxicity
Anorexia, vomiting, heartburn
Alopecia, thinning and curling of the hair
Dose related drowsiness, ataxia, tremors
Serious – hepatotoxicity, hepatitis
Teratogenic – spina bi

---