Flashcards in CNS Pharmacology 3 Deck (40):
What is epilepsy?
A group of chronic syndromes that involve the recurrence of seizures (limited period of abnormal discharge of cerebral neurons).
What are the 4 main categories of antiseizure drugs?
1. Drugs for tonic-clonic and partial seizures.
2. Drugs for absence seizures.
3. Drugs for myoclonic seizures.
4. Back up and adjunctive drugs.
How are most antiseizure drugs administered?
Orally - they have a good bioavailability.
Mention 2 antiseizure drugs that induce the hepatic metabolism?
Describe briefly the pharmacokinetics of phenytoin.
1. Non linear - elimanation kinetics shifts from first order to zero order at moderate to high dose levels.
2. The drug binds extensively to plasma proteins (97-98%).
What can increase the free phenytoin?
Transient increase occurs by drugs that compete for binding - carbamazepine/ sulfonamides/ valproic acid.
What is fosphenytoin?
A water soluble prodrug form of phenytoin that is used parenterally.
What drug related to carbamazepine is less likely to be involved in drug interactions?
What are the pharmacokinetics of valproic acid?
1. Compete for phenytoin plasma binding protein.
2. Inhibits the metabolism of many drugs.
3. Hepatic biotransformation of valproic acid leads to formation of a toxic metabolite that has been implicated in the hepatotoxicity of the drug.
Mention 5 drugs of which the metabolism is inhibited by valproic acid.
Mention 4 antiseizure drugs that are eliminated by the kidney largely in unchanged form.
Mention 3 antiseizure drugs that undergo both hepatic and renal elimination.
What antiseizure drug is eliminated by hepatic glucuronidation?
What is the general effect of antiseizure drugs?
To suppress repetitive action potentials in epileptic foci in the brain.
What antiseizure drugs block voltage gated Na channels at therapeutic concentrations?
+ Phenobarbital and valproic at high doses.
Mention 6 antiseizure drugs that may facilitate the inhibitory actions of GABA.
6. Valproic acid
What is the mechanism of action of vigabatrin?
Irreversibly inactivate the GABA aminotransferase (GABA-T).
Can valproic acid inhibit GABA-T?
Yes, at very high concentration.
What is the mechanism of action of Tiagabine?
Inhibits a GABA transporter (GAT-1) in neurons and glia prolonging the action of the neurotransmitter.
What is the mechanism of action of gabapentin?
A structural analog of GABA - it does not activate GABA receptors directly.
Mention 4 antiseizure drugs that function via calcium channel blockade.
2. Valproic acid
What is the mechanism of action of ethosuximide?
Inhibits low-threshold (T type) Ca currents, especially in thalamic neurons that act as pacemakers to generate rhythmic cortical discharge.
What drugs do we use in generalized tonic-clonic seizures?
1. Valproic acid
4. Phenobarbital (primarily in infants)
5. Lamotrigine + Topiramate
What drugs do we use in partial seizures?
1. Carbamazepine (oxcarbazepine)
What drugs do we use in absence seizures?
2. Valproic acid
What is the drug of choice for myoclonic seizures?
What drugs do we give in status epilepticus?
1. IV diazepam
3. Phenytoin for prolonged therapy.
What drug is usually used in the management of bipolar affective disorders?
Valproic acid + also carbamazepine and lamotrigine have been used successfully.
What is the drug of choice for trigeminal neuralgia?
What drug do we usually give in pain of neuropathic origin, including postherpetic neuralgia?
Gabapentin (also in migraine, like phenytoin).
What other antiseizure druges are approved for treatment of migraine and neuropathic pain?
Topiramate --> For the treatment of migraine.
Pregabalin --> Approved for neuropathic pain.
What teratogenic effects are associated with antiseizure drugs?
Valproic --> Neural tube defects (spina bifida)
Carbamazepine --> Cause of craniofacial anomalies + spina bifida.
Phenytoin --> Fetal hydantoin syndrome
What is the major problem with overdosage of anticonvulsants?
They are CNS depressants and respiratory depression may occur with OD.
What antiseizure drug can cause fatal hepatotoxicity, especially in children younger than 2 years?
What can lamotrigine cause?
1. Skin rashes
2. Life-threatening Stevens-Johnson syndrome
3. Toxic epidermal necrolysis
What are the 2 main categories of skeletal muscle relaxants?
1. Neuromuscular blockers (nondepolarizing/ depolarizing)
2. Spasmolytics (chronic/ acute use)
What is the structure of most neuromuscular blockers?
Quaternary amines structurally related to acetylcholine (ACh).
What are the two main types of neuromuscular blockers?
1. Most are ANTAGONISTS (nondepolarizing type) - the prototype is tubocurarine.
2. ONE is an AGONIST at the nicotinic end plate receptor (depolarizing type) - succinylcholine.
Describe briefly the pharmacokinetics of nondepolarizing neuromuscular blockers.
1. ALL PARENTERALLY.
2. HIGHLY POLAR - Do not cross BBB.
3. Variable metabolism (plasma cholinesterase/ bile/ kidneys/ liver/ Spontaneous Hofmann elimination).