ANTICONVULSANTS Flashcards
Define
1) Seizure
2) Fit / Convulsions
3) Epilepsy
1) A seizure is a sudden uncontrolled electrical disturbance that manifests either as motor , sensory or even psychic
2) Fit / convulsion - seizures that manifests as motor activity
3) Epilepsy - when seizure attacks are chronic
Give the classification of anticonvulsants
Hydantoins
Iminostilbenes
Barbiturates
Benzodiazepines
Give two examples of Iminostilbenes
Carbamazepine and Oxcarbazepine
Give the structure of carabmazepine
It is a dibenzazepine - two benzene rings fused to an azepine group
Give the moa of carbamazepine
It is a sodium channel blocker
Sodium channels exist in which three states
Closed (resting)
Open
Inactivated
Sodium chanels are multimeric complexes composed of which subunits
a - has four homologous repeats
b - two auxiliary units
Carbamazepine blocks sodium channels during which state
The inactivated state
Give two aspects of carbamazepine that enable it preferentially inhibit action potentials during seizure and less interfere with ordinary ongoing action potential
Use dependence and Voltage dependence
Explain
1) use dependant blocking action
2) voltage dependant blocking action
Carbamezapine has use dependant blocking action as it effectively blocks high frequency action potentials than low frequency action potentials due to more accumulation of the action potentials during high frequency firing.
They are also voltage dependant as most sodium channels exist in the inactivated state thus alows for more blocking at this voltage
Give and explain advantages of using carbamezapine in seizures
They are both voltage and use dependant thus prevent occurrence of seizures without causing unacceptable neurological impairment
State the effects of carbamezapine and food.
Giving carbamezapine after meals slows its absorption and reduces peak levels thus enables patients to tolerate high doses
State a unique feature in regards to carbamezapine and its metabolism
It is able to induce its own metabolism causing the serum concentrations to fall after a few weeks of trearment.
During the first week a half life of abput 36 hrs is seen but drops to about 8-12hrs in patients receiving continuous treatment
Dose adjusments are thus required during the first weeks of treatment
Carbamezapine is metabolized in which organ and to what metabolite and by which enzyme(s)
Liver
carbamezapine -10,11- epoxide
Mainly CYP3A4 but CYP3A5 and CYP2C8 may assist
Give PK of Carbamezapine
1) Volume of distribution is low at 1L/Kg
2) Plasma binding is ~ 70%
3) Metabolized in the liver by CYP3A4 and able to induce its own metabolism.
5) Only 5% is excreted unchanged
Give the clinucal uses of Carbamezapine , atleast four
1) Treatment of focal seizures
2) Treatment of focal to bilateral tonic clonic seizures
3) Trigeminal and glossopharyngeal neuralgia
5) Mania in bipolar disorder
6) Treatment of GTCS but should be used with caution as it may exacerbate absence and myoclonuc seizures
Give AEs of Carbamezapine
1) Diplopia - occurs first and may last less than an hour
2) Ataxia
3) Blurred vision
4) Git discomfort
5) Sedation at high doses
6) Benign leukopenia
7) SJS - especially wuth persons having HLA-B*1502 allele
8) Rash and hyponatremia - most common cause for dicontinuation
Gice the C/I of Carbamezapine
Absence seizures as it may cause increase in seizures
Give the structure of Oxcarbazepine
It is a 10 keto analogue of Carbamezapine
Oxcarbazepine results in an epoxide metabolite , true or false
False
The metabolites of Oxcarbazepine contribute to its activity and are termed as
Monohydroxy derivatives - MHDs
Oxcarbamezapine MHDs undergo what type of metabolism to give Dihydroxy derivative (DHD)
glucoronide conjugation
Between Carbamezapine and Oxcarbazepine which is less potent
Oxcarbazepine
Eslicarbzepine is a prodrug of
S(+) - licarbazepine a metabolite of Oxcarbazepine
Give the half life of S(+)- licarbazepine following oral administration of Eslicarbzepine
20-24hrs thus OD
Lamotrigine is classified as what in terms of its srructure
Phenyltriazine
Give the MOA of Lamitrogine
Block sodium channels
Lamotrigine is prefeered due to
its high tolerability
The main clinical use of Lamotrigine
Focal seizures
As an A/E instead of sedation Lamotrigine paradoxically causes
insomnia
Although well tolerated give A/ E of Lamotrigine that may occue
Dizziness , Diplopia , SJS , rash
Ethosuximide is primarily used to treat which type of seizures?
Absence seizures
Give the mechanism of action of ethosuximide as a succinimide
It is a T type calcium channel blocker in the thalamocortical neurons.
It can also block other ion channels such as Voltage dependent Na channels and the Ca dependent K channels
Ethosuximide is not protein bound , true or false
True
Give the half-life of ethosuximide.
40 hours . Has low clearance
Give the metabolism of ethosuximide
Metabolised by hydroxylation by CYP3A4 while 20% is excreted unchanged in urine
Give the dosage of ethosuximide
Due to the long half life , the drug can allow for OD but to reduce adverse GI effects it is guven BD or TDS
Give the DDI of ethosuximide and valproic acid
Administration of ethosuximide with valproic acid reduces the clearance due to inhibition of ethosuximide metabolism
Valproic acid was initially used as a
Solvent mixture for other antiseizure drugs
Give the stryctyre of valproic acid
simple branched chain carboxylic acid
Give the MOA od Valproic acid
1) Sodium channel blockade
2) Blocks NMDA receptor ( glutamate receptor)
3) Increases GABA by stimulating Glutamic acid decraboxylase for GABA synthesis and inhibiting GABA transaminase for GABA degradation
Give the effect pf absorption of Valproic acid and food
Absoption is slowed
Give the PK of Valproic acid
1) Rapidly absorbed after oral administration
2) Protein bound
3) 90% protein bound
4) Metabolised by CYP2C9
5) May indrrgo carrier mediated transport into and out of CSF
Give the most common A/ E of valproic acid
GIT symptoms such as nausea, vomiting, abdominal pain , heartburn
Give other A/E of Valproic acid
Sedation , ataxia and tremor
Acute pancreatitis
Rash
Weight hain and stimulation of appetite
What mist be measured in valproic acid use
LFTS due to hepatotoxicity that is increased in children less than 2 and polypharmacy
Use of valproic acid in 1st trimester can lead to
neural tube defects , CVS orofaciaal and digital abnormalities
Cognitive impairment
Valproic acid can lead to hyperammonia that presents as
The hyperammonia is more common in patients with
lethargy
Genetic defects of ammonia metabolism leading to fatal encephalopathy
Valproic acid inhibits metabolism of
phenytoin
phenobarbital
ethosuximide
lorazepam
Valproic acid inhibits metabolism of
phenytoin
phenobarbital
ethosuximide
lorazepam
Valproic acid reduces the clearance of
Lamotrigine
Valproic acid is termed as a broad spectrum antiseizure drug and is used in the treatment of
GTCs
Absence and Myoclonic
partial seizures
Migraine prophylaxis and Bipolar disorder
Give the structure of Topiramate
Substituted monosaccharide
Give the MOA of Topiranate
1) Blocks sodium channels
2) Potentiates / increases the inhibitory effects of GABA
Toxicity with Topiramate
Somnolence , fatigue , parasthesia , nervousness
Urolithiasis
Refuced verbal fluency , Conitive impairment
Acute glaucoma - withdraw drug
Congenital oral cleft formation
Weight loss
Oligohydrosis
Reduced serum bicarbonate due to inhibition of carbonic anhydrase
Give the oxazolidinediones
Trimetthadione
Dimethadione
Paramethadione
Trimethadione was used in the treatment of absence seizudes before introduction of succinimides
True
Give ghe Moa of dimethadione
inhibiton of T type calcium channels
Trimethadione is not protein bound
True
Trimethadione undergoes what type of metabolism
demethylation to dimethadione that has he major anticonvulsant activity
Give the half life of dimethadione
240hrs
Give the A/ E of oxazolidinediones
sedation
day blindness
