Anticonvulsants Part 2 (Drugs) Flashcards
Mechanism of action for carbamazepine (Tegretol)
Blocking sodium channels in neurons which blocks propagation of impulses
- inhibition of high-frequency repetitive firing in neurons
- decrease in synaptic transmission (presynaptically)
Tegretol is highly effective for what seizures?
simple and complex partial seizures
Other clinical uses for Tegretol
- Management of bipolar depression
- Management of chronic pain
DENTISTRY: Treatment of trigeminal neuralgia
Adverse drug reactions for Tegretol
- CNS effects
- GI adverse effects
- Hematologic: causes aplastic anemia (wipes out bone marrow)
- Dermatologic: rashes, photosensivity, etc.
- Has potential for inducing serious liver toxicity
- Congestive heart failure, altered blood pressure
- XEROSTOMIA
Drug interactions of Tegretol
“Classic Inducer”
- Decreases effectiveness of warfarin (Coumadin), doxycycline, theophylline (bronchodilator for asthma), oral contraceptives
- erythromycin-type antibiotics (macrolides) increase carbamazepine blood levels (toxicity)
- carbamazepine may increase hepatotoxicity of acetaminophen (Tylenol)
Mechanism of action for phenytoin (Dilantin)
Stabilizes neuronal membranes by decreasing the neuronal membrane passage of sodium ions
- reduces Na influx and Ca passage through membranes
- Interferes with calcium mediated release of neurotransmitters
- Reduces propagation of abnormal impulses in the brain to reduce the frequency of seizures
Dilantin is highly effective for what kind of seizures
- all partial seizures (both simple and complex partial)
- tonic-clonic seizures
- status epilepticus
what is Dilantin not effective against?
Absence seizures (petit mal)
Dental use of Dilantin
trigeminal neuralgia
Adverse effects of Dilantin
Nausea, vomiting
Loss of taste
Megaloblastic anemia - interferes with B12 metabolism
CNS - confusion, drowsiness, dizziness
Dermatologic: rash, hirsuitism
Vitamin D and folate deficiencies = osteoporosis;
- **FIRST symptom of folate deficiency may be oral mucosal ulceration or glossitis
- *Gyngival hyperplasia - overgrowth of connective tissue
Describe more in depth the adverse effect of gingival hyperplasia that Dilantin can have
50-60% of patients taking phenytoin experience GH
- Increased in presence of inflammation
- **Good oral hygiene reduces extent/severity
- Slowly regresses after termination of drug therapy
- May require surgical excision if severe (gingivectomy)
Describe the teratogenic effect of Dilantin
FDA category D
- Fetal syndrome includes cleft lip, cleft palate, congenital heart disease
Describe the drug interactions of Dilantin
Many drug interactions
- phenytoin (Dilantin) causes increases in the metabolism of many drugs
- Cytochrome P450 “Inducer”
Explain the action of GABAmimetic Agents
cause release of GABA from presynaptic interneurons
- encourage GABA fusion with presynaptic neuron
- **Inhibits the release of acetylcholine from the presynaptic neuron
- Many seizures are caused by tremendous release of acetylcholine across synapses in cortex
- GABA = inhibitory neurotransmitter (presynaptically)
Mechanism of action for phenobarbital (Luminal)
reduces Na and K transport along axonal membranes; potentiates the inhibitory effects of GABA-mediated neurons (GABAmimetic)
What is the GENERAL action of Luminal
General depressant to CNS
- Limits the spread of seizure discharge in the brain
What is the most common barbiturate used as an anticonvulsant?
phenobarbital (Luminal sodium)
phenobarbital (Luminal sodium) is indicated for what seizure types?
tonic-clonic
partial seizure types (both)
Most common side effect of phenobarbital (Luminal sodium)
Sedation
- Rarely = skin reactions;**Stomatitis may indicate onset of cutaneous reactions, some of which have been fatal
Describe the drug interactions of phenobarbital (Luminal sodium)
Strong “inducer”
- oral contraceptives, mycins, warfarin
- Enhances the hepatotoxicity of acetaminophen
- Additive CNS effects = all CNS depressants, narcotics, alcohol, antidepressants, BDZs = increased risk for respiratory depression
Which other anticonvulsant is chemically related to phenobarbital?
primidone (Mysoline)
- primidone metabolized in liver to phenobarbital (precursor to phenobarbital)
- Much of its actions come from phenobarbital
primidone (Mysoline) is used to treat what type of seizures?
Partial seizures and tonic-clonic seizures
Mechanism of action for valproates?
causes increased availability of GABA to neurons
- enhances action of or mimics the effects of GABA presynaptically
Valproic acid (Depakene) is used for:
Tonic-clonic seizures
Generalized seizures
- Absence (petit mal)
- Myoclonic
Adverse reactions to Valproates
- GI
- CNS effects
- Hepatotoxicity - not used as often as other drugs; monitor liver function
- Increases bleeding time= inhibition of platelet aggregation
- teratogenic
Drug interactions with Valproates
- macrolide antibiotics (mycins) = inhibit the metabolism of valproic acid
- aspirin and other salicylate displace valproic acid from protein-binding sites, leading to acute toxicity
- additive effect with other CNS depressants
What drug is the first choice in absence seizures
ethosuximide (Zarontin)
CHILDREN!!!
T or F, phenytoin (Dilantin) doesn’t work for absence seizures
True
Side effects of ethosuximide (Zarontin)
- GI
- CNS
- Blood dycrasias
- Hirsutism
- Systemic lupus erythematosus
- *** Oral: gingival hyperplasia; swelling of the tongue
clonazepam (Clonipin) is used for what seizures? What is its mechanism of action?
Used for ALL types of seizures
- Mechanism of action is unknown
What is the drug of choice for local anesthetic induced seizures in dental office
diazepam (Valium)
Describe mechanism of action of gabapentin (Neurontin)
Mechanism is unknown…
- Structurally related to GABA, but does not interact with GABA receptors
gabapentin (neurontin) is used for what seizures
Partial seizures
tonic-clonic
**Also used for chronic pain; post-herpetic neuralgia (shingles)
Main side effect of gabapentin (Neurontin)
Oral mucositis
- Many side effects
What is the major advantage of gabapentin (Neurontin)
Drug is NOT metabolized
- because it does not affect liver microsomal enzymes, lacks significant drug interactions
lamotrigine (Lamictal) is used for what type of seizures?
Used for partial seizures and tonic-clonic
Mechanism of action for lamotrigine (Lamictal)
inhibits the release of glutamate and inhibits voltage-sensitive Na channels, which stabilizes neuronal membranes
-* also weakly inhibits serotonin receptors = used as a part of treatment for bipolar disorder
Which drugs is sometimes used before phenytoin to avoid gingival hyperplasia
carbamazepine
T or F, Seizures may still occur in medicated patients?
True, always ask patients when they have had their most recent seizure and if they have known triggers
Which drugs are classic P450 inducers?
phenytoin (Dilantin) and phenobarbital
Liver toxicity is a concern with what drugs
carbamazepine (Tegretol) and valproic acid (Depakene) (valproates)
T or F, dental light can trigger a seizure
True
T or F, local anesthetic doesn’t usually have enough effect to trigger a seizure
False, it WILL trigger a seizure
