PharmII_Exam2(p1-3) Flashcards
Describe focal seizures
Neuronal excitation originates at specific cortical sites and potentially spreads to wider areas of the brain.
T/F?
Most seizures are of the focal nature?
True
60%
Describe generalized seizures
Begin on both sides of the brain at about the same time and can manifest as either full
“grand mal” convulsions or brief staring episodes.
Describe absense seizure (petit mal)
Loss of consciousness, stare, eye flicking, usually no motion (<30sec)
Describe myoclonic generalized seizure
Brief 1 sec shock like contractions of muscles.
Describe tonic-clonic generalized seizure
loss of consciousness, Sustained contractions (tonic) followed by relaxations
(clonic) of muscles throughout the body (1—2min).
Name of disorder associated with Generalized seizures?
juvenile myoclonic epilepsy.
MOA of generalized seizures?
(reciprocal firing through the thalamus via T-type Ca2+ channels)
Name the three MOA that anti-epileptic drugs work?
- Prolonging the inactivation of voltage gated Na+ channels
- Enhancement of synaptic inhibition by increasing GABA activity
- Treating a less common form of epilepsy, generalized absence seizures and myoclonic seizures, is
accomplished through the inhibition of T-type voltage gated Ca2+ channels.
Regardless
What condition will occur if you withdraw an anti-epileptic?
sudden withdrawal of the drug can cause status epilepticus.
T/F?
COnsciousness is not preserved in simple focal seizure?
False. It is preserved.
Name the two MOAs of drugs that treat focal seizures and tonic-clonic seizure?
- Prolonging Na+ channel inactivation
2. Enhancing GABA activity
Name the MOAs of drugs that treat generalized absence and myoclonic seizures?
Target T-Type Calcium channels.
Is there birth defect risk with the use of anti-epileptic drugs?
Yes. Trimethadione Paramethadione Phenytoin Phenobarbital
Carbamazepine and Phenytoin are 1st line agents for which type of seizures
partial seizures and generalized tonicclonic.
Ethosuximide and Valproate are preferred for
generalized absence seizures since they are non-sedating.
Clonazepam is highly effective for which seizure?
Generalized absence seizure.
Effective for myoclonic as well
Really bad because it causes sedation
Fosphenytoin?
More soluble pro-drug (converted to phenytoin in the body)
For phenytoin to work, what is it dependent upon?
Voltage dependent
Use dependent.
What does use dependent mean?
It only works on an active channel.
Regarding sodium ion channels.
At very low blood levels, which order kinetics does phenytoin follow?
First order.
Same percentage of drug is eliminated/ime
When phenytoin is saturated, what order kinetics is followed?
Zero order.
Same amt of drug is eliminated per unit time.
What will phenytoin do to warfarrin?
It will displace warfarin from albumin binding sites.
How are u supposed to administer an anti-epileptic to a patient?
Increase dose slowly to avoid toxicity.
Mephenytoin?
a phenytoin cogener with saturable metabolism Nirvanol is the active metabolite
Carbamazepine
Structurally related to tri-cyclic antidepressants. In addition to its anticonvulsant actions, it can treat bipolar depression.
It locks sodium channels in inactivated state
Which drug to you used if patient is hypersensitive to phenytoin?
Ethotoin
Is it ok to give MAOI in a patient taking carbamezipine?
NO!!!
It is structurally similar to imipramine.
If do, will get hpertensive crisis.
Oxcarbazepine
Similar to carbamazepine but better toxicity profile (less potent, less interactions.
Phenobarbital
Still among the most commonly used. increases GABA while decreasing Glutamate. Used for partial and
generalized tonic clonic and generalized myoclonic refractory to other agents.
Mephobarbital
Also a barbiturate used in epilepsy
Primidone
Metabolized to Phenobarbitol and PEMA. Action is more similsr to phenytoin.
Vigabatrin
an analog of GABA which reversibly inhibits GABA aminotransferase and promotes the
accumulation of GABA at the synapse thus increasing GABA activity and inhibits high frequency neuronal
firing.
What is the worse side effect of vigabatrin?
Irreversible visual impairment with long term therapy. 50% o patients experience AE
Causes psychosis
Which seizures is vigabatrin used in?
Used for partial and tonic-clonic.
Used as adjunctive therapy for refractive cases of these.
and West’s Syndrome.
Name two MOA of Lamotrigine
- Inactivates voltage gated sodium channels.
2. Block voltage gated calcium channels.
Which seizures and other condition can Lamotrigine treat?
- partial seizure and tonic clonic
- Absence and myoclonic
- Lennox-Gasaut syndrome
Bipolar disorder.
What is a major adverse effect in Lamotrigine?
Severe life threatening rashes
Felbamate
Thought to block NMDA. 3rd line drug for partial seizures or Lennox-Gastaut syndrome. Can
cause aplastic anemia and hepatic failure.
Gabapentin
GABA + a lipophilic hexane ring but does NOT activate GABA receptors. Binds Ca2+
channels to inhibit glutamate and may alter GABA metabolism and transport. Partial and generalized tonic-clonic and
for neuropathic pain in post herpetic neuralgia (shingles). NOT metabolized (eliminated by kidney unchanged).
Pregabalin
Also a GABA analog with similar mechanism. Partial seizures, surgical dental pain, diabetic
neuropathies, postherpetic neuralgia, and off label for anxiety.
Topiramate
Prevents seizure spread, used for partial and generalized tonic-clonic seizures, absence, and
myoclonic. Also TX for Lennox- Gastaut syndrome and West’s syndrome. May reduce efficacy of oral contraceptives
and cause Glaucoma and acute myopia (stop drug).
Tiagabine
–“Rationally” designed drug that blocks the GABA transporter GAT-1 to
Zonisamide
Sulfonamide derivative that blocks T-type Ca3+ channels and prolongs Na+ channel
inactivation. Partial, general tonic-clonic, and absence. May cause ataxia, psychosis and speech disturbances.
Keppra
– Binds synaptic vesicle SV2 protein altering release an glutaminergic and GABAergig
synapses. Partial and secondary tonic-clonic. Little metabolism. Can cause somnolence, asthenia, and dizziness.
Ethosuximide
Methusuximide
Phensuximide
Particularly effective for absence petit mal) seizures. Efficacious and safe. Can cause gastric effects (more common) and CNS effects (less common).
Valproate
Prolongation of Na channel inactivation, reduction of T-type
Ca+ currents, reduces NMDA currents and increased [GABA] in brain. The preferred choice for absence seizures
concomitant with tonic-clonic seizures (Ethosuximide is preferred for absence alone). Also used for bipolar
disorder, migraine headaches, alcohol withdrawal and dementia. It is contraindicated in liver disease and urea cycle disorders.
Benzodiazepines
effective at non-sedating doses and likely potentiate GABA activity on GABA-A receptor. Used IV
for status epilepticus to quickly reduce seizures. May, however, have a pronounced sedative effect and tolerance may develop within a few months.
Acetazolamide
a diuretic that inhibits carbonic anhydrase and likely produces a slight acidosis of the brain
or reduces the depolarizing activity of bicarbonate ions. Only use may be for women who have increased seizures
during menstruation.
What happens if you overdose on anti-epileptics?
U won’t die!!!
MOA of benzo?
These drugs potentiate GABA at the GABA-A Receptor (except Buspirone and Ramelton)
Increase Frequency of channel opening,
increasing infinity of GABA for receptor
What does barb do to gaba receptor
Increase mean open time, Increasing the infinity of GABA for receptor,
act directly as agonist
Which group of drugs is used for acute anxiety attacks?
Benzodiazepines
Which group of drugs is used for long term anxiety care?
SSRIs
SNRIs
Quetiapen, an atypical antipsychotic is used as an adjunct.
T/F?
Benzodiazepines are able to produce cardiovascular/respiratory depression
False
One exception is Midazolam.It is able to produce general anesthesia.
Can you use benzodiazepines with other CNS depressants like alcohol?
NOPE
Which receptor does Buspirone act on?
5-HT1a
Which receptor does Ramelteon act on?
Melatonin receptor.
Does barb or bdz produce a dose dependent CNS depression?
Barbs
Name the three non-benzodiazepines?
Ambien
Sonata
Lunesta
What is the name of the only drug that reverse BDZ overdose
Flumenazil.
Used to tx BDZ OD and reverse effects of BDZ and non BDZ used as anesthesia
adjucts. Does not block barbiturate, ethanol, or general anesthetic action. Can precipitate the
rapid development of withdrawal symptoms.
Can flumazenil reverse the efffects of barbs?
Nope
