PHARM - Seizures & Alzheimer's Flashcards
what is the overarching mechanism by which drugs treat seizures?
by decreasing hyperexcitability
what are the methods by which drug decrease hyperexcitability?
- ion channel modulation
- GABA enhancement
- Glutamate inhibition
- modulation of NT release
which cation channels can be modulated to decrease hyperexcitability?
how?
- Na+ channel: blockage
- Ca++ channel: blockage
- K+ channel: enhancement
sodium channel modulators
- includes which drugs?
- clinical use
- MOA
- AE/CI
- drugs: phenytoin, carbapezamine, lacosamide
- clinical use: seizures - focal, tonic-clonic
- MOA: bind to Na+ channels in the inactivated state, inhibiting high -frequency firing
- phenytoin, carbapezamine: fast-inactivation
- lacosamide: slow inactivation
- AE: drug-specific
- CI: absence seizures
phenytoin
- what kind of drug?
- clinical use
- MOA
- PK
- AE/CI
- sodium channel modulator
- clinical use: seizures - focal, tonic clonic
- MOA: enhance fast-inactivation of inactivated Na+ channels -> inhibitng high-frequency firing
- PK:
- narrow therepeutic range - small dose changes can lead to toxicity
- metabolized by CYP-2C9
- inhibits CYP-3A4
- AE:
- gingival hyperplasia
- facial feature coarsening
- mild cerebrovestibular effects - vertigo, ataxia, HA, nausea
- CI:
- absence seizures
- pregnancy & oral contraceptives - is teratogenic
what are the contraindications of phenytoin?
- absence seizure (like all Na modulators)
- in pregnancy - teratogenic
- with oral contraceptives - teratogenic
how id phenytoin metabolized?
by CYP-2C9
phenytoin inhibits…?
CYP-3A4
carbapezamine
- what kind of drug?
- clinical use
- MOA
- PK
- AE/CI
- sodium channel modulator
- clinical use: seizures - focal (simple & complex), tonic clonic
- MOA: enhance fast-inactivation of inactivated Na+ channels -> inhibitng high-frequency firing
- AEs:
- allergic reactions
- cerebrovestibular - nausea, ataxia
- CI:
- absence seizures
- SLE
what are the contraindications of carbapezamine?
- absence seizures
- SLE
explain the mechanism behind absence seizures
oscillations between the thalamus and cortex that are generated in the thalamus by T-type (transient) Ca++ current
what drugs are used to treat absence seizures?
- Ca++ channel modulators
- ethosuxamide
- valproate
Ca++ channel modulators
- include which drugs?
- clinical use?
- MOA?
- AE?
- drugs: valproate, ethosuximide
- clinical use: absence seizures
- MOA: block low threshold-Ca++ channels -> blocking T-type currents
- AE: drug specific
valproic acid
- what kind of drug?
- clinical use?
- MOA?
- AE/CI?
- is a calcium channel modulator
- clinical use: absence seizures
- MOA: block low threshold-Ca++ channels -> blocking T-type currents
- AE/CI: more severe than ethosuximide
- teratogenic / CI in pregnancy
- hepatoxic / CI in liver disease
- CNS depression / CI other depressants
ethosuxamide
- what kind of drug?
- clinical use?
- MOA?
- AE/CI?
- is a calcium channel modulator
- clinical use: absence seizures
- MOA: block low threshold-Ca++ channels -> blocking T-type currents
- AE: safer than valproic acid
- GI
- anorexia
- drowisniesss
which drugs are
- used to treat absence seizures?
- C/I in a pt with absence seizures?
- treated with:
- valproic acid
- ethosuximide
- C/I drugs:
- phenytoin
- carabemazepine
- lacosamide
benzodiazapines
- includes what drugs
- clinical use
- MOA
- AE
- drugs: -epams: diazepam, lorazepam, clonazepam
- clinical use: seizures - myoclonic, status epilepticus
- MOA: positive allosteric GABAA receptor modulators - enhance receptor-GABA affinity
- AE: drowsiness
barbituates
- includes what drugs
- clinical use
- MOA
- AE
- drugs: phenobarbital, primodone
- clinical use: seizures - status epilepticus, myoclonic
- MOA:
- positive allosteric modulators of GABAA receptors
- at higher concentrations - a direct GABA antagonist
- AE: general CNS depression
what tolerance risk do benzodiazepnies pose?
- DO lead to tolerance of AED (anti-epileptic effects)
- do NOT lead to tolerance of anti-hyponotic effects
how are benzodiazapenes / barbituates
- similar
- different
both
- are postiive allosteric regulators of GABAa receptors
- are used for myoclonic seizures & status epilepticus
- can lead to AED tolerance
only barbituates
- can be a direct GABAa agonist at high concentrations
diazepem - is what kind of drug?
benzodiazepine
- is what kind of drug?
benzodiazepines
lorazepam - is what kind of drug?
benzodiazepine
clonazepam - is what kind of drug?
benzodiazepines
phenobarbital - is what kind of drug?
barbarbituate
primidone - is what kind of drug?
barbarbituate
topiomarate
- clinical use
- MOA
- AE/CI
- clinical use: seizures - complex partial, generalized clonic tonic
- MOA:
- blocks Na+ channels
- blocks AMPA (Glu) channels
- enhances GAGA transmission
- AE: teratogenic - cleft palate
- CI: pregnancy
what AES are C/I in pregnancy
which one can lead to a cleft palate?
- phenytoin [Na+ blocker]
- valproic acid [Ca+ blocker]
- topiomarate - can cause a cleft palate
what is the #1 treatment for status epilepticus?
lorazepam
describe the imbalance that leads to Altheimers
- deficits in cholinergic signaling
- excess glutamate signaling
what are the three methods by which althzheimers is treated?
what drugs are utilized for each method?
- increase cholinergic activity: AChE inhibitors - donepezil, endophonium
- decrease glutmate activity: NMDA receptor antagonists - memantine
- reduce beta amyloid plaques: abudacumab
AChE inhibitors in the treatment of parkinsons
- which drugs are used?
- which is better tolerated?
- how are they administered?
- AEs?
- drugs: ribastigmine, donepezil
- better tolerated: donepezil
- administrated: often in combination w/ memantine
- AE: ACh excess - N &V, cramps, bradycardia, syncope
- CI: in pts w/ bradycardia / syncope
which NDMA antagonist is used to treat Parkinson’s?
memantine
(often given in combination with donepezil)
which medication potentially reduces plaques in Altzheimers?
aducunumab
