Week 10 (Test 4) Flashcards
What mechanisms can be used by AED’s to reduce excessive excitation?
A. Prevent repetitive action potential propagation of seizure discharges by inactivation of voltage-gated sodium channels B. Reduce excessive presynaptic glutamate release –binding to presynaptic Ca2+ channels at the a2d subunit – binding to presynaptic vesicle SV2A protein C. Block AMPA glutamate receptors
What mechanisms can be used by AED’s to increase inhibition?
A. Increase GABA-mediated neurotransmission 1. Enhancing post-synaptic GABA-A Receptor function 2. Increasing GABA synthesis 3. Reducing GABA breakdown B. Activate inhibitory potassium channels
Side effects of Sodium Channel AEDs:
- Double vision (diplopia), jerky eye movements (nystagmus) -Coordination problems (ataxia) and dizziness (vertigo)
- Sleepiness, lethargy, cognitive slowing
These problems are dose-dependent and reversible
Describe the metabolism of Phenytoin.
–95% hepatic, by a cytochrome P450 enzyme (CYP2C9)
–elimination is first order (concentration-dependent) until P450 enzymes saturated, then
–slows to zero-order – fixed amount metabolized per hour
•a small increase in dose can result in very high drug levels
What’s the mechanism of action of Phenytoin?
•Sodium channel inactivation
What are the long term adverse effects of Phenytoin?
gingival hyperplasia
osteopenia
What’s the mechanism of action of Carbamazepine?
Sodium channel inactivation
What are the long term adverse effects of Carbamazepine?
–aplastic anemia (rare)
–rash
–hyponatremia (low sodium)
What’s the mechanism of action of Valproic Acid (Depakote)?
•Sodium Channel inactivation
a good choice if you can’t tell whether the patient has a focal or generalized seizure disorder
Valproic Acid (Depakote)
What are the common adverse effects of Valproic acid (Depakote)?
–“fat, shaky, bald, yellow”
•weight gain (fat)
•Tremor (shaky)
•hair loss (bald)
•jaundice (yellow)
What is a very common side effect of Lamotrigine?
rash
What’s the mechanism of action of Topiramate (Topamax)?
sodium channel inactivation
What are the adverse effects we need to know for Topiramate (Topamax)?
–confusion/psychosis (“dopamax”)
–Renal stones (avoid in pts w/ history of renal stones)
What’s the mechanism of action of Gabapentin?
decreases presynaptic glutamate release by binding to a2d subunit of the voltage gated calcium channel
What’s the mechanism of action of Levatiracetam (Keppra) ?
–Binds to SV2A synaptic vesicle protein
•inhibits excessive neurotransmitter release
What are the adverse effects of Levatiracetam (Keppra)?
–Somnolence (sleepiness), ataxia, weakness (rare)
Irritability/personality change
What’s the mechanism of action of Perampanel (Fycompa)?
•Non-competitive AMPA glutamate receptor antagonist
–Only AED with this mechanism
What’s an important side effect of Perampanel (Fycompa)?
–risk of serious neuropsychiatric events: Violent thoughts or threatening behavior including homicidal ideation
What’s the mechanism of action of Phenobarbital?
–Enhances GABAa receptor currents
–also sodium channel inactivation
What are the adverse effects of phenobarbital ?
–sedation, cognitive slowing, dizziness, mood change
–paradoxical hyperactivity in kids
What’s the mechanism of action of Ezogabine?
–Activates voltage gated K+ channel
–Leads to hyperpolarization, decreased excitability
What are the adverse effects of Ezogabine?
–Urinary Retention
–Vision and skin problems
•Turns skin blue! (rare)
What is unique about the pharmacokinetics of Carbamazepine?
–Autoinduces cytochrome P450
•Increases expression of the same isozymes that metabolize it
•Start with low dose and increase gradually over 2-3 weeks.
What is the only use for the AED Ethosuximide?
•only against generalized absence
if generalized absence and + GTC or other type–> give valproic acid
What’s the mechanism of action of Ethosuximide?
–Inhibits “T” Ca++ channels in thalamus
Which AEDs are associated with neural tube defects?
•Valproic acid and carbamazepine associated with neural tube defects
Describe focal seizures
Focal seizures are conceptualized as originating at some point within networks limited to one hemisphere (how you can stay conscious)
Describe generalied seizures.
Generalized seizures are conceptualized as originating at some point within and rapidly engaging bilaterally distributed networks
Describe West syndrome
- Flexion or extension spasms
- 60-70% have lifelong epilepsy
- Hypsarrhythmia pattern on EEG
Think this syndrome when a young patient has mutiple types of seizure
Lennox-Gastaut Syndrome
What is the main metabolite of nicotine that is measured in the blood?
Cotinine
What’s the mechanism of action of Varenicline (Chantix)?
Partial agonist at α4β2 nicotine receptors
What’s the mechanism of action of Buproprione (Wellbutrin)?
Dopamine reuptake inhibitor & Nicotine antagonist
Who do you not give Buproprion to?
Don’t give buproprion to people who have eating disorders. Will mess up electrolyte balance and can cause seizure
How do you define binge drinking?
- Women, 4 or more drinks during a single occasion.
- Men, 5 or more drinks during a single occasion.
How do you define heavy drinking?
- Women, more than 1 drink per day on average.
- Men, more than 2 drinks per day on average.
- Result of thiamine deficiency in alcoholism
- Atrophy of mamillary bodies & regions of thalamus
Wernicke Encephalopathy
What are the triad of symptoms seen in patients with Wernicke Encephalophathy ?
- Confusion
- Nystagmus, opthalmoplegia, anisocora, sluggish pupillary reflexes
- Ataxia
- results from mother consuming alcohol her pregnancy
- mental retardation is common (44% have an IQ <79)
- wide-set eyes
- short palpebral fissure
- short and broad-bridged nose
- hypoplastic philtrum
- thinned upper lip
- flattened midface
Fetal alcohol syndrome
Which biomarker can be used to distinguish heavy drinking?
CDT - carbohydrate-deficient transferrin
How do you treat Withdrawal from: ALCOHOL,
BENZODIAZEPINES,
BARBITURATES?
benzodiazepines
What are the FDA approved pharmacological treatments for alcohol dependence?
Disulfiram
Naltrexone
Acamprosate
What’s the mechanism of action of Disulfiram?
inhibits aldehyde dehydrogenase which allows acetaldehyde to build up and cause adverse effects
Opioids cause miosis except _____.
Meperidine
What’s the opioid overdose/toxicity triad?
- miotic pupils
- abnormal mental status
- respiratory depression (<12/min)
What medication do you give for opioid intoxication/overdose?
naloxone (pure opioid antagonist)
In ______, you see CNS noradrenergic hyperactivity in the Locus ceruleus.
opioid withdrawal syndrome
What are your two drug choices for opioid maintenance treatment?
–Methadone
–Buprenorphine
What is the gold standard for opioid maintenance treatment in pregnant women?
methadone
What are the most common physician abused drugs?
- alcohol (number 1)
- opioids (highly associated with mortality )
What are the 3 D’s you see with impaired physicians (or any other addict for that matter)?
- Delusional
- Denial
- Defiance
What do you need to see in a patient to have the Clinical Determination of Brain Death ?
- absent brainstem reflexes
- apnea
- flaccid limbs
KORSAKOFF’S PSYCHOSIS symptoms triad consists of what?
- Amnesia
- Confabulation
- Hallucinations
may play an important role in the storage or retrieval of past, autobiographical memories.
anterolateral temporal lobes
