Anxiolytics, Antiepileptics, Antiparkinsonians, & Alzheimer Therapy Flashcards
What drugs (in addition to SSRIs and SNRIs) are used for chronic anxiety?
Buspirone
Benzodiazepines
Name 3 characteristics of buspirone.
Partial 5-HT1A agonist
No sedative or anticonvulsant activity
Caution with other serotonergic drugs
Benzodiazepines are a _________ __________ ________ of GABA at the GABA-A receptor which is a __ channel.
positive allosteric modulator; chloride
What makes midazolam an ideal benzo for anesthesia?
Short-acting (2-6 hours)
What benzos have active metabolites?
Diazepam and Flurazepam
Abrupt cessation of benzodiazepines can case _______ after _____ ________.
seizures; severe dependence
Name 2 “Z” compounds/novel benzodiazepine receptor agonists.
Zopidem
Zaleplon
What is the advantage of “Z” compounds over benzos for sleep?
Induce more normal sleep patterns
What is the benzodiazepine receptor antagonist?
Flumazenil
2 precautions concerning flumazenil?
Can precipitate seizures in patients with prolonged benzo use.
Effects last 30-60 minutes which is shorter than longer-acting benzos; may require repeat doses.
What is the general MOA of antiepileptics?
Keeping the cell polarized/hyperpolarized; preventing efflux of negative ions/promoting influx of positive ions. Involves Na+, Ca+, Cl-.
What antiepileptics suppress sodium influx?
Phenytoin
Carbamazepine
What antiepileptics decrease Ca influx?
Gabapentin
Pregabalin
What 2 antiepileptic classes potentiate GABA activity?
Benzos
Barbiturates
Name 3 mixed mechanism AEDs.
Valproate sodium
Topiramate
Laomtrigine
Name an AED with an uncertain mechanism.
Levetiracetam
What AEDs are associated with idiosyncratic reactions?
Phenytoin
Phenobarbital
Valproic acid
Carbamazepine
Name 4 idiosyncratic reactions to AEDs.
Hepatotoxicity
Pancreatitis
Exfoliative dermatitis
Blood dyscrasias
What is fosphenytoin?
The prodrug of phenytoin; both are indicated for status epiplepticus.
What are 3 key points about phenytoin levels?
Narrow therapeutic index - monitor levels
Induces multiple CYPs
Metabolism is variable (polymorphic CYP2C9/19) and easily saturable
Why is phenytoin easily saturable?
Nonlinear kinetic metabolism
Name 3 major s/s of phenytoin toxicity
CNS depression - nystagmus, diplopia, ataxia
Idiosyncratic reaction - rash, blood dyscrasias, hepatotoxicity
Vesicant - purple glove syndrome
What is the MOA of phenobarbital?
Potentiates GABA
Name 4 AEs for phenobarbital.
Cognitive dysfunction/respiratory depression
Idiosyncratic reactions - blood dyscrasias, exfoliative dermatitis, hepatotoxicity
Interferes with vitamins D and K metabolism (bleeding)
Birth defects
Why does phenobarbital have so many DDIs?
Potent inducer of hepatic enzymes
What is the MOA of carbamazepine?
Inhibits sodium influx into neuron
What are the 2 most notorious AEs of carbamazepine?
Hyponatremia
Bone marrow suppression
(Also an inducer of CYPS and subject to idiosyncratic reaction)
In addition to idiosyncratic reactions, what are 2 adverse reactions for which valproate is known?
HEPATOTOXICITY (monitor LFTs)
The MOST TERATOGENIC AED
What effect does valproate have on CYPs?
Inhibitor
What are some AEs of topiramate? (4)
Cognitive impairment
Metabolic acidosis
Weight loss
Kidney stones
What is the MOA of gabapentinoids?
Binds to alpha-2-delta subunit of voltage-gated Ca2+ channel leading to decreased Ca2+ influx and decreased excitatory neurotransmitter release
Which gabapentinoid is used for fibromyalgia and is schedule V for substance abuse?
Pregabalin
Name 3 AEs of gabapentinoids.
Sedation
Ataxia and vertigo
Peripheral edema
Which AEDs are notorious for inducing CYP450? Inhibiting?
Carbamazepine, phenytoin, phenobarbital
Valproate
Name the two pharmacologic steps to treating status epilepticus.
IV benzo
Longer acting AED (phenytoin, fosphenytoin, levetiracetam)
What infusions can be initiated for protracted status epilepticus?
Propofol or midazolam
What is the IV push drug of choice for status epilepticus?
Lorazepam (lasts greater than 6 hours)
What is the advantage of diazepam for status epilepticus? Disadvantage?
Available in rectal gel and intranasal prep (can give without IV access)
Effect usually lasts only 20 minutes
What labs should be monitored perioperatively (as indicated) with AED use?
CBC, liver function, drug levels
What is the mechanism of Parkinson’s disease?
Degeneration of DA producing neurons in substantia nigra leading to imbalance of DA and ACh neurotransmitters
What Parkinson’s drug increases DA synthesis?
L-Dopa/levodopa
What Parkinson’s drug inhibits dopa decarboxylase in the periphery?
Carbidopa
What Parkinson’s drug inhibits COMT in the periphery?
Entacapone
What Parkinson’s drug inhibits MAOI-B in the CNS?
Selegiline
What Parkinson’s drug stimulates DA receptors?
Ropinirole
What Parkinson’s drug promotes DA release?
Amantadine
What Parkinson’s drug decreases ACh action in the CNS?
Trihexyphenidyl
For what Parkinson’s patients is levodopa reserved?
Greater than 70 years old and advanced disease since drug efficacy decreases with time
What Parkinson’s drugs are the 1st choice for mild to moderate disease?
DA agonists - ropinirole and pramipexole
Remember ropidop[amine] and the pex!
DDIs with pro-dopamine Parkinson’s drugs?
DA2 receptor antagonists:
Antipsychotics
Antiemetics (promethazine, droperidol)
Prokinetics (metoclopramide)
Name 2 MAO-B inhibitors
Selegiline
Rasagiline
(Remember Mao’s B-geline for incredible style)
MAO-B DDIs?
MANY!
Avoid with opioids/serotonergic drugs d/t risk of serotonin syndrome
Name two centrally-acting antimuscarinics
Benztropine
Trihexyphenidyl
Abrupt withdrawal of levodopa can cause…?
Worsening muscle rigidity and interfere with ventilation
What drug classes are used to treat cognitive impairment in early to moderate Alzheimer disease?
Centrally acting acetylcholinesterase inhibitors (AChE-I)
NMDA type glutamate receptor antagonist
Name an NMDA type glutamate receptor antagonist
Memantine
Name 3 AChE-Is.
Galantamine
Donepezil
Rivastigmine
(Remember “gallantly down the river”)
What affect can AChE-Is have on a depolarizing NMB?
Effects prolonged (Sch)
What effect could AChE-Is have on nondepolarizing NMBs?
Diminished effects
In the PICU, a 76‐year‐old patient with Parkinson’s Disease
begins to show increasing signs of tremor and rigidity. Which of
the following perioperative medications is most likely to have
contributed to the exacerbation of PD symptoms?
A. Ondansetron (Zofran)
B. Haloperidol (Haldol)
C. Fentanyl (Duragesic)
D. Aprepitant (Emend)
E. Glycopyrrolate (Robinul)
B
Review Question 2 Which of the following drug/mechanism pair is correctly matched? A. Ropinirole/dopa decarboxylase inhibition B. Trihexyphenidyl/dopamine precursor C. Flumazenil/ MAOI‐A inhibitor D. Lorazepam/GABA‐A allosteric agonist E. Phenytoin/calcium channel antagonist
D
A 61‐year‐old woman with a history of a seizure disorder is admitted
for an appendectomy. She will receive lorazepam (Ativan) for anxiety
preoperatively. Lorazepam is inactivated by CYP3A4. Which of the
following AEDs is most likely to increase the serum concentration of
lorazepam?
A. Phenytoin (Dilantin)
B. Carbamazepine (Tegretol)
C. Divalproex (Depakote)
D. Topiramate (Topamax)
E. Lamotrigine (Lamictal)
C
