Anxiolytics, Antiepileptics, Antiparkinsonians, & Alzheimer Therapy

Question 1

What drugs (in addition to SSRIs and SNRIs) are used for chronic anxiety?

Answer 1

Buspirone

Benzodiazepines

Question 2

Name 3 characteristics of buspirone.

Answer 2

Partial 5-HT1A agonist
No sedative or anticonvulsant activity
Caution with other serotonergic drugs

Question 3

Benzodiazepines are a _________ __________ ________ of GABA at the GABA-A receptor which is a __ channel.

Answer 3

positive allosteric modulator; chloride

Question 4

What makes midazolam an ideal benzo for anesthesia?

Answer 4

Short-acting (2-6 hours)

Question 5

What benzos have active metabolites?

Answer 5

Diazepam and Flurazepam

Question 6

Abrupt cessation of benzodiazepines can case _______ after _____ ________.

Answer 6

seizures; severe dependence

Question 7

Name 2 “Z” compounds/novel benzodiazepine receptor agonists.

Answer 7

Zopidem

Zaleplon

Question 8

What is the advantage of “Z” compounds over benzos for sleep?

Answer 8

Induce more normal sleep patterns

Question 9

What is the benzodiazepine receptor antagonist?

Answer 9

Flumazenil

Question 10

2 precautions concerning flumazenil?

Answer 10

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.

Question 11

What is the general MOA of antiepileptics?

Answer 11

Keeping the cell polarized/hyperpolarized; preventing efflux of negative ions/promoting influx of positive ions. Involves Na+, Ca+, Cl-.

Question 12

What antiepileptics suppress sodium influx?

Answer 12

Phenytoin

Carbamazepine

Question 13

What antiepileptics decrease Ca influx?

Answer 13

Gabapentin

Pregabalin

Question 14

What 2 antiepileptic classes potentiate GABA activity?

Answer 14

Benzos

Barbiturates

Question 15

Name 3 mixed mechanism AEDs.

Answer 15

Valproate sodium
Topiramate
Laomtrigine

Question 16

Name an AED with an uncertain mechanism.

Answer 16

Levetiracetam

Question 17

What AEDs are associated with idiosyncratic reactions?

Answer 17

Phenytoin
Phenobarbital
Valproic acid
Carbamazepine

Question 18

Name 4 idiosyncratic reactions to AEDs.

Answer 18

Hepatotoxicity
Pancreatitis
Exfoliative dermatitis
Blood dyscrasias

Question 19

What is fosphenytoin?

Answer 19

The prodrug of phenytoin; both are indicated for status epiplepticus.

Question 20

What are 3 key points about phenytoin levels?

Answer 20

Narrow therapeutic index - monitor levels
Induces multiple CYPs
Metabolism is variable (polymorphic CYP2C9/19) and easily saturable

Question 21

Why is phenytoin easily saturable?

Answer 21

Nonlinear kinetic metabolism

Question 22

Name 3 major s/s of phenytoin toxicity

Answer 22

CNS depression - nystagmus, diplopia, ataxia
Idiosyncratic reaction - rash, blood dyscrasias, hepatotoxicity
Vesicant - purple glove syndrome

Question 23

What is the MOA of phenobarbital?

Answer 23

Potentiates GABA

Question 24

Name 4 AEs for phenobarbital.

Answer 24

Cognitive dysfunction/respiratory depression
Idiosyncratic reactions - blood dyscrasias, exfoliative dermatitis, hepatotoxicity
Interferes with vitamins D and K metabolism (bleeding)
Birth defects

Question 25

Why does phenobarbital have so many DDIs?

Answer 25

Potent inducer of hepatic enzymes

Question 26

What is the MOA of carbamazepine?

Answer 26

Inhibits sodium influx into neuron

Question 27

What are the 2 most notorious AEs of carbamazepine?

Answer 27

Hyponatremia Bone marrow suppression (Also an inducer of CYPS and subject to idiosyncratic reaction)

Question 28

In addition to idiosyncratic reactions, what are 2 adverse reactions for which valproate is known?

Answer 28

HEPATOTOXICITY (monitor LFTs) | The MOST TERATOGENIC AED

Question 29

What effect does valproate have on CYPs?

Answer 29

Inhibitor

Question 30

What are some AEs of topiramate? (4)

Answer 30

Cognitive impairment Metabolic acidosis Weight loss Kidney stones

Question 31

What is the MOA of gabapentinoids?

Answer 31

Binds to alpha-2-delta subunit of voltage-gated Ca2+ channel leading to decreased Ca2+ influx and decreased excitatory neurotransmitter release

Question 32

Which gabapentinoid is used for fibromyalgia and is schedule V for substance abuse?

Answer 32

Pregabalin

Question 33

Name 3 AEs of gabapentinoids.

Answer 33

Sedation Ataxia and vertigo Peripheral edema

Question 34

Which AEDs are notorious for inducing CYP450? Inhibiting?

Answer 34

Carbamazepine, phenytoin, phenobarbital | Valproate

Question 35

Name the two pharmacologic steps to treating status epilepticus.

Answer 35

IV benzo | Longer acting AED (phenytoin, fosphenytoin, levetiracetam)

Question 36

What infusions can be initiated for protracted status epilepticus?

Answer 36

Propofol or midazolam

Question 37

What is the IV push drug of choice for status epilepticus?

Answer 37

Lorazepam (lasts greater than 6 hours)

Question 38

What is the advantage of diazepam for status epilepticus? Disadvantage?

Answer 38

Available in rectal gel and intranasal prep (can give without IV access) Effect usually lasts only 20 minutes

Question 39

What labs should be monitored perioperatively (as indicated) with AED use?

Answer 39

CBC, liver function, drug levels

Question 40

What is the mechanism of Parkinson's disease?

Answer 40

Degeneration of DA producing neurons in substantia nigra leading to imbalance of DA and ACh neurotransmitters

Question 41

What Parkinson's drug increases DA synthesis?

Answer 41

L-Dopa/levodopa

Question 42

What Parkinson's drug inhibits dopa decarboxylase in the periphery?

Answer 42

Carbidopa

Question 43

What Parkinson's drug inhibits COMT in the periphery?

Answer 43

Entacapone

Question 44

What Parkinson's drug inhibits MAOI-B in the CNS?

Answer 44

Selegiline

Question 45

What Parkinson's drug stimulates DA receptors?

Answer 45

Ropinirole

Question 46

What Parkinson's drug promotes DA release?

Answer 46

Amantadine

Question 47

What Parkinson's drug decreases ACh action in the CNS?

Answer 47

Trihexyphenidyl

Question 48

For what Parkinson's patients is levodopa reserved?

Answer 48

Greater than 70 years old and advanced disease since drug efficacy decreases with time

Question 49

What Parkinson's drugs are the 1st choice for mild to moderate disease?

Answer 49

DA agonists - ropinirole and pramipexole | Remember ropidop[amine] and the pex!

Question 50

DDIs with pro-dopamine Parkinson's drugs?

Answer 50

DA2 receptor antagonists: Antipsychotics Antiemetics (promethazine, droperidol) Prokinetics (metoclopramide)

Question 51

Name 2 MAO-B inhibitors

Answer 51

Selegiline Rasagiline (Remember Mao's B-geline for incredible style)

Question 52

MAO-B DDIs?

Answer 52

MANY! | Avoid with opioids/serotonergic drugs d/t risk of serotonin syndrome

Question 53

Name two centrally-acting antimuscarinics

Answer 53

Benztropine | Trihexyphenidyl

Question 54

Abrupt withdrawal of levodopa can cause...?

Answer 54

Worsening muscle rigidity and interfere with ventilation

Question 55

What drug classes are used to treat cognitive impairment in early to moderate Alzheimer disease?

Answer 55

Centrally acting acetylcholinesterase inhibitors (AChE-I) | NMDA type glutamate receptor antagonist

Question 56

Name an NMDA type glutamate receptor antagonist

Answer 56

Memantine

Question 57

Name 3 AChE-Is.

Answer 57

Galantamine Donepezil Rivastigmine (Remember "gallantly down the river")

Question 58

What affect can AChE-Is have on a depolarizing NMB?

Answer 58

Effects prolonged (Sch)

Question 59

What effect could AChE-Is have on nondepolarizing NMBs?

Answer 59

Diminished effects

Question 60

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)

Answer 60

B

Question 61

``` 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 ```

Answer 61

D

Question 62

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)

Answer 62

C