Neurological Pharmacology

Question 1

Barbiturate-Containing Compounds

Answer 1

● Butalbital/Aspirin/Caffeine (Fiorinal)
● Butalbital/Acetaminophen/Caffeine
(Fioricet)

Question 2

Barbiturate-Containing Compounds MOA

Answer 2

○ Barbiturates are CNS depressants.
○ Another common example
includes Phenobarbital (for
seizures and sedation).
○ Barbiturates, like Butalbital,
increase the effects of GABA, an
inhibitory neurotransmitter. This
causes an influx of Chloride,
hyperpolarizing the cell.

Question 3

Barbiturate indications

Answer 3

○ Tension headaches (FDA indication) - Not first line
○ Sometimes used off-label for migraines

Question 4

Barbiturate BBW

Answer 4

BBW- Fioricet has FDA BBW for possible hepatotoxicity because it
contains Acetaminophen

Question 5

Contraindications of Barbiturate

Answer 5

○ Porphyria- Accumulation of porphyrins can occur with barbiturates.
○ Fiorinal is contraindicated in PUD, gastritis, uncontrolled hypertension,
G6PD deficiency, and bleeding disorders because it contains ASA.

Question 6

Barbiturate major adverse effects

Answer 6

○ Sedation
○ Respiratory Depression

Question 7

Because these can be abused and dependence can occur, these are
considered Schedule III Narcotics

Answer 7

Barbiturate-Containing Compounds

Question 8

Triptans (Serotonin Agonists)

Answer 8

Sumatriptan (Imitrex), Almotriptan (Axert),
Eletriptan (Relpax), Rizatriptan (Maxalt),
Zolmitriptan (Zomig), and
Sumatriptan/Naproxen (Treximet)

Question 9

Triptans MOA

Answer 9

○ Agonistic to Serotonin 5-HT receptors,
which is believed to decrease the release
of substance P and other pain NTs, as
well as causing cerebral vasoconstriction,
working against migraine-type HAs

Question 10

Triptans indications

Answer 10

○ Acute Migraine Headache
○ Sumatriptan (SC) is also
FDA-indicated for Acute
Cluster Headaches

Question 11

Triptans contraindications

Answer 11

○ Uncontrolled hypertension
○ Cerebrovascular Disease
○ Coronary Artery Disease
○ Peripheral Arterial Disease

Question 12

Triptans adverse effects

Answer 12

○ Coronary vasospasm
○ Myocardial ischemia
○ Myocardial infarction
○ Severe hypertension
○ Acute stroke
○ Cerebral hemorrhage
○ Intestinal ischemia
○ Ventricular tachycardia

Question 13

Ditan (5-HT 1F Agonist)

Answer 13

Lasmiditan (Reyvow)

Question 14

Ditan (5-HT 1F Agonist) MOA

Answer 14

○ Similar to the Triptans, Lasmiditan is
believed to work by binding to and
agonizing 5-HT receptors, but this one is
likely specific to the 1F subtype
○ It is thought that this medication may
inhibit peripheral trigeminal nerve firing,
helping to abort migraines

Question 15

Ditan (5-HT 1F Agonist) indications

Answer 15

Acute migraine headache (abortive only!)

Question 16

_____ is a controlled substance (schedule V)

Answer 16

Lasmiditan

Question 17

Ergotamines

Answer 17

● Dihydroergotamine (Migranal)
● Ergotamine/Caffeine (Cafergot)

Question 18

Ergotamines MOA

Answer 18

○ Like Triptans, 5-HT receptor agonists
that are believed to decrease Substance P release and cause vasoconstriction.
○ Additionally, Ergots are partial agonists of Alpha-1 adrenergic receptors, causing vasoconstriction

Question 19

Ergotamines contraindications

Answer 19

○ Like the Triptans, contraindicated in Peripheral Arterial Disease,
Coronary Vasospasm, Coronary Artery Disease, Hypertension.
○ Severe renal impairment
○ Severe hepatic impairment
○ Pregnancy
○ Breastfeeding
○ Sepsis

Question 20

Ergotamines BBW

Answer 20

○ Risk of severe peripheral
ischemia (vasoconstriction)

Question 21

Ergotamines adverse effects

Answer 21

○ Valvular Heart Disease
○ Pulmonary Fibrosis

Question 22

Ergotamines and pregnancy

Answer 22

○ Contraindicated during pregnancy!
Animal studies have revealed moderate
risk of teratogenicity.
○ Unsafe in lactation.

Question 23

Anti-CGRP Monoclonal Antibodies

Answer 23

● Erenumab (Aimovig)
● Fremanezumab (Ajovy)
● Galcanezumab (Emgality)

Question 24

Anti-CGRP Monoclonal Antibodies MOA

Answer 24

○ Binds to and blocks calcitonin gene-related peptide (CGRP) receptor, which is thought to be
related to migraine pathophysiology somehow
○ These are subcutaneous injections
that the patient does monthly.
■ Half-life: 27-31 days

Question 25

Anti-CGRP Monoclonal Antibodies indications

Answer 25

○ Migraine headache prophylaxis (prevention only!) ○ Emgality is also approved for Episodic Cluster Headaches

Question 26

Anti-CGRP Monoclonal Antibodies adverse effects

Answer 26

○ Anaphylaxis has occurred with Aimovig ○ No serious reactions reported with the others

Question 27

Dopamine Agonists

Answer 27

● Bromocriptine (Parlodel) ● Ropinirole (Requip) ● Pramipexole (Mirapex)

Question 28

Dopamine Agonists MOA

Answer 28

○ When dopaminergic neurons are lost and the D1 and D2 pathways are unbalanced, movements are not regulated (tremor, bradykinesia, etc). Medscape ○ Dopamine Agonists work by activating D1 and D2 receptors in the striatum, balancing the pathways as if dopamine levels from the substantia nigra were normal, thereby normalizing motor function (treats tremor, bradykinesia)

Question 29

Dopamine Agonists indications

Answer 29

○ All three are indicated in Parkinson’s Disease. ○ Ropinirole and Pramipexole are indicated for Restless Leg Syndrome. ○ Bromocriptine is indicated for Acromegaly and Hyperprolactinemia (as with Prolactinomas), as it also works to inhibit Prolactin and Growth Hormone release

Question 30

Dopamine Agonists adverse effects

Answer 30

○ Sudden onset sleep - Avoid activities like driving while taking. ○ Others include seizures, stroke, arrhythmias, severe hypotension, bradycardia, syncope, dyskinesia, Malignant Melanoma.

Question 31

Dopamine Agonists side effects

Answer 31

○ Lots and lots, unfortunately. The most common side effects include: ■ Nausea/vomiting ■ Peripheral edema ■ Hypotension ■ Hallucinations or vivid dreams

Question 32

Because of the risk of Melanoma, a regular dermatologic examination is recommended with _____

Answer 32

Dopamine Agonists

Question 33

Dopaminergic Agents

Answer 33

Levodopa/Carbidopa (Sinemet, Parcopa), Selegiline (Elderpryl), Rasagiline (Azilect), Entacapone (Comtan), and Amantadine (Symmetrel).

Question 34

Dopaminergic Agents MOA

Answer 34

○ Levodopa (L-Dopa): A precursor of Dopamine that is able to cross BBB. L-Dopa enhances dopamine synthesis in remaining dopaminergic neurons in SN. ○ Carbidopa: Inhibits a decarboxylase enzyme in the peripheral tissues that converts L-Dopa into Dopamine (Dopamine cannot cross BBB). ○ Entacapone: Inhibits peripheral Catechol-O-Methyltransferase (COMT), which normally inhibits L-Dopa in GI tract, so it extends effects of L-Dopa. ■ Adjunct to L-Dopa; no effect when given alone ○ Selegiline and Rasagiline: Irreversible inhibitors of MAO-B in the brain, which normally metabolizes Dopamine in the brain (increases Dopamine levels) ○ Amantadine: An antiviral drug that was found to increase the release of Dopamine in the brain. (Also blocks cholinergic and NMDA receptors)

Question 35

Dopaminergic Agents Indications

Answer 35

○ Levodopa/Carbidopa is considered the first-line drug for Parkinson Dz. ■ There are immediate and extended release forms ○ Entacapone: Adjunct to prevent “wearing off” of Levodopa. ○ Selegiline, Rasagiline, and Amantadine: Theses are all considered adjunct treatments in Parkinson Disease. Are sometimes used independently, but more often as adjuncts to Levodopa

Question 36

Anticholinergic Agents

Answer 36

Benztropine (Cogentin) and Trihexyphenidyl (Artane)

Question 37

Anticholinergic Agents MOA

Answer 37

○ These antagonize the parasympathetic nervous system by binding to and blocking the Muscarinic Acetylcholine receptors. ■ There is a theory that acetylcholine activity increases as dopaminergic neurons die in Parkinson Disease, theoretically being involved in some of the symptoms, including tremor. ■ These anticholinergic drugs theoretically block the effects of acetylcholine in hopes of treating the symptoms of Parkinson Dz. ● In reality, not extremely effective Medscape

Question 38

Anticholinergic Agents indications

Answer 38

○ Parkinson Disease ○ Extrapyramidal Symptoms (drug-induced movement disorders, such as dystonia, bradykinesia, and tardive dyskinesia)

Question 39

Anticholinergic Agents adverse reactions

Answer 39

○ Anticholinergic psychosis ○ Tachycardia ○ Severe anhidrosis ○ Heat stroke ○ Acute Angle-Closure Glaucoma ○ Tardive Dyskinesia (ironically)

Question 40

Anticholinergic Agents side effects

Answer 40

○ Constipation ○ Urinary retention ○ Sedation ○ Nausea/Vomiting ○ Dizziness ○ Headache ○ Tinnitus ○ Blurred vision ○ Flushing ○ Dry mouth

Question 41

Cholinesterase Inhibitors

Answer 41

● Donepezil (Aricept), Galantamine (Razadyne), Rivastigmine (Exelon), Neostigmine (Bloxiverz), and Pyridostigmine (Mestinon)

Question 42

Cholinesterase Inhibitors MOA

Answer 42

○ These drugs inhibit the enzyme Acetylcholinesterase that normally breaks Acetylcholine into Acetic Acid and Choline within the synaptic cleft. ○ By this mechanism, these drugs enhance acetylcholine transmission

Question 43

Cholinesterase Inhibitors indications

Answer 43

○ Donepezil, galantamine, and rivastigmine have stronger effects within the CNS, while neostigmine and pyridostigmine are more peripheral. ○ Donepezil, galantamine, and rivastigmine: Alzheimer’s Dementia ○ Neostigmine and pyridostigmine: Myasthenia Gravis ○ Neostigmine: Reversal of some neuromuscular blocking agents, as well as urinary retention

Question 44

Cholinesterase Inhibitors contraindications

Answer 44

○ Pyridostigmine is contraindicated in GI and GU obstruction. ○ Otherwise, for all, caution is advised in renal and hepatic impairment, as well as cardiac conduction defects and bradycardia

Question 45

Cholinesterase Inhibitors adverse effects

Answer 45

○ AV block ○ Bradycardia ○ Seizures ○ Steven-Johnson Syndrome ○ Urinary obstruction ○ GI bleeding ○ Hemolytic anemia

Question 46

NMDA Receptor Antagonist

Answer 46

Memantine (Namenda)

Question 47

NMDA Receptor Antagonist MOA

Answer 47

○ Alzheimer’s pathophysiology includes reduced production of Acetylcholine, as well as sustained and excessive stimulation of N-methyl-D-aspartate (NMDA) receptors, resulting in neuronal dysfunction and cell death. Medscape ○ NMDA receptors seem to play a strong role in learning and memory. ○ Namenda blocks NMDA receptors

Question 48

NMDA Receptor Antagonist indications

Answer 48

Alzheimer’s Disease