Neuro - Pharmacology (Neuromuscular blocking, Parkinson, Alzheimer, Huntington, & headache drugs)

Question 1

What are 2 uses for neuromuscular blocking drugs?

Answer 1

Used for muscle paralysis in surgery or mechanical ventilation.

Question 2

For what receptor are neuromuscular blocking drugs selective?

Answer 2

Selective for motor (vs. autonomic) nicotinic receptor

Question 3

What are the 2 types of neuromuscular blocking drugs?

Answer 3

(1) Depolarizing (2) Nondepolarizing

Question 4

Give an example of a depolarizing neuromuscular blocking drug.

Answer 4

Succinylcholine

Question 5

What is succinylcholine, and what action(s) does it have?

Answer 5

Succinylcholine - strong ACh receptor agonist (depolarizing neuromuscular blocking drug); Produces sustained depolarization and prevents muscle contraction

Question 6

What are the phases in the reversal of neuromuscular blockade due to succinylcholine? Briefly describe each.

Answer 6

Phase I (prolonged depolarization); Phase II (repolarized but blocked; ACh receptors are available, but desensitized)

Question 7

Does Phase I or Phase II reversal of blockade (due to succinylcholine) have an antidote? If so, what is it?

Answer 7

Phase I - no antidote; Phase II - antidote consists of cholinesterase inhibitors

Question 8

What effect do cholinesterase inhibitors have on Phase I versus Phase II of reversal of (succinylcholine) blockade?

Answer 8

Phase I - No antidote. Block potentiated by cholinesterase inhibitors.; Phase II - antidote consists of cholinesterase inhibitors

Question 9

What are 3 complications that may result from use of depolarizing neuromuscular blocking drugs?

Answer 9

Complications include (1) hypercalcemia, (2) hyperkalemia, and (3) malignant hyperthermia.

Question 10

Name 6 nondepolarizing neuromuscular blocking drugs.

Answer 10

(1) Tubocurarine (2) Atracurium (3) Mivacurium (4) Pancuronium (5) Vecuronium (6) Rocuronium

Question 11

What is the mechanism of nondepolarizing neuromuscular blocking drugs?

Answer 11

Competitive antagonists - compete with ACh for receptors

Question 12

What class of drugs work in the reversal of blockade due to nondepolarizing neuromuscular blocking drugs? What are 2 examples of such drugs?

Answer 12

Cholinesterase inhibitors; Reversal of blockade - neostigimine (must be given with atropine to prevent muscarinic effects such as bradycardia), edrophonium, and other cholinesterase inhibitors

Question 13

For what is neostigimine used in the context of neuromuscular blockade? What additional drug must be given with neostigime, and why?

Answer 13

Reversal of nondepolarizing neuromuscular blockade (as cholinesterase inhibitor); Must be given with atropine to prevent muscarinic effects such as bradycardia

Question 14

What is the mechanism of dantrolene?

Answer 14

Prevents the release of Ca2+ from the sarcoplasmic reticulum of skeletal muscle

Question 15

What are 2 clinical uses for dantrolene?

Answer 15

Used to treat (1) malignant hyperthermia and (2) neuroleptic malignant syndrome (a toxicity of antipsychotic drugs)

Question 16

For which toxicity of antipsychotic drugs is dantrolene used?

Answer 16

Neuroleptic malignant syndrome

Question 17

What causes Parkinsonism?

Answer 17

Parkinsonism is due to loss of dopaminergic neurons and excess cholinergic activity.

Question 18

What are the 4 different strategies behind Parkinson disease drugs?

Answer 18

(1) Dopamine agonists (2) Increased dopamine (3) Prevent dopamine breakdown (4) Curb excess cholinergic activity

Question 19

What are 3 examples of Dopamine agonists? Which type of Dopamine agonists are preferred for Parkinson disease?

Answer 19

(1) Bromocriptine (ergot) (2) Pramipexole (3) Ropinirole (non-ergot); Non-ergots are preferred

Question 20

What are 2 examples of Parkinson disease agents that work by increasing dopamine?

Answer 20

(1) Amantadine (may increase dopamine release) (2) L-dopa/carbidopa (converted to dopamine in CNS)

Question 21

By what mechanism can Amantadine be used for Parkinson disease? For what other conditions can it be used? What is a toxicity of Amantadine?

Answer 21

Amantadine (may increase dopamine release); also used as an antiviral against influenza A and rubella; Toxicity = ataxia

Question 22

What are 3 examples of Parkinson drugs that work by preventing dopamine breakdown?

Answer 22

(1) Selegiline (selective MAO type B inhibitor) (2) Entacapone (3) Tolcapone (COMT inhibitors - prevent L-dopa degradation –> increase dopamine availability)

Question 23

What is the ultimate effect of selegiline, and how does it accomplish this? For what disease is it used?

Answer 23

Prevent dopamine breakdown; Selegiline (selective MAO type B inhibitor): Parkinson disease

Question 24

What is the ultimate effect of entacapone, and how does it accomplish this? What other drug shares this effect and mechanism? For what disease are they both used?

Answer 24

Prevent dopamine breakdown; COMT inhibitors - prevent L-dopa degredaton –> increase dopamine availability; Tolcapone; Parkinson disease

Question 25

What type of drug is Benztropine? What is its ultimate effect? In what disease is it used?

Answer 25

Antimuscarinic; Curb excess cholinergic activity; Parkinson disease; Think: “Park your Mercedes BENZ”

Question 26

Again, what type of drug is Benztropine? What effects does it have in terms of alleviating Parkinson disease symptoms?

Answer 26

Antimuscarinic; Improves tremor and rigidity but has little effect on bradykinesia

Question 27

Name 5 drugs that can be used in Parkinson disease. In addition, what is used for essential or familial tremors?

Answer 27

(1) Bromocriptine (2) Amantadine (3) Levodopa (with carbidopa) (4) Selegiline (and COMT inhibitors) (5) Antimuscarinics; Think: “BALSA”; For essential or familial tremors, use a Beta-blocker (e.g., propranolol)

Question 28

What is the ultimate effect of L-dopa (levodopa)? How does it work, and how does it differ from dopamine?

Answer 28

Increase level of dopamine in brain; Unlike dopamine, L-dopa can cross blood-brain barrier and is converted by dopa decarboxylase in the CNS to dopamine

Question 29

What is carbidopa? What is its use in the treatment of Parkinson disease symptoms?

Answer 29

Carbidopa, a peripheral decarboxylase inhibitor, is given with L-dopa to increase the bioavailability of L-dopa in the brain and to limit peripheral side effects

Question 30

What is the clinical use of L-dopa (levodopa)/carbidopa?

Answer 30

Parkinson disease

Question 31

What is (more short-term) toxicity associated with L-dopa (levodopa)/carbidopa, and what causes it?

Answer 31

Arrhythmias from increased peripheral formation of catecholamines

Question 32

What is a long-term toxicity of L-dopa (levodopa)/carbidopa? What is this called? What occurs in between doses?

Answer 32

Long-term use can lead to dyskinesia following administration (“on-off” phenonmenon), akinesia between doses

Question 33

What is mechanism and effect of selegiline?

Answer 33

Selectively inhibits MAO-B, which preferentially metabolizes dopamine over norepinephrine and 5-HT, thereby increasing the availability of dopamine

Question 34

What is the clinical use of selegiline? What is a toxicity to consider?

Answer 34

Adjunctive agent to L-dopa in treatment of Parkinson disease; May enhance adverse effects of L-dopa

Question 35

Name 4 Alzheimer drugs.

Answer 35

(1) Memantine (2) Donepezil (3) Galantamine (4) Rivastigmine

Question 36

What is the mechanism and effect of Memantine?

Answer 36

NMDA receptor antagonist; helps prevent excitotoxicity (mediated by Ca2+)

Question 37

What are 3 toxicities associated with Memantine?

Answer 37

(1) Dizziness (2) Confusion (3) Hallucinations

Question 38

What is the mechanism of donepezil? Name 2 other drugs that share this mechanism and can also be used for Alzheimer disease.

Answer 38

AChE inhibitors; Galantamine, Rivastigmine

Question 39

Name 3 AChE inhibitors that can be used for Alzheimer disease. What are 3 toxicities associated with them?

Answer 39

Donepezil, galantamine, rivastigmine; (1) Nausea (2) Dizziness (3) Insomnia

Question 40

What are 3 neurotransmitter changes in Huntington disease?

Answer 40

Decreased GABA and ACh, Increased dopamine

Question 41

Name 3 treatments for Huntington disease.

Answer 41

(1) Tetrabenazine and (2) Reserpine (3) Haloperidol

Question 42

What is the mechanism and effect of Tetrabenazine? Which other Huntington drug shares this mechanism and effect?

Answer 42

Inhibit vesicular monoamine transporter (VMAT); limit dopamine vesicle packaging and release; Reserpine

Question 43

What type of drug is Haloperidol, and for what condition is it used?

Answer 43

Dopamine receptor agonist; Huntington disease

Question 44

What is the mechanism of Sumatriptan, and what 3 effects does it have?

Answer 44

5-HT 1B/1D agonist. Inhibits trigeminal nerve activation; Prevents vasoactive peptide release; Induces vasoconstriction

Question 45

For what is Sumatriptan used clinically?

Answer 45

Acute migraine, cluster headache attacks; Think: “a SUMo wrestler TRIPs ANd falls on your HEAD”

Question 46

What are 2 toxicities associated with Sumatriptan? In what patient populations is Sumatriptan contraindicated?

Answer 46

Coronary vasospasm (contraindicated in patients with CAD or Prinzmetal angina), Mild tingling

Question 47

What is the half-life of sumatriptan?

Answer 47

< 2 hours