8 CNS Drugs

Question 1

what are 2 types of CNS neurons

Answer 1

• excitatory - activates post-synaptic receptors that increase Na+/Ca2+ influx
• inhibitory - activate post-synaptic receptors that increase Cl- influx or K+ efflux

Question 2

4 classifications of CNS neurotransmitters and some of their examples

Answer 2

• amino acids
• • excitatory - glutamate
• • inhibitory - GABA
• acetylcholine
• monoamines
• • dopamine
• • norepinephrine
• • serotonin (5-HT)
• peptides
• • opioids

Question 3

• causes of Alzheimer’s
• tx
• side effects

Answer 3

• loss of cholinergic input to limbic system (impairs memory) and cortex (cognitive dysfunction)
• no Tx affects neurodegeneration
• acetylcholinesterase inhibitors (eg. donepezil) penetrates CNS, decreases loss of cognitive function in moderate AD
• ANS side effects - nausea, diarrhea, vomiting

Question 4

2 types of Parkinson’s

Answer 4

• naturally occurring
• drug-induced
• • reversible - neuroleptic drugs block dopamine receptor
• • irreversible - MPTP destroys dopaminergic neurons in substantia nigra

Question 5

effects of dopamine and ACh in a normal vs Parkinsonian brain?

Answer 5

• normal
• • substantia nigra produces dopamine, inhibits GABA
• • ACh excites GABA
• Parkinsonian
• • substantia nigra doesn’t produce GABA, dopmaine agonists needed to inhibit GABA
• • antimuscarinic drugs needed to lower excitatory response to GABA

Question 6

3 drugs used in Parkinsonism and overall purpose

Answer 6

• Levodopa & dopamine agonists
• MAO inhibitors
• antimuscarinic drugs

increase dopamine activity in brain or decrease muscarinic cholinergic activity or both

Question 7

• levodopa and dopamine agonists MOA

- AE

Answer 7

• levodopa converted to dopamine by DOPA decarboxylase
• dopamine agonists bind to dopaminergic receptors in brain
• improve sx until too few neurons left
• levodopa metabolism to dopamine –> dyskinseia, nausea, joint stiffness

Question 8

• MAO inhibitor eg.
• MOA
• AE

Answer 8

• eg. selegiline
• selective inhibitor of MAO-B –> decreases dopamine metabolism –> prolongs action
• adjunct to L-dopa
• dyskinesia, hallucination hypotension

Question 9

• antimuscarinic drugs eg.
• MOA
• AE

Answer 9

• eg. benztropine
• decreases overactivity of cholinergic neurons in basal ganglia
• used in early PD or with L-dopa
• drowsiness, confusion, hallucinations

Question 10

2 hypotheses of schizophrenia as related to the limbic system

Answer 10

• dopamine hypothesis
• • functional excess of dopamine
• • antipsychotic drugs decrease dopamine synaptic activity (D2 blockade) to reduce symptoms
• serotonin (5-HT) hypothesis
• • hallucinogenic drugs are 5-HT agonists
• • 5-HT receptors modulate dopamine release in limbic system, cortex, striatum
• • atypical antipsychotic drugs decrease serotonin synaptic activity (5-HT2a blockade)

Question 11

what are antipsychotic effects reversed by?

Answer 11

increasing dopamine by levodope or amphetamine

Question 12

2 typical antipsychotic drug types and examples

Answer 12

• phenothiazine derivative - eg. chlorpromazine

- butyrophenone derivative - eg. haloperidol

Question 13

1 typical antipsychotic drug example

Answer 13

clozapine

Question 14

pharmacodynamics (blockade) or haloperidol and clozapine

Answer 14

• haloperidol D2>D4>a1>5HT2A

- clozapine D4=a1>5HT2A>D2

Question 15

• clinical effects of all antispychotics? atypical (more so than typical)?

Answer 15

• all - decrease positive sx (hallucinations, delusions)

- atypical - decrease negative sx (apathy, impaired attention)

Question 16

• side effects of antipsychotics
• typical (more so than atypical)
• all
• atypical

Answer 16

• general: block D2 –> increase cholinergic activity
• typical&raquo_space; atypical - movement disorders, hyperactivity
• all - a receptor blockade –> hypotension
• atypical –> weight gain

Question 17

3 monoamines and what they are responsible for

Answer 17

• norepinephrine - alertness, energy, anxiety, attention, interest
• serotonin - anxiety, obsessions, compulsions
• dopamine - attention, motivation, pleasure, reward, interest

Question 18

• selective serotonin reuptake inhibitors (SSRI) eg.
• uses
• what’s serotonin syndrome?

Answer 18

• eg. fluoxetine (Prozac)
• less side effects than tricyclics
• antidepressant, obesity, OCD, bulimia
• serotonin syndrome when combined with other antidepressants (life-threatening seizures, CV instability etc)

Question 19

serotonin-NE reuptake inhibitors (SNRI)

Answer 19

• increase [ ] of NE and serotonin in synaptic cleft
• better than SSRi for major depressive disorders
• low affinity for other NT receptors = low AE

Question 20

• MAO inhibitor eg.
• MOA
• what’s hypertensive crisis?

Answer 20

• eg. phenelzine
• stops degradation of NE, dopamine and serotonin in nerve terminal
• used if other antidepressants not effective
• hypertensive crisis if tyramine-cntaining foods (cheese, beer, red wine) ingested with amphetamines

Question 21

clinical use of antidepressants?

Answer 21

• SSRIs 1st
• switch if ineffective
• monoamine levels change after 1 dose, action may not be observed immediately

Question 22

• bipolar disorder tx eg.

- side effects

Answer 22

• eg. lithium carbonate
• stabilizes mood, no drowsiness
• prevents mania, depression
• low TI, high toxicity, ataxia, tremors

Question 23

• anxiety disorder tx - first line? others?

Answer 23

• SSRI 1st
• anxiolytics (sedative) - eg. benzodiazepine
• risk of dependence
• no motor effect

Question 24

• benzodiazepine eg.

- MOA

Answer 24

• eg. diazepam (valium)
• enhances GABA (inhibitory) neutrotransmission
• binds to GABAa receptor –> increase FREQUENCY of GABA-mediated opening of Cl- channel –> increases inhibition of neurons in brain

Question 25

- barbiturates eg. | - MOA

Answer 25

- eg. phenobarbital/pentobarbital | - same as diazepam but increase DURATION

Question 26

toxicity of anxiolytics-sedative/hypnotics

Answer 26

- dose-dependent CNS depression - impaired judgement, amnesia, coma, death - additive CNS depression with other drugs - withdrawal when stopped - tolerance - increased toxicity if liver impaired

Question 27

- antiepileptic drugs that modify ionic conductances - 2 eg. | - MOA

Answer 27

- phenytoin, carbamazepine | - block Na+ channels (excitatory)

Question 28

- antiepileptic drugs that enhance inhibitory transmission - 1 new eg, 2 old eg. MOA

Answer 28

- eg. valproic acid - - inhibits GABA transaminase --> terminates action of GABA - eg. diazepam and phenobarbital - - opens GABA-mediated Cl- channel to enhance GABA neurotransmission

Question 29

- 2 toxicity problems with anti-epileptic drugs - withdrawal - drug interactions

Answer 29

- teratogenicity increases risk of fetal malformations (cardiac defects, cleft lip/palate [phenytoin, carbamazepine], neural tube effects [valproic acid]) - overdosage - CNS/resp depression - withdraw drug gradually if seizure-free for 4 years - alter metabolism by inducing/inhibiting hepatic enzymes - change binding of another drug to plasma proteins