Pharm - Adrenergic/Cholinergic Effects, Movement Disorders, Analgesia

Question 1

Adrenergic pathway in CNS

Answer 1

Norepinephrine distributed throughout brain; majority of noadrenergic neurons in locus ceruleus (sleep and arousal center)

Question 2

Adrenergic receptors

Answer 2

G protein coupled

Question 3

Cholinergic pathways in CNS

Answer 3

Mixture of both nicotinic and muscarinic

Question 4

Ach and NE brain functions

Answer 4

Ach - motivation, learning, memory; NE - arousal, attention, vigilence, and memory; both involved with wakefullness and cognition

Question 5

Antipsychotics

Answer 5

Work on many receptors in the brain (ex - muscarinic blockade, dopamine blockade); AE - xerostomia, constipation, Parkinson’s

Question 6

Effects of antidepressants

Answer 6

Similar to antipsychotics but with CV involvement - hypotension, reflex tachycardia

Question 7

Treatment for Parkinsonism

Answer 7

Benztropine, diphenhydramine, trihexyphenidyl

Question 8

Receptors in amygdala

Answer 8

Alpha and beta 1 adrenergic receptors

Question 9

PTSD treatment

Answer 9

Paroxetine and sertriline (SSRI), prazosin and propanolol (for amygdala)

Question 10

Lipophilic drugs that have central effects

Answer 10

Propanolol and diphenhydramine

Question 11

Pathogenesis of Parkinson’s

Answer 11

Indirect pathway predominates, loss of dopamine input from SNpc or blockade of dopamine receptors

Question 12

Dopamine replacement therapy

Answer 12

Primary treatment, use when symptoms show functional impairment, levodopa used bc DA cannot cross BBB, fluctuations in response “on-off phenomena”

Question 13

Stimulation of DA receptors

Answer 13

Activate D2 receptors to turn of indirect pathway

Question 14

Drugs that stimulate DA receptors

Answer 14

Bromocriptine (D2 agonist/D1 partial agonist), apomorphine (D1/D2 agonist), Pramipexole (D2 selective), Ropinirole (D2 selective)

Question 15

Enhancement of DA release

Answer 15

Amantadine

Question 16

Inhibition of DA metabolism

Answer 16

Selegiline (selective MAO-B inhibitor), Rasagiline (inhibitor of MAO-B), Entacapone/tolcapone (selective inhibitors of COMT)

Question 17

Muscarinic Antagonist for PD

Answer 17

To block cholinergic activation of striatum - benztropine, diphenhydramine, trihexyphenidyl

Question 18

Treatment for Huntington’s

Answer 18

Reserpine and tetrabenazine (DA depleting), chlorpromazine and haloperidol (DA antagonist)

Question 19

How opiates lead to death

Answer 19

Respiratory depression

Question 20

How opioids works

Answer 20

Inhibition of calcium presynaptically, activation of potassium postsynaptically

Question 21

What plays an important role in central sensitization

Answer 21

NMDA receptors

Question 22

NMDA blockers

Answer 22

Ketamine and Dextromethorphan used prior to surgery to avoid sensitization

Question 23

Common features of opiates and adjunctive agents

Answer 23

Sedation

Question 24

Common feature of alpha 2 adrenergic agonists

Answer 24

Reduced sympathetic outflow; hypotension, bradycardia

Question 25

Opiate receptor subtypes

Answer 25

Delta, kappa, mu (OP 1,2,3 - think alphabetic order) - highest affinity for enkephalins, dynorphins, and endorphins, respectively

Question 26

Opiate agonists (mu receptor)

Answer 26

Morphine (kappa a little too), Hydromorphone, Oxymorphone, Methadone, Meperidine, Fentanyl, Remifentanil

Question 27

Partial agonists of mu

Answer 27

Codeine, Hydrocodone, Oxycodone, Pentazocine, Nalbuphine, Buprenorphine, Butorphanol (more kappa activity in these)

Question 28

Transdermal opiate delivery

Answer 28

Fentanyl patches

Question 29

Opiate with low oral bioavailability? High?

Answer 29

Low oral bioavailabiltiy - morphine; high - codeine, oxycodone

Question 30

Mechanism of desensitization

Answer 30

Some like morphine only activate G-protein signaling but fail to activate endocytosis (recycling of receptors); enkephalin does both

Question 31

Mediators of receptor internalization

Answer 31

GRK2 and beta arrestin (arrested for using opiate drugs!)

Question 32

Tolerance in opiate drug use

Answer 32

High tolerance to most things like analgesia (which sucks) and low tolerance to constipation and convulsions which are persistent (double sucks)

Question 33

Adverse effects of opiates that may need management

Answer 33

Nausea/vomiting, constipation, pruritis, respiratory depression, somnolence

Question 34

Classic triad of opiate overdose

Answer 34

coma, pinpoint pupils, respiratory depression

Question 35

Opiate antagonists

Answer 35

Naloxone, nalmefene, naltrexone (the longer the name the longer the action)

Question 36

Converted to morphine

Answer 36

Heroin and codeine

Question 37

Meperidine

Answer 37

Anticholinergic effects, not used commonly because of diverse effects

Question 38

Best opiate to use in treating opiate withdrawal

Answer 38

Methadone - really long half life

Question 39

Tramodol

Answer 39

Little effect on respiratory or CV systems; increased risk of hypoglycemia compared to codeine (mnemonic: tremor-dol; tremors bc of low sugar)

Question 40

Opiates used in renal insufficiency

Answer 40

Hydromorphone and fentanyl (no active metabolites)

Question 41

Strategy for management of poorly responsive pain

Answer 41

Opiate rotation

Question 42

Signs of opiate withdrawal

Answer 42

Agitation, diaphoresis, increased lacrimation, piloerection, dilated pupils

Question 43

Short-term treatment of opiate withdrawal

Answer 43

Methadone and clonidine

Question 44

Buprenorphine combination

Answer 44

Has naloxone that works only IV and not oral so it discourages abuse of the drug

Question 45

Opiate for pregnancy

Answer 45

Methadone

Question 46

Adverse effects of methadone

Answer 46

Constipation, drowsiness, prolonged QTc and arrhythmia

Question 47

Buprenorphine for opiate withdrawal

Answer 47

Precipitates withdrawal due to high affinity to receptors, long duration, ceiling effect (hard to overdose)

Question 48

Gabapentin/Pregabalin

Answer 48

Inhibits neuron excitation by binding to alpha2-delta subunit

Question 49

Lamotrigine/Carbamazepine

Answer 49

Block sodium channels

Question 50

Anti-tussive opiates

Answer 50

Codeine and Dextromethorphan

Question 51

Antidiarrheal opiates

Answer 51

Loperamide and Diphenoxylate

Question 52

Treatment for alcohol dependence and cravings

Answer 52

Naltrexone

Question 53

Surgical management of pain

Answer 53

Neuroablation (last resort)

Question 54

Opiate found combined with acetaminophen

Answer 54

Codeine, oxycodone, and hydrocodone