PHARM: Opiates and Pain Pharmacotherapy Flashcards
(105 cards)
1
Q
Where do NSAIDs work in the pain pathway?
A
modulate the initial signal transduction
2
Q
Where do Na+ channel blockers work in the pain pathway?
A
act as local anesthetics to block signal conduction (AP generation) in nociceptive fibers
3
Q
Where do opiods work in the pain pathway?
A
spinal cord (block pre-synaptic Na+ channels and open post-synaptic K+ channels to decrease likelihood of action potential)
4
Q
How do NE and GABA work in the pain pathway?
A
act just like opiates
5
Q
What receptors play a prominent role in the sensitizaiton phenomenon?
A
NMDA glutamatergic receptor
6
Q
How is short-term sensitization achieved?
A
post-translational modifications (phosphorylation)
7
Q
How is long-term sensitization achieved?
A
altered gene expression (phosphorylation of GRPs)
8
Q
What is it called when pain arises from transection or mechanical damage to the nerve axon?
A
neuropathic pain
9
Q
What receptor is OP-1?
A
delta
10
Q
What receptor is OP-2?
A
kappa
11
Q
What receptor is OP-3?
A
mu
12
Q
What are OP-1 receptors specific for?
A
Enkephalins
13
Q
What are OP-2 receptors specific for?
A
Dynorphins
14
Q
What are OP-3 receptors specific for?
A
Endorphins
15
Q
What occurs with activation of OP-1 receptors?
A
modulation of hormone and neurotransmitter release
16
Q
What occurs with activation of OP-2 receptors?
A
psychotomimetic effects (decreased GI transit)
17
Q
What occurs with activation of OP-3 receptors?
A
sedation, decreased respiration, decreased GI transit, and modulation of hormone and neurotransmitter release
18
Q
Which opiates can be given rectally?
A
hydromorphone
morphine
oxymorphone
19
Q
What opiates can be given in a lozenge form?
A
codeine
oxycodone
20
Q
What opiate can be given in patch form?
A
fentanyl
21
Q
What opiate is contraindicated in renal failure and breastfeeding?
A
codeine
22
Q
Which opiates can be used in renal failure?
A
Fentanyl
Hydromorphone
23
Q
Which opiate has a long half-life and can be used to treat withdrawal?
A
Methadone
24
Q
Which opiate has a DDI with MAOIs?
A
Meperidine
25
Which opiate can cause long QT and reduced libido?
Methadone
26
Which opiate can cause peripheral and central anti-cholinergic effects?
meperidine
27
Which opiate can only be given IV?
remifentanil
28
Which opiates are NOT solely OP-3 agonists?
Codeine (OP-3 partial agonist)
| Morphine (OP-3 agonist AND OP-2 minor agonist)
29
Which opiate can be converted to morphine by CYP2D6?
codeine
30
Which opiate has the lowest potency?
meperidine
31
What is interesting about meperidine metabolism?
it is either broken down into an inactive form or into a form that is 3X more potent
32
What opiate is a substrate for P-gp and CYP?
methadone
33
What is the most potent opiate?
fentanyl
34
Which opiate is the same potency as morphine?
methadone
35
Which PD drugs are contraindicated with meperidine?
selegiline
| rasagiline
36
List the opiod partial agonists
```
Butorphanol
Buprenorphine
Hydrocodone
Nalbuphine
Pentazocine
```
37
Which opiod partial agonists are only IV?
Butorphanol
| Nalbuphine
38
Which opiod partial agonist has a very high potency and a ceiling effect?
Buprenorphine
39
Which opiod partial agonists is not simply a partial mu agonist?
Buprenorphine (partial Mu agonist and partial delta and kappa antagonist)
40
Which opiod partial agonist is metabolized by CYP3A4 and CYP2D6?
Hydrocodone
41
Which opiod partial agonist is used for withdrawal due to its very tight binding (long acting)?
Buprenorphine
42
What drug is given with Buprenorphine for withdrawal?
naloxene
43
True or false: opiates commonly relieve pain completely.
FALSE they make pain more tolerable
44
What is a strange toxicity of opiates?
pruritis around nose
45
What symptom of opiates is more common with parenteral or spinal administration?
urticaria
46
Which opiate toxicities have minimal or no likelihood of tolerance developing (will never get better as long as you are using the drug)?
MIosis
Constipation
Convulsions
47
Which opiate toxicity has moderate likelihood of tolerance developing?
bradycardia
48
Why does constipation occur with opiate treatment?
binding to opiate receptors in enteric nervous system produces anticholinergic action (Ach usually stimulates peristalsis, so anticholinergic leads to stasis and hardening of stool)
49
How do you treat opiate-induced constipation?
- prophylaxis with stool softener or laxative
| - careful titration with opiate antagonist
50
Why does N/V occur with some people who are treated with opiates?
they get rapid initiation at high doses (not as likely if slow titration!
51
What do you do to treat opiate-induced respiratory depression?
- If in hospital setting, do not give next dose
| - If overdose, try naloxone
52
Why does pruritis occur with opiate treatment?
central action or direct stimulation of mast cells
53
What is opiod rotation?
use of a different opiate to control pain and reduce adverse effects if a patient is "poorly responsive" to a treatment (has bad side effects)
54
What is the triad of opiate overdose?
- Coma
- Pinpoint pupils
- Respiratory depression
55
Why does coma occur with opiate overdose?
decreased cortical stimulation via thalamus and hypothalamus
56
Why does pinpoint pupils occur with opiate overdose?
Edinger-westphal complex sitmulated
57
What drugs increase sedation and respiratory depression of opiates?
Sedative-hypnotics
Antipsychotics
MAOIs
58
What is the mechanism by which tolerance occurs with opiates?
recycling of GPCRs
59
What protein phosphorylates opiate receptors to lead to internalization?
GRK (increases receptor affinity for beta-arrestin which enhances interaction between 2 proteins and leads to internalization)
60
How does endogenous enkephaline and morphine differ in respect to tolerance?
endogenous enkephalins have a relative balance between sensitization and resensitization while morphine has a slow perisstent desensitization and little recycling
61
How has the view of receptor recycling and resensitization changed?
resensitizaiton is now thought to be able to occur without the need for internalization (receptor dephosphorylation can occur if GRK2 and beta-arrestin proteins are inhibited with pharmacologic agents)
62
List the 3 opiate antagonists.
Naloxone
Nalmefene
Naltrexone
63
Which opiate antagonist has a very short half-life (30-80 minutes)?
Naloxone
64
Which opiate antagonist has a long half-life and can be used to treat opiate addiction and decrease alcohol cravings?
naltrexone
65
What is the indication for naloxone?
Opiate toxicity (treat respiratory depression or progressive obtundation suggestive of imminent decline)
66
Which opiate antagonist can precipitate withdrawal in dependent patients?
naltrexone
67
Which opiate antagonist can cause abstinence, aspiration and severe pain?
naloxone
68
What precipitates opiate withdrawal symptoms?
when the levels of opiate in the blood decline below a threshold level
69
What are the symptoms of opiate withdrawal?
- Drug seeking (craving)
- Crawling sensation of skin, diaphoresis, rhinorrhea
- Anxiety, fear, sleep disturbance
- Musculoskeletal pain
- Nausea and diarrhea
70
Which symptoms are NOT present in opiate withdrawal?
HTN, tachycardia, hallucinations, seizures, fever, delirium
71
What signs are present in opiate withdrawal?
```
Agitation
diaphoresis
Increased lacrimation
Piloerection
Dilated pupils
```
72
What is the short-term treatment for opiate withdrawal?
methadone
73
What is the long-term treatment for opiate withdrawal?
clonidine for 21 days
74
What receptors does clonidine bind to?
alpha-2 receptors that are regulators at both pre-synaptic and post-synaptic sites
75
What symptoms of withdrawal does clonidine NOT help with?
Insomnia
Muscle cramps
GI symptoms
76
What is the characteristic molecular occurence in addiction?
surge of dopamine signaling in the nucleus accumbens
77
What causes the surge of dopamine signaling in the nucleus accumbens during addiction?
- GPCR activation
- Activation of ionotropic receptors
- Modulation of biogenic amine transport
78
All addictive drugs increase dopamine concentration in what structure?
mesolimbic projection
79
True or false: every patient with physical dependence to opiates will become addicted.
FALSE
80
What is addiction?
compulsive, relapsing drug use despite negative consequences
81
What treatment for opiate addiction has a very poor adherence?
naltrexone
82
What treatment for opiate addiction is favored in pregnant women?
Methadone (may need to increase dose in 3rd trimester)
83
Which treatment for opiate addiction requires a special state and federal license?
methadone
84
What treatment for opiate addiction is given in combination with naloxone?
buprenorphine
85
Why do you give naloxone with buprenorphine?
because naloxone only works parenterally, so if the patient tries to crush up the pill and inject it to get high, it will activate the naloxone (which antagonizes the effect of the buprenorphine)
86
How does naltrexone block alcohol dependence craving?
block elevation of dopamine levels arising from signals in the VA and arcuate nucleus
87
List the NMDA antagonists.
Ketamine
| Dextromethorphan
88
When do you use ketamine?
- Prevent surgery-induced sensitizaiton
| - acute, severe pain
89
When do you use dextromethorphan?
-Post-operative or chronic pain
90
What are the toxicities of ketamine?
hallucinations
amnesia
CV pressor
increased intracranial pressure
91
What are the toxicities of dextromethorphan?
dizziness
confusion
fatigue
92
List the TCAs used for pain disorders and depression associated with chronic pain?
- Amitriptyline
- Nortriptyline
- Imipramine
- Desipramine
93
How do TCAs work in treating pain?
NE and 5-HT reuptake properties in ascending corticospinal monoamine pathways
94
Which anticonvulsants are used for ancillary pain?
pregabalin
| gabapentin
95
Which anticonvulsant can be used to treat trigeminal neuralgia and ancillary pain?
carbamazepine
96
Which anticonvulsant can be used to treat neuropathy, phantom, stroke and MS?
lamotrigene
97
What anti-convulsants work by blocking Na+ channels that get upregulated in neuropathic pain?
Lamotrigene
| Carbamazepine
98
What anti-convulsants work by inhibition of voltage gated Ca2+ channels via the alpha-2-delta subunit (prevent trafficking to the cell surface)?
pregabalin
| gabapentin
99
Which CYP interactions do TCAs have?
CYP2D6
100
Which anticonvulsant has a BBW for Stevens Johnson Syndrome?
Lamotrigene
101
Which anticonvulsants are dose adjusted in hepatic failure?
Lamotrigene
| Carbamazepine
102
Which anticonvulsants are dose adjusted in renal failure?
Pregabalin
| Gabapentin
103
Which anticonvulsants have an increased risk for suicidal ideation?
lamotrigene
104
Which anticonvulsant is associated with rare agranulocytosis?
carbamazepine
105
Which opiates are used to treat IBS diarrhea?
loperamide
| diphenosylate (prescription)
