PHARM: Opiates and Pain Pharmacotherapy Flashcards Preview

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Flashcards in PHARM: Opiates and Pain Pharmacotherapy Deck (105):
1

Where do NSAIDs work in the pain pathway?

modulate the initial signal transduction

2

Where do Na+ channel blockers work in the pain pathway?

act as local anesthetics to block signal conduction (AP generation) in nociceptive fibers

3

Where do opiods work in the pain pathway?

spinal cord (block pre-synaptic Na+ channels and open post-synaptic K+ channels to decrease likelihood of action potential)

4

How do NE and GABA work in the pain pathway?

act just like opiates

5

What receptors play a prominent role in the sensitizaiton phenomenon?

NMDA glutamatergic receptor

6

How is short-term sensitization achieved?

post-translational modifications (phosphorylation)

7

How is long-term sensitization achieved?

altered gene expression (phosphorylation of GRPs)

8

What is it called when pain arises from transection or mechanical damage to the nerve axon?

neuropathic pain

9

What receptor is OP-1?

delta

10

What receptor is OP-2?

kappa

11

What receptor is OP-3?

mu

12

What are OP-1 receptors specific for?

Enkephalins

13

What are OP-2 receptors specific for?

Dynorphins

14

What are OP-3 receptors specific for?

Endorphins

15

What occurs with activation of OP-1 receptors?

modulation of hormone and neurotransmitter release

16

What occurs with activation of OP-2 receptors?

psychotomimetic effects (decreased GI transit)

17

What occurs with activation of OP-3 receptors?

sedation, decreased respiration, decreased GI transit, and modulation of hormone and neurotransmitter release

18

Which opiates can be given rectally?

hydromorphone
morphine
oxymorphone

19

What opiates can be given in a lozenge form?

codeine
oxycodone

20

What opiate can be given in patch form?

fentanyl

21

What opiate is contraindicated in renal failure and breastfeeding?

codeine

22

Which opiates can be used in renal failure?

Fentanyl
Hydromorphone

23

Which opiate has a long half-life and can be used to treat withdrawal?

Methadone

24

Which opiate has a DDI with MAOIs?

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)