Opioids - Review, General info Flashcards Preview

Summer Pharm (2016) ** > Opioids - Review, General info > Flashcards

Flashcards in Opioids - Review, General info Deck (98):
1

firing of a neuron that is not indicative of of physical damage, but is a pathalogical firing

Neuropathic pain

2

Pain out of proportion to noxious stimuli

Hyperalgesia

3

Pain evoked by a non-noxious stumuli

Allodynia

4

pain with no apparent stimuli - it is NERVE pain

spontaneous pain

5

Peripheral nociceptive neuron activated by intense noxious stimimuli (tissue damage) via 

*  Mechanical * thermal * chemical 

6

slow conduction, dull, burning, diffuse

non-mylinated C fibers

7

fast conduction - sharp and well localized

A-delta fibers

8

nociceptiv impulse depends on the balance between

excitatory and inhibatory receptors

9

excitatory cation channel activated by: * Protons * heat * capsaisin * Endovanilloids

TRIP1

10

hyperpolarization related to opioid receptor activation

cells will need a stronger stimulus to fire

11

promotes depolarization and stimulates pain

Bradykinin and Prostaglandins

12

Area of dorsal horn that is very rich in opioid peptides and receptors 

substantia geletinosa

13

Lamina for A delta fibers

Lamina I and V

14

Lamina for C fibers

Lamina II and III (substantia gelatinosa)

15

Located in lamina II and III

Substantia gelatinosa

16

where do opioids act at the brain level

pre and post synaptically to activate descending inhibatory pathways

17

where do opioids act at the spinal cord level

work directly on the dorsal horn of the spinal cord

18

where do opioids act at the periphery level

act on peripheral teminals of nociceptive neurons

19

why is the perception of noxious stimuli not the same as pain?

it is lacking the emotional component

20

Opioids can change patients ___ without necessarily changing the patients ability to _____ noxious stimuli

* tolerance of pain  * perceive   ie- they can still tell you where the wound is

21

The main use of opioids on anestehsia 

Attenuate the SNS response to noxious stimuli- Laryngoscopy

22

opoids and inhaled anesthetics

act as an adjunct allowing for less use of inhaled agent

23

natrurally occuring drugs derrived from opium from the poppy plant

Opiate * Morphine * Codeine

24

Opioids produce analgesia without loss of

* Touch * Propioception * Conciousness

25

naturally occuring opioids

Morphine

26

semisynthetic: analogs of morphine

heroine dihydromorhone codeine

27

Synthetic Opioids

* Exogenous  Has 4 classifications * agonist * partial aginist * mixed agonist/antagonist * antagonist

28

Synthetic antagonist

Narcan

29

can reach maximum eficacy on dose response curve their potency is what varries

Synthetic agonists (full)

30

will have a ceiling effect cannot reach maximum effect on dose response curve

Synthetic partial agnosts

31

Synthetic opioid agonist / antagonist

agonist at kappa receptors antagonist and mu receptors

32

if their is any potential you will need to switch to a full agonist you want to start with 

a parial agonist and NOT  an agonist / antagonist

33

Opioids - Mechanism of action

Activate stereo-specific G-protein coupled receptors and act post-synaptically to directly decrease neurotransmission by: increase K conductance (hyperpolarization) and Ca++ channnel inactivation (decreased NT release), inhabition of adenylate cyclase (decreased cAMP) Modulation of phospinositide- signaling cascade for phospholipase C increase MAP kinase which affects gene expression and increases phospholipase A2 (increase in leukotriens) and act Pre synaptically Decrease ACh, dopamine, norepi and Substance p release *anytime you hyperpolarize a membrane you decrease NT release*

34

anytime you hyperpolarize a cell you 

decrease neurotransmitter release

35

Opioids PRE-synaptic mechanism of action

inhibits the release of excitatory neurotransmitters * ACh * Dopamine * Norepi * Substance P 

36

Opioid receptors

* Mu (agnoist binding site) * Kappa (antagonist binding site) * Delta

37

All endogenous and exogenous opiois agonists work at these receptors 

Mu-1 and Mu-2

38

May actually cause immunosupression and accelerate some types of cancer

Mu-3

39

Mu receptors location

* brain- supraspinal * spinalcord * periphery

40

Mu 1 site of analgesia

Supraspinal is thought to be the principal site of action but also works at spinal cord in a lesser degree (and periphery)

41

Mu-1  receptor activation causes

cardio - bradycardia no respiratory effects CNS effects: euphoria, sedation, prolactin release, hypothermia, catalepsy, indifference to environmental stimuli Pupil - miosis no Gi effects GU - urinary retention no pruritus low abuse potential

42

Mu-2 receptor activation effects

cardio - bradycardia respiratory - depression ->hypoventilation CNS: euphoria, pruritus, dopamine turnover, possible growth hormone release pupils - miosis GI - inhibition of peristalsis (constipation), nausea, vomiting GU - urinary retention Physical dependence

43

Mu 2 analgesia

principal site of action is the spinal cord (but also has some supruaspinal action as well)

44

kappa receptor analgesia

supraspinal, spinal

45

kappa receptor endogenous agonists

dynorphins

46

Kappa receptor activation effects

no cardio effects respiratory - possible depression ->hypoventilation CNS: sedation, dysphoria, hallucinations, delirium pupils - miosis GU - diuresis (inhibition of vasopressin release) Low physical dependence (low potential abuse)

47

Delta receptor endogenouas ligand

enkephalin

48

delta receptor analgesia

supraspinal, spinal modulates mu receptor activity

49

Delta receptor activation

no cardio respiratory - depression ->hypoventilation no CNS effects GI - minimal inhibition of peristalsis (some constipation) GU - urinary retention Pruritus Physical dependence

50

Located on Chromosome 6q24-q25

Mu opoid receptor

51

aspartated in place of asparagine 10-20% of the population

* Nucleotide 118 polymorphism * Gene Effects agonist binding to Mu receptor 

52

valine in place of alanine 1-10% of population

* Nucleotide 17 polymorphism * Gene Effects agonist binding to Mu opioid receptor 

53

Codine has unpredictable pharmacokinetics and half lives due to 

CYP2D6 gene polymorphisms

54

Opioid least likely to be impacted by genetic variability. Predictable pharmacokinetics.

Fentanyl

55

side effect rate can be influenced by ....

The rate of metabolism

56

Ultra-rapid metabolizers are at risk for 

PONV

57

Opioids and Perioperative cardiovasucular effects (4)

Minimal impairment of CV function  but has additive effect with other analgesics profound vasodilation/ decrease SVR- most evident in patients with hypovolemia Dose dependant bradycardia- via vagal stimulation (nuclei in medula) and Direct SA/AV nodal depression Impairmennt of SNS response and baseline tone orthostatic hypotension that is pronounced with hypovolemia

58

morphine and meperedine and cardiovascular effects

Have a dose dependant histamine release * risk more vasodilation - decreased BP and SVR * risk bronchospasm

59

Why is meperidine an exception to the CV effects of opioids

It will cause tachycardia - due to its atropine like structure

60

When a large dose of opioids are given and the BP drops what is it likely due to? 

Hypovolemia with vasodilation it is NOT likely a contractility isusse, Opioids are pretty cardiac stable

61

Opioids and HR

Dose dependant bradycardia * Central vagal stimulation * act directly on SA/AV nodal depression

62

Opioids and vasculature

Vasodilation/ Decreased SVR * decreased SNS response and baseline tone decreased CO and venous pooling = orthostatic hypotension * Pronounced effect on vasculature

63

What opiods do we want to avoid in astmatics? Why?

Morphine and meperidiene- dose and infusion rate dependant histamine release causes more vasodilation and BRONCHOSPASM

64

Do opioids produce amnesia

No

65

Opioids and patients with increased ICP

*minimal decrease in ICP * Must have ventilations controlled prior to giving opioids * Hypoventilation and Increased CO2 will cause cerebral vasodilation and increased ICP

66

Opioids and urination

Increased Uregency and reduced ability to void * Increased tone and peristaltic activity of ureter * incresed tone of detrusor

67

Why do opioids cause nausea and vomiting

* decreased gastric emptying * stimulation of chemoreceptor zone of the 4th ventricle * balanced depression of medulary vomiting center

68

Puritis and Opioids

cause is unknown, could be the histamine release with morphine and meperidine, but fentanyl it is unknown (fentanyl nose itch)

69

drugs that cause adverse affect: muscle rigidity in chest, abdomen, jaw and extremeties

* Fentanyl * Sufentanyl * Hydromorphone (Dilaudid)

70

issues with adverse affect: muscle rigidity from opioids

High airway pressures from increased intrathoracic pressure and decreased veonus return difficult/impossible to ventilate only releived my non-depolarizing muscle relaxant glottic rigidity and closure reported

71

Smaller dose of opioids - respiratory effects

Increased Tidal voume and decreased RR Increased CO2 and decrease O2

72

Larger dose of opioids

Decreased TV and Decreased RR 

73

ventilatory effects of opioids

Dose dependant respiratory depression Decreased chest wall compliance constriction of pharyngeal and laryngeal muscles cough suppression Dramatically decreased response to hypercarbia and hypoxia

74

Factors that increase the magnitude and duration of opioid induced respiratory depression

higher doses Intermittent boluses have higher degree of respiratory depression than contiuous infusion Speed of injection Concurrent admin with other anesthetics Decreased clearance (active metabolites build up) Age - older and younger alkalosis - opioid are weak bases secondary peaks in plasma levels from reuptake from muscle, fat, lung and intestines

75

Morphine active metablolite

morphine-6-glucuroninde

76

prodrug- active form is morphine

Codeine (3-methylpmorphine)

77

Long plasma half life 8-59 hours or 13-100, sources vary * High variability among individuals

Methadone

78

How long does it take to develop tolerance to opioids?

48 hours - need to taper

79

effects of tolerance

reduction of adverse effects (less respiratory, nausea and CNS side effects) shorter duration of analgesia decrease in effectiveness does not work

80

What side effect dies NOT go away with tolerance

Constipation - a stimulant laxative w/ or without stool softener should be started early in treatment

81

Neuralaxial analgesia (diffusion)

Cross the dura onto mu receptors to the substantia geletinosa  difuses into the vasculature to get systemic effect

82

given neuroaxial: very lipid soluable 

fentanyl

83

Given neuroaxial: very water soluable - will circulate with CSF

Morphine

84

Opioids in the epeidural space may diffuse into  * _______ * _______ * _______

* fat * systemic absorbtion (vasculature) * CSF

85

Cephalad movemnt of opioid in CSF depends on ____________. 

Lipid solubility

86

lipid solubility and migration of neuroaxial opioids

more lipid soluble = limited migration, penetrates the dura more readily and has quicker peak in CSF/systemic concentration; resp depression seen immediately or early on Less lipid soluble = will remain in CSF for transfer to cephalad location; resp depression not seen until hrs later

87

Why is the dose for an epidural 5x higher than that for a spinal?

Because the spinal is directly at the site

88

side effects with neuraxial opioids

ventilatory depression pruritus N/V urinary retention

89

This can be given to treat muscle rigidity from opioids

NDMRs

90

What should you do if you see a localized reaction at the site of morphine injection?

DON'T PANIC Morphine causes histamine release, so this is a common reaction

91

These meds can be used to relieve sphincter of oddi spasm

Glucagon, nubain, and NTG

92

Opioids are weak (acids/bases)

Bases

93

Vd is related to

Lipid solubility and protein binding

94

A large Vd will equate to a long or short DOA?

Long

95

Do opioids produce amnesia?

NO

96

How do opioids produce bradycardia?

Vagal stimulation and inhibition of the SA node

97

The bradycardia and ventilatory depression caused by opioids are

dose dependent

98

Where do agonists/antogonists work?

They are Mu antagonists and full or partial kappa agonists