Intro to Narcotics Flashcards Preview

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Flashcards in Intro to Narcotics Deck (84):
1

Non opiate drug examples

local anesthetics,
GABA agonists
non N-methylD asparate (NMDA) antagnists,
COX inhibitors
corticosteroids

2

Antidepressants are useful in treating chronic pain because

they increase the availability of serotonin or norepi in pain modulating descending pathways

3

NSAIDs

ibuprofen
aspirin
acetominophen

4

NSAID action

non specific COX inhibitors, peripheral and spinal

5

COX 2 inhibitor example and action

celecoxib
COX 2 selective inhibitor
Peripheral and spinal

6

Opioids example and action

morphine
mu receptor agonist
supraspinal and spinal

7

Anticonvulsants example and action

Gabapentin
Na+ channel block
alpha2delta subunit of Ca+ channel
supraspinal and spinal

8

Tricyclic antidepressants example and action

amitryptiline
inhibits uptake of serotonin and Norepi (therefor prolongs the effect of these)

9

Opium contains

Morphine (10-15%)
Codeine (1-3%)
Thebaine (1-2%)

10

Opioid receptors in the brain

expressed in many parts of the brain, cerebellum, nucleus accumbens and hypothalamus
many of the regions are involved in pain perception, emotion, reward and addiction

11

Opioid activity in the brainstem

can affect breathing by quieting neurons that control respiration
respiratory depression is serious side fx and commonly sited in case of opioid overdose

12

opioid receptors in the spinal cord

Pain transmission in the dorsal horn is dampened by opioids.
This a useful and intended target for pain treatment

13

Opioid receptors in the periphery neurons

opioid drugs can bind pain sensing neurons and curb nociceptive messages

14

Opioid receptors in the intestines

expressed in neurons regulating peristalsis
inhibition of these cells can lead to constipation

15

Examples of pain pathways

afferent neuron - AS (alpha delta neurons) (fast and myelinated) and C fiber (slow, visceral, unmyelinated)
Dorsal root & ganglia
Substantia gelatinosa
Contralateral Spinothalamic tract - Neospinal (sharp) and Paleospinal (dull)
Supraspinal thalamic nuclei that project to the cortex

16

Gate theory

cutaneous sensory input activate inhibitory interneurons or descending projections release various NTs: GABA, NE or endogenous opioids
These NTs bind to presynapse of afferent pain fibers and inhibit Ca+ channels leading to reduced vesicle release
They bind post synaptically and signal via G proteins to cause K+ efflux or Cl- influx (both of which hyperpolarize)

17

Descending control of pain

PAG --> Nucleus Raphe Magnus and Lateral tegmental nucleus ---> excitatory to Enkephalin neurons in Lamina 2 (sub gelatinosa) ---> inhibit Spinothalamic tract

18

4 step model of Pain

Transduction, transmission, perception, modulation
acute stimulation in form of noxious input, impulses to thalamus and cortex. Cortical and limbic structures in brain are involved in awareness and interpretation of pain. Pain is inhibited or facilitated by mechanisms in the ascending and descending pathways

19

Physiology of Endogenous Opioids

released by pituitary gland and hypothalamic neurons in response to pain, stress, exercise and labour
-act to relieve pain and anxiety
-asso. with feelings of euphoria, increased appetite and enhancement of immune response
-"runner's" high = increased release during long, strenuous exercise and results in euphoria and increased pain threshold
-play a role in social bonding

20

Examples of endogenous opioids

proorphanin
prodynorphin
proenkephalin
POMC - beta endorphins

21

What produces POMC? what is it a precursor for?

...

22

Beta endorphin

31 AA
tyr-gly-gly-phe-met (Met Enkephalin) , replace met with Leu for Leu enkephalin
the Leu sequence is seen in number of endogenous opioids

23

Analgesia

stimulation of AS (alpha delta) and C afferents can stimulate release of endogenous opioid beta endorphin from hypothalamus
Dynorphin released from PAG

24

Analgesia pathway

Transmission cell sends spinoreticular tract to RF which sends to hypothalamus. Hypothalamus (B endorphin) --> PAG ----> Raphe nucleus (serotonin) ----> via Dorsolateral tract acts on Enkephalin interneuron which releases enkephalin on the transmission cell
From transmission cell receives from (As and C fibers)
enkephalin interneuron from transmission cell

25

Endorphin is selective for

mu opioid receptors

26

How do opioid receptors work?

decrease synaptic transmission
binding activates G proteins that, in turn, activate potassium channels (neuronal membrane hyperpolariztion) inhibit voltage operated calcium conductance and neurotransmitter release

27

Dynorphin is co released with

Orexin

28

neuropeptides that modulate neurotransmitter action

Endorphins

29

Mechanism of Action of Endorphins

directly stimulate opioid receptors on the pre and post synaptic membranes
rapidly degraded peptidases
each binds a different opioid receptor
-B endorphin and endomorphin (mu)
-enkephalin (delta)
-dynophin (kappa)

30

Nociceptin receptor

ORL-1

31

synthetic agonists for mu receptors

Morphine
codeine
heroin

32

synthetic agonists for kappa opioid receptor

pentazocine
oxycodone?

33

What receptor Naloxone not an antagonist for?

ORL-1

34

What type of receptors are opioid receptors?

G protein receptors

35

B-FNA is an antagonist for?

Mu receptor

36

Natrindole is an antagonist for?

Delta receptor

37

In general, stimulation of opioid receptors result in

hyperpolarization of neurons
inhibition of NT release

38

Effects of mu receptors

analgesia
relief of anxiety
euphoria
nausea
constipation
cough suppression
dependence

39

Effects of delta receptor

like mu but less marked

40

Effects of Kappa receptor

Analgesia
aversion
Diuresis

41

Leu and Met enkephalin

short interneurons associated with pain pathways emotional behavior and motor control

42

what are endorphins co released with?

from pituitary with ACTH (Stress hormone)

43

Dynorphins are co localized with ....

vasopression, suggesting role in fluid homeostasis
in the spinal cord lowers pain threshold

44

Name opioid therapeutic for diarrhea

diphenoxylate
loperamide

45

Opioid for relief of cough

dextromethorphan

46

Treatment for opioid withdrawal

methadone

47

Treatment for opioid overdose

naltrexone

48

Treatment for constipation

methylnaltrexone

49

Treatment for postoperative ileus

alvimonpan

50

Narcotic analgesics

morphine
codeine
hydrocodiene
oxycodone
fentany

51

Mu opioid receptor

Main pharma site
mu1 = analgesia
mu2 = analgesia, respiratory depression
Euphoria (m1), miosis, dependence (m2)
sedation

52

Kappa opioid receptor

predominantly endogenous opiates
spinal analgesia
miosis
sedation dysphoria

53

Delta opioid receptor

analgesia
respiratory depression

54

dysphoria

state of unease or general dissatisfaction with life

55

Non opiate approaches: Transduction

nonsteriodal anti inflam. drug (NSAIDs) and cyclooxygenase (COX) 2 inhibitors - target the inflam. processes

56

Strong opioid agonists

Fentanyl
Heroin - rapid brain entry increases abuse
Meperidine - physician's drug of choice
Methadone - withdrawal less severe
Morphine - the original

57

Moderate opioids agonists

Codeine
Propoxyphene

58

Opioid antagonists

Naloxone-short acting must provide adequate breathing
Naltrexone

59

What limits narcotic analgesic clinical use?

induction of tolerance and dependence
which are influenced by their efficacy

60

Morphine is a _____ agonist

Full
-very potent analgesic
-High degree of dependence

61

Codeine/ Dextropropoxyphene

milder analgesia and dependence
lower first pass metabolism

62

Tramadol

weaker full agonist
less respiratory suppression

63

Methadone

full agonist for treating addicts

64

Mu opioid receptor (m1)

central analgesia
miosis*
bradycardia
euphoria
physcial dependence
increased prolactin release
inhibits Ach release*

65

Mu opioid receptors (m2)

Respiratory depression **
GI motility
spinal analgesia
GH release
miosis*
bradycardia

66

Kappa opioid receptor effects

central analgesia with k1
sedation **
disorientation, hallucinations
depersonalization
less miosis
dysphoria
ADH release - (diuresis) k1
Central analgesia

67

Delta opioid receptor

positive reinforcement of central analgesia
suppresses noxious thermal stimuli at spinal cord
enhances m agonists

68

Pharma action of Morphine

analgesia
euphoria/sedation
decreased respiration
suppression of the cough reflex
miosis
emesis
GI effects
cardiovascular effects
Hormones - CRH and ACTH, Gonadotropin releasing hormone

69

Tolerance develops to most of morphine's effects, with the exception of

miosis
constipation
pruritis

70

What is different about codeine's structure that reduces its first pass metabolism in comparison to Morphine?

The H on OH in Morphine is replaced by CH3 for codeine which makes it more resistant to glucuronidation

71

Morphine chemical structure

about four rings with O between two
Has two OH groups vulnerable to glucuronidation
N-CH3 group open to demethylation (minor)
Glucuronidation of the OH not subbed in codeine will increase potency of analgesia

72

Morphine mechanism of action

via activation of mu receptors and to lesser extent kappa
Analgesia: inhibition of ascending nociceptive info
activate descending pain control circuits
25% effective for oral vs. parenteral admin

73

Does morphine cross the BBB?

Yes but to a lesser extent that many opioids

74

Therapeutic uses for Morphine

acute pain (do NOT use in chronic malignant pain)
dyspnea and pulmonary edema
pre anesthetic medication
open heart surgery
to decrease fear in dying

75

Opioid analogs are designed after

morphine, thebaine, codeine
-simplification of morphine structure
-mod by addition to thebaine

76

Effects of Morphine on respiration

primary and continuous depression of respiration related to dose
-decrease in rate
-decrease volume
-decrease tidal exchange

77

Effects of morphine on N&V

stimulation of CTZ (?) in area postrema of medulla
sitmualtion by stretch receptors causes nausea and vomiting
has afferents from gut and ear
involved in motion sickness

78

Constipation as side effect from Morphine results from

increase in tone in stomach, small intestine and large intestine
decrease in mobility
decrease concentration of HCl secretion
altogether delays passage of food so more reabsorption of water
Tolerance to this effect does NOT occur

79

CV effects of Morphine

vasodilation which leads to decrease in BP
cause release of histamine
suppression of central adrenergic tone
suppression of reflex vasoconstriction

80

Morphine effects on the biliary tract

marked increase in pressure
10 fold over normal
due to contraction of sphincter of Oddi

81

Urinary bladder effects of Morphine

tone of detrusor muscle increased
feel urinary urgency
urinary retention due to increased muscle tone where sphincter closed off

82

Bronchial muscle effects of Morphine

bronchoconstriction
**is contraindicated in asthmatics, particularly before surgery

83

Uterine effects of Morphine

contraction uterus can prolong labour

84

Neuroendocrine effects of opioids

inhibit release of GnRH and CRF thus decreasing LH, FSH, ACTH and b-endorphin
as a result, decreased concentration circulating which leads to less testosterone and cortisol in plasma
-Thyrotropin is unaffected