Opioids & antagonists Flashcards Preview

4Qpharm3-test1 > Opioids & antagonists > Flashcards

Flashcards in Opioids & antagonists Deck (39):
1

Endogenous Opioid peptides (3)
and functions (2)

enkephalins
beta-endorphin
dynorphin

released in response to pain ↓responsiveness to pain

2

Mu receptor: effects of stimulation

analgesia
euphoria
sedation
side effects

3

Kappa: effects of stimulation

analgesia in some ppl, dysphoria in others

4

Delta, sigma: effects of stimulation

dysphoria

5

3 major opioid receptors
how do they work

Mu, Kappa, Delta
ALL are coupled to Gi/o
ALL CLOSE VOLTAGE GATED Ca2+ CHANNELS on PREsynaptic nerve terminals ( ↓ neurotransmitter release & ↓ neuronal activity in these pathways)

Mu receptors also OPEN K+ CHANNELS, causing hyperpolarization-inhibiting nerve transmission

6

Stimulation of mu, kappa & delta receptors does what?

↓Ca2+ influx-> ↓release of excitatory transmitters

7

stimulation of mu receptors on post-synaptic cell does what?

hyperpolarizes & ↓transmission

8

alpha2 receptors do what

↓pain transmission in this region (also where TCAs work to ↓pain)

9

Effect of Opioids on Pain transmission (5 plus 2 possibles)

A. Direct Action at inflamed & damaged tissue
B. inhibition of release of excitatory transmitters in the dorsal horn: spinal anesthesia
C. Thalamic action
D. periaqueductal gray, may cause release of endogenous opioids as well
E. Rostral Ventral medulla

-NE pathway from locus coeruleus to dorsal horn may also ↓pain
-inhibition of neurons may ↑ the activity of pathways that inhibit pain

10

Pain & GABA

GABA (U) inhibits descending neuronal pathways that modulate pain
-opioids ↓ the release of GABA, allowing the pathways to be activitated
this ↓pain transmission in the DORSAL HORN of the SPINAL CORD

11

Effects of Opioids (14)

-Analgesia
-Sedation/mental clouding
-Euphoria or dysphoria
-Emesis
-Depression of cough reflex (antitussive)
-Respiratory depression
-Elevated intracranial pressure
-MIOSIS (pupil constriction)
- ↓body temp
-Truncal rigidity
-Cardiovascular
-GI
-GU
-Uterus

12

Opioid analgesia

a. ↓sensation of pain
b. ↓reaction to pain
c. tolerance develops to analgesia

13

Opioid sedation/mental clouding

NOT used as sleep aids, different quality of sedation
disrupt REM
morphine causes CNS depression in overdose
codeine, meperidine may cause excitement in overdose

14

Which opioid is different, a strange drug?

Meperidine

15

Opioid Euphoria or dysphoria

-sense of floating, pleasure
-prob depends on receptor distribution in different individuals
-some fine experience dysphoric
KAPPA & DELTA receptors INVOLVED in DYSPHORIA

16

Opioid emesis

N/V in some ppl
Opioid stimulate chemoreceptor trigger zone in the brain (CTZ)

17

Opioid antitussive: doses, which work, which don't

LOWER doses than those for analgesia
VERY EFFECTIVE: CODEINE & DEXTROMETHORPHA
DXM is NOT analgesic

Meperindine (Demerol) DOESN'T suppress cough

18

Opioid respiratory depression: when, why, good for, bad for

-more common in OD, but also at therapeutic doses
-↓ response of brain stem to elevated CO2
-USEFUL IN PULMONARY EDEMA
NOT good in ppl w/PULMONARY DZ
-may also cause bronchoconstriction

19

Opioid effect on intracranial pressure

Elevated intracranial pressure ↑CO2 causes vasodilation, ↑cerebral blood flow & ↑pressure
WATCH OUT IN PATIENTS WITH HEAD TRAUMA!

20

Effect of opioids in the eye, how to block

PUPIL CONSTRICTION (except w/meperidine)
-NO tolerance develops
-parasympathomimetic: blocked by atropine
-common in OD, but may convert to dilation in comatose patients

21

Opioid effect on body temp

decreases body temp due to dysregulation in hypothalamus

22

Truncal rigidity in opioids: why, what does it effect, which drugs do this, what to block

-supraspinal effect ↑tone of the large trunk muscles
-may interfere with respiration or w/attempts to ventilate patient
-most (C) with HIGHLY LIPID SOLUBLE DRUGS, like FENTANYL, IV
-use neuromuscular blockers to prevent this effect

23

Opioid effects: cardiovascular

BRADYCARDIA may occur
↓BP common
may result from CNS vasomotor depression &/or release of histamine (vasodilates)

but TACHYCARDIA may occur with MEPERIDINE (anticholinergic)

24

Opioid effects: GI

↓ gastric activity both local & CNS
CONSTIPATION
↓ gastric motility
biliary colic, constriction of sphincter of Oddi
↓ biliary, pancreatic, intestinal secretions
PREPARE PATEINT & BE PRO-ACTIVE ABT PREVENTING CONSTIPATION

25

Opioids: GU effects

antidiuretic effect: ↓urine output
↓renal blood flow
↑sphincter tone-harder to urinate
↑urethral tone: harder to pass kidney stone
so DON'T GIVE PPL. W KIDNEY STONES opioids, it makes it HARDER TO PASS STONE

26

Opioids: Uterus effects

may prolong labor
(but Miperideine DOES NOT prolong labor, unlike others)

27

Opioids: tolerance & dependence

TOLERANCE: ↑doses needed to control pain, occurs very rapidly, more (C) w/lower efficacy drugs [eg. codeine is terrible for dependence]

PHYSICAL DEPENDENCE: may result from desensitization of mu receptors
-NMDA receptor antagonists may ↓ development of tolerance

28

Hyperalgesia: when and why in opioids

may occur w/long-term use of opioids
-may be mediated by ↑ in dynorphin in the spinal cord that makes transmission of pain MORE effective

29

Does tolerance develop to all the effects of opioids?

tolerance develops to: analgesia, sedation, euphoria, N/V, respiratory depression

NO TOLERANCE to: MIOSIS, CONSTIPATION, SEIZURES

30

Opioid AEs

N/V: better if take w/food
Constipation: be aggressive to tx it BEFORE it occurs

Urinary retention: worse if BPH present, due in part to constriction of urinary sphincter

Respiratory depression: dose dependent, worse w/higher doses, more naïve users, caution in pulmonary dz

31

Opioids & histamine

opioids can produce histamine release in some peeps-> flushing, itching sweating
-more (C) when opioids are injected
-this is generally tx or pretx with antihistamines such as diphenhydramine (Bendryl)

32

Who develops tolerance and/or addiction

tolerance & dependence occurs in ANYONE who uses opioids chronically, for any reason
ADDICTION most (C) when used for euphoric effect, but can occur w/med use of opioids
-ADDICTION MORE LIKELY IF UNDERPRESCRIBED:
~if pt dvlps sever pain, which is relieved by opioid, this provides reinforcement-> reward pathyway activated
~if OPIOIDS GIVEN BEFORE PAIN GETS TO SEVERE, BYPASSES THE REWARD PATHWAY

33

Opioid withdrawal sxs, how to reduce them & what can precipitate withdrawal

sxs: dysphoria, anxiety, insomnia, anorexia, yawning, chills, goose bumps, vomiting, diarrhea, ↑BP, ↑HR, ↑temp, muscle aches & twitches

SXS CAN BE REDUCED BY CLONIDINE or another opioid (METHADONE)

Opioid antagonists can precipitate withdrawal if dependent

34

Opioid OD presents as: (3)

CNS depression
Respiratory depression
Pin point pupils
[may dilate if severely hypoxic]

35

What to do in opioid OD?

first: ABCs
Tx by: SUPPORTING RESPIRATION
then, use opioid antagonist like NALOXONE (NARCAN)

36

Clinical uses of opioids (5)

ANALGESIA: acute pain trauma, CA, post surgery, chronic pain [combine w/non-opioids when possible, titrate to degree of pain]
ACUTE PULMONARY EDEMA: relieves dyspnea, mechanism not clear
RELIEF OF COUGH: codeine & dextromethorphan
TREATMENT OF DIARRHEA: Loperamide (Imodium), diphenoxylate/atropine (Lomotil)
ANESTHESIA:
general-adjunct to control pain
spinal-epidural w/local anesthetics (direct access to dorsal horn ↓ some side effects, but itching worse)

37

Opioid drug interactions (4 classes and the result)

Sedative hypnotics: ↑CNS & respiratory depression

Antipsychotics: sedation, maybe respiratory depression

MAO Inhibitors: (MEPERIDINE & DXM CAUSE WORST INTRXNS), may inhibit serotonin reuptake to some degree but BEST TO AVOID ALL opioids w/MAOIs

CYP2D6 inhibitors:
-codeine, oxycodone, hydrocodone NOT metabolized to active compounds
-FLUOXETINE, paroxetine the worst for inhibition

38

Opioids: CONTRAINDICATIONS (6)

USE OF PARTIAL AGONIST W/FULL AGONIST: can impair analgesia, cause withdrawal

Pts w/head injuries (↑intracrantial pressure)

Pregnancy (esp. at delivery can cause resp. depression in the baby)

Impaired pulmonary fxn

Impaired hepatic or renal fxn

Some endocrine dzs

39

Opioid precautions (11)

-severe liver dz/kidney dz
-pulmonary dz
-biliary tract probs
-seizures (esp. meperidine)
pain of unknown cause (esp. abdominal)
-head trauma
-chronic non-terminal pain?
-inflammatory bowel dz
-pregnancy/breast feeding
-urinary retention/BPH