Opioids Flashcards Preview

Cology 2 Exam 1 > Opioids > Flashcards

Flashcards in Opioids Deck (63):
1

What are the key pharmacological effects of mu receptors?

Analgesia
Respiratory depression
Reward
***Constipation also mu mediated

2

What are key pharmacological effects of delta receptors?

Analgesia
Affective disorder (Anxiety)
****Also Seizures

3

What are key pharmacological effects of kappa receptors?

Analgesia
Dysphoria
Psychomimetic effect
***Also Diuresis

4

What are the endogenous opioid peptides that act at mu receptors?

B-endorphin
Endomorphin 1 and 2

5

What are the endogenous opioid peptides that act at delta receptors?

Met-Enkephalin
Leu-Enkephalin

6

What are the endogenous opioid peptides that act at kappa receptors?

Dynorphin peptides

7

Mu receptors are how many amino acids?

398

8

Delta receptors are how many amino acids?

372

9

Kappa receptors are how many amino acids?

380

10

Where do antagonists bind?

Extracellular tail

11

Where do agonists bind?

Extracellular domain

12

All opioid receptors are coupled to what proteins?

Gi and Go

13

What is the result of opioid receptor binding?

INHIBITION. ALWAYS.

14

Activation of opioid receptors induces G-proteins to:

Inhibit adenylyl cyclase activity (Gi) - decreases cAMP

Activate receptor-operated K+ channels (Gi) - Increases K+ leaving the cell, hyperpolarizes it, less action potentials

Suppress voltage-gated Ca2+ currents (Go) - influx of Calcium also hyperpolarizes

15

Analgesia is the result of what receptor(s) in what area(s)?

Mu, Kappa, Delta

Spinal cord, PAG, Thalamus, Cortex, Limbic system

16

Respiratory depression is the result of what receptor(s) in what area(s)?

Mu

Medulla

17

Reward is the result of what receptor(s) in what area(s)?

Mu and delta in the striatum increase reward

Kappa in striatum decrease reward

18

Pupil constriction is the result of what receptor(s) in what area(s)?

Mu and Kappa receptors

Edinger-Westphal nucleus

19

Cough relief is the result of what receptor(s)?

Dextramorphan receptors! Not opioid receptors, but opioids can bind to it

20

Nauseant and emetic effects are due to what receptor(s) in what area(s)?

Mu

Chemoreceptor Trigger Zone

21

Sedation is due to what receptor(s) in what area(s)?

Mu and Kappa

Inhibition of the locus ceruleus

22

Describe the pain pathway

Dorsal root ganglia (Delta and Kappa, few Mu)

Substantia gelatinosa - incoming pain signals (hyperpolarize these cells to decrease pain signals)

Spinal cord ventral horn (Dynorphin interneurons synapse on spinothalamic axons)

Thalamus (Spinothalamic neurons connect cortex to limbic system, also have input to PAG and RAS)

Descending pathways from PAG, Locus ceruleus (NE) and Raphe nuclei (5HT) - serve to inhibit incoming pain activity in primary afferent arteriole

23

How can Kappa agonists be used against addiction? Why aren't they used?

There are kappa receptors on the PRESYNAPTIC TERMINAL (test Q!) of dopamine receptors to inhibit release. So you have inhibition of dopamine release and you lose inhibition of inhibiting dopamine release.

This leads to dysphoria, which can lead to depression. Patients would rather be in pain.

24

What effects do opioids have on the CV system?

Nothing directly
Histamine indirectly causes vasodilation and CO2 blunting reflex of vasoconstriction

25

What effects do opioids have on bronchial smooth muscle?

Constriction bc histamine
Contraindication in asthmatics

26

What effects do opioids have on urinary bladder smooth muscle?

Mu agonists decrease voiding and increase ADH

K agonists at kidney increase voiding and indirectly decrease ACTH to increase urination rate

27

What effects do opioids have on the GI tract?

Mu agonists decrease gastric acid secretions in the biliary tract, food concentrates so it's harder to pass (CONSTIPATION!)
Decreases GI transit

28

What effects do opioids have in the uterus?

Decrease oxytocin
Increase labor time

29

What effect do opioids have on muscular rigidity?

Mu, kappa, delta receptors in the NIGROSTRIATAL TRACT all contribute

Increase muscle rigidity, easier to cut thru in surgery

But delta agonism - too far can cause seizures!

30

What effect do opioids have on skin?

Indirect effect - histamine release increases flushing and increases pruitus/itching

31

What effect do opioids have on the immune system?

Complex - all 3 receptors found

Mu decreases cytotoxic activity (morphine)
or increases cytotoxicity (in cell culture)

Increases speed and replication of viruses - bad with HIV!

32

What effect do opioids have on the endocrine system?

Mu receptors in the hypothalamus inhibit gonadotropins

Chronic use influences homeostasis

33

Antagonists have no effect on the side effects of opioids except which ones?

Feeding and prolactin/growth hormone secretion
Antagonists will decrease feeding and decrease secretion

34

Onset of action of opioids is determined by....

route of admin (mostly parenteral)
lipid solubility (usually high - crosses BBB faster)

35

What chemical change decreases likelihood of metabolism?

Methylation of C3 on morphine ring

36

Describe protein binding of morphine

Significantly protein bound - 1/3 of morphine is bound to protein for distribution, but there is rapid departure in highly vascularized areas

37

How is morphine metabolized?

Glucoronidation in the liver to M6G (2x potency) and M3G (Inactive - does not bind opioid receptors but could actually induce pain...)

Both excreted in the urine

38

What are the indications of opioid use?

Acute pain (Best against dull, continuous pain)
Chronic pain (less effective)
Cough (DM binding site)
Diarrhea (mu receptors)

39

What are the contraindications of opioid use? (8)

Head injury (Stroke)
Respiratory depression (COPD)
Chronic pain (Long term opioid use - don't just keep increasing the dose)
Pregnancy (threat of w/d for fetus)
Allergy/asthma
Impaired liver function (metab in liver)
Renal disease (buildup of metabolites)
History of opioidabuse

40

What drug interactions exist between opioids and CNS depressants?

Benzos, barbiturates, ethanol, etc

Increases sedation, euphoria, RESP DEPRESSION

Both PK and PD mechanism of action

41

What drugs should you NEVER give with an opioid?

MAO INHIBITORS!!!!!

42

What drug interaction exists between opioids and MAO inhibitors, antidepressants with mACh or H1 blockade?

Increase sedation and respiratory depression
Increase risk of seizures
Increase analgesia
Risk of serotonin syndrome (increase 5HT to the point it becomes excitatory)

Severe HTN (not sure why)

43

What drug interaction exists between opioids and antipsychotic agents with mACh or H1 receptor blockade?

Increases sedation and respiratory depression
Increases CV effects

44

What drug interaction exists between opioids and amphetamine?

Increase euphoria, increase analgesia
Decrease sedation

"Speed balling" Take opioid + heroin to increase euphoria

45

What drug interaction exists between opioids and NSAIDs?

Synergistic, increases analgesia

Some opioids are packaged with NSAIDs to decrease the dose of opioid necessary (ie Percocet)

46

What drug interaction exists between opioids and SSRI's, NSSRI's, and some atypical antidepressants?

They increase analgesia

47

What drug interaction exists between opioids and apha-2 agonists?

Helps treat spinal pain by decreasing transmission of pain as well as the analgesic property of the opioid

48

What are the symptoms of opioid overdose?

Stupor, coma (Mental clouding)
Very low respiratory rate (2-4 breaths per minute)
Symmetrical pinpoint pupils (miosis)
Increased intracranial pressure (bad for stroke)
N/V (Bad teeth)
Constipation (Severe, lasts for days)
Increased itching
Increased urinary retention (mu)
Postural hypotension

49

Define Tolerance, Physical dependence, and Withdrawal syndrome

Tolerance: Reduction in response to an opioid after repeated administration

Physical dependence: Require continued opioid administration to maintain normal function (shift in homeostasis)

Withdrawal syndrome: Only actual evidence of physical dependence; occurs when opioid administration in a physically dependent organism is abruptly discontinued

50

You do not know the degree of dependence until...

Either the drug is withdrawn or an antagonist is given

51

In dependence, there is a compensatory increase in...

neuronal cyclic AMP production, particularly in the locus ceruleus

52

What happens in morphine-dependent rats?

Basal adenylyl cyclase activity and cyclic AMP-dependent protein kinase activity are increased

53

Injection of cAMP in physical independence did what?

Potentiates the development of dependence and withdrawal symptoms

54

What is believed to be involved in the manifestation of withdrawal symptoms?

Opiods normally suppress adenylyl cyclase activity

When opioid is removed or an antagonist is given, there is no inhibitory influence on adenylyl cyclase activity.

At the onset of withdrawal, cyclic AMP levels are very high, and is believed ti be involved in the manifestation of withdrawal symptoms

55

What happens in the first 6 hours of heroin/mu agonist withdrawal?

Goose like flush
Muscle spasm
Pupil dilation
Sweating
Insomnia
Anxiety
Yawning
Increased HR/BP
Danger of tachycardia
CRAVING

56

What happens in the 24-72 hours of heroin/mu agonist withdrawal?

Chills
Diarrhea-SEVERE (need fluids)
Sneezing
Aching
Nausea
Vomiting
Cramps

70% of patients fail at this point

57

What happens 7 days after heroin/mu agonist withdrawal?

Protracted withdrawal symptoms

58

What happens 6 months after heroin/mu agonist withdrawal?

Considerable anxiety, significant cravings, sense of feeling "not right"

Lasts for an unknown amount of time

59

What is the long term prognosis for heroin/mu agonist addiction?

Very poor

70% relapse in the first 72 hours
40% relapse even if they go through withdrawal under clinician care

60

Tolerance and dependence is highest in what receptor order?

Mu > Delta > Kappa

61

Abuse liability is highest in what receptor order?

Mu > Delta > Kappa

62

What is the abuse liability order for lipid solubility?

Worse for more lipid soluble

Fentanyl > Heroin > Meperidine > Morphine > Methadone

63

What are the treatment options for dependence?

"Cold turkey" ONLY for light abusers

Decrease dose for several days

Substitution detox - methadone, buprenorphine - decreases cravings

Long-acting opiate ANTAGONISTS - naltrexone - alleviates environmental cravings

Clonidine - activates alpha 2 adrenergic autoreceptors in LC (decreases NE hyperactivity to alleviate w/d symptoms but NOT cravings)