Opioids Flashcards Preview

Pharmacology > Opioids > Flashcards

Flashcards in Opioids Deck (47):
1

Diphenoxylate, Loperamide Class
Opioids

Opioids
Antimotility agents

2

Diphenoxylate, Loperamide description
Opioids

Widely used in the **treatment of diarrhea** at doses that lack analgesic effects

Several mechanisms, but mostly act on mu and delta receptors

3

Dextromethorphan, Codeine class
Opioids

Antitussives

4

Dextromethorphan, Codeine description
Opioids

Most effect *cough suppressants*
Lower dose than necessary for analgesia

5

Dextromethorphan, Codeine other
Opioids

Receptors are different than those associated with other action

6

Naloxone, Naltrexone class
Opioids

mu and kappa antagonists

7

Naloxone, Naltrexone description
Opioids

Opioids
Nalaxone -> acute opioid overdose**
Naltrexone -> opioid addiction; also *decrease EtOH craving in chronic alcoholics*

8

Pentazocine, Butorphanol, Nalbuphine, Buprenorphine class opioids

Mixed agonist and antagonist

9

Pentazocine, Butorphanol, Nalbuphine, Buprenorphine description
Opioids

Potent analgesics in opioid naive patients, but precipitate withdrawal in patients that are physically dependent on opioids
Used in *mild to moderate pain* but are *not routine* due to **ceiling effect**
1st three may cause **psychotomimetic effects**, but not buprenorphine

10

Pentazocine, Butorphanol, Nalbuphine, Buprenorphine other
Opioids

Developed to *reduce addiction potential of opioids* especially buprenorphine

11

Tramadol description
Opioids

Weak mu agonist and NE/serotonin reuptake inhibitor
Useful for *neuropathic pain*

12

Tramadol other
Opioids

Increased risk of *seizures*
May cause *serotonin syndrome*

13

Propoxyphene class
Opioids

mild to moderate agonist

14

Tramadol class
Opioids

mild to moderate agonist

15

Propoxyphene description
Opioids

NOT recommended for routine dosing and withdrawn from market in 2010 due to cardiotoxicity

Metabolized to norpropoxyphene with a half life of 30hrs -> toxicity

16

Codeine, Oxycodone, Hydrocodone description
Opioids

Less efficacious than morphine
Usually combined with aspirin or acetaminophen
Codeine has *low affinity for opioid receptors*

17

Codeine, Oxycodone, Hydrocodone Metabolism
Opioids

Analgesic effect is due to metabolism by ****CYP2D6***** to morphine
Metabolites have greater potency

18

Methadone, Levorphanol class
Opioids

Strong agonist

19

Methadone, Levorphanol description
Opioids

Equal potency to morphine but with **less euphoria and longer half life**
**mu agonist, NMDA antagonist and serotonin/NE reuptake inhibitor**
**Levorphanol is even longer acting** than methadone

20

Methadone, Levorphanol other
Opioids

Used to *manage opioid withdrawal* in heroin addiction

Can cause QT prolongation, etc.

21

Fentanyl, Sufentanil, Alfentanil, Remifentanil class
Opioids

Strong agonists

22

Fentanyl, Sufentanil, Alfentanil, Remifentanil description
Opioids

Rapid onset and short duration of action
100x more potent than morphine

Metabolized by **CYP3A4** in the liver
No active metabolites

23

Meperidine class
Opioids

Strong agonist

24

Meperidine description
Opioids

mu receptor agonist, but has *high metabolite toxicity* (normeperidine) ->tremor, twitching, mydriasis, hyperactive reflexes and convulsions*****

Serotonin syndrome -> delirium, hyperthermia, HA, rigidity, coma, dysregulation of BP, death (DO NOT combine with MAO-Is)

25

Meperidine mechanism
Opioids

Accumulation of normeperidine can occur in patients with decreased renal function and cause seizures

26

Meperidine other
Opioids

*Normeperidine* half life 15-20 hrs so it *accumulates* with frequent dosing
Meperidine half life = 3 hrs

27

Heroin description
Opioids

6-monoacetylmorphine and heroin are more *liposoluble* than morphine and cross BBB

Rapid hydrolysis to 6-MAM -> morphine which can then be conjugated

Pharmacological actions are due to 6-MAM and morphine

28

Hydromorphone, Oxymorphone description
Opioids

Severe pain

29

Morphine description
Opioids

High affinity for mu receptor; **standard for analgesia**

30

Morphine mechanism
Opioids

Conjugated to *M3G -> neuroexcitation*
10% -> M6G -> 4-6x more potent

31

Morphine other
Opioids

Metabolites are polar and do not readily cross BBB
Metabolite effects may be increased in renal impairment

32

Opioid analgesic mechanism

Produce analgesia primarily by *activating receptors in the brain and spinal cord*

*Close voltage gates Ca2+ channels on presynaptic nerves and open K+ channels on postsynaptic nerves -> decreased NT release*

Can also cause analgesia at peripheral mu receptors (i.e.knee)

33

Spinal analgesia
Opioids

*Inhibit ascending pain transmission*

34

Supraspinal analgesia
Opioids

Activate descending pain-inhibitory circuits* -> block inhibitory *GABAergic* neuron transmission

35

Systemic administration
Opioids

Both spinal and supraspinal are acted on concurrently increasing overall analgesic efficacy

Peripheral mu receptors also acted on

36

Opioid receptors

Mu, delta, kappa -> Gi
Majority act at the mu receptor and produce analgesia, euphoria, respiratory depression and physiologic dependence

delta and kappa are found primarily at the spinal level ->analgesia
kappa-> psychotomimesis (psychosis, delirium, hallucinations, etc)***

37

Opioid tolerance, dependence, addiction

Frequent use -> loss in effectiveness -> tolerance
*Dependence -> physiologic withdrawal* or abstinence syndrome

Addiction -> euphoria leads to compulsive use

Physical dependence is common when use therapeutically, but addiction is not

38

Opioid CNS effects

Analgesia -> reduce *sensory and emotional* components of pain
Euphoria -> floating sensation with decreased anxiety and distress
Sedation and drowsiness

Respiratory depression - decreased central response to CO2 -> not usually a life threatening complication, because pain is a power stimulus to breath

Cough suppression - decreased central cough center reflex
Miosis - excites PS -> *pinpoint pupils are pathognomonic following toxic dose* (mediated by mu receptor)

Truncal rigidity *
Nausea and vomiting -> activate brain stem trigger zone

39

Opioid use

Analgesia-> moderate to severe pain
Acute pulmonary edema -> decrease anxiety, preload and afterload
Cough -> dextromethorphan, codeine, levopropoxyphene and noscapine
Diarrhea - loperamide and diphenoxylate
Shivering - meperidine (activates alpha 2 receptors)
Anesthesia - premedication and intraoperatively

40

Opioids for cough

Dextromethorphan, codeine, levopropoxyphene and noscapine

41

Opioids for diarrhea

loperamide and diphenoxylate

42

Opioids for shivering

meperidine (activates alpha 2 receptors)

43

Opioid metabolism and excretion

Mainly converted to *glucuronides* and excreted by the *kidney* but small amounts of unchanged drug may be found in urine

Very small amount of *enterohepatic circulation*

*Codeine, oxycodone, hydrocodone are metabolized by CYP2D6 -> metabolites with increased potency

44

Supraspinal analgesia pathway

The descending pain inhibitory neuron is inhibited by GABA

Opioids inhibit the GABAergic neuron

This results in enhanced inhibition of pain transmission

45

Opioid AE

Nausea, vomiting,
sedation
itching
*Constipation*
Urinary retention
Hypotension
Respiratory depression

46

Opioid Peripheral effects

Hypotension -> due to peripheral vasodilation, inhibition of baroreceptor reflex and increase in histamine release

*Constipation -> universal (concomitant laxative use)*

Biliary colic -> contraction of biliary smooth muscle

Decreased renal function -> decreased renal blood flow

Prolong labor by unknown mechanism on uterus

Pruritus -> due to central effects and histamine release

47

Opioid contraindication/interactions

Using a *pure agonist with a weak partial agonist* -> diminishing analgesia or inducing a *state of withdrawal*

Head injuries -> CO2 retention causes *cerebral vasodilation*
Pregnancy -> fetal dependence
Impaired pulmonary function -> acute respiratory failure
Impaired hepatic function -> decreased metabolism of morphine
Impaired renal function -> longer half - life
Endocrine disease-> adrenal insufficiency or hypothyroidism can have prolonged or exaggerated response to opioids

Sedatives/hypnotics -> increase CNS depression (respiratory)
Antipsychotics -> increase sedation, variable effects on respiratory depression and accentuate CV effects of anti-M and alpha-blockers
***MAO-I's -> life threatening rxn especially with meperidine and tramadol****