Opioid Analgesics I

Question 1

Enkephalins

Answer 1

act as modulatory neurotransmitters at synapses

made from pro-enkephalin

Question 2

Endorphins:

Answer 2

larger than and different distribution than enkephalins; act as both neurotransmitters and neurohormones (“runner’s high”). Made from POMC

B- endorphin: most active

Question 3

Dynorphin

Answer 3

physiological role less clear than enkephalins and endorphins.
Dynorphin A (peptides 1-17) most biologically active- k selective

Question 4

Endomorphins:

Answer 4

new family of opioid peptides-not well characterized
Variation of opioid ligand motif: (Tyr-Pro-Trp/Phe-Phe)
-u-receptor selective

Question 5

Nociceptin

Answer 5

regulates pain transmission and related to “true opioids” but binds to distinct receptors-not a target of opiate analgesic drugs

Question 6

Effects of enkephalin, endorphin and dynorphin peptides can be antagonized by:

Answer 6

naloxone.

Question 7

Opioid receptors

Answer 7

u, d, k

all are coupled to GTP-binding proteins- Gi and Go

Question 8

Most clinically useful drugs are somewhat selective for ____- opioid receptors

Answer 8

u

Question 9

Opioid Receptor G-protein Signaling Mechanisms

Answer 9

↓ neuronal excitability
inhibition of presynaptic VGCCs –> inhibition of neurotransmitter release.

activation of potassium channels (GIRK) leading to membrane hyperpolarization.
inhibition of cAMP synthesis.

Question 10

Opioid Inhibition of spinal cord/ascending pain pathway:

Answer 10

• inhibition of presynap excitatory NT release from afferent terminals in dorsal horn of the spinal cord (substance P, glutamate)
• inhibition of excitatory postsynap spinothalamic “ascending” output neurons.

Question 11

Opioid Activation of descending pain pathway

Answer 11

activation of “descending” inhibitory output systems in the medulla, PAG, and locus coeruleus; mediated by 5-HT and NE

Question 12

Opioid drugs relieve_________ better than sharp, intermittent pain (1st pain).

Answer 12

dull, constant pain (2nd pain)

Question 13

Opioid drugs effectively reduce nociceptive pain, but are frequently less effective in treating _________ pain

Answer 13

neurogenic/neuropathic

Question 14

Opioid drugs are not

Answer 14

antipyretics

Question 15

Typical Clinical Uses of Opioids

Answer 15

• pain associated with malignancy: chronic use
• painful diagnostic procedures: in combination with other drugs such as local anesthetics and tranquilizers (benzodiazapines)
• post-operative pain
• obstetrical anesthesia
• Patient-controlled analgesia (PCA)
• cough (lower doses): separable from analgesic actions

Question 16

the potential adverse interactions of opioids

Answer 16

CNS Depressants
Antipsychotics
MOAi and Tricl

Question 17

Most Dangerous Side Effect of Opioids

Answer 17

Respiratory Depression:

Primary cause of opioid-induced death (overdose). Respiratory fx is depressed even at analgesic doses.

Due to a decrease in sensitivity to CO2 in brain stem respiratory centers (can ↑ ICP)

Question 18

Main Contraindications for Opioid

Answer 18

Respiratory dysfunction of any cause:

Emphysema, Asthma, Sleep Apnea, Severe Obesity

Question 19

Other contraindications for Opioids

Answer 19

Suspected head injury-because ICP increased due to cerebral vasodilation
Hypotension- opiates decrease BP (histamine)
Shock- endogenous opioid systems might be active in shock response
Histamine Release
Hypothyroidism
Impaired hepatic function

Question 20

Opioids sign of acute toxicity (behavioral)

Answer 20

Behavioral Excitation:

Question 21

Some Side effects of opioids

Answer 21

Resp depression
NV
Cough suppression 
Pupillary Constriction 
Constipation 
Bile Stones
Urine retention

Question 22

Many opioids can cause ______ release from mast cells and basophils (not seen with Fentanyl)

Answer 22

-severe allergic rxn (rare)
-mild allergy (respond to antihistamines).
S/s
-itching
-urticaria
-local vasodilation
-headache
-exacerbate asthmatic symptoms
-peripheral vasodilation and decreased blood pressure

Question 23

Cardiovascular Effects of Opioids

Answer 23

Myocardial infarction: (Fentanyl/ morphine)

• analgesia
• alleviates apprehension
• decreases cardiac load

significant effects are indirect (some through histamine).
↓ cardiac work load
inhibition of baroreceptor reflex–> orthostatic hypotension

Question 24

use opioids with caution in cases of hypovolemia due to:

Answer 24

decreased blood pressure.

Question 25

μ-receptors

Answer 25

Exist mostly presynaptically in the periaqueductal gray region, and in the superficial dorsal horn of the spinal cord (specifically the substantia gelatinosa

Question 26

μ receptors are also found in the

Answer 26

intestinal tract.

Activation of these receptors inhibits peristaltic action which causes constipation, a major side effect of μ agonists

Question 27

Morphine

Answer 27

widely used to relieve severe pain post-operatively and in acute trauma (IV/IM).

Also available in oral sustained release form (MS Contin®) for chronic pain treatment.

Question 28

Heroin

Answer 28

Schedule I. not approved for medicinal use.
2-3 X more potent than morphine but same efficacy
highly lipophilic: rapid onset, high abuse potential

Question 29

Codeine

Answer 29

most commonly used opioid analgesic.

10% metabolized to morphine by CYP2D6, but 10% of caucasians are deficient in this pathway, so not an effective analgesic for everyone

Question 30

Codeine–> 10% metabolized to morphine by ______, but 10% of caucasians are deficient in this pathway, so not an effective analgesic for everyone.

Answer 30

CYP2D6

Question 31

Oxycodone

Answer 31

equipotent with morphine. Recent dramatic increase in abuse of Oxycontin® sustained release form. Good oral availability

Question 32

Hydrocodone

Answer 32

antitussive, weak analgesic, similar to Codeine.

Question 33

Tramadol

Answer 33

acts at  receptors but also blocks monoamine uptake to potentiate descending pain pathway.

Question 34

Meperidine

Answer 34

faster onset and offset than morphine
decreased biliary spasm
decreased constipation
not antitussive 
slower development of tolerance.
toxic metabolites (normeperidine) cause CNS excitation, limits use to short-term such as painful diagnostic procedures.
frequently abused by physicians

Question 35

Methadone

Answer 35

good oral bioavailability, and long half-life.
used in opioid maintenance therapy for addiction
suppresses withdrawal symptoms
orally not much euphoria
full-agonist produces profound analgesia

Question 36

: A decreased response to a drug as a result of previous exposure

Answer 36

Tolerance:

Question 37

Factors involved in the development of tolerance

Answer 37

frequency of drug administration (higher frequency)
dose at which the drug was administered (higher doses)
duration of drug use (longer)

Question 38

easily produced by opioids; most common in pain-free individuals abusing opioid drugs or long-term chronic pain treatment.

Answer 38

Dependence

Question 39

Physical dependence is produced in patients using opioids to treat constant pain but ______________ usually works

Answer 39

gradual withdrawal

Question 40

Symptoms of withdrawal are opposite those caused by acute opioids, and are described as

Answer 40

“flu-like”