Opioids

Question 1

Describe the major opioid receptors in the following regards:

• neuron expression
• tissue expression
• fxn

Answer 1

DELTA

• pre-synaptic
• brain
• analgesia, sedation, dependence

KAPPA

• pre-synaptic
• brain, spinal cord
• spinal analgesia, sedation, miosis, inhibition of ADH, dysphoria

MU

• pre- and post-synaptic
• brain, spinal cord, GI
• supraspinal analgesia, respiratory depression, miosis, euphoria, reduced GI motility, dependence

NOCICEPTIN

• brain, spinal cord
• anxiety, depression, appetite

Question 2

Describe the effects of opioid receptor agonists on the response to pain. Describe the MOA by which opioid receptor activation promotes analgesia.

Answer 2

MOA - inhibit pain pathway at various levels (peripheral tissue, spinal cord, or cortex)

• presynaptic (mu, kappa, delta) => decreased Ca2+ influx, increased K => decreased transmitter release
• postsynaptic (mu) => increase K conductance => increase IPSP

Question 3

Describe the following for morphine:

• MOA
• indications
• side effects

Answer 3

MOA
- mu receptor agonist

INDICATION - severe analgesia
- prototype

SIDE EFFECTS

• constipation
• addiction
• tolerance (desensitization, downregulation)
• withdrawal
• overdose (antidote = naloxone)

Question 4

Describe the following for meperidine:

• MOA
• indications
• side effects

Answer 4

MOA

• k receptor agonist
• also bind to K channels, dopamine receptors, and muscarinic receptors

INDICATION - analgesia (strong)

SIDE EFFECTS

• due to metabolite norpethidine
• serotonin syndrome
• seizure
• dysphoria
• tremor
• respiratory depression
• CANNOT be countered by naloxone

Question 5

Describe the following for codeine:

• MOA
• PD
• indications
• side effects
• drug interactions

Answer 5

MOA
- mu receptor agonist

INDICATIONS

• moderately strong analgesic
• cough suppressant
• diarrhea
• IBS
• narcolepsy

SIDE EFFECTS

• euphoria
• itching
• urinary retention
• depression
• constipation
• erectile dysfunction
• withdrawal

NOTE: active metabolite is codeine

Question 6

Describe the following for naloxone:

• MOA
• indications
• side effects
• drug interactions

Answer 6

MOA
- mu, kappa, delta ANTagonist

INDICATIONS
- antidote

SIDE EFFECTS

• change in mood
• trembling
• change in heart rhythm
• blocks endorphine action

NOTE
- overdose can come back once naloxone wears off b/c the opioid is still around the system

Question 7

Describe the CNS effects of opioids.

Answer 7

• analgesia of sensory and emotional pain
• euphoria (sometimes dysphoria)
• sedation
• cough suppression (maintain ventilation during endotracheal intubation)
• miosis
• temperature
• respiratory depression

Question 8

List the opioids that belong in each category:

• strong
• moderately strong
• receptor agonist-antagonist
• antagonist

Answer 8

STRONG

• morphine
• methadone
• meperidine

MODERATELY STRONG

• codeine
• oxycodone

AGONIST-ANTAGONIST

• pentazocine
• buprenorphine

ANTAGONIST
- naloxone

Question 9

Describe the following for hydrocodone:

• MOA
• indications
• side effects
• drug interactions

Answer 9

MOA

• mu receptor agonist
• delta receptor agonist

INDICATION

• moderate analgesic (moderately strong)
• cough suppression

SIDE EFFECTS

• sleepiness
• respiratory depression
• constipation, N/V
• loss of consciousness
• miosis
• overdose

DRUG INTERACTIONS
- can be combined with aspirin or ibuprofen for enhanced effect

Question 10

How do opioids lead to euphoria?

Answer 10

1. opioid binds to mu receptor
2. inhibits release of GABA
3. GABAb receptor is not inhibited =>
4. release of dopamine

Question 11

Describe the following for pentazocine:

• MOA
• indications
• side effects
• drug interactions

Answer 11

MOA

• mu antagonist
• kappa agonist
• delta agonist

INDICATION

• analgesic
• dental extraction

SIDE EFFECTS

• weak antagonist of morphine and meperidine
• hallucinations
• psychotomimetic effects
• CV effects
• withdrawal

Question 12

Describe the following for methadone:

• MOA
• indications
• side effects
• drug interactions

Answer 12

MOA

• mu agonist
• delta agonist
• decreased desire for opioid intake
• inhibitory effect that stops withdrawal manifestation

INDICATION

• partial treatment of opioid dependence
• used in heroin addicts (high lasts longer, less societal damage)

Question 13

Describe opioid overdose.

Answer 13

• sedation
• stupor, coma
• decreased HR, blood flow
• cough suppressant
• respiratory depression
• hyperventilation
• constipation, N/V
• loss of sexual interest