Bind opioid receptors

1. Mu - morphine like analgesia, resp depression, euphoria, physical dependence, typical agonist like effects, supraspinal (CNS)

2. Delta - analgesia (spinal) - ENK interact selectively

3. Kappa - Analgesia (spinal), miosis, sedation, pentazocine-like

Opium Alkaloids and Derivatives: Strong Agonists

1. Morphine Sulfate

2. Heroin

3. Codeine

4. Hydromorphone

5. Levorphanol

1. Use:

a. relieves pain by increasing threshold at spinal cord & altering brain's perception of pain.

b. decreases pain transmission neurons

c. activates descending pain inhibitory neurons by inhibiting GABAergic

2. MOA - analgesia by activating Mu receptor in CNS and agonizing (without binding) delta & kappa receptors.

3. SE - euphoria, dysphoria, sedation, respiratory depression. Avoid combo with agonist-antagonist group.

1. Use - cough suppression, relieve diarrhea and dysentery, relieve pain (can be patient controlled), pulmonary edema, and MI

2. SE - Coma, airway obstruction, atelectasis, respiratory depression (esp w/ asthma & COPD). NV. Miosis, constipation, biliary spasm, histamine release, urinary retention, decrease LH & FSH secretion. High doses can cause orthostatic hypotension.

1. Withdrawal - Abstinence syndrome (autonomic hyperactivity: anxiety, restlessness, yawning, tremor, insomnia). 

Treat with: methadone (withdrawal or maintenance), clonidine (decrease sympathetic symptoms), buprenophine (long acting), naltrexone (for maintenance)

2. OD - treat w/ atropine & Nalaxone

3. Caution - COPD, asthma, increased ICP, elderly, neonate & pregnancy, liver or kidney disease, hypotension. 

High Abuse Potential - psychological & Physical dependence.

1. Phenylpiperidines

a. Meperidine

b. Fentanyl

c. Sufentanyl

2. Phenylheptylamines

a. Methadone

1. similar to morphine but weaker & shorter duration

2. Use - moderate to severe pain. obstetric analgesia b/c does not prolong labor as long as morphine

3. SE - convulsions. antimuscarinic.

Toxic doses (CNS excitation)

1. highly potent w/ rapid onset & short duration.

2. abused by medical personnel

3. Use - post op or during labor. 

4. transdermal or transmucosal patch for cancer pain

1. µ agonist. Glutamate antagonist

2. Use - chronic pain, treatment of opioid dependence

3. SE - withdrawal symptoms milder but more prolonged than morphine

1. Codeine

2. Oxycodone

3. Propoxyphene

4. Diphenoxylate

1. Use - moderate to severe pain. Orally effective

2. SE - #1 killer of abusers

1. Use 1/2 as potent as codeine. D-isomer of methadone. combo w/ aspirin or acetaminophen for mild to moderate pain.

2. SE - no significant physical dependence or withdrawal syndromes. 

3. Nausea, anorexia, constipation.

4. Toxic doses - resp depression, convulsion, hallucination

1. Pentazocine

2. Buprenorphine

3. Butorphanol

1. MOA - Kappa receptor agonist in spinal cord

2. Use - intermediate potency analgesic for mod to severe pain when given orally

3. when given Parenteral - Psychomimetic (anxiety, hallucinations, nightmares, tachycardia) 

Ceiling effect (less resp depression)

1. 25 to 50 times more potent than morphine on a weight basis. 

2. MOA - partial Mu receptor agonist w/ long duration of action

3. Use - office based opioid detox

4. SE - precipitate withdrawal in morphine users. Resp depression, resistant to Naloxone.

1. MOA - strong kappa agonist and Mu antagonist

2. Use - parenteral and nasal spray. provide analgesis

3. SE - similar to Pentazocine except less psychomimetic. Ceiling effect.

1. MOA - binds weakly to Mu receptors. Inhibits reuptake of NE and serotonin thus increasing availability of NE & serotonin

2. Use - analgesis for moderate pain

3. SE - OD can result in resp depression, seizure, and anaphylaxis

1. MOA - short duration (1 to 4 hrs)

2. Use - injected. DOC opioid OD

1. MOA - long duration (24 to 48 hrs)

2. Use - oral for opioid dependence and alcoholism