B/25. Natural opiates, opioid receptors

Question 1

Drugs need to know in this topic

Answer 1

Morphine Codein

Question 2

Endogenous opioid peptides

Answer 2

1. β-endorphin 2. Enkephalin 3. Dynorphin

Question 3

opioid receptors

Answer 3

μ (mu) δ (delta) κ (kappa)

Question 4

Physiologic effects of opioids

Answer 4

Acute

1. Analgesia (pain relief)
2. Sedation (additive with other CNS depressants)
3. Respiratory depression (desensitization of CO2 center)
4. Antitussive action (suppression of cough reflux)
5. Nausea and vomiting (stimulation of chemoreceptors in the area postrema)
6. Intestinal motility ↓
7. Circular smooth muscle contraction (urinary tract, biliary)
8. Miosis (pupillary constriction)
9. Histamine release, ADH release

Chronic

1. Tolerance (pharmacodynamic tolerance; occurs to all effects except miosis and constipation)
2. Dependence (physical and psychologic)

Question 5

Morphine

Answer 5

Strong agonist

Natural

1. Analgesic use (post-operative pain, chronic pain syndromes, post-MI)
2. Anesthesia
3. Acute pulmonary edema

Question 6

Codeine

Answer 6

Weak agonist

Natural

1. Antitussive
2. Analgesic effect in combination with NSAID’s or acetaminophen
   *NE and 5-HT reuptake inhibition (dextromethorphan)

Question 7

Pharmacokinetic properties

Answer 7

1. Hepatic metabolism by CYP450 enzymes
2. Morphine is metabolized into an intermediate compound (morphine-6-glucoronide), which has much higher activity than the original compound; elevated serum levels (as in renal impairment) may cause life-threatening toxicity
3. Excretion via the kidneys
4. Alcohol increases opioid peak concentration in serum
5. T1/2 → short-acting (1-2 h’), intermediate-acting (6-8 h’), long-acting (24 h’)

Question 8

Adverse effects and toxicity

Answer 8

1. Constipation (may cause paralytic ileus in severely high doses)
2. Biliary colic
3. Sedation and CNS depression (dose-dependent effect, additive with other CNS depressants)
4. Opioid-induced hyperalgesia – nociceptive sensitization caused by long-term exposure to opioids
5. ‘Psuedo-allergy’ – IgE-independent mast cell degranulation (histamine release induces rash, wheezing, tachycardia)

Question 9

Acute toxicity

Answer 9

Presentation (classic triad):

1. Pupillary constriction (‘pinpoint pupils’)
2. Respiratory depression
3. Coma

Management:

1. IV Naloxone
2. Supportive

Question 10

Dependence

Answer 10

• *Withdrawal presentation (abstinence syndrome):**
  1. Yawning
  2. Increased secretion: lacrimation, rhinorrhea, salivation
  3. Anxiety, sweating, hyperthermia
  4. Muscle cramps, spasm, CNS-originating pain
  5. Piloerection

Management:
1. Methadone, Buprenorphine, Naltrexone
2. Clonidine
3 Supportive

Question 11

Teratogenicity

Answer 11

1. Respiratory depression
2. Preeclampsia
3. Fetal death
4. Physical dependence → ‘Neonatal abstinence syndrome