Opioids and analgesics

Question 1

Classification of these drugs?

Answer 1

1. Natural compounds
2. Semi - synthetic derivatives (Codeine, morphine and Thebaine)
3. Synthetic compounds (codeine analogue and opioids).
4. Opioid receptor modulators
5. Morphine antagonists
6. Combined preparations.

Question 2

Pharmacokinetics?

Answer 2

Poor oral absorption, due to first pass metabolism. IV, IM and subcutaneous administration is more effective. Opioids have a very wide distribution, can pass through the placental barrier causing dependence in the foetus. Morphine is the least lipophilic and has the lowest BBB penetration through endothelium lipid bilayer.
Elimination is mostly in the urine and very little in the bile.

Question 3

Metabolism of Morphine?

Answer 3

By “Glucuronic acid conjugation”, into 2 metabolites.

1. Morphine-6-glucuronide (Potent analgesic)
2. Morphine-3-glucoronide (neuro-excitory effects)

Question 4

What is the antidote for opioid overdose?

Answer 4

“Naloxone”, used to reverse coma and respiratory depression side effects of opioid overdose. Another antidote that can be used is “Naltrexone” which blocks heroin effects.

Question 5

What are the opioid receptors, effects of their stimulation?

Answer 5

Mu, kappa and delta receptors. Their effects are as follows:

1. Inhibition of Adenylyl Cyclase (Adenylyl cyclase is the enzyme that synthesizes cyclic AMP “CAMP” from adenosine triphosphate (ATP).
2. Opening of K+ Channels which cause hyperpolarisation due to efflux of k+ ions in the post synaptic membranes. Reducing potassium reduces conductance (neuronal firing)
3. Closure of Ca2+ Channels which do no permit release of neuro-trasmitter.

Overall effects are reduced pain transmission.

Question 6

What are the “Central Effects” of the opioids on the body?

Answer 6

1. Miosis
2. Respiratory depression (They reduce the sensitivity of the respiratory centre to the CO2 levels, is a great cause of death)
3. Depression of thermoregulatory centre of the body (shivers and fever development).
4. Nausea and Vomiting.
5. Pain Relief, without loss of consciousness. This is done by altering the brains perception towards pain (receptor stimulation) and increasing the pain threshold at the level of the spinal cord.
6. Hormonal Effects: FSH,LH and ACTH levels are lowered. GH, ADH and prolactin levels are increased.

Question 7

What are the “Peripheral Effects” of the opioids on the body?

Answer 7

1. GI-tract : Reduced motility, develops constipation.
2. Urinary retention in bladder.
3. No cardiac effects at low dose, but in therapeutic dose may cause bradycardia/ hypotension due to increased histamine.
4. Increased Histamine release : vasodilation and broncho-constriction.
5. Reduces uterine contractions.

Question 8

Contraindications for Opioid use?

Answer 8

1. Children less than 12 (effects on respiratory depression).
2. Renal or hepatic failure.
3. Shock patients.
4. Pregnancy (risk for drug dependency).
5. Acute/Chronic respiratory diseases (COPD/Asthma)

Question 9

Therapeutic Uses for Opioids?

Answer 9

1. Treatment of acute left ventricular failure (they reduce venous return to the heart, which reduces the effects of dyspnea caused by the congestion in the lung, pulmonary oedema).
2. Dry coughs : Codeine and ethyl-morphine act as antitussive drugs.
3. Diarrhoea : Laperamide is a opioid agonist, that acts on mu and delta receptors in the intestines to reduce peristalsis and counteract diarrhoea.

Question 10

Drug interactions of the opioids ?

Answer 10

1. CNS depressants further enhance the depressing capabilities of the morphine.
2. Neuroleptic drugs (anti-psychotics) potentiate the analgesic effects of the opioids.