B15 Natural opiates, Opioid receptors

Question 1

The natural opiates are

Answer 1

Morphine and Codeine

Question 2

Relative potency of the natural opiates

Answer 2

Morphine is the archetype strong u receptor agonist.

Codeine is A weak u receptor agonist.

Question 3

What are the opioid receptors

What other receptors do opioates interact with

Answer 3

mu, kappa, delta
opioid receptor ligands are stereospecific.

All are Gi coupled receptors that inhibit adenylyl cyclase.

They also increase postsynaptic K+ channel conductance, and decrease presynaptic Ca++ channel conductance.

Question 4

Actions of morphine (13)

Answer 4

Analgesia: increased spinal pain threshold, altered central pain perception, decreased emotional response to pain.

Euphoria

Respiratory depression: reduces CNS resp center sensitivity to CO2.

Cough suppression: via a mechanism apparently unrelated to analgesic effect.

Miosis: due to mu and kappa receptor stimulation. No tolerance to this effect. Patients with morphine intoxication will always have pinpoint pupils.

Emesis: Direct stimulation of the chemoreceptor trigger zone in the area postrema.

GI constipation: decreased motility, increased sphinctyer tone. No tolerance to this effect.

Urinary retention: Due to increased ADH release.

Cardiovascular: No effect at low doses. Bradycardia or hypotension at high doses

Increased ICP: due to resp depression and increased CO2, CNS vasodilation and increased cranial pressure.

Histamine release: Morphine causes urticaria, sweating, vasodilation, and some bronchoconstriction. Contraindicated in COPD or asthma.

Hormonal stimulation: Increases GH and PRL release.

Labor: Suppresses strength and frequency of uterine contractions, can prolong labor. Also can cause dependency in babies. Should not be used during labor.

Question 5

What are the opioid receptor antagonists?

Answer 5

Naloxone. 
non-selectively antagonist of all the receptors. 
duration is about 1-2 hours. 
morphines is ~3-4 hours by i.v. 
multiple doses usually needed.

Naltrexone
oral formulation of naloxone, has a longer duration, used for maintenance therapy of opioid addiction.

Question 6

Basic components of the opioid chemical structure

Answer 6

1 aromatic ring, and 4 other ringed structures, one of which has a Nitrogen in the ring.

Question 7

What are the Opiopeptins

Answer 7

The endogenous opioids. Peptide hormones

Beta-Endorphins (endomorphins by semmelweis idiots)
met-Enkephalin
leu-Enkephalin
Dynorphins A and B (D-morphines by semmelweis idiots)
Neoendorphins alpha and beta

Question 8

What receptors do the endogenous opioids have highest affinity for.

Answer 8

Beta-Endorphin - mu receptors

met-Enkephalin - delta receptors
leu-Enkephalin - delta receptors

Dynorphins - kappa receptors

Question 9

What dosage is used for pain management with morphine

Answer 9

Morphine sulphate, orally.
30-100mg
twice daily.

Oral administration with the slow release morphine sulfate form is preffered to maintain a steady state, and prevent the euphoric stages, which induce tolerance.
Causing cycles of euphoria, pain, increased dosage, and addiction/death.

Question 10

Dosage of morphine if it is given parenterally

Answer 10

Morphine hydrochloride.
10-20mg by s.c.

1mg by i.v. up to a maximum of 10mg.

Question 11

What areas in the CNS mediate the analgesic effect of opiates

Answer 11

Ascending pain pathways

• the Substantia gelatinosa (lamina 2) in the dorsal horn of the spinal cord.
• the Ventral caudal thalamus, VPL.

Descending pathways

• the Periaqueductal Gray of the midbrain
• the Rostral Ventral Medulla, Raphe nuclei

Question 12

How is morphine metabolized?

Answer 12

glucuronidation by the liver.

Increased effects in the elderly or liver impaired.