OPIOID ANALGESICS

DR.SOBAN SADIQ

OPIOID AGONISTS

Morphine(strong mu receptor agonist)CodeineHeroinPholcodineMeperidine(pethidine)Loperamide(over the counter for diarrhea)DiphenoxylateDextromethorphan

Opioid agonist-antagonist/partial agonistNalbuphinePentazocine

Opioid antagonistsNalorphineNaloxoneNaltrexone

Opioid receptorsMuKappaDelta

MOA OF MORPHINE

Certain opioid receptors are located on primary afferent and spinal cord pain transmission neurons(ascending pathways) and on neurons in the midbrain and medulla(descending pathways) that function in pain modulation.

All 3 receptors appear to be involved in anti nociceptive and analgesics mechanisms.

Presynaptically: Opioid receptor activation can close voltage –

gated calcium ion channels to inhibit neurotransmitter release.

( serotonin, glutamate and substance P)

Postsynaptically:Activation of these receptors can open potassium ion

channels to cause membrane hyperpolarization(inhibitory post synaptic potential).

-Direct inhibition of neurons in ascending pathways.

Pharmacological effectsCNS: Analgesia: most powerful drug available for relief of

painEuphoria: addict experiences a pleasant floating

sensation and freedom from anxiety and distress.SedationRespiratory depression: Main cause of death

from opioid overdosedue to reduced responsiveness of respiratory centre in

brainstem to blood levels of CO2.

Increase arterial CO2 retention causes cerebral vasodilation resulting in increase intracranial pressure

Cough suppression: suppression of cough centre in nucleus of tractus solitarius

Miosis: results from stimulation of Edinger- Westphal nucleus causing pin-point pupils except meperidine.

Emesis: due to stimulation of brainstem chemoreceptor trigger zone results in nause and vomiting

CVS: No significant direct effect on CVSHypotension may occur if CVS is already stressed.

Due to the peripheral arterial and venous dilation resulting from histamine release.

GIT: Decrease intestinal propulsive peristalsis and stomach motility leads to constipation

Biliary tract:Constriction of biliary smooth muscles leads to biliary colic except meperidine

Constriction of sphincter of oddi leads to increase biliary pressure,reflux of biliary and pancreatic secretions and elevated plasma and lipase levels

Renal functions: depressed due to decrease renal plasma flow.

Also has antidiuretic effect.Mechanism involve both CNS and peripheral site

Ureteral and bladder tone is increasedIncreased sphincter tone….urinary retentionOccasionally, ureteral colic caused by renal calculus

is made worse by opioid induced increase in ureteral tone

Uterus: decrease uterine tone lead to prolong laborSkin: flushing and warming ,sweating,itching due to

histamine release

Summary

Biliary, bladder,ureter tone inc. except meperidine (which block M receptors)

GIT,uterine tone dec.

Clinical usesAnalgesia for MI, terminal illness, surgery, obstetrical procedures, cancer.

CoughDiarrhea

Acute pulmonary edema: decrease dyspneaProposed mechanism : Reduced anxiety(perception of shortness of

breath) Reduced cardiac preload(reduced venous tone) Reduced afterload(decreased peripheral resistance)If respiratory depression is there then use furosemide

Adverse effects

Tolerance

Tolerance occur due to receptor uncoupling.Physical dependence:It results in withdrawal(Abstinence)

syndrome if there is failure to continue administer drug. Sudden withdrawal(abstinence syndrome)has following

signs/symptoms:

lacrimation,yawning,chills,hyperventilation,hyperthermia,diarrhea,vomiting,anxiety

Psychological dependence: euphoria,Indifference to stimuli and Sedation

Morphine poisoning….antidote is naloxone

1-A 57 year old man presented with steady, severe pain in the right hypochondrium, nausea, vomiting and temperature of 102 F. If hepatobiliary imaging reveals an obstructed cystic duct, which of the following agents would be the drug of choice for the treatment of this patient’s pain?

a-Meperidine b-Morphine c-Naproxen d-Diphenoxylate e-Loperamide

Fentanyl patches(opioid) have been used to provide analgesia. The most dangerous adverse effect of this mode of administration is

a-Cutaneous reactions b- Diarrhea c- Hypertension d- Relaxation of skeletal muscle e- Respiratory depression

Mr. Naseem is on his way to take an examination and he suddenly gets an episode of diarrhea. He stops at a nearby drug store for an over the counter opioid with anti diarrheal action, what would be his choice:

a-Codeine b-Dextromethorphan c-Diphenoxylate d-Loperamide e-Nalbuphine

Which of the following opioid analgesics is a strong mu receptor agonist?

  a- Naloxone b- Morphine c-Nalbuphine d- Hydrocodone e-Naltrexone

Morphine causes the following effects EXCEPT:

a) Constipationb) Dilatation of the biliary ductc) Urinary retentiond) Respiratory depression

The antidote of choice for morphine poisoning is

A-NaltrexoneB-NaloxoneC-NalbuphineD-Codeine

Which of the following opioid analgesic is used for relieving the acute, severe pain of renal colic:

  a-Morphine b- Naloxone c- Codeine d- Meperidine e-Naltrexone

Opioid acts presynaptically by blocking Sodium channelsPotassium channelsCalcium channelsSerotonin channelsGABA channels