Download OPIOID ANALGESICS

DR.SOBAN SADIQ
OPIOID AGONISTS
 Morphine(strong mu receptor agonist)
 Codeine
 Heroin
 Pholcodine
 Meperidine(pethidine)
 Loperamide(over the counter for diarrhea)
 Diphenoxylate
 Dextromethorphan
Opioid agonist-antagonist/partial agonist
 Nalbuphine
 Pentazocine
 Opioid antagonists
 Nalorphine
 Naloxone
 Naltrexone
 Opioid receptors
 Mu
 Kappa
 Delta
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 effects
CNS:
 Analgesia: most powerful drug available for relief of
pain
 Euphoria: addict experiences a pleasant floating
sensation and freedom from anxiety and distress.
 Sedation
 Respiratory depression: Main cause of death from
opioid overdose
 due 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 CVS
 Hypotension 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 increased
 Increased sphincter tone….urinary retention
 Occasionally, ureteral colic caused by renal calculus is
made worse by opioid induced increase in ureteral
tone
 Uterus: decrease uterine tone lead to prolong labor
 Skin: 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 uses
 Analgesia for





 Cough
 Diarrhea
MI,
terminal illness,
surgery,
obstetrical procedures,
cancer.
 Acute pulmonary edema: decrease dyspnea
 Proposed 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,hyperther
mia,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) Constipation
 b) Dilatation of the biliary duct
 c) Urinary retention
 d) Respiratory depression
 The antidote of choice for morphine poisoning is
 A-Naltrexone
 B-Naloxone
 C-Nalbuphine
 D-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 channels
 Potassium channels
 Calcium channels
 Serotonin channels
 GABA channels