L37 Drugs Used in The Control of Pain→↑↓

Question 1

Classification of Opioids Analgesics

Answer 1

Natural opium alkaloids
→Morphine
→ Codeine

Semi-synthetic opioids
→Diamorphine

Synthetic opioids
→Pethidine (meperidine)
→ Fentanyl
→ Methadone
→ Tramadol

Question 2

Functional Classification of Opioids

Answer 2

Pure (full) agonists
→ Morphine
→ Fentanyl
→ Remifentanil

Partial agonists
→ Buprenorphine
→ Tramadol

Agonists-antagonists (having lower abuse potential)
→Pentazocine

Pure (full) antagonists
→Naloxone
→Naltrexone

Question 3

MoA of Opioids

Answer 3

Agonist Binding
→Conformational changes in GPCR
→→inhibition of adenylyl cyclase
→→stimulation of K+ current
→inhibitoin of voltage gated ca2+ channels

→decreased release of neurotransmitter

Question 4

Major Uses of Opioids

Answer 4

Anesthesia
→ fentanyl, alfentanil, remifentanil

Severe pain
→morphine, hydromorphone, meperidine

Moderate-to-severe acute or chronic pain
→transdermal fentanyl, codeine, oxycodone, hydrocodone, methadone

Diarrhea
→ loperamide, diphenoxylate

Cough
→codeine, hydrocodone

Question 5

Effect, Mechanism, Contraindication, S/E of of Opioid

Answer 5

Central Nervous System (CNS)
Analgesia
→ Most effective in relieving dull, continuous and poorly localized pain
arising from deeper structures
→ Less effective against superficial and sharp pain
→ Neuropathic pain can be very resistant
Sedation (NOT true hypnotics)
→ Drowsiness
→ Sleep may occur with relief of pain

Dysphoria
→ Morphine use without pain

Hallucination
→ More common with KOP agonists
→ May also occur with morphine and other MOP agonists

Cardiovascular System (CVS)
Mild bradycardia
→ Common (except meperidine ) →Decreased sympathetic drive
→ A direct effect on the sino-atrial node

Mild hypotension
→ Peripheral vasodilatation
→ →Histamine release
→→ Reduced sympathetic drive
→ May be significant in hypovolaemic patients

Respiratory System
Respiratory depression
→ Mediated via MOP receptors at the respiratory centres in the
brainstem
→ Respiratory rate falls more than tidal volume
→Sensitivity of the brainstem to CO2 is reduced
→ Response to hypoxia is less affected
→ Synergistic respiratory depression with concurrent use of other CNS depressants, e.g. benzodiazepines or halogenated anesthetic

Cough suppression
→ Codeine suppresses coughing to a degree similar to morphine,
but has lesser analgesic activity

Gastrointestinal System
Nausea and vomiting
→ Stimulation of the chemoreceptor trigger zone (CTZ)

Smooth muscle tone is increased but motility is decreased resulting in
→ Delayed absorption
→ Increased pressure in the biliary system, i.e. spasm of
sphincter of Oddi)
→ Constipation

Endocrine System
→The release of adrenocorticotropic hormone (ACTH), prolactin and gonadotrophic hormone is inhibited

→Secretion of antidiuretic hormone (ADH; also known as vasopressin) is increased

Other Body Systems
Ocular effects
→ MOP and KOP receptors in Edinger-Westphal nucleus of the
occulomotor nerve (parasympathetic) are stimulated by opioids
resulting in constriction of the pupils (miosis)

Histamine release
→Morphine, codeine and meperidine cause non-immunologic
displacement of histamine from tissue mast cells
→ NOT an allergy

Urinary tract
→Increase contractions of the ureter and tone of the urinary sphincter
→ Decrease force of detrusor muscle contraction
→ Urinary retention can occur

Question 6

Name of Opioids

Answer 6

A naturally occurring phenanthrene derivative
→Morphine
Natural opioid
→Codeine
→→An antitussive
→→ An antidiarrheal

Synthetic phenylpyperidine derivative
→Meperidine
→Fentanyl
→Remifentanil (derivative of fentanyl)
→Alfentanil

Codeine

Tramadol
A phenylpyperidine analogue of codeine
Mechanism of analgesic action
→ Weak agonist at all opioid receptors (20x preference for MOP
receptors)
→ Inhibits neuronal reuptake of norepinephrine & 5-HT
→ Potentiates release of 5-HT and causes descending inhibition of nociception
Advantages:
→ Less respiratory and cardiovascular depression in equi-analgesic
dose to morphine
→ Less constipation
→ Shares most of the common side effects of opioids
→ Nausea, vomiting, drowsiness and ambulatory dizziness
→ Rapid psychomotor recovery

Question 7

Mechanism, Contraindication, S/E of Partial Opioid Agonists

Answer 7

NO antagonistic but diminished effects at opioid receptors
→buprenorphine
⎼ Cannot be used during labor (respiratory depression NOT completely reversed by naloxone)

S/E
Nausea and vomiting are severe and prolonged Postural hypotension is marked

Long lasting pain such as in cancer
Treatment of morphine dependence

MIXED agonist-antagonist
→ Agonist effects at one opioid receptor and antagonistic effects at
the others
→ pentazocine, nalbuphine and meptazinol

pentazocine

→ To relieve moderate to severe pain
→ To act as a preoperative medication
→ To act as a supplement to anesthesia

Question 8

Mechanism, Contraindication, S/E of Competitive opioid receptor antagonist

Answer 8

Naloxone

MoA
Antagonizes all morphine actions at MOP, KOP and DOP receptors with a higher affinity for the MOP receptor

S/E
acute withdrawal state Hypertension, pulmonary edema and cardiac arrhythmias

Uses:
Morphine poisoning
Diagnostic test for opioid addiction
 Revert neonatal respiratory depression due to opioid use during
labor

Naltrexone
→Opioid addiction
→Compulsive eating disorder with morbid obesity