Download Opioid Anelgesics

PAIN MANAGEMENT:NARCOTIC ANELGESICS
Lecture Objectives
•
•
•
•
•
At the end of the lecture, you should be able to:
State Mechanism of action of opioids
State actions and uses of opioids
State adverse effects of opioids
Enlist individual differences between different opioid drugs
Analgesics
Narcotic
Analgesics
OPIOIDS
Non
narcotic
Mainly NSAIDS
Opioid Anelgesics
•
Mechanism of Action:
– Act in part via receptors for endogenous opiopeptides such as
enkephalins, dynoprhins, and β endorphins
– Opioid receptors are of multiple types, all G-protein-linked
•
•
•
Μ (mu)
δ (delta)
Κ (kappa)
MOA
•
•
•
•
Effects of specific opioid drugs depend on the receptor subtype with
which they interact as
– Full agonist
– Partial agonists
– Antagonists
Some drugs (mixed agonist-antagonist) may activate one receptor
subtype and act as antagonist at another subtype
MOA
Activation of pre-synaptic opioid receptors causes inhibition of Ca+2
influx through voltage regulated ion channels  ↓ neurotransmitter
activation of post synaptic opioid receptors results in ↑ K+
MOA
•
•
•
Opioid receptors are also located presynapticaally on primary
afferents (type C and A fibres) in the dorsal horn of the spinal cord
Activation of these receptors  ↓ release of substance P
Substance P is a peptide neurotransmitter that cuases excitatory
actions in pain pathways
•
•
•
Opioid receptors involved in spinal anelgesia are of both of μ (mu)
and Ќ( kappa) subtypes
Opioid Anelgesic Phamracology
Variations exist between individual drugs in terms of the following
actions which are based on morphine as the prototype drug of the
class
Anelgesia:
– Increase pain tolerance and ↓ peception and reaction to pain
– Variable efficacy
– Morphine is full agonist and gives maximum pain relief
– Persistent dull aching pain responds better than intermittent
•
Sedation
•
Respiratory Depression
– Drowsiness
– Possible euphoria
– Short term memory loss
– Decreased response to ↑ pCO2 (even at Rx doses) via
depression of neurons in brainstem respiratory center-major
problem in overdose
•
Cardiovascular
– Minimal effects on heart
– Cerebral vasodilation  ↑ intracerebral pressure (avoid in head
traumma)
– Morphine (but not most of the other opitates) releases
•
•
•
GI tract
–
–
–
Decreased peristalsis
Constipation
(potential clinical use in diarrheal state) e.g. loperamide,
diphenoxylate
Smooth muscle
–
–
–
Increased tone of biliary system, bladder, ureter
Possible spasm (except meperidine) which blocks M receptors
↓ tone of vasculature (hypotension via histamine) and uterus
(slow delivery)
Pupils
– Miosis via cholinrgeic activity (except meperidine)
•
Cough supression
•
Nausea and emesis
– Anti tussive action
– Stimulation of CTZ in the area postrema
– Dual action
Kinetics
•
•
Morphine undergoes first pass metabolism in the liver (low oral
bioavailibity)
One of its metabolites morphine-6-glucuronide is highly active,
contributing greatly to anelgesia and causing possible toxicity in
renal dysfunction
Clinical Corelate
•
Contraindication and caution for opioids
•
Pulmonary dysfunction
•
Hepatic/ renal dysfunction
•
Adrenal or thyroid deficiencies
– Head injuries
– (possible increased intracranial pressure)
– Except pulmonary edema
– Possible accumulation
•
– Exaggerated responses
Pregnancy
– Possible neonatal depression or dependence
Adverse Effects
•
Acute toxicity
– Extensions of the pharmacodynamic actions
– Severity greatest with full agonists like morphine
– Characteristic triad: pin point pupils, respiratory depression,
comatose state
•
Management
– Maintain patent airway and assist ventilation
– Avoid oxygen (  decreased breathing)
– IV naloxone
Adverse Effects
•
Tolerance
– Occurs with continued use
– Changes in cellular adaptive responses but not receptor numbers
– Tolerance is marked for CNS actions such as analgesia,
euphoria, respiratory depression
– Occurs minimally in terms of miosis and GI motility
– Cross tolerance between individual opioid analgesics
Dependence
•
Both psychological and physical components
•
•
•
•
•
•
•
Latter evident by withdrawal syndrome which may include anxiety,
lacrimation, rhinorrhea, sweating, goosebumps, hot or cold flushes,
mucle cramps and spasms
Intensity of the symptoms depend on drug use, the dosage that the
individual had been using
Full agonists cause most severe withdrawal
Management involves oral methadone with gradual dose tapering
Methadone maintenance programs: provision of daily oral doses to
registered clinics at methadone clinics
Properties of Various Opioid Analgesics
Properties of Various Opioid Analgesics
Abuse liability
Prescription regulations for most CNS drugs are based on their
abuse liability
Potent opioids such as morphine, meperidine, methadone etc are
judged to have the highest potential for abuse
THANK YOU