OPIOID ANALGESICS by Dr. Monika lall.pptx

1. Opioid Analgesics
(Narcotic analgesics)
Dr. Monika Sharma

2. PAIN
2
• Pain is defined as an unpleasant sensory and emotional
experience with actual or potential tissue damage.
• It is a common every day experience that performs
essential defensive function.
• uncontrolled pain can severely diminish quality of
life.
• pain can be acute or chronic

3. Pain transmission and processing
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Noxious stimuli
Activation of nociceptors
Transmission of information through dorsal horn of s.cord
(release of stimulatory transmitter peptides like sub.P ,gultamete ,NO)
Onward transmission to higher brain centers
Processing in the higher brain centers
Release of inhibitory trasnsmitters
(endogenous peptides like enkephalins ,endorphins ,dynorphins)

5. Mechanism of analgesia
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• Endogenous Opioid
neurotransmitters:
Endorphins
Dynorphins
Enkephalins
These endogenous chemicals in the spinal cord and
brain constitute pain inhibiting system.
Analgesia: it is a state in which a painful
stimuli are moderated (modulated) , although
perceived but felt no more painful.

6. Opioid receptors
• There are 3 types of opioid receptors:
• μ receptors
• κ receptors
• δ receptors
• The opioids can act on these receptors as:
• Agonists
• Antagonists
• Mixed agonist-antagonist
(agonist at one receptor & antagonist at the other)

8. OPIOIDS
Agonists Mixed Agonist-Antagonists
Strong Agonists
•Morphine
•Heroin
•Methadone
•Pethidine (Meperidine)
•Fentanyl
•Sufentanil
•Alfentanil
•Remifentanil
Mild to Moderate Agonists
•Codeine
•Oxycodone
•Hydrocodone
•Propoxyphene
•Loperamide
Antagonists
•Naloxone
•Naltrexone
•Nalmefene
Used as Antagonists
•Nalorphine
Used as Analgesics
•Pentazocine
•Buprenorphine
•Butorphanol
•Nalbuphine

9. On binding to receptors at
presynaptic nerve fiber they cause
decrease in Ca++ influx
which results to ↓ in release of
excitatory neurotransmitters like
glutamate .
Post synaptically activation of
receptors
↑K+ efflux.
This leads to ↓ the response of post
synaptic neuron to excitatory
neurotransmitter.(i.e.
hyperpolarization
Mechanism of action

10. Opioids: Clinical Uses
• As Analgesic:
• Opioids are the most effective analgesics available
• Very effective in relieving visceral pains e.g. of Ac. M.I.
(NSAIDs are used in mild to moderate somatic pains e.g. musculoskeletal pains)
• DOC in severe pain (e.g. in fracture) and cancer pain
• Acute LVF (Acute pulmonary oedema):
• Rapidly relieves dyspnoea
• Acts by its vasodilator action
• Balanced anesthesia:
• Because of their strong analgesic effect,  the dose of anaesthetic needed
• Opioids like Fentanyl are used with Droperidol (Neuroleptic) and N20 to produce “Neurolept
anaesthesia”
• Cough:
• Morphine acts by suppressing the cough centre
• Codeine is preferred because of its more specific action on cough centre
• Diarrhoea:
• Opioids act by inhibiting the g.i. motility and secretions
• Synthetic derivatives like Loperamide are preferred in diarrhoea because of their more specific action
on GIT

11. Opioids: Adverse effects
• Apnoea: respiratory depression
• Allergy: Can cause urticaria & itching around the nose
• B.P. falls: Postural hypotension,  by hypovolemia
• Blurring of vision
• Constipation
• Chronic use leads to tolerance & dependence
• Dysphoria: Feeling not well and restlessness
• Dysuria: Difficulty in urination & urinary retention

12. Tolerance & Dependence
• Tolerance develops rapidly to central effects like analgesia & sedation
• Tolerance does not develop to the peripheral effects like constipation &
miosis
• Cross tolerance is also seen among different opioids acting on mu
receptors
• Physical dependence is confirmed by the presence of a marked
withdrawal (abstinence) syndrome
• Withdrawal occurs after chronic use either due to suddenly stopping the
drug or with the use of an antagonist like Naloxone
• Withdrawal syndrome is more severe with the use of strong rapid acting
agonists e.g. Morphine & Heroin
• Symptoms of withdrawal are usually just the opposite e.g. anxiety,
diarrhoea, mydriasis etc.

13. Opioid overdose toxicity
• Diagnosis:
• Pin-point pupil and signs of CNS depression
• May be history of addiction and needle marks
• Treatment:
• Gastric lavage by sodium bicarbonate in case of recent
oral use
• Respiratory support by ventilator is most important as
the death is always due to respiratory failure
• Naloxone is the specific antagonist
• Rapidly reverses all signs and symptoms of toxicity
• It is given 0.4 mg IV and repeated whenever necessary

14. Opioids: Contraindications & Precautions
• Head injury: Opioids should never be used, the reason is:
Opioids cause respiratory depression
CO2 retention
Cerebral vasodilatation
Intracranial tension
Dangerous alteration of brain functions
• Pregnancy: Respiratory depression in foetus
• Respiratory diseases like asthma & COPD
• Endocrine diseases like Addison’s disease & hypothyroidism
• Hepatic & renal dysfunction

15. Strong Agonists
• Morphine:
• An alkaloid obtained from poppy plant (Papaver somniferum)
• A strong analgesic very useful in severe pain
• Heroin (Diacetyl morphine):
• Fast acting & highly potent analgesic
• Banned in most countries because of addiction liability
• Methadone:
• Preferred for de-addiction of heroin & morphine addicts by substitution treatment
because:
• Orally used and is longer acting
• Tolerance & dependence develops slowly
• Withdrawal symptoms are milder

16. Strong Agonists
• Pethidine (Meperidine):
• This synthetic opioid has significant anticholinergic effects
• So,  H.R.→ Contraindicated in Acute MI
• Fentanyl:
• A strong analgesic preferred by transdermal route
• Sufentanil:
• 5-7 times more potent than fentanyl
• Alfentanil:
• Less potent than fentanyl but acts more rapidly and is shorter acting
• Remifentanil:
• Very short acting because of rapid metabolism by cholinesterases in blood and
tissues

17. Mild to Moderate Agonists
• Propxyphene:
• Has lower analgesic efficacy
• Analgesic effect is additive with NSAIDs
• Usually used in combination with aspirin or Paracetamol in mild to
moderate pain
• Has lower potential of abuse
• Codeine, Oxycodone, Hydrocodone:
• Much less effective analgesic than morphine
• Rarely used alone as analgesic
• Usually used in combination with other analgesics like Paracetamol in
mild to moderate pain

18. Mixed agonist-antagonists
• Used alone act as agonist and produce analgesic effect
• But if used after an agonist act as antagonists and can cause a dangerous
withdrawal syndrome
• Nalorphine is used as an opioid antidote if pure antagonist, naloxone is
not available
• The mixed agonist-antagonists used as analgesic are:
1. Pentazocine: Agonist at κ & weak antagonist at μ receptors
• Used orally & parenterally as analgesic
2. Buprenorphine: Partial agonist at μ receptors
• Given sublingually or parenterally as analgesic
• Also found to be useful as Methadone in heroin addiction
3. Butorphanol: Agonist at κ & partial antagonist at μ receptors
• Produces analgesia similar to others but is more sedative
4. Nalbuphine: Agonist at κ & antagonist at μ receptors
• Given parenterally for analgesia

19. Opioid Antagonists
• These are pure antagonists at all opioid receptors
• Used as antidotes to reverse the effects in cases of opioid
poisoning and opioid adverse effects
• There are 3 pure opioid antagonists available:
1. Naloxone:
• Not absorbed well so given IV, 0.1-0.4 mg
• Half-life only 1-2 hours, so to be repeated as needed
2. Naltrexone:
• Given orally in heroin addiction
• Also now found useful in alcohol addiction
3. Nalmefene:
• Given IV like naloxone but has  half-life of 8-10 hours