This document summarizes opioids and their use as analgesics. It discusses: 1. The classification of opioids including natural alkaloids like morphine and codeine, semi-synthetic opioids like heroin, and synthetic opioids like fentanyl and methadone. 2. The mechanism of action of opioids, which involves binding to mu, kappa, and delta opioid receptors in the central nervous system. 3. Important opioids like morphine, codeine, fentanyl, methadone, and tramadol as well as mixed agonist-antagonists and opioid antagonists.

1. Opioid Analgesics
• Opium is a dark brown resinous material
obtained from poppy capsule of plant
Papaver somniferum.
• It consists of alkaloids that are used
clinically as analgesics.
e.g: Morphine, Codeine, Thebaine,
Papaverine, Noscapine
• Algesia-Pain
• Analgesic – Drugs that relieves pain

4. Classification:
1. Natural opium alkaloids:
Morphine, Codeine
2. Semi-synthetic opiates:
Diacetylmorphine (Heroin),
Pholcodeine, Ethylmorphine
3. Synthetic opioids:
Pethidine (Meperidine), Fentanyl,
Methadone , Tramadol

5. Mechanism of action
• Opioid analgesics bind with specific opioid receptors in
the CNS to produce analgesic action similar to those of
endogenous opioid peptides or endorphins.
• The main opioid receptors are:
• µ (mu) receptors
• κ (kappa) receptors
• δ (delta) receptors
• All three opioid receptors are coupled to inhibitory G
protein (Gi) and inhibit adenylyl cyclase, increase
postsynaptic K+
efflux (hyperpolarization) or decrease
presynaptic Ca2+
influx.
• In this way it blocks neurotransmitter release and pain
transmission.

6. Morphine is principal alkaloid in opium & widely used
analgesic. It blocks neurotransmitter release and pain
transmission, inhibits neural activity by opening of K
channels and reducing Ca influx.
Pharmacological actions:
• Analgesic
• Euphoria
• Respiratory depression
• Depression of cough reflex
• Miosis
• Emesis
• Decreases motility of smooth muscle
• Inhibits hormone release
• Vasodilation & bronchoconstriction due to histamine
release from mast cells

7. Uses:
• Analgesic: surgery, injury, post operative, cancer
• Preanaesthtetic medication
• Balanced anaesthesia
• Treatment of diarrhoea
• Relief of cough
Adverse effects: respiratory depression, vomiting,
blurring vision, constipation, apnea, idiosyncrasy &
allergy, tolerance & dependence
Contraindication: infants & elderly, hypotension,
bronchial asthma, head injury, undiagnosed acute
abdominal pain, hypothyroidism, unstable
personality

8. MORPHINE TOLERANCE AND DEPENDENCE
• Opioid withdrawal signs:
12-16 hours : irritability, body shakes, signs of
aggression, lachrymation, yawning, tachypnoea,
mydriasis
24-72 hours : muscular aches , goose pimples ,
diarrhoea , vomiting , bladder spasms , abdominal
pain

9. Morphine poisoning
• Unconsciousness
• Miosis
• Extreme respiratory depression
• Cold clammy skin
• Low body temp
• Loss of muscle tone
• Absence of reflexes
• Cyanosis
Management
• Gastric lavage
• Activated charcoal
• Specific antidote : naloxone
• Keep the patient awake by pinching
• Supportive measures : respiratory stimulant (doxapram)

10. Codeine
• Codeine is methyl morphine which partly converts
to morphine in the body.
• It has higher oral efficacy but lower analgesic
action(1/10) than morphine.
• Frequently combined with acetaminophen or
aspirin for more effective pain relief.
• It has good antitussive activity.
Uses: Analgesic, Antitussive, Antimotility
Adverse effects: sedation, constipation, xerostoma
Contraindication: infants, asthma, hepatic disease

11. Pethidine (Meperidine) is a synthetic opioid used for acute
pain.
• It binds to opioid receptors & inhibits nociception.
• Well absorbed (50-100mg i.m. /s.c.)
Uses: Analgesic, Preanaesthetic medication
Adverse effects: Tremors, Convulsions, Dependence
Contraindication: Hypersensitivity, MAO inhibitors,
Asthma
Fentanyl is a pethidine congener which is 80-100 times
more potent than morphine.
Uses: Anaesthesia, Transdermal Fentanyl available for
cancer & chronic pain
Adverse effects: respiratory depression, cardiac depression
Contraindication: hypersensitivity, use with MAO inhibitors

12. Methadone is a synthetic, orally effective opioid which has
variable equianalgesic potency compared to that of
morphine. It induces less euphoria and has longer
duration of action.
Mechanism of action: The actions of methadone are
mediated by µ receptors. In addition, methadone is an
antagonist of the N-methylD-aspartate (NMDA) receptor,
which is useful in the treatment of neurogenic pain.
Actions: Methadone is well absorbed when administered
orally, unlike morphine (partially absorbed from GI tract)
Uses: Methadone is used as an analgesic in nociceptive and
neurogenic pain, controlled withdrawal from heroin and
morphine dependent abusers.
Adverse effects: respiratory depression, hypotension

13. Tramadol is centrally acting analgesic that binds to the
µ-opioid receptor. In addition, it weakly inhibits
reuptake of norepinephrine and serotonin. It is used
to manage moderate to severe pain.
Adverse effect: respiratory-depressant Anaphylactoid
reactions CNS excitation and seizures.
Contraindications: patients taking MAOIs
Heroin (Diacetylmorphine)
• It is produced synthetically by acetylation of
morphine.
• It is 3 times more potent than morphine.
• It is more euphoric & highly addicting.
• Banned on most of the countries!

14. Mixed agonist –antagonist
• Nalorphine, Pentazocine, Butorphanol,
Buprenorphine
• Pentazocine is agonist-antagonist used as
analgesic. It acts as an agonist on κ receptors and
is a weak antagonist at µ and δ receptors.
• It can precipitate a withdrawal syndrome in a
morphine abuser.
• Adverse effects: respiratory depression,
decreases the activity of the GI tract, increase
blood pressure, hallucinations, nightmares,
dysphoria, tachycardia, dizziness, tolerance and
dependence

15. Opioid Antagonist
• Naloxone is used to reverse the coma and respiratory depression
of opioid overdose.
• It rapidly displaces all receptor-bound opioid molecules and,
therefore, is able to reverse the effect of a morphine overdose.
• Within 30 seconds of IV injection (0.4-0.8mg) of naloxone, the
respiratory depression and coma due to high doses of morphine
are reversed, causing the patient to be revived and alert.
• Naloxone produces no pharmacologic effects in normal
individuals, but it precipitates withdrawal symptoms in opioid
abusers.
• Naltrexone has actions similar to those of naloxone. It has a
longer duration of action than naloxone, and a single oral dose of
naltrexone blocks the effect of injected heroin for up to 48 hours.
• Naltrexone in combination with clonidine (also buprenorphine) is
used for rapid opioid detoxification.

16. OPIOID
WITHDRAWL
SYNDROMES

17. DRUG DEPENDENCE AND ADDICTION

19. DRUG DEPENDENCE AND ADDICTION
• Tolerance is a gradual decrease in responsiveness to
a drug, taking days or weeks to develop.
• Tachyphylaxis is a sudden decrease in response to
drug which may develops with initial dose.
• Drug abuse : Self administration of drugs for non
therapeutic use.
• Drug habituation: Drug habituation (habit) is a
condition resulting from the repeated consumption
of a drug.

20. DRUG DEPENDENCE
• Drug dependence is a state arising from repeated
administration of a drug that results in harm to
the individual and sometimes to society.
• The common features with such drugs are:
• an initial pleasurable or euphoric sensation ('kick')
• tolerance with repeated use so that the subject
feels a desire
• need or compulsion to continue using the drug
and feels ill if abruptly deprived of it (abstinence
or withdrawal syndrome).

21. Types:
 Psychological dependence :
A subjective sense of a need for a specific psychoactive
substance, either for its positive effects or to avoid
negative effects associated with its abstinence.
e.g: nicotine, tea, coffee, marijuana
 Physical dependence :
Physical (physiological) dependence implies continued
exposure to drugs inducing adaptive changes in body
tissues so that tolerance occurs and withdrawal
symptoms are seen on discontinuation.
e.g:morphine, codeine, barbiturates, benzodiazepines,
cocaine, alcohol, amphetamine

22. DRUG ADDICTION
• It is a state of periodic or chronic intoxication produced
by repeated consumption of certain drugs.
• Addiction is characterized by behaviors that include
impaired control over drug use, compulsive use,
continued use despite harm, and craving.
• Drugs producing addiction : morphine , codeine , heroin,
alcohol, amphetamine, cocaine
Features:
1. Compulsion to take the drugs, use of physical force to
obtain the drug
2. Tendency to increase the dose
3. Psychic and physiologic dependence
4. Effect on individual and society
5. Withdrawal symptoms

23. Treatment of addiction
• Motivational interviewing
• Brief intervention (FRAMES) by Hester and Miller :
• Feedback based upon a thorough assessment
• Responsibility for changing
• Advice on what behavior must change
• Menu of options for making the change
• Empathy for the ambivalence and difficulty
• Self-efficacy to foster commitment and confidence

24. PHARMACOTHERAPY FOR SUBSTANCE ABUSE
Alcohol:
1. Disulfiram (Antabuse)
2. Oral naltrexone (ReVia)
3. Injectable naltrexone (Vivitrol)
4. Acamprosate (Campral)
Tobacco/Nicotine:
1. Nicotine patches (Nicoderm)
2. Nicotine gum (Nicorette)
3. Bupropion (Zyban)
Opioids :
1. Methadone maintenance
2. Buprenorphine & Naloxone (Suboxone) maintenance
3. Oral Naltrexone maintenance
• Hospitalisation
• Counselling
• Nutrition and Exercise