Opiods MBBS Pharmacology

1. D R R . R A H U L M D
Opioids

2. ANALGESIC
A drug that selectively relieves pain by acting in the
CNS or an peripheral pain mechanism,without
significantly altering consciousness

5.  Opioids-Narcotic/Morphine like
 Non opioids-Non narcotic/Aspirin like
 Adjuvant-Anticonvulsants&Antidepressants

6. OPIOID ANALGESICS
Opium
Dark brown resinous material obtained from
poppy(Papaver somniferum) capsule

8. Alkaloids
PHENANTHRENE DERIVATIVES
 Morphine (10%)
 Codeine (0.5% Analgesics
 Thebaine
BENZOISOQUINOLINE DERIVATIVE
 Papaverine
 Noscapine

9.  Opiates
Compounds that are derived from Opium/chemically
related to Morphine
 Opioids
Morphine like action

10. MORPHINE
 Principal alkaloid
 Widely used till today

11. Opioid Receptors

12. Pharmacological Actions
1.CNS
 Analgesia
 Sedation
 Subjective effects & euphoria
 Respiratory depression
 Cough supression
 Temperature regulation
 Vasomotor center
•CTZ
•EWN
•Vagal
center
•Cortex

13. 2.Neuroendocrine
3.Peripheral actions
 CVS
 GIT
 Smooth muscles

14. Pharmacological actions
CNS-Analgesia

16. Mood &Subjective effects
Euphoria

17. Morphine.
19
Respiratiory centre- depressed
Cough centre – depressed
Temperature regulation centre- depressed

18. 20
Morphine stimulates
 CTZ
 Edinger westphal nucleus – miosis
 Vagal centre- Bradycardia
 Certain cortical centres & hippocampal cells
excitation, muscular rigidity, immobility,
(high i.v doses)convulsions.

19. Neuro-endocrine efects:
FSH, LH, ACTH, sex hormones& corticosteroids-
decreased
increases Prolactin, GH and ADH release

20. CVS:
Vasodilation
1. Histamine release
2.Depression of Vasomotor centre
3. Decrease tone of Blood Vessels

21. G.I.T:
Constipation
 Increase of tone- enteric plexus
 Spasm of sphincters
 Decrease of all gastrointestinal secretions
 Inattention to defecation reflex
No tolerance

22. Smooth muscles
 Spasm of sphincter of oddi
 Increase tone of Detrusor & Bladder sphincter
 Uterine muscle-insignificant
 Bronchoconstriction- histamine release

23. PHARMACOKINETICS
 High first pass metabolism
 30% protein bound
 Wide distribution- cross placenta
 Metabolism-Glucuronide conjugation
 Plasma t1/2 2-3 hours
Morphine 6 glucuronide-active metabolite
Morphine 3 glucuronide-Neuroexcitatory

24. Adverse effects
 Side effects
Sedation,mental
Clouding,lethargy
Elderly(blurred vision
Urinary retention)
Vomiting & constipation

25.  Idiosyncracy & allergy
 Apnoea in new born
 Tolerance & dependence-
 Tolerance to all actions except miosis, constipation
and proconvulsant actions
 Withdrawl- oral Methadone f/b gradual withdrawl

26. Acute Morphine Poisoning
Accidental/suicidal/Drug abuse
Toxic dose50 mg
Lethal dose-250 mg
Extension of Pharmacological actions
Coma/miosis/Respiratory depression
ABC
Gastric lavage-Potassium permanganate
Antidote-NALOXONE

28. Precautions&Contraindications
1.Infants & Elderly
2. Respiratory insufficiency
3. Bronchial asthma
4. Head injury
5. Hypotensive states
6. Acute abdominal pain
7. Elderly male ( urinary retention)
8. Hypothyroidism
9. Unstable personalities

29.  H-Hypotension
 H-Hepatic damage
 H-Hypertrophy of prostate
 H-Head injury
 H-Hypothyroidism
 B-Bronchial Asthma
 B-Biliary colic
 B-Babies

30. Opioid analgesics
Natural
• Morphine
• Codeine
Semisynthetic
• Diacetylmorphine
• Pholcodine
• Ethylmorphine
Synthetic
• Pethidine
• Methadone
• Fentanyl
• Ramifentanyl
• Tramadol
• Tapentadol

31. CODEINE
 Methyl morphine
 Less potent(1/10th as analgesic)
 Selective cough supressant
 Good oral Bioavailability
 Analgesic dose –Constipation(Used to control
diarrhoea)

32. HEROIN
 Diamorphine/Diacetylmorphoine
 Highly lipophilic
 Three times more potent than Morphine
 More Euphorient & highly addicting
 Banned

33. PETHIDINE/MEPERIDINE
 Atropine substitute/chemically unrelated to
Morphine
 1/10th in Analgesic potency
 Efficacy similar to Morphine
 Rapid onset of action-short duration
 Does not effectively suppress cough
 Spasmogenic action --less marked
 Tachycardia--Antimuscarinic action

34.  Better oral absorption
 Metabolism

35.  Excitation, tremors, mydriasis, delirium,
convulsions- norpethidine
 SSRI-Serotonin syndrome
 Clinical use –very much declined
 Used to control shivering during recovery from
anaesthesia

36. Fentanyl
 Pethidine congener
 80-100 times more potent than Morphine
 Highly lipid soluble
 Rapid & short duration of action(30-40 mins)
 Injectable form-Anaesthesia

37. Remifentanil
 Faster acting congener of Fentanyl
 Very brief action(10-15 minutes)
 Used exclusively in anaesthesia

38. Methadone
 Synthetic Opioid
 Chemically dissimilar but Pharmacologically
similar to Morphine
 High oral:Parenteral activity
 Firm binding to tissue proteins
Cumulates in tissues on repeated
administration
Chronic use-t1/2=24-48 hrs

39. Methadone
 Slow & Persistent action
 Sedative & subjective effects are less-Less Abuse
potential
Substitution therapy for Opioid
dependence
Maintenance therapy in Opioid
Addicts(40-80mg –long term)

40. TRAMADOL
 Atypical Opioid
 µ agonist
 Inhibits reuptake of NA &
5HT-Spinal inhibition of Pain
 Good oral bioavailability
 Well tolerated
 Nausea & dizziness
 Serotonin syndrome

41. Tapentadol
 Similar to Tramadol
 Inhibition of NET is more marked
 Serotonin syndrome
 Risk of precipitating seizures

42. USES
ANALGESIC
 Morphine/parenteral congeners-Visceral
,ischaemic,post operative,cancer pains,burns,renal
colic
 Mild pain-Tramadol,tapentadol

44.  Preanaesthetic medication-Morphine/Pethidine
 Balanced Anaesthesia-
Fentanyl/Remifentanil/Morphine
 Relief of Anxiety & apprehension
 Cough-Codeine
 Diarrhoea- Codeine,Loperamide & Diphenoxylate

45.  Acute Left Ventricular failure
Reduces Preload
Shift blood from
Pulmonary to Systemic
circuit
Allays air hunger &
Dyspnoea
Calms the patient &
reduces Sympathetic
stimulation

46. Opioid Receptors

48. Complex action Opioids
Agonist-Antagonist
• Nalorphine
• Pentazocine
• Butorphanol
• Nalbuphine- MI
Partial µ agonist &
Kappa antagonist
• Buprenorphine

49.  Analgesics of limited efficacy equivalent to lower
doses of Morphine
 Less addiction & submaximal respiratory depression

50. Nalorphine
 First opioid antagonist introduced – reverse
morphine actions
 Proved to have agonist action
 κ agonist & μ antagonist
 Analgesic action present – low ceiling effect, not
used because of dysphoric & psychotomimetic
effect (σ – omega receptor action)
 Replaced by Naloxone as antagonist

51. Pentazocine
 First agonist-antagonist to be used as antagonist
 Marked κ agonistic action & weak μ antagonistic
action
 Analgesic effect – primarily spinal with different
character, less potent than morphine, lower ceiling
 Sedation & respiratory depression less than morphine
with a low ceiling (no depression ↑beyond 60mg)

52.  CVS – tachycardia & ↑BP due to sympathetic
stimulation → ↑cardiac work, to be avoided in coronary
ischemia & MI patients
 Biliary spasm & constipation – less marked
 Less vomiting
 Morphine like subjective effects (pleasurable) – become
unpleasant as dose increased & psychomimetic effect
produced (κ & σ mediated)

53.  Repeated administration – tolerance, psychological
& physical dependence develop
 Withdrawal symptoms with mild intensity
 Positive drug seeking effect
 Less abuse potential than morphine
 Ppts withdrawal features in morphine addicts (μ
antagonistic action, but less than naloxone – not
useful in morphine poisoning)

54.  Kinetics – effective orally, first pass metabolism,
metabolism by oxidation & glucuronide conjugation,
t½ - 3-4hrs, duration of action 4-6hrs
 Use – postoperative pain, severe pain in burns,
trauma, fracture & cancer pain (dysphoric &
psychotomimetic effect limitation)

55. Butorphenol
 κ analgesic – more potent than pentazocine
 Analgesia & respiratory depression – lower ceiling
than morphine
 Sedation, nausea, cardiac stimulation & side effects –
similar to pentazocine
 Less dysphoric & psychomimetic (weak σ agonist)
 Less abuse potential
 Physical dependence
 Withdrawal effects – mild, ppted by high dose of
naloxone

56.  Very weak action on μ receptor – cannot be used
as a substitute or antagonist for morphine
 Use – post operative pain, short lasting painful
conditions like renal colic (to be avoided in pts with
cardiac ischemia because of cardiac effects)

57. Buprenorphine
 Synthetic thebaine congener
 Highly lipid soluble
 Analgesic – μ agonist, 25 times potent than
morphine, slow onset, longer duration of action,
action increase with repeated dosing upto 24hrs
 Sedation, vomiting, miosis, subjective & CVS effects
– similar to morphine
 Constipation – less marked
 Postural hypotension marked

58.  Respiratory depression – low ceiling
 Substitutes morphine in low level of dependence,
ppts withdrawal effect in highly dependent
patients (partial agonist at μ, κ antagonist)
 Chronic use – low level of tolerance, physical &
psychological dependence
 Withdrawal symptoms – similar to morphine,
but delayed for several days, milder & long lasting
 Drug seeking

59.  Less abuse potential
 Only partial reversal of effects with high dose of
naloxone – due to tight binding of
buprenorphine to opioid receptors
 Kinetics – effective sublingually, high plasma
protein binding, remains in tissue for longer
duration, t½ - 40hrs, elimination in urine
unchanged in urine

60.  Use – long lasting painful conditions like cancer
pain, premedication, postoperative pain, MI, in
morphine addiction
 Not used for labour pain – foetal respiratory
depression cannot be effectively reversed

61. PURE OPIOID ANTAGONIST
 Naloxone
 Naltrexone
 Nalmefene

62. Naloxone
 Morphine Poisoning(0.4-0.8 mg iv every 2-
3min:max 10mg
 Reverses Neonatal Asphyxia(10µg/Kg in cord)
 Treats overdose of other Opioids except
Buprenorphine
 Inactive orally

63. Naltrexone
 Same effect of naloxone except it is used orally
 long duration of activity
 Also used for treatment of alcoholism
 High dose-Hepatotoxicity
Nalmefene
 Long acting/high oral bioavailability
 No Hepatotoxicity

64. Peripheral µ receptor antagonist
• Reverses constipation in cancer patients
• Those on Methadone maintenance
therapy
Methyl
Naltrexone
• Post operative ileus
Alvimopan

65. Endogenous Opioid peptides
 Peptides with morphine like actions
 Present in brain, Pituitary, Spinal cord & GIT
 Active in very small amounts
 Actions blocked by naloxone
 Very high affinity for opioid receptors
 Normally modulates pain perception, mood, hedonic
& motor behaviour, emesis, pituitary hormone
release & GIT motility
 3 families – endorphins, enkaphalins &
dynorphins

66.  β endorphins – 31 AA, important, μ & δ agonist,
from POMC, 20-40 times more potent than
morphine, neurohormone function, long t ½
 Enkephalins – methionine, leucine ENK
important, m-ENK – μ & δ, l-ENK – δ affinity
 Dynorphins – A & B type, more affinity for κ & also
activate μ & δ
 ENK, DYN – short t ½ , function as neuromodulator
or neurotransmitter

67. THE END