opioid analgesics with detailed description of introduction, mechanism of action, adverse effect, uses and contraindication along with examples for under graduates.

1. OPIOID
ANALGESICS
BY: BIBI UMEZA

2. OPIUM
• Opium-They are obtained from poppy (papave r
so m nife rum ) capsule.
• Analgesic- A drug that selectively relieves pain by
acting in the CNS or on peripheral pain
mechanisms,without significantly
altering consciousness.

4. CLASSIFICATION
• NATURALOPIUMALKALOIDS–
Morphine, Codeine.
• SEMISYNTHETIC OPIATES-
Diacetyl morphine (heroin), pholcodeine.
• SYNTHETIC OPIOIDS–
Pethidine, fentanyl, Methadone, Dextropropoxyphene,
Tramadol.

5. ANTAGOINIST -
Naloxone , Naltrexone.
MIXEDAGONISTS- ANTAGONISTS–
Pentazocine, Nalorphine, Nalbuphine, Butorphanol,
Buprenorphine.

6. MORPHINE
• PHARMACOLOGICAL ACTIONS –
•1) CNS –
•A) Analgesia– morphine is a strong
analgesic.
• Dull, poorly localized visceral pain is relieved
better than sharply defined somatic pain.
• Perception of pain is altered so that pain is no
longer as unpleasant or distressing.

7. • Analgesic action has spinal and supraspinal
component
• Analgesic action is exerted through interneurones
which are involved in gating of pain impulse.
• Release of glutamate from primary pain afferents in
the spinal cord and its postsynaptic action on dorsal
horn neurones is inhibited by morphine.
• Action at supra spinal sites in medulla, midbrain,
limbic and cortical areas.

8. • B) SEDATION –
• Drowsiness and indifference to surrounding and one’s
own body occurs without motor in coordination, ataxia,
excitement.
• Higher doses progressively induce sleep and coma.
• Morphine has no anticonvulsant action, it may precipitate
fits.

9. C) MOOD AND SUBJECTIVE EFFECTS
• These are prominent.
• Morphine has a calming effect, there is loss of
apprehension, feeling of detachment, lack of initiative,
limbs feel heavy and body warm, mental clouding and
inability to concentrate.
• Rapid i.v injection by addicts gives them a kick or rush –
which is intensely pleasurable – akin to orgasm.

10. D) RESPIRATORY CENTRE
• Morphine depresses respiratory centre in a dose
dependent manner, rate and tidal volume both are
decreased.
• Death in poisoning is due to respiratory failure.
• E) COUGHCENTRE –
• Is depressed, more sensitive than respiratory centre.

11. • F) TEMPERATURE REGULATING CENTRE -
• It is depressed, hypothermia occurs in cold surroundings.
• G) VASOMOTORCENTRE –
• doses and contributes to the fall of BP.

13. • MORPHINE STIMULATES –
• CTZ – nausea and vomiting.
• emetics should not be tried in morphine poisoning.
• Edingerwestphal nucleus of III nerve – miosis.
• No effect on topical application.
• Other ocular effects are decrease in intraocular tension.

14. • Vagal centre – is stimulated – bradycardia.
• Certain cortical areas and hippocampal cells -
• Excitation , muscular rigidity and immobility at high doses.
• Convulsions may occur in morphine poisoning.
• CVS- Fall in BP,decrease in HR
• GIT-Constipation

15. • PRECAUTIONS AND CONTRAINDICATIONS
• Morphine is a drug of emergency, but care has to be taken
• Infants and the elderly are more susceptible to the
respiratory depressant action of morphine.
• It is dangerous in patients with respiratory insufficiency
(emphysema, pulmonary fibrosis, cor pulmonale) sudden
deaths have occurred.
• Bronchial asthma : morphine can precipitate an attack by its
histamine releasing action.

16. • Head injury :
• By retaining CO2, it increases intracranial tension
which will add to that caused by head injury itself.
• Even therapeutic doses can cause marked
respiratory depression in these patients.
• Vomiting, miosis and altered mentation produced
by morphine interfere with assessment of
progress in head injury cases.
• Hypotensive states and hypovolaemia

17. • Undiagnosed abdominal pain.- diverticulitis,
biliary colic, pancreatitis.
• Elderly male – causes urinary retention.
• Hypothyroidism, liver and kidney disease patients
are more sensitive to morphine.
• Unstable personalities – become addicted.

18. • INTERACTIONS
• Phenothiazines, tricyclic antidepressants, MAO
inhibitors, amphetamine and neostigmine
potentiate morphine. – either by retarding its
metabolism or by a pharmacodynamic interaction
at the level of central neurotransmitter.
• Retards absorption of many orally administered
drugs by delaying gastric emptying.

19. • CODEINE
• It is methyl morphine, occurs naturally in opium and is
partly converted in the body to morphine.
• Less potent than morphine (1/10 as analgesic) and
also less efficacious.
• It is a partial agonist at µ receptor with a low ceiling
effect.
• Degree of analgesia is comparable to aspirin (60mg of
codeine ~ 600 mg of aspirin), - mild to moderate pain.

20. • More selective cough suppressant.
• Analgesic activity is ascribed to morphine generated by
demethylation by CYP2D6.
• Has good activity by oral route.
• Acts for 4-6hrs.
• Constipation is a prominent side effect. – used to control
diarrhoea.
• Abuse liability is low.

21. • PHOLCODEINE –
• used as antitussive,
• less constipating.
• HEROIN –
• 3 times more potent than morphine,
• more lipid soluble,
• highly addicting.

22. • PETHIDINE
• Chemically unrelated to morphine, but interacts with
opioid receptors and its actions are blocked by
naloxone.
• Differences with naloxone are
• 1. dose to dose 1/10th
in analgesic potency.
• 2. onset of action is rapid but duration is short.
• 3. does not suppress cough.
• 4. spasmodic action is less marked .

23. • 5. equally sedative and euphoriant and similar abuse
potential.
• 6. tachycaridia occurs instead of bradycardia.
• 7. less histamine release and safer in asthmatics.
• 8. has local anaesthetic action.
• 9.well absorbed orally, completely metabolized in
liver. T1/2 is 2-3 hrs.

24. • SE –
• atropinic effects – dry mouth, blurred vision,
tachycardia.
• Overdose – tremors, mydriasis, hyperreflexia,
delirium, myoclonus and convulsions.
• Tolerance and dependence develops slowly – short
duration of action.
• USE –
• used as analgesic
• preanaesthetic medication.

25. FENTANYL
• Pethidine congener.
• 80 -100 times more potent than Morphine
In Resp. & Analgesic
• Least effect on Histamine release& CVS effects
• High lipid solubility – More & quick Entry to CNS
• Peak effect ion 5 min.
• Used as IV Gen Anesthetic
• Transdermal Fentanyl Used to reduce pain in Cancer &
other chronic pain

26. METHADONE
• Chemically dissimilar to Morphine BUT similar
in PA to morphine
• Analgesic, Resp. depression, Emetic,
Antitussive, Constipation etc.
• Firm biding with tissue proteins, high Plasma
proteins, cumulate in tissues
• Plasma t ½ 24 -36 hours on chronic
administration

27. • SLOW & PERSISTANT action- thus sedative &
subjective effects are less intense.
• Tolerance develops SLOWLY- progressive filling
of tissues.
• Withdrawal symptoms is gradual – take
1-2 days to develop after discontinuation, Less
severe also.
• Incapable of giving “ KICK”

28. • Abuse potential is lower than Morphine
• TU :-
• Primarily as substitution therapy of opioid
dependence ( 1mg. Of Methadone can substitute
– 4 mg. Morphine, 20 mg. of Pethidine, 2mg. of
Heroin
• Methadone Maintenance therapy in Opioid
addicts- sufficient dose of methadone given orally
to produce

29. • High degree tolerance so that IV Morphine
Would not produce that amount of Pleasurable
effects , Subject may give the habit.
• Used as Analgesic
• Occasionally used as Antitussive

30. DEXTRO PRO PO XYPHEN
• Chemically & Pharmacologically similar to
Methadone
• Poor anti-tussive & constipating
• Abuse liability is Lower – less potent, Delirium,
Convulsions, & cardio toxicity at Higher doses.
• User as Analgesic Always with Aspirin ,
Paracetamol ( supra additive drug synergism )

31. TRAMADO L
• Acts as Analgesic By following Mech. :-
• Affinity for µ receptors is modest , while affinity
for ķ & δ is weak
• It inhibit reuptake of NA & 5HT – thus activates
Spinal inhibition of pain
• Less resp. depressant, sedation, Constipation,
Urinary retention, intrabiliary pressure, CVS
( safer in patients with Cardiovascular
diseases),

32. • Well tolerated
• AE :- Dizziness , ANV, Dry mouth , Sweating
• TU :-
• In medium intensity short lasting pain – injury,
surgery, diagnostic procedures
• In chronic Pain – Cancer pain
• Less effective in SEVERE pain

33. USES
• 1. As analgesic
• 2. preanaeshtetic medication.
• 3. balanced anaesthesia and surgical analgesia.
• 4. relief of anxiety and apprehension.
• 5. acute LVF.
• 6. Cough.
• 7. Diarrhoea.

34. OPIOID RECEPTORS
• µ - mu
• Ḱ - kappa
• δ - delta

35. TRANSDUCER MECHANISM

36. COMPLEX ACTION OPIOID AND
OPIOID ANTAGONISTS
• AGONIST- ANTAGONIOST -
• Nalorphine, Pentazocine, Butorphanol.
• Partial /Weakµ Agonist
• Buprenorphine.
• Pureantagonists
• Naloxone, Naltrexone, Nalmefene.

37. AGO NIST- ANTAGO NIO ST
• PENTAZOCINE :- Ķ – Acting – USED AS
ANALGESIC
• More marked Agonist & weak Antagonist
• Action similar to Morphine :- Diff. are
• Analgesia mainly Spinal in nature
• ( No dose dependant Analgesic action )
• Less sedation & Resp. depression
• Less Action on Biliary track , CTZ

38. • Cause Tachycardia & Rise in BP – due to
Sympathetic stimulation ( Avoided in IHD patients)
• Produce Pleasurable effects at LOW doses but high
doses Produce Unpleasant (Dysphoria) &
Psychotomimetic effects (Ķ)
• Tolerance, Physical Dependence & Psychological
Dependence – seen
• Withdrawal symptoms mild in intensity
• Abuse liability lower

39. • TU :-
• Post operative pain,
• moderately severe pain in Burns,
• Trauma,
• Fracture,
• Cancer,

40. PARTIAL / WEAK µ AGO NIST• Buprenorphine:-
• Highly lipid soluble µ Agonist (Antagonistic action on ķ) – Analgesic
(25 times more potent than Morphine) Duration dependant t ½ ( 8-
24 hours)
• Sedation , CTZ action, Miosis, CVS effects, Respiratory depression
same as Morphine
• Less constipation
• Cause Postural Hypotension

41. • Substitutes Morphine at low level of dependence.
• Lowed degree of Tolerance, Physical
Dependence & Psychological Dependence on
chronic use.
• Withdrawal symptoms delayed for several days,
is milder, long lasting.
• Abuse liability Lower than Morphine

42. • Naloxone partially reverses it’s effects & does not
precipitate withdrawl because of more Tight
binding with Opioid receptors.
• TU :-
• Can be given SUBLINGUALY / IM/ slow IV/ SC
• Long lasting painful conditions – Cancer pain
• Also used in Premedication , Post operative pain,
MI
• Not recommended during lobour – Neonatal Resp.
depression ( which can not be easily reversed by

43. PURE ANTAGO NIST
• Naloxone:-
• Competitive Antagonist of all opioid receptors
(blocks µ at lower doses than needed to block ķ & δ)
• No agonistic activity at any dose
• No effect on those people who have not received
opioid
• Antagonise all action of Morphine

44. • Analgesia is gone , Respiration Normalized
( some times stimulated), Pupil dilates,
• Sedation is less completely reversed
• Dysphoria & Psychotomimetic effects are
incompletely suppressed (б )
• Precipitate Morphine Withdrawal
• Naloxone Blocks action endogenous opiods
(Endorphins, Enkephalins, & Dynorphines)

45. • TU:-
• Drug of choice for Morphine poisoning & other
opioids (except Buprenorphine)
• Reversing neonatal poisoning due to use opioid
during lobour
• Diagnosis of Opioid dependence
• Partially reverse Alcohol intoxication

46. NALTREXONE
• It is chemically ralated to naloxone.
• It is a pure opioid antagonist, that is devoid of
subjective and other agonistic effects.
• It is orally active and has long duration of action –
used for opioid blockade therapy of postaddicts.
• It reduces alcohol craving.
• SE - nausea and headache, hepatotoxicity.

47. ENDOGENOUS OPIOD
PEPTIDES
• 1. ENDORPHINS
• 2. ENKEPHALINS.
• 3. DYNORPHINS.

48. • Modulate –
• Pain perception, mood, emesis, pituitary harmone release
and g.i.t motility.
• END – more potent analgesic than morphine. Decreases
LH, FSH release and Increases GH and Prolactin
release.
• ENK and DYN regulate pain responsiveness at spinal and
supraspinal levels.