Opioid Receptors and Opioid Analgesics.

1. OPIOID
ANALGESICS
PRESENTED BY
- Dr. Gurunath.
- Dr. Tarannum.

2. WHAT ARE ANALGESICS?
Any drug that relieves pain selectively without blocking the
conduction of nerve impulses, markedly altering sensory
perception, or affecting consciousness.
ANALGESIC
ANAESTHETIC

3. Types Of Opioid Receptors
• MU(u)
• Kappa(k)
• Delta
μ1, μ2,
μ3
BRAIN
• Cortex (lamina
II & IV)
• Thalamus
• Periaqueductal
Grey
SPINAL CORD
• Substansia
gelatinosa
μ1
•Dependence
• Analgesia (Supraspinal)
μ2
• Depression
• Miosis
• Euphoria
• ↓ GI motility
• Dependence
μ3
?

4. Location Of Opioid Receptors
Ƙ1,ƙ2,
ƙ3
BRAIN
•Hypothalamus
•Periaqueductal Grey
•Claustrum
SPINAL CORD
Substansia gelatinosa
•Spinal analgesia
•Sedation
•Miosis
•Inhibition of ADH
release.
•(dysphoria)
δ1,δ2 BRAIN
•Pontine nuclei
•Amygdala
•Olfactory bulb
•Deep cortex
•Analgesia
•Antidepressant
effects
•Physical
dependence

5. Mechanism of action

6. CLASSIFICATION
Morphine
Codeine
Pholcodine.
Ethylmorphine.
Pethidine(Meperidine)
Fentanyl
Methadone
Dextropropoxyphene
Tramadol
Synthetic opioids
Natural Opium
alkaloids
Semi- Synthetic
Opiates

8. F. SERTURNER
(1783–1841)
Morphine
Papaver somniferum L.
•Opium
- morphine (1806)
- codeine
- papaverine
..
Afghanistan
Pakistan
Thailand

9. EFFECTS
 Analgesia
 Euphoria
 Sedation
 Respiratory depression
 Cough suppression
 Temp. regulating centre
depression
 Vasomotor centre depression
 Chemoreceptor
Trigger Zone
(vomiting, nausea)
 Edinger Westphal
Nucleus of III nerve
(miosis)
 Vagal centre-
(bradycardia)
 Cardiovascular system
 GIT
 Biliary tract
 Renal
 Uterus
 Neuroendocrine
 Pruritis
Depressor effect
Stimulation

10. ANALGESIA
Pain consists of both sensory and affective (emotional)
components.
Opioid analgesics reduce both aspects of the pain experience,
especially the affective aspect.
In contrast, nonsteroidal anti-inflammatory analgesic drugs have
no significant effect on the emotional aspects of pain.
EUPHORIA
Intravenous drug users experience a pleasant floating
sensation with lessened anxiety and distress (Dopamine
release in nucleus accumbens).
However, dysphoria, an unpleasant state characterized by
restlessness and malaise, may sometimes occur.

11. SEDATION
Drowsiness
Mental clouding
little or no amnesia
No motor incoordination
Sleep is induced in the elderly (can be easily aroused
from this sleep)

12. By inhibiting brainstem respiratory mechanisms.
Alveolar PCO2 may increase, but the most reliable indicator
of this depression is a depressed response to a carbon
dioxide challenge.
In individuals with increased intracranial pressure, asthma,
chronic obstructive pulmonary disease, or cor pulmonale,
this decrease in respiratory function may not be tolerated.
RESPIRATORY DEPRESSION

13. Codeine in particular
However, cough suppression by opioids may allow accumulation of
secretions and thus lead to airway obstruction and atelectasis
Chances of hypothermia
Fall in BP
COUGH SUPPRESSION
TEMP. REGULATING CENTRE
DEPRESSION
VASOMOTOR CENTRE DEPRESSION

14. Morphine stimulates:
• CTZ (nausea, vomiting)
• Edinger Westphal nucleus of III nerve is stimulated (miosis)
• Vagal centre (bradycardia)

15. Cardiovascular System-
• Bradycardia
Meperidine is an exception (can result in tachycardia)
• Hypotension - due to
-peripheral arterial and venous dilation
-depression of vasomotor centre
-release of histamine.
• Increased PCO2 leads to cerebral vasodilation associated with a
decrease in cerebral vascular resistance, an increase in cerebral blood
flow, and an increase in intracranial pressure.

16. Gastrointestinal Tract-
Constipation
• no tolerance
• Opioid receptors exist in high density in the gastrointestinal tract
• constipating effects of the opioids are mediated through an action on
the enteric nervous system as well as the CNS
• gastric secretion of hydrochloric acid is decreased.
• propulsive peristaltic waves are diminished
• tone is increased
• this delays passage of the fecal mass and allows increased absorption
of water, which leads to constipation
• so used in the management of diarrhea.

17. Biliary Tract-
• sphincter of Oddi may constrict
• contract biliary smooth muscle
• result in biliary colic
Renal System-
• Renal function is depressed by opioids
• decreased renal plasma flow
• enhanced renal tubular sodium reabsorption
• Ureteral and bladder tone are increased
• Increased sphincter tone may precipitate urinary retention
• ureteral colic caused by a renal calculus is made worse by opioid-induced
increase in ureteral tone

18. Uterus-
• may prolong labor
• both peripheral and central actions of the opioids can reduce
uterine tone
Neuroendocrine-
• stimulate the release of ADH, prolactin, and somatotropin
• inhibit the release of luteinizing hormone
Pruritus-
• CNS effects and peripheral histamine release may be responsible for
these reactions
• pruritus and occasionally urticaria (when administered parenterally)

19. •
Analgesia
Cough
Diarrhoea
Acute Pulmonary Edema
Preanaesthetic Medication
Relief Of Anxiety &
Apprehension

20. Therapeutic Uses:
Analgesic: Long bone fracture, MI,
Terminal stages of cancer, Burn
patients, Post-operative patients,
Obstetric analgesia, Segmental
analgesia,
Visceral pains: pulmonary embolism,
pleurisy, Acute pericarditis
Adverse Effects:
Respiratory depression: Infant & old,
Vomiting, Miosis, sedation, Mental
clouding, Hypotensive effect, Rise in
Intracranial pressure, Apnea, Urinary
retention ,Idiosyncrasy & Allergy, Acute
Morphine poisoning ,Tolerance &
Dependence
OTHER USES:
Preanesthetic Medication, Balanced & surgical
Anesthesia, Acute LVF-Cardiac asthma, Diarrhea-
colostomy-Loperamide, Diphenoxylate.

21. Contraindicated:
Head injury, Bronchial Asthma,
Respiratory insufficiency,
Hypotension, Hypothyroidism, liver
& Kidney disease
Drug Interactions:
Phenothiazines, TCA’S,MAO
Inhibitors, Amphetamine
Pharmacokinetics:
Well absorbed orally; Morphine,
Hydromorphone , Oxymorphine
undergo first-pass metabolism, Cross
placental barrier & affects Fetus ;
Metabolism by Hepatic enzymes,
Inactivated by Glucuronide conjugation
before elimination from Kidneys.

22. TOLERANCE & DEPENDENCE
• With frequently repeated therapeutic doses of morphine, there is a
gradual loss in effectiveness
• To reproduce the original response, a larger dose must be
administered
• Along with tolerance, physical dependence also develops
• Physical dependence is defined as a characteristic withdrawal or
abstinence syndrome when a drug is stopped or an antagonist is
administered.

23. Withdrawal of morphine
• Associated with marked drug seeking behaviour.
• Physical manifestations are—lacrimation, sweating, yawning,
• anxiety, fear, restlessness, gooseflesh, mydriasis,
• tremor, insomnia, abdominal colic, diarrhea,
• dehydration, rise in BP, palpitation and rapid
• weight loss
• Delirium and convulsions are seen only occasionally

24. ACUTE MORPHINE POISONING
• >50 mg of morphine
• Lethal dose is 250mg
• Stupor, coma, shallow breathing, cyanosis, pinpoint pupil, fall in BP,
convulsions
• Death due to respiratory failure
Treatment-
• Positive pressure respiration
• Iv fluids
• Gastric lavage with potassium permagnate
• Naloxone –Antidote for morphine toxicity

26. Title Lorem
Ipsu
Sit Dolor Amet
CODEINE
 It is methyl-morphine.
 It is less potent than morphine (1/10th as analgesic)
 Also less efficacious: the degree of analgesia is comparable to aspirin (60
mg codeine ~ 600 mg aspirin); can relieve mild to-moderate pain only.
 It is more selective cough suppressant (only 1/3rd as potent as morphine);
subanalgesic doses (10–30 mg) suppress cough.
 Codeine has good activity by oral route (oral: parenteral ratio 1:2). A single
oral dose acts for 4–6 hours.
DISADVANTAGES
• Constipation is a prominent side effect, but others are mild.

27. Pholcodeine
It has codeine like properties and has been used mainly as
antitussive; claimed to be less constipating.

28. Pethidine (Meperidine)
Pethidine was synthesized as an atropine substitute in 1939, and has some actions like it.
Important differences in comparison to morphine are:
 Dose to dose 1/10th in analgesic potency.
 After i.m. injection, the onset of action is more rapid but duration is shorter (3–4 hours).
 It does not effectively suppress cough.
 Spasmodic action on smooth muscles is less marked.
 It causes less histamine release and is safer in asthmatics..
 It has local anaesthetic action: corneal anaes thesia is seen after systemic doses.
 It is well absorbed, oral: parenteral activity ratio is high (1/3–1/2).

29. SIDE EFFECTS
Overdose of pethidine produces many excitatory effects—tremors, mydriasis, hyperreflexia,
delirium, myoclonus and convulsions. This is due to accumulation of norpethidine which has
excitant effects.

30. USE OF PETHIDINE
• Pethidine is primarily used as an analgesic (substitute of
morphine) and in preanaesthetic medication, but not for cough or
diarrhoea.
• Potential adverse effects due to accumulation of norpethidine
limit its utility in patients who require repeated dosing.

32. FENTANYL
• APETHIDINEcongener, 80–100 timesmorepotentthanMORPHINE, bothinproducingbothanalgesia
andrespiratorydepression.Atanalgesicdosesitproducesfewcardiovasculareffectsandhaslittle
propensitytoreleasehistamine.
• Becauseof highlipidsolubility,itentersbrainrapidlyandproducespeakanalgesiain5minafteri.v.
injection.Thedurationofactionisshort:startswearingoffafter30–40minduetoredistribution,
whileeliminationt½is~4hr.
• Intheinjectableformitisalmostexclusivelyusedinanaesthesia.TRANSDERMAL FENTANYL has
becomeavailableforuseincancerorothertypesof chronicpainforpatientsrequiringopioid
analgesia.
• DUROGESIC transdermalpatchdelivering25µg/hr,50µg/hr,75µgperhour,100mg/hr.Thepatchis
changedevery2to3days.5.

33. METHADONE
• It has analgesic, respiratorydepressant,emetic, antitussive,constipating and biliary
actions similar to MORPHINE.
• The most important feature of METHADONE is high oral: parenteralactivity ratio (1 : 2) and
its firm binding to tissue proteins
• It is metabolizedin liver, primarily by demethylationand cyclization.Because of slow and
persistentaction, sedative and subjective effects are less intense.
• Withdrawal syndrome is of gradual onset, taking 1–2 days after discontinuation,is
prolongedand less severe. METHADONE has been used primarily as substitutiontherapy of
opioid dependence.
• Another technique is METHADONE maintenance therapyin opioid addicts— sufficient dose
of METHADONE is given ORALLY to produce high degree of tolerance so that pleasurable
effects of i.v. doses of MORPHINE or HEROIN are not perceived and the subject gives up the
habit.

34. DEXTROPROPOXYPHENE
• Its very similar in ANALGESIC action and in side effects to CODEINE, except
that it is poor ANTITUSSIVE and probably less CONSTIPATING.
• Its nearly ½ as potent as CODEINE and has a lower oral: parenteral activity
ratio
• Marketed only in combination with PARACETAMOL for relief of mild to
moderate pain, the contribution of DEXTROPROPOXYPHENE to the analgesic
effect is questionable. The demethylated metabolite of
DEXTROPROPOXYPHENE is CARDIOTOXIC.
• Its OVERDOSE can produce rapid onset RESP DEPRESSION , DELIRIUM AND
CONVULSIONS. However , the abuse potential of DEXTROPROPOXYPHENE
is negligible because of low potency and unpleasant side effects at higher
doses.

35. TRAMADOL
• This centrally acting analgesic relieves pain by opioid as well as additional
mechanisms.
• Its affinity for µ opioid receptor is modest while that for κ and δ is weak.
• . Unlike other opioids, it inhibits reuptake of NA and 5-HT, and thus activates
monoaminergic spinal inhibition of pain.
INDICATION
Tramadol is indicated for mild-to-medium intensity short-lasting pain due to
diagnostic procedures, injury, surgery, dentistry.
It is well tolerated; side effects are dizziness, nausea, sleepiness, dry mouth
and sweating. Haemodynamic effects are minimal—safer in patients with
compromised cardiovascular function.

36. Opioids in dental pain
Dental pain is mostly either due to or associated with inflammation
As such, the antiinflammatory analgesics or NSAIDs are more effective and more suitable than
opioid analgesics.
The latter are primarily employed as additional drugs with aspirin, paracetamol, ibuprofen or the like
to boost their analgesic effect.
When an opioid has to be given, an oral drug like codeine is most suited, because dental patients are
mostly ambulatory and suffer from dull, continuous, short-lasting pain.
Role of injected opioids like morphine, pethidine or fentanyl in dentistry is limited to occasional
intraoperative or periope rative use to supplement the local anaesthetic and allay apprehension.
Clearly, the place of analgesics in dental pain is secondary to treatment of the cause of pain by
appropriate local (antiseptics, cavity filling, root canal therapy, etc.) and systemic (antibiotics)
measures.

37. CONCLUSION
Opioid analgesics play a crucial role in pain management,
providing effective relief for various conditions. However,
their potential for abuse and addiction necessitates
responsible prescribing and monitoring. It is imperative for
healthcare professionals to strike a balance between
alleviating suffering and minimizing the risks associated with
opioid use.