Opiod analgesics used in Dentistry by Dr. Amit T. Suryawanshi (MDS) Facial Cosmetic Surgeon Oral & Maxillofacial Surgeon Dental Surgeon & Implantologist Hair Transplant Surgeon (Germany) Consulting Surgeon in Kolhapur, Sangli, Pune & Mumbai (India) & founder of Face Art International Super speciality at Kolhapur (India)

1. A
Dr. Amit T. Suryawanshi
Presentation

2. Created & Presented byCreated & Presented by
Dr. Amit T. SuryawanshiDr. Amit T. Suryawanshi (MDS)(MDS)
Facial Cosmetic SurgeonFacial Cosmetic Surgeon
Oral & Maxillofacial SurgeonOral & Maxillofacial Surgeon
Dental Surgeon & ImplantologistDental Surgeon & Implantologist
Hair Transplant Surgeon (Germany)Hair Transplant Surgeon (Germany)
Consulting Surgeon in Kolhapur, Sangli, Pune & Mumbai (India)Consulting Surgeon in Kolhapur, Sangli, Pune & Mumbai (India)
&&
founder offounder of
Face Art International Super specialityFace Art International Super speciality
at Kolhapurat Kolhapur
Cell Phone no.Cell Phone no. +91 9405622455+91 9405622455
Clinic LandlineClinic Landline - +91 7758976097- +91 7758976097
Email– amitsuryawanshi999@gmail.comEmail– amitsuryawanshi999@gmail.com
Created & Presented byCreated & Presented by
Dr. Amit T. SuryawanshiDr. Amit T. Suryawanshi (MDS)(MDS)
Facial Cosmetic SurgeonFacial Cosmetic Surgeon
Oral & Maxillofacial SurgeonOral & Maxillofacial Surgeon
Dental Surgeon & ImplantologistDental Surgeon & Implantologist
Hair Transplant Surgeon (Germany)Hair Transplant Surgeon (Germany)
Consulting Surgeon in Kolhapur, Sangli, Pune & Mumbai (India)Consulting Surgeon in Kolhapur, Sangli, Pune & Mumbai (India)
&&
founder offounder of
Face Art International Super specialityFace Art International Super speciality
at Kolhapurat Kolhapur
Cell Phone no.Cell Phone no. +91 9405622455+91 9405622455
Clinic LandlineClinic Landline - +91 7758976097- +91 7758976097
Email– amitsuryawanshi999@gmail.comEmail– amitsuryawanshi999@gmail.com

3. • Dr. Amit T. Suryawanshi has published various
articles in many national & International Journals
regarding Oral Sub mucous Fibrosis & other
topics in the field of Maxillofacial Plastic
Surgery, Advanced Hair Transplant & Advanced
dentistry .
(MDS) Facial Cosmetic Surgeon
Oral & Maxillofacial Surgeon
Dental Surgeon & Implantologist
Hair Transplant Surgeon (Germany)
Know Your Doctor

4. DEFINITION
 Opioid analgesics, also known as
narcotic analgesics, are pain relievers
that act on the central nervous
system.
 Like all narcotics, they may become
habit-forming if used over long
periods
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5. HISTORY
 opium obtained from poppy plant (Papaver
somniferum)
 active ingredient (morphine) extracted --- into
heroin
 long history (dates from B.C.) of use for tx. for
diarrhea, for sleep
 recreational use & addiction were common
 1843 Dr. Alexander Wood (Edinburgh) invented
 used in Civil War in USA for pain control
 “soldier’s disease” referred to heroine addiction
in self-injecting abuser
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6. CLASSIFICATION
I)
1.NATURAL OPIUM ALKALOIDS
- morphine
- codeine
2.SEMISYNTHETIC OPIATES
- Diacetyl morphine(heroin)
- Pholcodiene.
3.SYNTHETIC OPIOIDS
- Pethedine
- Fenyanyl
- Methadone
- Tramadol
- Dextropropoxyphene
- Ethoheptazine

7. II) Based on intrinsic activity
Agonist: morphine
Fentanyl
Pure antagonist: naloxone
Naltrexone
Mixed agonist-antagonist: nalbuphine
Butorphanol

8. III)BASED ON FUNCTION:
Agonists:
Strong moderate weak
Morphine codeine propoxyphene
Pethedine oxycodone
methadone
Antagonists : naloxone
Antitussive : coediene
Dextromethorphan
Antidiarrheals diphenoxylate
loperamide

9. OPIOID RECEPTORS
• Opioids bind to specific receptor
molecule
• Opioid specific receptors : Mu (µ),
Kappa (x), and Delta (S) receptors.
• These receptors belong to G protein-
coupled seven transmembrane
receptor family
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10. OPIOID RECEPTOR EXPRESSION
µ receptor periaqueductal gray,
spinal trigeminal
nucleus, cuneate and
gracile nuclei,
thalamus regions
nucleus of solitract,
nucleus ambiguus
parabrachial nucleus
neurons of the
postrema
Pain perception
(morphine analgesia)
Morphine-control
respiration
Morphine- depress
respiration
Nauesea and vomiting
K receptor hyphothalamic region Neuroendocrine
effects
S receptor dorsal horn of the
spinal cord

11. MECHANISM OF ACTION

12. • Activates receptor-activated K+ currents
which increase IC efflux
(hyperpolarization)
• Reduces voltage-gated Cat+ entry.
• Hyperploarization of membrane potential
by K+ currents and inhibition of the Cat+
influx prevents neurotransmitter release
and pain transmission in varying neuronal
pathways.

14. PHARMACOLOGICAL ACTIONS
Central Nervous System
1. Analgesia
– produces selective attenuation of pain
perception; effect is dose-dependent
– therapeutic dose (10 mg; parentral) (pain
threshold not elevated)
– higher doses (15 - 20 mg; parentral) pain
threshold elevated
– drowsiness
– respiratory depression

15. 2 . SEDATION
In humans, Opioids usually produce sedation
However, in extremely high doses opioids
produce convulsions (e.g., meperidine)
3. EUPHORIA
Euphoria is often produced by opioids
Euphoria is more prominent in those
previously addicted to opioids

16. 4. MENTAL CLOUDING
The environment is perceived as indistinct and unreal
5. RESPIRATORY DEPRESSION
 Produced even in small doses
 Large doses may induce respiratory failure
 Death from morphine overdose is usually due to
respiratory failure
 Opioids decrease sensitivity of brain stem centers
to CO2 (i.e., depress CO2 sensing capacity)
 Pure oxygen can induce apnea during severe
respiratory depression

17. 6.NAUSEA AND VOMITING
 Opioids can stimulate the
chemoreceptor trigger zone (CTZ)
 Located in the area postrema in the
medulla oblongata
 Symptoms can be controlled by
Phenothiazines (agonist on x receptor
weak antagonist on µ receptor

20. 7) COUGH REFLEX (antitussive effect)
 Opioids suppress the cough reflex
 Produced by depression of neurons in
medulla which control the cough reflex
 Codeine is a potent inhibitor of the cough
reflex
 Meperidine has a weak effect

21. 8) PUPILLARY DIAMETER
 Opioids cause miosis (pupillary constriction).
 Opioids act on µ and x receptors to stimulate
oculomotor nucleus to constrict pupil.
 Pin point pupils are characteristics of
morphine overdose. There is very little
tolerance to this effect.

22. GASTROINTESTINAL TRACT
• Increases GI tone
• Produces constipation (Diphenoxylate-
meperidine derivative [Lomotil])
• GI spasms can be controlled by atropine
(acetyl choline receptor antagonist)

23. CARIOVASCULAR SYSTEM
 No prominent effects
 Peripheral vasodilatation most prominent
effect due to histamine release and
decreased adrenergic tone
 Very high doses may produce
bradycardia
 Orthostatic hypotension

24. URINARY TRACT
• Opioids produce urinary retension Increase tone of
urinary sphincter
• Decrease urine production (increased ADH secretion
UTERUS
• Duration of labor may be prolonged
BRONCHIAL SMOOTH MUSCLE
• Therapeutic doses have no effect
• High doses produce constriction (can aggravate
asthma)

25. PHARMACOKINETICS
1)Absorption
 Readily absorbed from all sites of administration
2)Distribution
 Distributed to all tissues
 Morphine is poorly transported across the blood-brain
barrier
3)Metabolism
 It is conjugated with glucuronic acid in the liver.
 Morphine and naloxone are subject to significant "first-
pass" metabolism in the liver, but naltrexone is not.
4)Excretion
 Free and conjugated morphine are excreted in the urine

26. THERAPEUTIC INDICATIONS
• PAIN
• Chronic pain (only under some circumstances)
Most chronic pain states are not relieved by opioid drugs:
1)central pain
2)trigeminal neuralgia (tic douloureux)
3)causalgia
4)phantom limb pain
5)cancer pain
These pain states require continuous medication Therapy limited by
tolerance and physical dependence
• Chronic pain arising from terminal illness can be relieved by opioid
drugs .

27.  Acute Pain
 postoperative pain
 diagnostic procedures
 orthopedic manipulations
 myocardial infarction
 Preanesthetic medication (fentanyl-
derivatives)
 Dyspnea
 Cough Suppression (codeine,
dextromethorphan)
 Diarrhea and dysentery

28. CONTRAINDICATIONS
1) Decreased respiratory reserve
emphysema
severe obesity
asthma
2) Biliary colic
3) Head injury
4) Reduced blood volume
5) Hepatic insufficiency
6) Convulsant states

29. Side Effects of Opioid Analgesics
1. Constipation
a) Due to effects on the myenteric plexus, inhibiting
propulsive peristaltic contractions.
b) Stimulative laxatives are almost always
prescribed as an adjuvant medication when a
patient is prescribed morphine.

30. 2) Nausea
a) Stimulation of the chemoreceptor
trigger zone
b) Incidence (about 50%)
c) Antiemetics are prescribed
 Scopolamine
 droperidol
 ondansetron

31. 3. Sedation
Central stimulants such as
amphetamine or ritalin may be
prescribed as an adjuvant therapy in
cancer patients who require chronic
analgesics.

32. 4. Pruritus (itching)
 Occurs more frequently with epidural or
intrathecal opioid administration and it is
not a drug allergy, but rather the result of
opioid induced histamine release from the
mastcells.
 Treatment : antihistamine and low dose
naloxone

33. 5. Miosis
 Opioids excite the autonomic
segment of the oculomotor nerve.
 Usually It does not interfere with
the patient’s vision.
 Tolerance to this does not develop

34. 6) Confusion, hallucinations
1. Particularly a problem with mixed agonists-
antagonists opioid analgesics such as
pentazocine, butorphanol, or Nalbuphine.
2. Elderly patients are much more susceptible
to morphine induced confusion or
hallucinations.
3. Hydromorphone and meperidine are usually
better tolerated in this patient population

35. 7. Euphoria
Intravenous administration of opioids
has a much higher incidence of
euphoria and dysphoria than orally
administered opioids.

36. 8. Hypotension
a) Most often associated with rapid
intravenous opioid administration.
b) Morphine, meperidine, and hydromorphone
are most frequently associated with
hypotension.
c) Fentanyl usually does not cause
hyptension, (preferred analgesic agent in
patients with compromised hemodynamics)
d) Post surgical opioid induced hypotension is
almost always associated with hypovolemia
and that could be managed with hydration.

37. 9. Respiratory depression
a) The most important adverse effect
b) Mediated at brainstem respiratory centers
c) Reduce responsiveness of respiratory
centers to increase in carbon dioxide
tension (PCO2)
d) Occurs at low doses and increases in a
dose-dependent fashion
e) Death from overdose is almost always from
respiratory arrest.

38. 10. The Toxicity triad
a) Catastrophic respiratory depression,
as low as 2-4 breaths per minute:
patient may be conscious
b) Stupor or coma
c) Pinpoint pupils
Treatment of toxicity involves IV
administration of the antagonist naloxone

39. DRUG INTERACTIONS
 CNS depressants
(antihistamines,tranquilisers,pain
killers,seizure medicine,muscle
relaxants,sleeping pills and some
anesthetics)
 MAO inhibitors (phenelzine)
 Tricyclic antidepressants
(carbamazepine)

40. PHYSICAL DEPENDENCE
Abnormal physical state in which the
drug must be administered to maintain
"normal" function.
Physical dependence is manifested by
"withdrawal symptoms" when
administration of the drug is stopped.

41. Symptoms:
• 8 - 12 hrs: lacrimation, rhinorrhea, yawning,
sweating
• 12 - 14 hrs: restless sleep
• 48 - 72 hrs: symptoms peak, dilated pupils,
anorexia, gooseflesh (cold turkey), restlessness,
irritability, tremor, nausea/vomiting, intestinal
spasm and diarrhea, muscle spasm
• 7 - 10 days: symptoms end

42. Tolerance
a) Defined as a gradual loss in effectiveness
with frequently repeated administration
b) Marked tolerance develops to the analgesic,
euphoric, and respiratory depressant
c) Tolerance does not develop to morphine-
induced miosis and constipation
d) No tolerance develops to antagonists

43. Cross-tolerance
 Develops between drugs that act at the
same receptor types, e.g. patients tolerant
to morphine are tolerant to the other opioid
agonist drugs.
 Cross-tolerance may not be complete, and
therefore one needs to be more careful
when switching from one opioid to another.

44. F) Tolerance is often mistaken for
worsening pathology that then leads to
dose escalation.
g) For unknown reasons, pain actually
contributes to tolerance of the
respiratory system. Thus, if the cause
of the pain is eliminated, tolerance may
not protect the patient from opioid
toxicity. In such cases, the opioid dose
must be reduced quickly.

45. OVERDOSE
• Can be fatal
• Mechanism occurs through depression
of the respiratory drive, resulting in
hypoxia and eventually death.
• Opioid overdose can be rapidly
reversed with an opioid antagonist such
as naloxone or naltrexone.

46. These competitive antagonists bind to
the opioid receptors with higher
affinity than agonists but do not
activate the receptors. This displaces
the agonist, attenuating and/or
reversing the agonist effects.
However, the elimination half-life of
naloxone can be shorter than that of
the opioid itself, so repeat dosing or
continuous infusion may be required.

47. Opioid substitution
• Opioid substitution is switching from one
drug to another.
• With the increasing availability of a range
of opioid drugs, it has become common
practice for patients with inadequate
analgesia or troublesome adverse effects
to be tried on a different drug.
Substitution of one opioid drug for another
has been termed opioid switching or opioid
rotation. Opioid substitution results in
improved analgesia and fewer adverse
effects for many patients.

48. • Opioid substitution should be
considered carefully.
• Discussion with a physician
experienced in this process is
recommended.

49. Guidelines for opioid substitution
• Calculate the equianalgesic dose of the
new drug
• Decrease the dose by 25-50% to
accommodate cross-tolerance.
• reduce by 75% if changing to methadone
• do not reduce if changing to TD fentanyl
• initial opioid needs to be continued for 12-
24h if changing to TD fentanyl
• Adjust according to prior pain control

50. • reduce less if patient in severe pain
• Adjust according to the patient’s
general condition
• reduce more if elderly, frail, or
significant organ dysfunction
• Give 50-100% of the 4-hourly dose
for breakthrough pain
• Reassess and titrate new opioid
against pain and side effects

51. OPIOID TAPERING
• Safely discontinuing, or tapering opioid
analgesics is an ongoing concern, both in
times of crisis and on a daily basis.
• reasons for opioid tapering
– adverse effects
– inadequate pain relief
– medication costs.

52. • Each situation must be handled on
an individual basis.
• The universal goal is to taper
quickly as the patient’s physiologic
and psychologicalstatus allows.

53. Katrina Disaster Working Group
Suggested Tapering Regimens
● Reduction of daily dose by 10% each
day, or…
● Reduction of daily dose by 20% every 3-
5 days, or…
● Reduction of daily dose by 25% each
week.

54. • "RAPID DETOX"
• relatively new technique that uses opioid
antagonists to cause acute withdrawal while
the patient is under general anesthesia to
eliminate the otherwise extreme discomfort.
• Controversy
 High cost and risk
 Fatal
Many pain specialists think that the procedure
unnecessary, and addiction specialists criticize it for
doing nothing to keep an addict from relapsing into
opioid abuse after the procedure is complete.

55. OPIOID ANTAGONISTS
• Naloxone
• Naltrexone
• Nalmefene
These agents have relatively high affinity for
mu opioid binding sites. Having low affinity
for other receptors can also reverse
agonists at S and K receptors.

56. NALOXONE
 poor efficacy when given orally.
 short duration of action(1-2 hrs) when
given iv.(0.4 to o.8mg i.v every 2 -3 min).
NALTREXONE
well absorbed after oral adm
undergo rapid first pass metabolism.
 half life (10 hrs)
 single dose of 100 mg will block
effects of injected heroin for up to 48
hrs.

57.  When given to morphine treated patient the
antagonist will completely & dramatically
reverse the opioid effects within 1-3 min.
 Normalise the respiration,level of
conciousness,pupil size,bowel movements.
 No tolerance to antagonist action.
 no withdrawl symptoms.
 Treatment for acute opioid overdose.
 Dose----0.1 to0.4 mg iv,adult dose
 0.02 mg/ml for neonatal use.
 Proposed as maintenance drug becoz of long
duration of action.
 Naltrexone decreases craving for alcohol in
chronic alcoholics.

58. Morphine Pump
• A method of controlling Morphine application byA method of controlling Morphine application by
fitting an external supply with a pump under thefitting an external supply with a pump under the
patient's control that administers doses into thepatient's control that administers doses into the
body as needed.body as needed.
• Direct infusion of a medication into theDirect infusion of a medication into the
intrathecal space around the spinal cord canintrathecal space around the spinal cord can
suppress severe back or extremity pain.suppress severe back or extremity pain.
• The surgery involves placing a reservoir under theThe surgery involves placing a reservoir under the
skin of the lower anterior abdomen.skin of the lower anterior abdomen.
Simultaneously, a catheter is placed into theSimultaneously, a catheter is placed into the
spinal fluid space and then connected to thespinal fluid space and then connected to the
reservoir.reservoir.
• The contents of the reservoir can be programmedThe contents of the reservoir can be programmed
to infuse into the spinal fluid in a controlledto infuse into the spinal fluid in a controlled
fashion . The reservoirs can be refilled asfashion . The reservoirs can be refilled as

59. • The infusion pump provides a steady flow of
Morphine or Dilaudid into the spinal fluid to
help manage the severe chronic pain, which
has not responded to the standard
treatments. The infusion pump is only
effective if the patient limits the intake of
pain medications to only through the pump
administering medication in the spinal fluid.
• Because the Morphine or Dilaudid has a
higher specific gravity than the spinal fluid,
the infusion of such medications (definitely
not together) into the spinal fluid provides
mainly pain relief in the lumbar spine and
lower extremities.

60. CODEINE(sulfate/phosphate)
Pharmacology active PO
metabolised in liver,
excreted in urine
duration of action 4-6h
Indications mild to moderate pain
diarrhoea
cough
Cautions severe hepatic or renal impairment other causes
of CNS depression
Adverse effects qualitatively similar to morphine - generally mild,
more constipating
Dose analgesic 30-60mg PO q4-6h
antitussive 8-20mg PO q4-6h
Preparations tablets, syrup combined preparations with
aspirin or paracetamol

61. TRAMADOL
Pharmacology active PO, PR, SC, IM, IV
actions: opioid agonist,
metabolised in liver,
excreted in the urine
duration of action 4-6h
Indications mild and moderate pain
Contraindication patients taking MAOIs
Caution severe hepatic or renal impairment epilepsy,
drugs that reduce seizure threshold e.g. TCAs,
Dose 50-100mg PO q4-6h or 100-200mg SR PO
q12h, and titrate against effect and toxicity
Preparations capsules, SR tablets, injection

62. BUPRENORPHINE (buprenex)
Pharmacology active SL, IM
metabolised in the liver,
excreted in bile and urine
duration of action 6-9hr
equire larger doses of naloxone to treat respiratory
depression
Indications moderate and severe pain
Cautions patients on opioid agonists-
buprenorphine can act as an antagonist and may
produce withdrawal symptoms
- another opioid agonist will have no or delayed
effect
Adverse effects qualitatively similar to morphine
Dose 0.3-0.6mg IM or 0.4-0.8mg SL, q6-8h
Preparations injections, sublingual tablets

63. FENTANYL TRANSMUCOSAL
• is a ‘lozenge on a stick’ containing fentanyl in a hard sweet
matrix
• used by placing it against the mucosa of one cheek and
constantly moving it up and down, and changed at intervals from
one cheek to the other
• provided safe and effective treatment for breakthrough pain in
75% of patients studied in trials
• 25% of patients either do not achieve analgesia with the
highest dose (1600µg) or suffer unacceptable adverse effects
• there is no relationship between the effective dose of OTFC
for breakthrough pain and the dose of opioid being used for
background analgesia
• each patient has to be individually titrated to find the
appropriate OTFC dose
• OTFC lozenges are expensive.

64. HYDROMORPHONE
Pharmacology active PO, PR, SC, IM, IV and spinal
metabolised in the liver, excreted in urine
duration of action 4h
Indications moderate and severe pain
morphine intolerance
Cautions renal impairment
severe hepatic dysfunction
significant pulmonary disease
other causes of CNS depression old age, debility
Adverse effects similar to morphine
Dose no standard dose for chronic pain
titrated against pain and adverse effects for each
individual patient
Preparations tablets, liquid, suppositories, injection

65. PETHIDINE
Pharmacology active IV, IM, PO, PR
metabolised in the liver,
excreted in the urine
duration of action 2-3h
Indications moderate and severe pain
NOT RECOMMENDED for chronic usage in
palliative care
Contraindications patients taking MAOIs renal impairment
Adverse effects CNS toxicity due to norpethidine accumulation
- agitation, tremor, sedation, narcosis
Dose NOT RECOMMENDED for chronic usage in
palliative care (50-100mg)
neurotoxic & short duration of action

66. METHADONE (dolophine)
Pharmacology active PO, PR, IM, IV, SC
actions: µ opioid agonist,
metabolized in liver,
mainly excreted by faecal route
duration of action: 4-6h initially, 8-12h with continued
use
Indications moderate and severe pain pain
poorly responsive to morphine,
especially neuropathic pain
intolerance to morphine or other opioid
renal failure
Cautions frail, elderly, confused
significant hepatic or renal impairment
significant pulmonary disease
other causes of CNS depression
Adverse effects similar to morphine
cumulative toxicity heralded by sedation

67. Dose calculated from previous therapy, adjusted for
effect and toxicity
frequency: q4-6h for first 1-3d, then q6-12h
Preparations tablet, mixture, injection
Methadone has cumulative toxicity due to the
progressive prolongation of the half-life with
continued therapy.
It is necessary to reduce both the dose and the
frequency after the first few days. Failure to
do this will result in narcosis

68. REFERENCES
 GOODMAN &GILMAN’S—The
pharmacological basis of theurapeutics.
9th
edition
 Basic &clinical pharmacology by Bertram
G.katzung -7th
Edition
 Essentials of MEDICAL PHARMACOLOGY by
KD Tripati.
 Pharmacology & pharmacotherapeutics- R S
Satoskar
 Internet.
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69. Don’t forget
to Smile 
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