opiod analgesics by dr. amit t. suryawanshi
TRANSCRIPT
ADr. Amit T. Suryawanshi
Presentation
Created & Presented byCreated & Presented byDr. Amit T. Suryawanshi Dr. Amit T. Suryawanshi (MDS)(MDS)
Facial Cosmetic SurgeonFacial Cosmetic SurgeonOral & Maxillofacial SurgeonOral & Maxillofacial Surgeon
Dental Surgeon & ImplantologistDental Surgeon & ImplantologistHair Transplant Surgeon (Germany)Hair Transplant Surgeon (Germany)
Consulting Surgeon in Kolhapur, Sangli, Pune & Consulting Surgeon in Kolhapur, Sangli, Pune & Mumbai (India) Mumbai (India)
& & founder of founder of
Face Art International Super specialityFace Art International Super specialityat Kolhapurat Kolhapur
Cell Phone no. Cell Phone no. +91 9405622455+91 9405622455Clinic Landline Clinic Landline - +91 7758976097- +91 7758976097
Email– [email protected]– [email protected]
• 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 SurgeonOral & Maxillofacial SurgeonDental Surgeon & ImplantologistHair Transplant Surgeon (Germany)
Know Your Doctor
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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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 abuserFollow us on SlideShare &
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CLASSIFICATIONI)
1.NATURAL OPIUM ALKALOIDS - morphine
- codeine
2.SEMISYNTHETIC OPIATES - Diacetyl morphine(heroin) - Pholcodiene.
3.SYNTHETIC OPIOIDS - Pethedine
- Fenyanyl - Methadone - Tramadol - Dextropropoxyphene - Ethoheptazine
II) Based on intrinsic activity Agonist: morphine Fentanyl
Pure antagonist: naloxone Naltrexone
Mixed agonist-antagonist: nalbuphine Butorphanol
III)BASED ON FUNCTION: Agonists: Strong moderate weak Morphine codeine
propoxyphene Pethedine oxycodone methadone
Antagonists : naloxone
Antitussive : coediene Dextromethorphan Antidiarrheals diphenoxylate
loperamide
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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OPIOID RECEPTOR EXPRESSIONµ receptor periaqueductal
gray, spinal trigeminal nucleus, cuneate and gracile nuclei, thalamus regionsnucleus of solitract, nucleus ambiguus
parabrachial nucleus
neurons of the postrema
Pain perception (morphine analgesia)
Morphine-control respiration
Morphine- depress respirationNauesea and vomiting
K receptor hyphothalamic region
Neuroendocrine effects
S receptor dorsal horn of the spinal cord
MECHANISM OF ACTION
• 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.
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
2 . SEDATIONIn humans, Opioids usually produce
sedationHowever, in extremely high doses opioids
produce convulsions (e.g., meperidine)
3. EUPHORIAEuphoria is often produced by opioidsEuphoria is more prominent in those
previously addicted to opioids
4. MENTAL CLOUDINGThe 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
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
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
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.
GASTROINTESTINAL TRACT
• Increases GI tone• Produces constipation
(Diphenoxylate-meperidine derivative [Lomotil])
• GI spasms can be controlled by atropine (acetyl choline receptor antagonist)
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
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)
PHARMACOKINETICS1)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
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 .
Acute Pain postoperative pain diagnostic procedures orthopedic manipulations myocardial infarction
Preanesthetic medication (fentanyl-derivatives)
Dyspnea Cough Suppression (codeine,
dextromethorphan) Diarrhea and dysentery
CONTRAINDICATIONS 1) Decreased respiratory reserve emphysema severe obesity asthma2) Biliary colic3) Head injury4) Reduced blood volume5) Hepatic insufficiency6) Convulsant states
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.
2) Nausea
a) Stimulation of the chemoreceptor trigger zone
b) Incidence (about 50%)c) Antiemetics are prescribed
Scopolamine droperidol ondansetron
3. Sedation Central stimulants such as
amphetamine or ritalin may be prescribed as an adjuvant therapy in cancer patients who require chronic analgesics.
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
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
6) Confusion, hallucinations1. 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
7. Euphoria Intravenous administration of
opioids has a much higher incidence of euphoria and dysphoria than orally administered opioids.
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.
9. Respiratory depressiona) The most important adverse effectb) Mediated at brainstem respiratory
centersc) 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.
10. The Toxicity triad
a) Catastrophic respiratory depression, as low as 2-4 breaths per minute: patient may be conscious
b) Stupor or comac) Pinpoint pupils
Treatment of toxicity involves IV administration of the antagonist
naloxone
DRUG INTERACTIONS CNS depressants
(antihistamines,tranquilisers,pain killers,seizure medicine,muscle relaxants,sleeping pills and some anesthetics)
MAO inhibitors (phenelzine) Tricyclic antidepressants
(carbamazepine)
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.
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
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
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.
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.
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.
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.
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.
• Opioid substitution should be considered carefully.
• Discussion with a physician experienced in this process is recommended.
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
• 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
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.
• Each situation must be handled on an individual basis.
• The universal goal is to taper quickly as the patient’s physiologic and psychologicalstatus allows.
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.
• "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.
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.
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.
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.
Morphine Pump• A method of controlling Morphine application by fitting an A method of controlling Morphine application by fitting an
external supply with a pump under the patient's control that external supply with a pump under the patient's control that administers doses into the body as needed.administers doses into the body as needed.
• Direct infusion of a medication into the intrathecal space Direct infusion of a medication into the intrathecal space around the spinal cord can suppress severe back or around the spinal cord can suppress severe back or extremity pain. extremity pain.
• The surgery involves placing a reservoir under the skin of The surgery involves placing a reservoir under the skin of the lower anterior abdomen. Simultaneously, a catheter is the lower anterior abdomen. Simultaneously, a catheter is placed into the spinal fluid space and then connected to the placed into the spinal fluid space and then connected to the reservoir. reservoir.
• The contents of the reservoir can be programmed to infuse The contents of the reservoir can be programmed to infuse into the spinal fluid in a controlled fashion . The reservoirs into the spinal fluid in a controlled fashion . The reservoirs can be refilled as necessary.can be refilled as necessary.
• 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.
CODEINE(sulfate/phosphate)Pharmacology active PO
metabolised in liver, excreted in urineduration of action 4-6h
Indications mild to moderate paindiarrhoeacough
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
TRAMADOLPharmacology 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
BUPRENORPHINE (buprenex)Pharmacology active SL, IM
metabolised in the liver, excreted in bile and urineduration of action 6-9hrequire 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
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.
HYDROMORPHONEPharmacology active PO, PR, SC, IM, IV and spinal
metabolised in the liver, excreted in urineduration 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 morphineDose no standard dose for chronic pain
titrated against pain and adverse effects for each individual patient
Preparations tablets, liquid, suppositories, injection
PETHIDINEPharmacology 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
METHADONE (dolophine)Pharmacology active PO, PR, IM, IV, SC
actions: µ opioid agonist,metabolized in liver, mainly excreted by faecal routeduration 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 opioidrenal 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
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
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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