OPIOIDS akanksha

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OPIOIDS

Overview :

Overview History Introduction Pain pathway Opioid receptors & regulation Classification MOA Pharmacological actions Individual drugs ADR Recent Advances Summary References

Objective :

Objective Discuss pain pathway Opioids as analgesic Adverse drug reaction

History :

History 1500 B.C.- Eber’s papyrus 300 B.C. -Theophrastus 1806 - Frederich Serturner isolated 1860s- Civil war in U.S. soldier’s joy soldier’s disease.

Slide 5:

1874 – Heroin isolated - C.R. Alder Wright Endogenous opioids Radioligand binding studies

PAIN PATHWAY:

PAIN PATHWAY

ANALGESICS:

ANALGESICS

Classification :

Classification

Classification II:

Classification II

Mechanism of action :

Mechanism of action

PHARMACOLOGICAL ACTIONS:

PHARMACOLOGICAL ACTIONS CNS ANALGESIA Dull visceral pain Higher doses – acute pain Dampens anxiety Supra-spinal actions

Slide 13:

Sedation Mood alterations “ kick ” or “ high ” RESPIRATORY CO 2 drive hypoxic drive decrease Upper airway potency Chest wall rigidity Anti- tussive action

ENDOCRINE :

ENDOCRINE

Slide 15:

CVS vasodilator (systemic > pulmonary) cardiac workload TEMPERATURE GIT – Constipation, decreased secretions BILIARY DUCT OTHER SMOOTH MUSCLES

PHARMACOKINETICS:

PHARMACOKINETICS Highly lipid soluble High plasma protein binding High 1st pass metabolism (can cross the placental barrier)

Slide 18:

METABOLISM half-life : 2-3 hr Elimination within 24hr

USES:

USES Analgesia

VISUAL ANALOGUE SCALE:

VISUAL ANALOGUE SCALE

W.H.O. STEPLADDER :

W.H.O. STEPLADDER

OPIOIDS and types of pain :

OPIOIDS and types of pain

PAIN:

PAIN ORAL (5-15 mg ) I/V (2-5 mg ) Reassess efficacy+ADR Reassess ADR 15 min (1 hour) unchanged decreased Dose 50% repeat dose

ADJUVANT ANALGESICS:

ADJUVANT ANALGESICS SSRI TCA (amitriptyline) Local anaesthetics Antiepileptics ( carbamazapine , gabapentin ) Corticosteroids

OTHER USES:

OTHER USES Anaesthesia Antitussives Antidiarrheal Balanced anaesthesia & surgical analgesia Acute LVF

ROUTES OF ADMINISTRATION:

ROUTES OF ADMINISTRATION

Cont….:

Cont …. Patient controlled analgesia

Opioids S/E:

Opioids S/E

OPIOID DILEMMA:

OPIOID DILEMMA

LEVORPHANOL:

LEVORPHANOL Opioid agonist D isomer - analgesic property + inhibits NMDA receptors Affinity for δ , ƙ mu i /v, i /m & p/o Similar to morphine but has less nausea & vomiting Accumulation (t 1/2 )

Meperidine (Pethidine) :

Meperidine ( Pethidine ) Mu agonist Analgesic action Nor meperidine – t1/2 15-20 hours Acute narcotic overdose Serotonin syndrome

Mepiridine metabolism:

Mepiridine metabolism MAO inhibitors (-) hydrolysis ? Mepiridine demethylation nor- mepiridine

Uses :

Uses Analgesia Post anesthetic shivering, Infusion related rigors Epidural anesthesia – safe Overdose - Treatment with naloxone

Diphenoxylate Hydrochloride :

Diphenoxylate Hydrochloride Diarrhea Less abuse liability + atropine ADR - constipation

LOPERAMIDE :

LOPERAMIDE M/A - Decreases GIT motility and secretion Use - diarrhea ADR - cramps P GLYCOPROTEIN (efflux protein)

FENTANYL :

FENTANYL Drugs - Fast onset, short duration, fast termination DOC - day care surgery Decreases the dose of volatile agents Severe pain states Ramifentanyl – metabolized by esterase

CNS EFFECTS :

CNS EFFECTS High doses muscle rigidity Do not affect ICP Decrease the heart rate Used for CVS surgeries BBB - 5 min

Uses :

Uses Anesthetic adjuvant Post op. pain In epidural with L/A Chronic pain treatment Routes of delivery ???

Methadone:

Methadone Long acting MOR agonist Tissue binding - high T ½ is long (15-40hours) BBB ½ hour Buccal mucosa Uses: Chronic pain Drug abusers ADR: Prolonged Qt interval

Dextromethorphan:

Dextromethorphan

Tramodol :

Tramodol Synthetic opioid M/A – mild opioid agonist+ NA, 5HT reuptake inh . IM – 100% f Metabolism – CYP 2D6

LIMITATIONS :

LIMITATIONS Miosis Pain Hypothesis – functional uncoupling of a fraction of receptors

ACUTE OPIOID POISONING:

ACUTE OPIOID POISONING Potentially dangerous in a opioid naïve patient – 50 mg Human Lethal Dose – 250 mg Chronic addicts can tolerate larger doses

SYMPTOMS:

SYMPTOMS DEATH – RESPIRATORY DEPRESSION GASTRIC LAVAGE –KMnO 4 Slow infusion – ppt. withdrawal treatment NALOXONE- 0.4mg (0.01mg/kg)

Opioid addiction & Treatment:

Opioid addiction & Treatment Temporary relief from withdrawal WITHDRAWL SYMPTOMS RETURN NARCOTIC USE

Slide 47:

Addiction – drug seeking behavior Treatment modalities Cold turkey Traditional drugs Rapid detoxification

Agonist, partial agonist and antagonist :

Agonist, partial agonist and antagonist

Narcotics Drug Act:

Narcotics Drug Act The Narcotic Drugs and Psychotropic Substances Act is an act of the Parliament of India which was passed in 1985 and came into effect in India from November 14, 1985.

RECENT ADVANCES:

RECENT ADVANCES NMDA antagonist Nitric oxide synthase inhibitors Iontophoresis 5-HT 4(a) Receptors

summary:

summary Opioids mainstay of pain treatment Effective Dependence

REFERENCES :

REFERENCES Goodman & gillman 12 th edition Katzung K.D. Tripathy 5-ht 4(a) receptors avert opioid-induced breathing depression without loss of analgesia science 11 july 2003: vol. 301 no. 5630 pp. 226-229 NCCN- Clinical practice guidelines in oncology. Version 1, 2001 .

Slide 53:

Thank you

SUPRASPINAL ACTION:

SUPRASPINAL ACTION MOR agonist blocks the release of GABA in the medulla Release of NE &5HT Dorsal horn excitability Decrease in the perceived pain

SPINAL ACTION:

SPINAL ACTION discharge of the spinal dorsal horn Presynaptic Postsynaptic

Acute /Chronic activation of receptors:

Acute /Chronic activation of receptors DESENSITIZATION - internalization TOLERANCE – days to weeks (DRC) CROSS TOLERANCE( hypothesised the difference in receptors) DEPENDENCE ADDICTION – positive reward, drug seeking behavior COUNTER ADAPTATION- bulbospinal pathway+NMDA receptors

TOLERANCE:

TOLERANCE Controversial Receptor disposition Terminal transmitter release is enhance during opioid withdrawal Tolerance to analgesia – continuous agonism of mu receptors leads to activation of bulbospinal pathway- it increases pain transmission Chronic opiate receptor occupancy leads to activation of PKC which can enhance activation of NMDA receptors – enhance pain transmission

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