Opioids in Anaesthesia

Balkrishna Bhattarai

Among the remedies which it has pleased Almighty God to give to man to relieve his sufferings, none is so universal and so efficacious as opium -Thomas Sydenham (1680)

Introduction
Opium- juice in Greek Theophrastus first used as analgesic in 3rd century Morphine isolated from opium by Serturner in 1806. Morpheus- Greek god of dream Opioid anaesthesia Opiate & opioids Narcotics Narkotikos deadening

Mechanism of action
Opioid receptors: mu-1, mu-2, kappa, delta, sigma Agonist/ antagonist (ceiling effects) Endogenous peptides

Endorphins Encephalin Dynorphin

Structure-activity relationship: diverse compds

Classification of opioid receptors

Receptor Clinical effect Mu Supra-sp. analgesia (1) Resp. depression (2) Phys depend., rigidity Sedation Spinal analgesia Analgesia, Behavioral, Epileptogenic Dysphoria, Hallucination, Resp. stimulation Agonists Morphine Met-enkephalin* Beta-endorphin* Morph, Nalbuph, Butorph, Dynorph* Leu-enkephalin*, Beta-endorphin* Pentazocine, Nalorph., ? Keta.

Kappa Delta Sigma

Pharmacokinetics: routes
Iv, im, sc, epid, intrathecal (bolus/infusion) Intranasal Sublingual Trans-dermal: e.g. patch Inhalational Local application Oral: including lollipop

Pharmacokinetics: absorption
Usually rapid after iv, im Slow after trans-dermal: peak 14-24 hrs, duration- 72hrs

Determinants of distribution
Drug Ionz. (%) 23 7 Prot. Lip. Bind. Solu. (%) 35 1.4 70 84 93 92 39 813 1778 145 Vdss T1/ 2 2-4 3-5 2-4 pKa Hep. Extr. ratio 8.0 0.8-1.0 8.5 0.7-0.9 8.4 0.8-1.0 8.0 0.7-0.9 6.5 0.3-0.5

Mor Peth

3-5 3-5 3-5

Fenta 8.5 Sufen 20 Alfen 90

2.5-3.0 2-3 0.4-1.0 1-2

Distribution
Alfentanil: rapid onset & shorter duration (small Vd) Remifentanil (ester compd): shortest duration

Pharmacokinetics: biotransformation
Primarily in the liver High hepatic extraction ratio Morphine: M6G (active), M3G Pethidine: norpethidine seizure Remifentanil: ester hydrolysis rapid wake up time Context sensitive half time

Pharmacokinetics: excretion
Mainly kidney <10% biliary 5-10% morphine excreted unchanged: ARF/CRF narcosis Pethidine seizure Fentanyl secondary peak level Sufentanil urine and bile

Pharmacodynamics: CVS
Vagus mediated bradycardia except peth. No myocardial depression except peth. Hypotension

Pharmacodynamics: RS
resp rate PaCO2 & apnoeic threshold hypoxic drive Bronchospasm: peth, morph (histamine release) Chest wall rigidity

Pharmacodynamics: CNS
CMRO2, CBF, ICP in general Nausea vomiting (stimulation of CTZ) Physical dependence Amnesia- unreliable

Pharmacodynamics: GI & endocrine

Slow gastric emptying Biliary colic Block release of stress hormone (useful in IHD)

Drug interaction

MAO inhibitors ( pethidine) Synergistic respiratory depression with barbiturates, benzodiazepines etc

USES
Premedication Intraoperative anaesthesia analgesia Post operative analgesia Post-anaesthesia shivering (Peth) Chronic pain

Morphine: doses in anaesthesia

Premedication: 0.05-0.2mg/kg im Intraop anaesthesia: 0.1-1.0mg/kg iv Postop analgesia: (0.05-0.2mg/kg) im, (0.03-0.15mg/kg) iv

Pethidine: doses in anaesthesia

Premedication: 0.5-1.0mg/kg im Intraop anaesthesia: 2.5-5.0mg/kg iv Postop analgesia: (0.5-1.0mg/kg) im, (0.2-0.5mg/kg) iv

Other drugs: doses in anaesthesia

Fentanyl
Intraop anaesthesia: 2-150mcg/kg iv Postop analgesia: 0.05-1.5mcg/kg iv

Sufentanil: Intraop anaesthesia: 0.2530mcg/kg iv Alfentanil: intraop anaesthesia:

loading (8-100mcg/kg) iv infusion (0.5-3.0mcg/kg) iv

Special technique: PCA

Bolus dose Lock out interval Background infusion rate 30-50% of total 24hr dose can be given as background infusion

General guidelines for PCA

Opioid Morphine Pethidine Fentanyl Sufentanil Bolus dose 1-3mg 10-15mg 15-20mcg 2.5-5mcg Lockout time (min) 10-20 5-15 10-20 10-20 Infusion rate 0-1mg/hr 0-20mg/hr 0-50mcg/hr 0-10mcg/hr

PCA: problems

Incorrect programming Siphoning Mechanical malfunctioning

Eidural/ intrathecal oipids

Devoid of sensory and motor block Often combined with LA

Epidural opioids
Opioid Morph. Dose (mg) 2-5 Onset Peak (min) (min) 15-30 60-90 Duration Infusion (hrs) rate 4-24 0.3-0.9 mg/hr

Fenta.

0.05-0.1 5-10

10-20

1-3

25-50 mcg/hr

Butorph 1-2

2-3

Epidura/intrathecal morphine: side effects

Respiratory depression (early and late) Itching Urinary retention Nausea vomiting

Summary and conclusion

Opioids are indispensable drugs in anaesthesia practice Opioid provide high quality analgesia in overall Several routes available for administration Caution needed in renal failure patients Respiratory depression, nausea vomiting and dependence are most fearing side effects PCA/spinal opioids provide high quality analgesia and satisfaction

Thank you