PHARMACOLOGY OF ALFENTANIL

AND REMIFENTANIL

SPEAKER:DR SHRIRANGMODERATOR:DR CHANDRAPPA

1)Naturally Occurring: Morphine,Codeine,Papaverine,Thebaine2)Semisynthetic    Heroin Dihydromorphone/morphinone Thebaine derivatives (e.g.,etorphine,buprenorphine)3)Synthetic A)Morphinan series (e.g., levorphanol,butorphanol)

B)Diphenylpropylamineseries(e.g.,methadone) C)Benzomorphan series(e.g.pentazocine) D)Phenylpiperidine series (e.g., meperidine, fentanyl, sufentanil, alfentanil, remifentanil)

Classification of Opioids

Alfentanil is synthetic opioid Phenylpiperidine series-Tetrazole derivative of fentanyl Introduced in 1980. Less potent(1/5th to 1/10th ) and Has 1/3rd the duration of action of fentanyl. It is Agonist at µ-receptor.

ALFENTANIL

µ-receptors actions: ANALGESIA: RESPIRATORY-Respiratory depression. GASTROINTESTINAL ↓ Gastric secretion ↓GI transit supraspinal and peripheral antidiarrheal ENDOCRINE: Skeletal muscle rigidity,prolactin release. OTHER: Pruritus

Urinary retention (and/or δ)Biliary spasm (probably >1 receptor type)

Cardiovascular effects(µ2)

ALFENTANIL

PHARMACODYNAMICS Central nervous system: Generalized slowing of the EEG. Intense muscle rigidity accompanied by loss of

consciousness. No significant changes in ICP. Increases CSF pressure in patient with brain

tumour(Jung R et al;Anaesth Analog 1990).

ALFENTANIL

RESPIRATORY SYSTEM Decreases respiratory rate,Tidal volume and increases

airway resistance Ventilatory response to CO2 is decreased by 50% of

the baseline value. Higher doses may produce apnea and a longer duration

of respiratory depression.

CARDIOVASCULAR SYSTEM: Blunt cardiovascular and catecholamine responses to

laryngoscopy and intubation. MAP,SVR and Pulmonary capillary wedge pressure are

unaffected. Bradycardia and hypotension occurs when combined

with propofol(1mg/kg).

ALFENTANIL

GASTROINTESTINAL SYSTEM Nausea and vomting. Decreases GI motility and secretions. Increases common bile duct pressure-spasm of

Sphincter of Oddi.

PHARMACOKINETICS Less lipid soluble, weaker base than other opioid pKa

6.8(others>7.4) results in 90% unbound plasma alfenatanil being non ionized at 7.4.

Distribution:85-92% protein bound,volume of distribution(0.4-1 L/kg)smaller than fentanyl(3-8L/kg).

ALFENTANIL

Distribution half life:1 to 3.5 minutes. Elimination half life:84 to 90 minutes. Context-sensitive half life(time necessary for the

plasma concentration to decrease 50% after discontinuation of the infusion):after 4 hours of infusion is 60 mins.

ALFENTANIL

DOSAGE AND USES: Premedication: Dose: 250-500mcg.

Induction with hypnotic: Dose:25-50mcg/kg IV

ALFENTANIL

Maintenance of anaesthesia: Intermittent bolus dose:- 5-10mcg/kg. Infusion:- 0.5-2mcg/kg/min.Total dose: Dependent on duration of procedure

ALFENTANIL

MONITORED ANESTHESIA CARE (MAC) (For sedated and responsive,spontaneously breathing

patients). Induction of MAC: 3-8 mcg/kg Maintenance of MAC: 0.25 to 1 mcg/kg/min Total dose: 3-40 mcg/kg.

ALFENTANIL

Anilidopiperidine derivative. Introduced in 1991. Analgesic potency similar to fentanyl. (20-30 times more potent than alfentanil) Ultra short acting

REMIFENTANIL

PHARMACODYNAMICS CNS: Concentration dependent slowing of EEG. Muscle rigidity-bolus doses. No effect on ICP. Preserves cerebral autoregulation. Less suppression of MEP compared to other opioids. Dose dependent decrease in CPP. No seizure activity.

REMIFENTANIL

CARDIOVASCULAR SYSTEM: Dose dependent decrease in MAP. Dose dependent hypotension and bradycardia

RESPIRATORY SYSTEM: Dose dependent respiratory depression. Ventilatory response to CO2 is decreases by 50% of the

baseline value. Recovery from remifentanil-induced respiratory

depression is rapid-minute ventilation returns to baseline by 5-10 mins after the infusion s stopped.

GASTROINTESTINAL SYSTEM: Nausea(44%) and vomiting(21%). Delays gastric emptying and biliary

drainage

PHARMACOKINETICS: Smaller volume of distribution Vd-100ml/kg. Rapid clearance-40ml/min/kg. Metabolised by non specific plasma and tissue

esterases to inactive metabolites. Clearance is not affected by Cholinesterase deficiency

or anticholinergics.

REMIFENTANIL

Distribution half life:1 minute Elimination half life:3-10 minutes. Context-sensitive half life:4 minutes-independent of

the duration of infusion.

DOSAGE AND USES:1)Induction: Dose:0.5-1mcg/kg IV over 60 to 90 seconds.2)Maintenance of anaesthesia: -N2O(66%)+Isoflurane(0.4-1.5MAC) Dose:0.05-0.2mcg/kg/min. -Propofol(100-200mcg/kg/min) Dose:- 0.05-0.2mcg/kg/min

REMIFENTANIL

3)Maintenance of anaesthesia in pediatric patients: -Birth to 2mnths of age N2o(70%):- 0.4-1mcg/kg/min. -1 to 12 yrs of age halothane/sevoflurane/isoflurane dose:-0.05-1.3mcg/kg/min.

4) Monitored Anesthesia Care: -Single dose: 0.5-1mcg/kg over 30 to 60 seconds,give

90 seconds before the local anaesthetics. -Conti.infusion:Begining 5mins before local

anaesthetics 0.1mcg/kg/min. after local anaesthetics 0.05mcg/kg/min.

REFERENCES: 1)Clinical Anesthesia 6th edn,Paul G.Barash.2)Pharmacology and Physiology in Anesthetic Practice

4th edn,Robert K. Stoelting.3)Miller’s Anesthesia 7th edn.4)Internet references.

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