This document discusses the opioid analgesics alfentanil and remifentanil. It describes them as synthetic phenylpiperidine derivatives that are shorter acting than fentanyl, with alfentanil being less potent than fentanyl and remifentanil having similar potency to fentanyl. Their pharmacokinetics are summarized, with alfentanil having an elimination half-life of 84-90 minutes and remifentanil having an extremely short context-sensitive half-life of 3-10 minutes. Their clinical uses, dosages, and pharmacodynamic effects such as respiratory depression are also outlined.

1. SPEAKER:DR SHRIRANG
MODERATOR:DR CHANDRAPPA

2. 1)Naturally Occurring:
 Morphine,Codeine,Papaverine,Thebaine
2)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, remi
fentanil)

3.  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.

4. 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)

6. 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).

7.  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.

8. 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).

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

10. 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).

11.  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.

12. DOSAGE AND USES:
 Premedication:
Dose: 250-500mcg.
 Induction
with hypnotic:
Dose:25-50mcg/kg IV

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

14.  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.

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

16.  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.

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

18.  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.

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

20.  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.

21.  Distribution half life:1 minute
 Elimination half life:3-10 minutes.
 Context-sensitive half life:4 minutes-independent of the
duration of infusion.

22. 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

23. 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.

24.  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.

25.  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.

26. THANK YOU