Meperidine Fentanyl Sufentanil Alfentanil Remifentanil Metabolism Extensive Hepatic metabolism Extensively Metabolized by: Rapidly metabolized by: 2 independent Pathways: Unique among the opioids – 90% demethylated to active N-demethylation N-dealkylation Noralfentanil major rapid metabolism metabolite Normeperidine O-demethylation metabolite Inactive metabolite = Efficiently cleared by liver Not affected by Normeperidine norfentanyl Inactive and active metabolism within 60 min Pseudocholinesterase -hydrolyzed to an acid and metabolites formed Deficiency excreted in urine Excreted by kidneys Redistributes to inactive Detected in urine 72 hrs after <1% unchanged in urine tissue sites Can be used in renal and Normeperidine E ½ x = 15 hrs single dose hepatic disease *Seizure Activity* High solubility -> max renal tubular reabsorption E ½ x of Meperidine = 3-5 hrs Clearance sensitive to hepatic 60% Protein Bound blood flow Use Cautiously in Elderly and Renal Disease Side Effects Causes Histamine Release No Histamine release No Histamine release No Histamine release No Histamine release Orthostatic BP Marked Bradycardia Hypotension Hypotension Hypotension HR and Mydriasis- modest Possible seizure activity Bradycardia Bradycardia Bradycardia atropine like effect Chest wall and skeletal Opioid tolerance Myocardial contractility muscle rigidity ↓ w/large doses Skeletal muscle rigidity with Itchy nose large doses Delirium and Seizures ***Life threatening interaction = Serotonin Syndome*** Type I Rxn: Hypertension Agitation Skeletal Muscle Rigidity Headache Hyperpyrexia Type II Reaction: Hypotension Respiratory Depression Coma
Meperidine Fentanyl Sufentanil Alfentanil Remifentanil Metabolism Extensive Hepatic metabolism 90% demethylated to active metabolite Normeperidine Normeperidine -hydrolyzed to an acid and excreted in urine Normeperidine E ½ x = 15 hrs *Seizure Activity* E ½ x of Meperidine = 3-5 hrs 60% Protein Bound Use Cautiously in Elderly and Renal Disease Extensively Metabolized by: N-demethylation Inactive metabolite = norfentanyl Excreted by kidneys Detected in urine 72 hrs after single dose Rapidly metabolized by: N-dealkylation O-demethylation Inactive and active metabolites formed <1% unchanged in urine High solubility -> max renal tubular reabsorption Clearance sensitive to hepatic blood flow 2 independent Pathways: Noralfentanil major metabolite Efficiently cleared by liver metabolism within 60 min Redistributes to inactive tissue sites Unique among the opioids – rapid metabolism Not affected by Pseudocholinesterase Deficiency Can be used in renal and hepatic disease Side Effects Causes Histamine Release Orthostatic BP HR and Mydriasis- modest atropine like effect ↓ Myocardial contractility w/large doses Delirium and Seizures ***Life threatening interaction = Serotonin Syndome*** Type I Rxn: Hypertension Agitation Skeletal Muscle Rigidity Headache Hyperpyrexia Type II Reaction: Hypotension Respiratory Depression Coma No Histamine release Marked Bradycardia Possible seizure activity Chest wall and skeletal muscle rigidity Itchy nose No Histamine release Hypotension Bradycardia No Histamine release Hypotension Bradycardia No Histamine release Hypotension Bradycardia Opioid tolerance Skeletal muscle rigidity with large doses