TY - CHAP M1 - Book, Section TI - Chapter 33. Porphyria A1 - Tinklepaugh, Mark S. A2 - Atchabahian, Arthur A2 - Gupta, Ruchir PY - 2013 T2 - The Anesthesia Guide AB - Pathophysiology:Autosomal dominant defect in heme synthesis; 90% of gene carriers are asymptomatic; 80% of symptomatic patients are women from puberty to menopauseHeme is a porphyrin critical in the formation of hemoglobin and cytochrome P450 complex (drug metabolism)Aminolevulinic acid (ALA) synthase is the enzyme involved in the rate-limiting step of heme formation: Glycine + succinyl CoA → ALAALA synthase is induced by feedback inhibition when heme requirements increasePartial enzyme defect in heme pathway leads to buildup of ALA and other intermediaries leading to neurotoxicity, especially when need for heme (catabolism increased by menstrual hormones) or need for cytochrome P450 enzymes by inducing drugsClassified as:Erythropoietic porphyrias:Günther disease and protoporphyriaPatients are children; no acute crisesHepatic porphyrias:Cutaneous porphyriaAcute porphyrias with related symptomatology (most often problematic with anesthesia): Acute intermittent porphyria (AIP), most common formVariegate porphyria (VP), protoporphyrinogen oxidase deficiencyHereditary coproporphyria (HC), coproporphyrinogen oxidase deficiencyPlumboporphyria (PP), ALA dehydrase deficiencyPrecipitating factors:Clinical conditions:Dehydration, fasting, infection, emotional stress, hormonal changes (menstruation/pregnancy), alcoholEnzyme-inducing drugs:Barbiturates, etomidate (Amidate®), ethanol, hydantoin anticonvulsants, phenytoin (Dilantin®), hormonal steroids (progesterone, estrogen)Lab diagnosis:Urgently: urinary porphyrin precursors (delta-ALA and porphobilinogen)Porphyrins in urine and stool (uroporphyrin, coproporphyrin, protoporphyrin)Specialized lab: enzyme activities, gene mutationChem 7: Hyponatremia due to SIADH, more common if neuro involvementTreatment of crisis:Analgesia (morphine), anxiolysis (benzodiazepine, phenothiazine)D10% at 125 mL/hHeme arginate 3–4 mg/kg per day IVSS over 30–40 minutes × 4 days; very effective on digestive symptoms; will prevent neurological symptoms, but not effective if already present. Possible thrombophlebitisOther symptomatic treatment as needed (e.g., beta-blockers for tachycardia) SN - PB - The McGraw-Hill Companies CY - New York, NY Y2 - 2024/03/29 UR - accessanesthesiology.mhmedical.com/content.aspx?aid=57260727 ER -