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Acute Porphyria Medication

  • Author: Richard E Frye, MD, PhD; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
 
Updated: Apr 07, 2016
 

Medication Summary

Conservative therapy includes IV fluid with a substantial carbohydrate supply (eg, dextrose 500 g/d), pain control with opiates, and relief of nausea and vomiting with phenothiazines. If conservative treatment proves unsatisfactory, an IV heme infusion is indicated. Seizure control using anticonvulsants is also indicated.

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Heme analogues

Class Summary

Iron-containing metalloporphyrins reduce hepatic and marrow synthesis of porphyrin by inhibiting aminolevulinic acid (ALA) synthetase, the rate-limiting enzyme in the porphyrin biosynthetic pathway. Clinical symptoms (eg, pain, hypertension, tachycardia, mental status changes, neuropathy) may be controlled.

Heme arginate (Normosang; Leiras Medica, Finland) is not approved for use in the United States. Heme arginate may have a lower frequency of thrombophlebitis than hemin (Panhematin) and improves drug metabolism mediated by the cytochrome P-450 system.

Hemin (Panhematin)

 

Heme analogue for treatment of acute episodes. Enzyme inhibitor derived from processed RBCs and iron-containing metalloporphyrin. Was known as hematin, term used to describe chemical reaction product of hemin and sodium carbonate solution.

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Anticonvulsants

Class Summary

Seizures, which can occur as a neurologic manifestation of acute porphyria, are best treated with a drug not metabolized by the liver.

Gabapentin (Neurontin)

 

Structurally related to GABA but does not interact with GABA receptors; not metabolically converted into GABA or a GABA agonist; does not inhibit GABA uptake or degradation. Among safest anticonvulsants, no significant interactions, and not metabolized by the liver. Usually used as adjunct anticonvulsant but can be first-line medication for long-term seizure control in some circumstances.

Magnesium sulfate

 

Depresses CNS, possibly by inhibiting acetylcholine release by motor nerve impulses. Blocks peripheral neuromuscular transmission. Used for acute seizure control. Elemental magnesium 49.3 mg (4.1 mEq) = 500 mg magnesium sulfate

Diazepam (Valium, Diastat)

 

Long-acting PO, parenteral, and PR benzodiazepine, with antianxiety properties useful for acute seizure control. PR diazepam particularly useful for outpatients in whom seizures may occur.

Lorazepam (Ativan)

 

A benzodiazepine with antianxiety properties used for acute seizure control. Minimal respiratory and circulation adverse effects. Primarily eliminated by kidneys and metabolized by liver but not cytochrome pathway.

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Analgesic agents

Class Summary

Opiates are first-line agents for pain control in porphyria because the pain is usually intense and because these medications are safe to use for this condition.

Morphine (Generic, Astramorph PF, Duramorph)

 

DOC for analgesia. Can be administered IV or IM. Wide spectrum of pharmacologic effects, including analgesia, dysphoria, euphoria, somnolence, respiratory depression, diminished GI motility, and physical dependence. Continuous infusion useful for extended use and minimizes tolerance. Hepatic glucuronidation to morphine-3-glucuronide pharmacologically inactivates morphine; major excretion pathway of conjugate is through kidneys. Half-life 1.5-4.5 h.

Meperidine (Demerol)

 

Analgesic with multiple actions similar to those of morphine; may produce less constipation, smooth muscle spasm, and depression of cough reflex than similar analgesic doses of morphine. Do not exceed administration >48 h because of risk of seizures secondary to accumulation of normeperidine metabolite.

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Antipsychotics/antiemetics

Class Summary

Phenothiazines have antiemetic and antipsychotic properties, making them the medication of choice for acute porphyria episodes.

Chlorpromazine (Thorazine, Ormazine)

 

Principally psychotropic but also exerts sedative and antiemetic activity. Acts at all levels of CNS but primarily subcortical levels. Strong antiadrenergic and weak anticholinergic, antihistaminic, and antiserotonergic activity.

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Beta-adrenergic blocking agents

Class Summary

These agents reduce sympathetic hyperactivity during acute episodes.

Propranolol (Inderal)

 

Competitive beta-adrenergic antagonist that blocks chronotropic, inotropic, and vasodilator responses to beta-adrenergic stimulation. Reduces increased sympathetic outflow due to acute neuropathy associated with porphyria, but insufficient to treat hypertensive emergencies associated with acute porphyria episodes.

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Hormones

Class Summary

Premenstrual episodes occur in some women. Inhibiting or controlling the menstrual cycle can control these episodes.

Leuprolide (Lupron)

 

Gonadotropin-releasing hormone agonist; potent inhibitor of gonadotropin secretion when given continuously. Long-term stimulation causes downregulation of gonadotropins and suppression of ovarian and testicular steroidogenesis, essentially inducing menopause. Effects reversible on discontinuation. Use under guidance of specialist in reproductive medicine.

Lynestrenol (Orgametril)

 

Not currently available in United States. Progestogen structurally similar to norethisterone. Low-dose estrogen-progesterone oral contraceptives, standard oral contraceptive pill, and daily estrogen used successfully to control menstrual exacerbations of porphyria; however, standard contraceptive pills may provoke porphyria symptoms in about 15% of women or cause acute episodes in about 5% of women at start. Treatment should be performed with specialist in reproductive medicine.

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Contributor Information and Disclosures
Author

Richard E Frye, MD, PhD Associate Professor, Department of Pediatrics, University of Arkansas for Medical Sciences

Richard E Frye, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, International Neuropsychological Society, American Academy of Pediatrics

Disclosure: Nothing to disclose.

Coauthor(s)

Thomas G DeLoughery, MD Professor of Medicine, Pathology, and Pediatrics, Divisions of Hematology/Oncology and Laboratory Medicine, Associate Director, Department of Transfusion Medicine, Division of Clinical Pathology, Oregon Health and Science University School of Medicine

Thomas G DeLoughery, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American College of Physicians, American Society of Hematology, International Society on Thrombosis and Haemostasis, Wilderness Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Associate Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology, American Federation for Clinical Research, Council on Medical Student Education in Pediatrics, Hemophilia and Thrombosis Research Society, American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA Executive Vice President, Chief Medical and Academic Officer, Renown Heath

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American College of Healthcare Executives, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Sharada A Sarnaik, MBBS Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Associate Hematologist/Oncologist, Children's Hospital of Michigan

Sharada A Sarnaik, MBBS is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, Society for Pediatric Research, Children's Oncology Group, American Academy of Pediatrics, Midwest Society for Pediatric Research

Disclosure: Nothing to disclose.

References
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Heme production pathway. Heme production begins in the mitochondria, proceeds into the cytoplasm, and resumes in the mitochondria for the final steps. Figure outlines the enzymes and intermediates involved in the porphyrias. Names of enzymes are presented in the boxes; names of the intermediates, outside the boxes. Multiple arrows leading to a box demonstrate that multiple intermediates are required as substrates for the enzyme to produce 1 product.
Table 1. Known Chromosomal Location of Enzymes Involved in Porphyria and Inheritance Patterns
Type of Porphyria Deficient Enzyme Location Inheritance Pattern Band  
ALAD deficiency ALAD Cytosol Autosomal recessive 9q34  
AIP PBG deaminase Cytosol Autosomal dominant 11q23  
HCP Coproporphyrinogen oxidase Mitochondrial Autosomal dominant 3q12  
VP Protoporphyrinogen oxidase Mitochondrial Autosomal dominant 1q22-23  
Table 2. Frequencies of Porphyria
Type of Porphyria Age of Onset Incidence Male-to-Female Ratio
ALAD deficiency Mostly adolescence to young adulthood, but variable (2-63 y) 6 cases total 6:0
AIP After puberty (third decade) General 0.01/1000



Sweden 1/1000



Finland 2/1000



France 0.3/1000



M>F
HCP Predominantly adulthood (youngest patient aged 4 y) Japan 0.015/1000



Czech 0.015/1000



Israel 0.007/1000



Denmark 0.0005/1000



1:20



1:4



2:1



1:1



VP Heterozygous mutation: after puberty (fourth decade) Homozygous mutation (rare): childhood South Africa 0.34/1000 1:1
Table 3. Quantitative Urine Porphyrin Levels
Level ALAD Deficiency Acute Intermittent Porphyria (AIP) Congenital Erythropoietic Porphyria (CEP) and Porphyria Cutanea Tarda (PCT) HCP and VP
ALA Significantly increased Significantly increased Normal Significantly increased
PBG Increased Significantly increased Normal Significantly increased
Uroporphyrin Normal Increased Significantly increased Increased
Coproporphyrin Significantly increased Increased Increased Significantly increased
Table 4. Quantitative Stool Porphyrin levels
Level HCP VP
Coproporphyrin Significantly increased Increased
Protoporphyrin Increased Significantly increased
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