Acute Intermittent Porphyria

Author: Thomas G DeLoughery, MD; Chief Editor: Emmanuel C Besa, MD more...

Updated: Jan 10, 2012

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Background
Pathophysiology
Epidemiology
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Background

Acute intermittent porphyria (AIP) is one of the porphyrias, a group of diseases involving defects in heme metabolism and that results in excessive secretion of porphyrins and porphyrin precursors. AIP manifests itself by abdomen pain, neuropathies, and constipation, but, unlike most types of porphyria, patients with AIP do not have a rash.

Pathophysiology

AIP is an autosomal dominant disease that results from defects in the enzyme porphobilinogen-deaminase. This enzyme speeds the conversion of porphobilinogen to hydroxymethylbilane. In AIP, the porphyrin precursors, porphobilinogen and amino-levulinic acid (ALA), accumulate. The predominant problem appears to be neurologic damage that leads to peripheral and autonomic neuropathies and psychiatric manifestations.^[1]

Although patients with acute attacks always have elevations of porphobilinogen and ALA, how this leads to the symptomatic disease is still unclear because most patients with the genetic defect have excessive porphyrin secretion but no symptoms.

Frequency

United States

Estimates vary from 1-5 cases per 100,000 population.

International

Prevalence can be as high as 60-100 cases per 100,000 population in northern Sweden.

Sex

In most series, AIP affects women more than men, with a ratio of 1.5-2:1.

Age

Most patients become symptomatic at age 18-40 years. Attacks occurring before puberty or after age 40 years are unusual unless a major provocation, such as new use of phenobarbital or estrogens, had occurred.

Proceed to Clinical Presentation

Contributor Information and Disclosures

Author

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, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Clarence Sarkodee-Adoo, MD Consulting Staff, Department of Bone Marrow Transplantation, City of Hope Samaritan BMT Program

Disclosure: Takeda Millenium Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, and Southwest Oncology Group

Disclosure: No financial interests None None

Rajalaxmi McKenna, MD, FACP Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

References

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Table 1. Drugs Thought Safe in Porphyria*

Acetazolamide acetylcholine Actinomycin D Acyclovir Adenosine monophosphate Adrenaline Alclofenac Allopurinol Alpha tocopheryl Acetate Amethocaine Amiloride Aminocaproic acid Aminoglycosides Amoxicillin Amphotericin Ampicillin Ascorbic acid Aspirin Atenolol Atropine Azathioprine Beclomethasone Benzhexol HCl Beta-carotene Biguanides [Bromazepam] Bromides Buflomedil HCl Bumetanide Bupivacaine Buprenorphine Buserelin Butacaine SO₄ Canthaxanthin Carbimazole [Carpipramine HCl] Chloral hydrate [Chlormethiazole] [Chloroquine] [Chlorothiazide] Chlorpheniramine Chlorpromazine Ciprofloxacin Cisapride Cisplatin Clavulanic acid Clofibrate Clomiphene Cloxacillin Co-codamol Codeine phosphate Colchicine [Corticosteroids] Corticotrophin (adrenocorticotropic hormone [ACTH])	Coumarins Cyclizine Cyclopenthiazide Cyclopropane [Cyproterone acetate] Danthron Desferrioxamine Dexamethasone [Dextromoramide] Dextrose Diamorphine Diazoxide Dicyclomine HCl Diflunisal Digoxin Dihydrocodeine Dimercaprol Dimethicone Dinoprost Diphenoxylate HCl Dipyridamole [Disopyramide] Domperidone Doxorubicin HCl Droperidol [Estazolam] Ethacrynic acid Ethambutol [Ethinyl oestradiol] Ethoheptazine citrate Etoposide Famotidine Fenbufen [Fenofibrate] Fenoprofen Fentanyl Flucytosine Flumazenil Fluoxetine HCl Flurbiprofen Fluvoxamine Maleate Folic acid Fructose Fusidic acid Follicle-stimulating hormone Gentamicin Glafenine Glucagon Glucose Glyceryl trinitrate Goserelin Guanethidine Guanfacine HCl Haem arginate [Haloperidol] Heparin Heptaminol HCl Hexamine [Hydrocortisone] Ibuprofen Indomethacin Insulin Iron Josamycin [Ketamine]	Ketoprofen Ketotifen Labetalol Luteinizing hormone–releasing hormone Liquorice Lithium Salts lofepramine Loperamide [Lorazepam] Magnesium-sulphate [Mebendazole] Mecamylamine Meclofenoxate HCl Meclozine Mefloquine HCl [Melphalan] Meptazinol Mequitazine Metformin Methadone [Methotrimeprazine] Methylphenidate Methyluracil Metipropranolol Metopimazine Metoprolol [Metronidazole] [Midazolam] Minaprine HCl Minaxolone Morphine Nadolol Naftidrofuryl Oxalate [Naproxen sodium] Natamycin Nefopam HCl Neostigmine Netilmicin Niflumic acid Nitrous oxide Norfloxacin Ofloxacin Oxolinic acid Oxybuprocaine [Oxyphenbutazone] Oxytocin [Pancuronium bromide] Paracetamol Paraldehyde Parapenzolate Br Penicillamine Penicillin Pentolinium Pericyazine Pethidine Phenformin Phenoperidine Phentolamine mesylate Pipotiazine	Palmitate Piracetam Pirbuterol Pirenzepine Pizotifen [Prazosin] [Prednisolone] Primaquine Probucol Procainamide HCl Procaine Prochlorperazine Proguanil HCl Promazine Propantheline Br Propofol Propranolol Propylthiouracil [Proxymetacaine] Pseudoephedrine HCl Pyridoxine [Pyrimethamine] Quinidine Quinine [Ranitidine] Reserpine Resorcinol Salbutamol Senna Sodium bromide Sodium ethylenediaminetetraacetic acid Sodium fusidate Sorbitol Streptomycin Sulbutiamine Sulindac Sulfadoxine Suxamethonium Talampicillin Temazepam Tetracaine [Tetracyclines] Thiouracils Thyroxine Tiaprofenic acid Ticarcillin Tienilic acid Timolol maleate Tolazoline Tranexamic acid Triacetyloleandomycin Triamterene Triazolam [Trichlormethiazide] Trifluoperazine Trimeprazine Tartrate Trimetazidine HCl Tripelennamine Tubocurarine Vancomycin [Vincristine] Vitamins Warfarin sodium Zidovudine Zinc Preparations
*Bracketed [] drugs are those in which experimental evidence of porphyrin genicity is conflicting.

Table 2. Drugs Thought Unsafe in Porphyria^†

Alcuronium Alphaxalone Alphadolone Alprazolam Aluminium Preparations Amidopyrine Aminoglutethimide Aminophylline Amiodarone Amitriptyline [Amphetamines] Amylobarbitone Antipyrine Auranofin Aurothiomalate Azapropazone Baclofen Barbiturates Bemegride Bendrofluazide Benoxaprofen Benzbromarone [Benzylthiouracil] [Bepridil] Bromocriptine Busulphan Butylscopolamine Captopril Carbamazepine Carbromal Carisoprodol [Cefuroxime] [Cephalexin] [Cephalosporins] [Cephradine] [Chlorambucil] Chloramphenicol Chlordiazepoxide Chlormezanone Chloroform Chlorpropamide Cinnarizine Clemastine [Clobazam] [Clomipramine HCl] [Clonazepam] Clonidine HCl Clorazepate Cocaine [Colistin] Co-trimoxazole	Cyclophosphamide Cycloserine Cyclosporin Danazol Dapsone Dexfenfluramine Dextropropoxyphene Diazepam Dichloralphenazone Diclofenac Na Dienoestrol Diethylpropion Dihydralazine Dihydroergotamine Diltiazem Dimenhydrinate Diphenhydramine [Dothiepin HCl] Doxycycline Dydrogesterone Econazole NO₃ Enalapril Enflurane Ergot compounds Ergometrine maleate Ergotamine tartrate Erythromycin Estramustine Ethamsylate Ethanol Ethionamide Ethosuximide Ethotoin Etidocaine Etomidate Fenfluramine Flucloxacillin Flufenamic acid Flunitrazepam Flupenthixol Flurazepam Frusemide Glibenclamide Glutethimide Glipizide Gramicidin Griseofulvin [Haloperidol] Halothane Hydantoins Hydralazine Hydrochlorothiazide Hydroxyzine Hyoscine Imipramine Iproniazid Isometheptene mucate [Isoniazid] Kebuzone Ketoconazole Levonorgestrel Lignocaine Lisinopril Loprazolam Loxapine *Lynestrenol Lysuride	Maleate Maprotiline HCl Mebeverine HCl Mecillinam Medroxyprogesterone [Mefenamic acid] Megestrol acetate Mephenytoin Mepivacaine Meprobamate Mercaptopurine Mercury compounds Mestranol [Metapramine HCl] Methamphetamine Methohexitone Methotrexate Methoxyflurane Methsuximide Methyldopa Methylsulphonal Methyprylone Methysergide Metoclopramide Metyrapone Mianserin HCl Miconazole [Mifepristone] Minoxidil Nandrolone Nalidixic acid Natamycin Nandrolone [Nicergoline] Nifedipine Nikethamide Nitrazepam Nitrofurantoin Nordazepam Norethynodrel Norethisterone [Nortriptyline] Novobiocin Oral contraceptives Orphenadrine Oxanamide [Oxazepam] Oxybutynin HCl Oxycodone Oxymetazoline Oxyphenbutazone Oxytetracycline Paramethadione Pargyline Pentazocine Perhexiline Phenacetin Phenelzine Phenobarbitone Phenoxybenzamine Phensuximide Phenylbutazone Phenylhydrazine Phenytoin Pipebuzone Pipemidic Acid Piritramide *Piroxicam	Pivampicillin Pivmecillinam Prazepam Prenylamine Prilocaine Primidone [Probenecid] Progesterone Progabide Promethazine [Propanidid] Pyrazinamide Pyrrocaine Quinalbarbitone Rifampicin Simvastatin Sodium aurothiomalate Sodium oxybate [Sodium valproate] Spironolactone Stanozolol Succinimides Sulfacetamide Sulfadiazine Sulfadimidine Sulfadoxine Sulfamethoxazole Sulfasalazine Sulfonylureas Sulfinpyrazone Sulpiride Sulthiame Sultopride Tamoxifen Terfenadine Tetrazepam Theophylline Thiopentone Na Thioridazine Tilidate Tinidazole Tolazamide Tolbutamide Tranylcypromine Trazodone HCl Trimethoprim [Trimipramine] Troxidone Valproate Valpromide Veralipride Verapamil Vibramycin Viloxazine HCl [Vinblastine] [Vincristine] Zuclopenthixol
*These drugs have been associated with acute attacks of porphyria. †Bracketed [] drugs are those in which experimental evidence of porphyringenicity is conflicting.

View Table List

Read more about Acute Intermittent Porphyria on Medscape

Alcuronium Alphaxalone Alphadolone Alprazolam Aluminium Preparations Amidopyrine Aminoglutethimide Aminophylline Amiodarone Amitriptyline [Amphetamines] Amylobarbitone Antipyrine Auranofin Aurothiomalate Azapropazone Baclofen Barbiturates Bemegride Bendrofluazide Benoxaprofen Benzbromarone [Benzylthiouracil] [Bepridil] Bromocriptine Busulphan Butylscopolamine Captopril Carbamazepine Carbromal Carisoprodol [Cefuroxime] [Cephalexin] [Cephalosporins] [Cephradine] [Chlorambucil] Chloramphenicol Chlordiazepoxide Chlormezanone Chloroform Chlorpropamide Cinnarizine Clemastine [Clobazam] [Clomipramine HCl] [Clonazepam] Clonidine HCl Clorazepate Cocaine [Colistin] Co-trimoxazole	Cyclophosphamide Cycloserine Cyclosporin Danazol Dapsone Dexfenfluramine Dextropropoxyphene Diazepam Dichloralphenazone Diclofenac Na Dienoestrol Diethylpropion Dihydralazine Dihydroergotamine Diltiazem Dimenhydrinate Diphenhydramine [Dothiepin HCl] Doxycycline Dydrogesterone Econazole NO₃ Enalapril Enflurane Ergot compounds Ergometrine maleate Ergotamine tartrate Erythromycin Estramustine Ethamsylate Ethanol Ethionamide Ethosuximide Ethotoin Etidocaine Etomidate Fenfluramine Flucloxacillin Flufenamic acid Flunitrazepam Flupenthixol Flurazepam Frusemide Glibenclamide Glutethimide Glipizide Gramicidin Griseofulvin [Haloperidol] Halothane Hydantoins Hydralazine Hydrochlorothiazide Hydroxyzine Hyoscine Imipramine Iproniazid Isometheptene mucate [Isoniazid] Kebuzone Ketoconazole Levonorgestrel Lignocaine Lisinopril Loprazolam Loxapine *Lynestrenol Lysuride	Maleate Maprotiline HCl Mebeverine HCl Mecillinam Medroxyprogesterone [Mefenamic acid] Megestrol acetate Mephenytoin Mepivacaine Meprobamate Mercaptopurine Mercury compounds Mestranol [Metapramine HCl] Methamphetamine Methohexitone Methotrexate Methoxyflurane Methsuximide Methyldopa Methylsulphonal Methyprylone Methysergide Metoclopramide Metyrapone Mianserin HCl Miconazole [Mifepristone] Minoxidil Nandrolone Nalidixic acid Natamycin Nandrolone [Nicergoline] Nifedipine Nikethamide Nitrazepam Nitrofurantoin Nordazepam Norethynodrel Norethisterone [Nortriptyline] Novobiocin Oral contraceptives Orphenadrine Oxanamide [Oxazepam] Oxybutynin HCl Oxycodone Oxymetazoline Oxyphenbutazone Oxytetracycline Paramethadione Pargyline Pentazocine Perhexiline Phenacetin Phenelzine Phenobarbitone Phenoxybenzamine Phensuximide Phenylbutazone Phenylhydrazine Phenytoin Pipebuzone Pipemidic Acid Piritramide *Piroxicam	Pivampicillin Pivmecillinam Prazepam Prenylamine Prilocaine Primidone [Probenecid] Progesterone Progabide Promethazine [Propanidid] Pyrazinamide Pyrrocaine Quinalbarbitone Rifampicin Simvastatin Sodium aurothiomalate Sodium oxybate [Sodium valproate] Spironolactone Stanozolol Succinimides Sulfacetamide Sulfadiazine Sulfadimidine Sulfadoxine Sulfamethoxazole Sulfasalazine Sulfonylureas Sulfinpyrazone Sulpiride Sulthiame Sultopride Tamoxifen Terfenadine Tetrazepam Theophylline Thiopentone Na Thioridazine Tilidate Tinidazole Tolazamide Tolbutamide Tranylcypromine Trazodone HCl Trimethoprim [Trimipramine] Troxidone Valproate Valpromide Veralipride Verapamil Vibramycin Viloxazine HCl [Vinblastine] [Vincristine] Zuclopenthixol
*These drugs have been associated with acute attacks of porphyria. †Bracketed [] drugs are those in which experimental evidence of porphyringenicity is conflicting.