Variegate Porphyria Medication
- Author: Maureen B Poh-Fitzpatrick, MD; Chief Editor: Dirk M Elston, MD more...
The goals of pharmacotherapy are to reduce morbidity and to prevent complications. Acute attack episodes often require use of many medications in intensive care settings, too numerous to list exhaustively here. Consultation with experts in the management of acute porphyrias is strongly recommended to obtain up-to-date guidance, especially in crisis situations. Judicious selection of agents, dosages, and routes of administration should take into account not only avoiding drugs known or suspected to be unsafe in acute porphyrias, but also best practices and continuously evolving guidelines for optimal use of agents generally considered safe.
Infusion of hemelike agents rapidly restores the free-heme pool in hepatocytes, thereby exerting negative feedback repression on the rate-limiting enzyme of heme synthesis. Prompt use may prevent an attack from causing neuronal degeneration.
This agent is an enzyme inhibitor derived from processed red blood cells that is an iron-containing metalloporphyrin. It was previously known as hematin, a term used to describe the chemical reaction product of hemin and sodium carbonate solution. It has an anticoagulant effect and may cause thrombophlebitis at the infusion site. It must be reconstituted from lyophilized powder. Reconstitute it with human serum albumin 25% (132 mL of 25% human serum albumin to 1 vial of hemin [301 mg heme]) and infuse it into large vein to reduce the risk of thrombophlebitis.
Heme arginate (Normosang)
Heme arginate is not currently available in the United States. It has fewer adverse effects than hemin.
Luteinizing hormone-releasing hormone analogues
These agents decrease endogenous estrogen and progesterone production. The infrequency of menses-related attacks in variegate porphyria would make this therapy infrequently considered.
Leuprolide suppresses ovarian and testicular steroidogenesis by decreasing luteinizing hormone and follicle-stimulating hormone levels.
Beta-adrenergic blocking agents
These agents reduce sympathetic hyperactivity.
Propranolol has membrane-stabilizing activity and decreases the automaticity of contractions. It is not suitable for emergency treatment of hypertension. Do not give intravenously in hypertensive emergencies.
These agents provide relief of severe abdominal and/or other pain. Very large doses may be required over the course of a day.
Morphine sulfate is the drug of choice for analgesia, owing to its reliable and predictable effects, safety profile, and ease of reversibility with naloxone. Various intravenous doses are used; it is commonly titrated until the desired effect is obtained.
These drugs reduce nausea and vomiting, control anxiety and agitation, and potentiate analgesia.
Chlorpromazine’s mechanisms responsible for relieving nausea and vomiting include blocking postsynaptic mesolimbic dopamine receptors, anticholinergic effects, and depression of RAS. It blocks alpha-adrenergic receptors and depresses the release of hypophyseal and hypothalamic hormones. Use a slow intravenous infusion (patient lying flat) when symptoms persist (25-50 mg with 500-1000 mL of normal saline); monitor blood pressure.
Ondansetron is one of a class of agents termed serotonin 5-HT3 receptor antagonists. It blocks the action of serotonin, a neurotransmitter manufactured in the brain that may cause nausea and vomiting.
These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.
Gabapentin is structurally related to GABA but does not interact with GABA receptors; it is not converted metabolically into GABA or a GABA agonist and is not an inhibitor of GABA uptake or degradation. Gabapentin does not exhibit an affinity for other common receptor sites.
Diazepam is for acute seizure control by intravenous infusion. It depresses all levels of the CNS (eg, limbic and reticular formation), possibly by increasing the activity of GABA. Individualize the dose and increase cautiously to avoid adverse effects.
Clonazepam is a long-acting benzodiazepine that increases presynaptic GABA inhibition and reduces monosynaptic and polysynaptic reflexes. It suppresses muscle contractions by facilitating inhibitory GABA neurotransmission and other inhibitory transmitters. It has multiple indications, including suppression of myoclonic, akinetic, or petit mal seizure activity and focal or generalized dystonias (eg, tardive dystonia). It reaches peak plasma concentrations 2-4 hours after oral or rectal administration. It is not often used intravenously in the United States.
Levetiracetam is most often used in combination with other medications to treat partial (focal), myoclonic, and tonic-clonic seizures in people with epilepsy.
Magnesium sulphate corrects hypomagnesemia and helps control seizures. It is a nutritional supplement in hyperalimentation; it is a cofactor in enzyme systems involved in neurochemical transmission and muscular excitability.
These agents may reduce cutaneous photosensitivity.
The effectiveness of beta carotene is uncertain in variegate porphyria, but a trial may be warranted in view of its low-risk profile. The mechanism of action is not completely elucidated. The patient must become carotenemic before effects are observed. This agent may provide a limited level of photoprotection. It causes yellowing of the skin (carotenoderma). Any photoprotection afforded increases slowly after the drug is commenced over a 4- to 6-week period. When it is discontinued, skin color and benefit fade over several weeks.
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