Variegate Porphyria Medication
- Author: Maureen B Poh-Fitzpatrick, MD; Chief Editor: Dirk M Elston, MD more...
Medication Summary
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Heme analogues
Class Summary
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.
Hemin (Panhematin)
Enzyme inhibitor derived from processed red blood cells that is an iron-containing metalloporphyrin. Previously known as hematin, a term used to describe the chemical reaction product of hemin and sodium carbonate solution. Has anticoagulant effect and may cause thrombophlebitis at infusion site. Must be reconstituted from lyophilized powder. Reconstitute with human serum albumin 25% (132 mL of 25% human serum albumin to 1 vial of hemin [301 mg heme]) and infuse into large vein to reduce risk of thrombophlebitis.
Heme arginate (Normosang)
Not currently available in the United States. Fewer adverse effects than hemin.
Luteinizing hormone-releasing hormone analogues
Class Summary
These agents decrease endogenous estrogen and progesterone production. The infrequency of menses-related attacks in variegate porphyria would make this therapy infrequently considered.
Leuprolide (Lupron)
Suppresses ovarian and testicular steroidogenesis by decreasing LH and FSH levels.
Beta-adrenergic blocking agents
Class Summary
These agents reduce sympathetic hyperactivity.
Propranolol (Inderal)
Has membrane-stabilizing activity and decreases automaticity of contractions. Not suitable for emergency treatment of hypertension. Do not give IV in hypertensive emergencies.
Opiate analgesics
Class Summary
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 (Duramorph, Astramorph, MS Contin)
DOC for analgesia owing to reliable and predictable effects, safety profile, and ease of reversibility with naloxone. Various IV doses are used; commonly titrated until desired effect obtained.
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.
Antiemetics/sedatives
Class Summary
These drugs reduce nausea and vomiting, control anxiety and agitation, and potentiate analgesia.
Chlorpromazine (Thorazine)
Mechanisms responsible for relieving nausea and vomiting include blocking postsynaptic mesolimbic dopamine receptors, anticholinergic effects, and depression of RAS. Blocks alpha-adrenergic receptors and depresses release of hypophyseal and hypothalamic hormones. Slow IV infusion (patient lying flat) when symptoms persist; 25-50 mg with 500-1000 mL of NS; monitor blood pressure.
Anticonvulsants
Class Summary
These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.
Magnesium sulfate
Corrects hypomagnesemia and helps control seizures. Nutritional supplement in hyperalimentation; cofactor in enzyme systems involved in neurochemical transmission and muscular excitability.
Gabapentin (Neurontin)
Structurally related to GABA but does not interact with GABA receptors; not converted metabolically into GABA or a GABA agonist; not an inhibitor of GABA uptake or degradation. Does not exhibit affinity for other common receptor sites.
Diazepam (Valium)
For acute seizure control by intravenous infusion. Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA. Individualize dose and increase cautiously to avoid adverse effects.
Clonazepam (Klonopin)
Long-acting benzodiazepine that increases presynaptic GABA inhibition and reduces monosynaptic and polysynaptic reflexes. Suppresses muscle contractions by facilitating inhibitory GABA neurotransmission and other inhibitory transmitters. Has multiple indications, including suppression of myoclonic, akinetic, or petit mal seizure activity and focal or generalized dystonias (eg, tardive dystonia). Reaches peak plasma concentration at 2-4 h after oral or rectal administration. Not often used IV in United States.
Oral photoprotectants
Class Summary
These agents may reduce cutaneous photosensitivity.
Beta-carotene (Lumitene)
Effectiveness is uncertain in variegate porphyria, but a clinical trial may be warranted in view of its low-risk profile. Exact mechanism of action not completely elucidated. Patient must become carotenemic before effects are observed. More than an internal light screen may be responsible for effects. May provide a limited level of photoprotection. Causes yellowing of skin (carotenoderma). Any photoprotection afforded increases slowly after drug is commenced over a 4- to 6-wk period. When discontinued, skin color and benefit fade over several weeks.
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