Porphyria drug effects

Hydroxychloroquine is approved for the treatment of both systemic and cutaneous lupus erythematosus. Both chloroquine and quinacrine (Atabrine) are also effective in this skin disease. Low-dose chloroquine is used for the therapy of porphyria cutanea tarda in patients in whom phlebotomy has failed or is contraindicated. Other skin diseases in which the drugs are useful (after sunscreens and avoidance of sun exposure) include polymorphous light eruption and solar urticaria. 

Hydroxychloroquine (Plaquenil), like chloroquine, is a 4-aminoquinoline derivative used for the suppressive and acute treatment of malaria. It also has been used for rheumatoid arthritis and discoid and systemic lupus erythematosus. Hydroxychloroquine has not been proved to be more effective than chloroquine. Adverse reactions associated with its use are similar to those described for chloroquine. The drug should not be used in patients with psoriasis or porphyria, since it may exacerbate these conditions. 

Barbiturates reduce hepatic blood flow and glomerular filtration rate, but these drugs produce no adverse effects on hepatic or renal function. Barbiturates can exacerbate acute intermittent porphyria by inducing the production of hepatic ct -aminolevulinic acid (ALA) synthase (see Chapter 22). On rare occasions, thiopental has precipitated porphyric crisis when used as an induction agent in susceptible patients. 

Symptomatic porphyria patients usually show urinary porphyrin concentrations that exceed the upper limit of normal by twofold or more. Table 7.3.1 lists most of the diagnostic abnormalities of the different porphyrias. Only slightly abnormal or even fully normal values may be seen in asymptomatic patients. But alcohol overconsumption, enzyme-inducing drugs, stress, and other factors may also induce slightly abnormal values that should not be mistaken for porphyria. A characteristic sign for such a secondary effect is the isolated elevation of coproporphyrin, especially of its... 

Goldstein, J.A., Friesen, M., Linder, R.E., Hickman, P, Hass, J.R. Bergman, H. (1977) Effects of pcntachlorophenol on hepatic drug-metabolizing enzymes and porphyria related to contamination with chlorinated dibenzo-/i-dioxins and dibenzo-furans. Biochem. Phamiacol., 26, 1549-1557... 

Some mild forms of intermittent porphyria may go unrecognized. However, ingestion of drugs can precipitate an acute attack, probably by inducing excessive synthesis of 8-aminolevulinate synthase. Among compounds having this effect are hexachlo-robenzene and tetrachlorodibenzodioxin. 

The effect of enflurane on heme metabolism has been tested in mice (381) the authors suggested that enflurane be added to the list of drugs that can precipitate acute attacks of porphyria. 

Precautions As noted previously, barbiturates induce the P-450 system and therefore may decrease the effect of drugs that are metabolized by these hepatic enzymes. Barbiturates increase porphyrin synthesis, and are contraindicated in patients with acute intermittent porphyria. 

A 28-year-old man with porphyria cutanea tarda took oxcarbazepine withont adverse effects, suggesting that oxcarbazepine may be nsed in patients with this disorder (16) most other antiepileptic drugs cannot. 

Short-term administration of barbiturates has no clinically significant effect on the hepatic, renal, or endocrine systems. A single induction dose of thiopental does not alter tone of the gravid uterus, but may produce mild transient depression of newborn activity. Drug-induced histamine release is occasionally seen. Barbiturates can induce fatal attacks of porphyria in patients with acute intermittent or variegate porphyria and are contraindicated in such patients. Unlike inhala-tional anesthetics and succinylcholine, barbiturates and all other parenteral anesthetics apparently do not trigger malignant hyperthermia. 

Other adverse effects Barbiturates and carbamates (but not benzodiazepines, buspirone, zolpidem, or zaleplon) induce the formation of the liver microsomal enzymes that metabolize dmgs. This enzyme induction may lead to multiple drug interactions. Barbiturates may also precipitate acute intermittent porphyria in susceptible patients. Chloral hydrate may displace coumarins from plasma protein binding sites and increase anticoagulant effects. 

Phensuximide occasionally is used for the treatment of absence seizures refractory to other drugs, although it is considered to be less effective than ethosuximide. It is excreted in both urine and bile, and it may cause harmless pink to red discoloration of the urine. It should be used with caution in patients with acute intermittent porphyria. 

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