A young female has severe pain in abdomen, constipation, irrelevant talking, BP 160/110, hea rate 120/mm, fever and +ive Watson-Schwaz test in urine. Which of the following drugs should not be used in this condition-
The Watson-Schwaz test for porphobilinogen is an excellent, simple screening procedure for porphyria and ceainly its use should be considered in any patient with a history of abdominal pain, constipation, obscure neurological disorder, mental disturbance, multiple abdominal operations, or dark urine. The porphyrias are a group of inherited disorders of porphyrin metabolism manifested chemically by an increased excretion of the porphyrins and their precursors or both. Porphyrins are normally synthesized from glycine and succinic acid which combine to yield a-amino-b-ketoadiptic acid. Decarboxylation results in d-aminolevulinic acid. Two molecules of d-aminolevulinic acid condense, forming the monopyrolle, porphobilinogen. Four molecules of porphobilinogen condense producing the various tetrapyrolle porphyrinogens (copro-, uro-, protoporphyrinogen), the reduced, colorless precursors of the porphyrins.1 Porphyrins linked to metal and protein constitute the impoant biological compounds: hemoglobin, myoglobin, cytochrome, and catalase. Carbohydrate administration Often, empirical treatment is required if the diagnostic suspicion of a porphyria is high since acute attacks can be fatal. A high-carbohydrate diet is typically recommended; in severe attacks, a dextrose 10% infusion is commenced, which may aid in recovery by suppressing heme synthesis, which in turn reduces the rate of porphyrin accumulation. However, this can worsen hyponatraemia and should be done with extreme caution as it can prove fatal. Heme analogs Hematin (trade name Panhematin) and heme arginate (trade name NormoSang) are the drugs of choice in acute porphyria, in the United States and the United Kingdom, respectively. These drugs need to be given very early in an attack to be effective; effectiveness varies amongst individuals. They are not curative drugs but can shoen attacks and reduce the intensity of an attack. Side effects are rare but can be serious. These heme-like substances theoretically inhibit ALA synthase and hence the accumulation of toxic precursors. In the United Kingdom, supplies of NormoSang are kept at two national centers; emergency supply is available from St Thomas's Hospital, London. In the United States, Lundbeck manufactures and supplies Panhematin for infusion. Heme arginate (NormoSang) is used during crises but also in preventive treatment to avoid crises, one treatment every 10 days. Any sign of low blood sodium (hyponatremia) or weakness should be treated with the addition of hematin, heme arginate, or even tin mesoporphyrin, as these are signs of impending syndrome of inappropriate antidiuretic hormone (SIADH) or peripheral nervous system involvement that may be localized or severe, progressing to bulbar paresis and respiratory paralysis Cimetidine Cimetidine has also been repoed to be effective for acute porphyric crisis and possibly effective for long-term prophylaxis. Symptom control Pain is severe, frequently out of propoion to physical signs, and often requires the use of opiates to reduce it to tolerable levels. Pain should be treated as early as medically possible. Nausea can be severe; it may respond to phenothiazine drugs but is sometimes intractable. Hot baths and showers may lessen nausea temporarily, though caution should be used to avoid burns or falls. Early identification It is recommended that patients with a history of acute porphyria, and even genetic carriers, wear an ale bracelet or other identification at all times. This is in case they develop severe symptoms, or in case of accidents where there is a potential for drug exposure, and as a result they are unable to explain their condition to healthcare professionals. Some drugs are absolutely contraindicated for patients with any form of porphyria. Neurologic and psychiatric disorders Patients who experience frequent attacks can develop chronic neuropathic pain in extremities as well as chronic pain in the abdomenIntestinal pseudo-obstruction, ileus, intussusception, hypoganglionosis, and encopresis in children have been associated with porphyrias. This is thought to be due to axonal nerve deterioration in affected areas of the nervous system and vagal nerve dysfunction. Pain treatment with long-acting opioids, such as morphine, is often indicated, and, in cases where seizure or neuropathy is present, Gabapentin is known to improve outcome. Seizures often accompany this disease. Most seizure medications exacerbate this condition. Treatment can be problematic: barbiturates especially must be avoided. Some benzodiazepines are safe and, when used in conjunction with newer anti-seizure medications such as gabapentin, offer a possible regimen for seizure control. Gabapentin has the additional feature of aiding in the treatment of some kinds of neuropathic pain.Magnesium sulfate and bromides have also been used in porphyria seizures; however, development of status epilepticus in porphyria may not respond to magnesium alone. The addition of hematin or heme arginate has been used during status epilepticus. Depression often accompanies the disease and is best dealt with by treating the offending symptoms and if needed the judicious use of antidepressants. Some psychotropic drugs are porphyrinogenic, limiting the therapeutic scope. Other psychiatric symptoms such as anxiety, restlessness, insomnia, depression, mania, hallucinations, delusions, confusion, catatonia, and psychosis may occur. Underlying liver disease Some liver diseases may cause porphyria even in the absence of genetic predisposition. These include hemochromatosis and hepatitis C. Treatment of iron overload may be required. Patients with the acute porphyrias (AIP, HCP, VP) are at increased risk over their life for hepatocellular carcinoma (primary liver cancer) and may require monitoring. Other typical risk factors for liver cancer need not be present. Hormone treatment Hormonal fluctuations that contribute to cyclical attacks in women have been treated with oral contraceptives and luteinizing hormones to shut down menstrual cycles. However, oral contraceptives have also triggered photosensitivity and withdrawal of oral contracetives has triggered attacks. Androgens and feility hormones have also triggered attacks. Ref Harrison20th edition pg 2445
Na Valproate
Alcohol
Griseofulvin
All
C.N.S