Triggers
Acute porphyria can be triggered by a number of drugs, most of which are believed to trigger it by interacting with enzymes in the liver which are made with heme. Such drugs include:
Sulfonamides, including sulfadiazine, sulfasalazine and trimethoprim/sulfamethoxazole. Sulfonylureas like glibenclamide, gliclazide and glimepiride, although glipizide is thought to be safe. Barbiturates including thiopental, phenobarbital, primidone, etc. Systemic treatment with antifungals including fluconazole, griseofulvin, ketoconazole and voriconazole. (Topical use of these agents is thought to be safe due to minimal systemic absorption.) Certain antibiotics like rifapentine, rifampicin, rifabutine, isoniazid, nitrofurantoin and, possibly, metronidazole. Ergot derivatives including dihydroergotamine, ergometrine, ergotamine, methysergide, etc. Certain antiretroviral medications (e.g. indinavir, nevirapine, ritonavir, saquinavir, etc.) Progestogens
Some anticonvulsants including: carbamazepine, ethosuximide, phenytoin, topiramate, valproate. Some painkillers like dextropropoxyphene, ketorolac, metamizole, pentazocine
Some cancer treatments like bexarotene, busulfan, chlorambucil, estramustine, etoposide, flutamide, idarubicin, ifosfamide, irinotecan, ixabepilone, letrozole, lomustine, megestrol, mitomycin, mitoxantrone, paclitaxel, procarbazine, tamoxifen, topotecan
Some antidepressants like imipramine, phenelzine, trazodone
Some antipsychotics like risperidone, ziprasidone
Some retinoids used for skin conditions like acitretin and isotretinoin
Miscellaneous others including: cocaine, methyldopa, fenfluramine, disulfiram, orphenadrine, pentoxifylline, and sodium aurothiomalate. Pathogenesis
In humans, porphyrins are the main precursors of heme, an essential constituent of hemoglobin, myoglobin, catalase, peroxidase, and P450 liver cytochromes.The body requires porphyrins to produce heme, which is used to carry oxygen in the blood among other things, but in the porphyrias there is a deficiency (inherited or acquired) of the enzymes that transform the various porphyrins into others, leading to abnormally high levels of one or more of these substances.
Causes
Carbon dioxide is a normal metabolic product but it accumulates in the body if it is produced faster than it is cleared. During strenuous exercise the production rate of carbon dioxide can increase more than tenfold over the production rate during rest. Carbon dioxide is dissolved in the blood and elimination is by gas exchange in the lungs during breathing. Hypercapnia is generally caused by hypoventilation, lung disease, or diminished consciousness. It may also be caused by exposure to environments containing abnormally high concentrations of carbon dioxide, such as from volcanic or geothermal activity, or by rebreathing exhaled carbon dioxide. In this situation the hypercapnia can also be accompanied by respiratory acidosis.Acute hypercapnic respiratory failure may occur in acute illness caused by chronic obstructive pulmonary disease (COPD), chest wall deformity, some forms of neuromuscular disease (such as myasthenia gravis, and obesity hypoventilation syndrome. AHRF may also develop in any form of respiratory failure where the breathing muscles become exhausted, such as severe pneumonia and acute severe asthma. It can also be a consequence of profound suppression of consciousness such as opioid overdose. During diving
Normal respiration in divers results in alveolar hypoventilation resulting in inadequate CO2 elimination or hypercapnia. Lanphiers work at the US Navy Experimental Diving Unit answered the question, "Why dont divers breathe enough?