Browsing Pathways

Isoniazid is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Isoniazid passes through the liver and is then excreted from the body mainly through the kidney.

Isoniazid is an antibiotic drug used to treat tunerculosis, as well as other types of mycobacteria. Through a currently unknown reaction that may be spontaneous or enzymatic, pyruvic acid or oxoglutaric acid can undergo a dehydration reaction with isoniazid, forming isoniazid pyruvate or isoniazid alpha-ketoglutaric acid. Isoniazid may also react with hydrogen peroxide in the lysosome, forming an isonicotinoyl radical catalyzed by myeloperoxidase. The isonicotinoyl radical can then have either NAD or NADP added in a non-enzymatic reaction, forming isonicotinoyl-NAD and NADP adducts. Isoniazid can have an acetyl group added to it by arylamine N-acetyltransferase 2, fvorming acetylisoniazid. This can then enter the endoplasmic reticulum and, with the addition of a water molecule, can form isonicotinic acid and acetylhydrazine. Isoniazid can also be converted to hydrazine and isonicotinic acid via the same reaction, and the hydrazine can have an acetyl group added to it by arylamine N-acetyltransferase 2 in order to form acetylhydrazine. Acetylhydrazine can have another acetyl group added to it by arylamine N-acetyltransferase 2 to form diacetylhydrazine which is then excreted. It can alternatively be processed by cytochrome P450 2E1 into hepatotoxins, which are then joined to glutatione by glutatione S-transferase omega-2 to form R-S-glutatione, which is then excreted. Finally, isonicotinic acid can react with a glycine in an unclear reaction, potentially requiring ATP and coenzyme A and forming an intermediate, producing isonicotinylglycine, which is also excreted.

Isoprenaline (also known as isoproterenol) is a selective beta adrenergic bronchodilator that can be used for treating slow heart rate (bradycardia), heart block, and rarely for asthma. Isoprenaline can bind and inhibit beta-1 adrenergic receptor on both vascular smooth muscle, which lead to inhibition of vasoconstriction in peripheral blood vessels and adrenergic stimulation of endothelial cell function.

Isoprenaline (also called isoproterenol) is a non-selective beta-adrenergic agonist. It is administered via IV or oral inhalation and is used to treat conditions including mild or transient episodes of heart block that do not require pacing, serious episodes of heart block and Adams-Stokes attacks (except when caused by ventricular tachycardia or fibrillation), cardiac arrest until electric shock or pacemaker therapy is available, bronchospasm occurring during anesthesia, and as an adjunct to in the treatment of hypovolemic and septic shock, low cardiac output states, congestive heart failure, and cardiogenic shock. The actions of isoprenaline are mostly observed in heart muscle, where it binds to beta-1 adrenergic receptors, and smooth muscle (bronchi, blood vessel, GI tract and uterus), where it exerts it’s effects via beta-2 adrenergic receptors. In the heart, isoprenaline binds to and activates the beta-1 adrenergic receptor, which is coupled to the G-protein signaling cascade. Activation of the receptor activates the signaling cascade which leads to activated protein kinase. Protein kinase activates calcium channels in the membrane, causing them to open and allow Ca2+ to enter the cell. Due to this effect, there is high concentration of Ca2+ in the cell. Ca2+ activates the ryanodine receptor on the sarcoplasmic reticulum, which transports Ca2+ from the sarcoplasmic reticulum into the cytosol. the high concentration of Ca2+ in the cytosol binds to troponin to cause muscle contraction. The high concentration of Ca2+ means that more Ca2+ binds to troponin, increasing inotropy. In non-cardiac myocytes, an increase in intracellular Ca2+ increases the slop of phase 4 of the action potential. The threshold is reached faster, therefore, the heart rate is increased. In the smooth muscle, Ca2+-calmodulin complex activates myosin-LC kinase which activates myosin-LC. The activated myosin-LC causes contraction. Isoprenaline binds to and activates beta-2 adrenergic receptor, activating the G-protein signaling cascade. The G-protein signaling cascade produces cAMP, which inhibits myosin-LC kinase. This prevents the activation of myosin-LC and as a result, decreases smooth muscle contraction. Possible side effects from taking isoprenaline include headache, dizziness, upset stomach, flushing, fatigue, nervousness, angina, hypotension, hypertension, palpitations, ventricular arrhythmia, tachycardia, adams-stokes syndrome, dyspnea, edema, blurred vision, nausea, vomiting, tremor, weakness.

Isoprenaline is predominantly metabolized to glucuronide conjugates. Isoprenaline can also be O-methylated by catechol O-methyltransferase to the metabolite 3-O-methylisoprenaline, which can also be further glucuronidated. (DrugBank)

Metabolites of Isopropamide are predicted with biotransformer.