Pathways

Atovaquone is an hydroxynaphthoquinone antimicrobial indicated for the prevention and treatment of Pneumocystis jirovecii pneumonia (PCP) and for the prevention and treatment of Plasmodium falciparum malaria. Atovaquone is a highly lipophilic drug that closely resembles the structure [ubiquinone]. Its inhibitory effect being comparable to ubiquinone, atovaquone can act by selectively affecting mitochondrial electron transport and parallel processes such as ATP and pyrimidine biosynthesis in atovaquone-responsive parasites. The mechanism of action against Pneumocystis carinii has not been fully elucidated. In Plasmodium species, the site of action appears to be the cytochrome bc1 complex (Complex III). Several metabolic enzymes are linked to the mitochondrial electron transport chain via ubiquinone. Inhibition of electron transport by atovaquone will result in indirect inhibition of these enzymes. The inhibition of the electron transport chain prevents the release of energy, therefore it inhibits nucleic acid and ATP synthesis. This eventually leads to cell death..

Atropine is a muscarinic agents used to treat poisoning by muscarinic agents such as organophosphates and other muscarinic drugs. Organophosphates are insecticides used on many crops, and are also poisonous to mammals. Organophosphate inhibits acetylcholinesterase which prevents the breakdown of acetylcholine. This leads to a high concentration of acetylcholine which continuously activates muscarinic acetylcholine receptors, causing muscle contractions.The high concentration of acetylecholine from organophosphate poison causes contraction of skeletal, smooth, and cardiac muscles throughout the body which causes defecation/diaphoresis, urination, miosis, bronchospasms/bronchorrhea, emesis, lacrimation, and salivation, remembered by the mnemonic DUMBELS.The poison can also cause anxiety, confusion, drowsiness, emotional lability, seizures, hallucinations, headaches, insomnia, memory loss, and circulatory or respiratory depression. Atropine antagonizes muscarinic acetylcholine receptors M1-M5 in order to counteract the high concentration of acetylcholine causes by muscarinic poisons. These receptors are coupled to the Gq cascade which is being prevented by Ipratropium. The inhibition of the Gq cascade prevents the acitvation of phospholipase C, which would convert Phosphatidylinositol (3,4,5)-trisphosphate to inositol (3,4,5)-trisphosphate (IP3) and diacylglycerol (DAG). IP3 would then activate IP3 receptors on the sarcoplasmic reticulum leading to the release of stored calcium into the cytosol. the muscarinic acetylcholine receptors being inhibited prevents calcium from entering the cell which means calcium does not readily bind to calmodulin, and calmodulin isn't present to activate myosin light chain kinase. Since myosine light chain kinase is not activated, Serine/threonine-protein phosphatase continues to dephosphorylate myosin LC-P, and more cannot be synthesized so myosin remains unbound from actin causing muscle relaxation. This relaxation prevents the muscles from seizing due to organophosphates or another muscarinic drug. Atropine can be administered in a variety of ways, including intravenous injection, oral tablet, opthamalic solution, and intramuscular injections.

Atropine is a muscarinic antagonist that is used to treat atrioventricular heart block, bradycardia and for organophosphate anticholinesterase/pesticides poisoning. Atropine is an alkaloid originating from the plant Atropa Betalldonna and can be found in some other plants. Naturally it is a racemic mixture of equal parts d-hyoscyamine and l-hyoscyamine. Althought is is classified as a muscarinic antagonist it is more commonly classified as an anti-cholinergic or an antiparasympathetic drug. Sufficient doses of atropine will inhibit carious types of reflex vagal cardiac asystole as well as bradycardia and asystole produced by choline esters, anticholinesterase agents, parasympathomimetic drugs or cardiac arrest produced by vagus nerve stimulation. It is also possible that atropine may lessen the degree of partial heart block if vagal activity is the etiological (causing or contributing) factor. In clinical dose administrations it counteracts the peripheral dilation and low blood pressure produced by choline esters. If it given by itself it does not exert a large or even effect on blood vessels and/or blood pressure. Atropine binds to and inhibits muscarinic acetylcholine receptors which produces a large range of anticholinergic effects. In the heart (the main use for atropine) muscarinic 2 receptors (M2) receptors reside in the SA and VA node in the atria and ventricles respectively are affected by atropine. Atropine inhibits the binding of acetylcholine and other choline esters causing an inhibitory effect increasing the concentration of cAMP produced. Higher cAMP concentration promote action potentials in the cells as well as increasing calcium influx from membrane channels. All of these downstream effects increase heart rate and blood pressure therefore abolishing bradycardia and low blood pressure. Atropine is administered in an intravenous, endotracheal, intramuscular, or intramedullary injection or subcutaneously.

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