Browsing Pathways

Etidronic Acid is a first-generation bisphosphonate used for the treatment of osteoporosis, preventing bone resorption from osteoclast activity. Etidronic acid binds to hydroxylapatite and during bone resorption, it is released and taken up into the osteoclast by endocytosis. Once absorbed etidronic acid is then transported into the cytosol, where it then goes to the mitochondrial matrix to inhibit ADP/ATP translocase. Through this inhibition, it halts the transportation of ATP into the rest of the cell, without energy all processes come to a stop. Its structure mimics that of pyrophosphate, where it can also incorporate itself into ATP analogues that cannot be hydrolyzed further disrupting osteoclast function and survival. This should be taken on an empty stomach, avoiding multivalent ions for at least two hours after administration. If a patient experiences an overdose they may present hypocalcemia, diarrhea, vomiting and paresthesia. This can be treated with administering electrolytes and calcium gluconate intravenously.

Pemetrexed is an antifolate, it contains a pyrrolopyrimidine base within its structure that inhibits DNA synthesis and de novo biosynthesis of nucleotides. Once inside the cell via a folate transporter, it is converted to by folylpolyglutamate synthétase into its polyglutamate form. This new form is better retained in the cells and goes on to inhibit enzymes such as dihydrofolate reductase, thymidylate synthase and bifunctional purine biosynthesis protein (PURH). This drug is used to treat cancer specifically that of lung cancer or mesothelioma can be used in combination with pembrolizumab or cisplatin. It is not metabolized by much of the liver but excreted via the urine.

Parecoxib, also known as Dynastat, is a selective COX-2 inhibitor (NSAID) used for the short-term management of perioperative pain. It is an injectable prodrug of valdecoxib. The COX-2 is part of the cyclooxygenase pathway. The cyclooxygenase pathway begins in the cytosol with phospholipids being converted into arachidonic acid by the action of phospholipase A2. The rest of the pathway occurs on the endoplasmic reticulum membrane, where prostaglandin G/H synthase 1 & 2 convert arachidonic acid into prostaglandin H2. Prostaglandin H2 can either be converted into thromboxane A2 via thromboxane A synthase, prostacyclin/prostaglandin I2 via prostacyclin synthase, or prostaglandin E2 via prostaglandin E synthase. COX-2 is an inducible enzyme, and during inflammation, it is responsible for prostaglandin synthesis. It leads to the formation of prostaglandin E2 which is responsible for contributing to the inflammatory response by activating immune cells and for increasing pain sensation by acting on pain fibers. Valdecoxib inhibits the action of COX-2 on the endoplasmic reticulum membrane. This reduces the formation of prostaglandin H2 and therefore, prostaglandin E2 (PGE2). The low concentration of prostaglandin E2 attenuates the effect it has on stimulating immune cells and pain fibers, consequently reducing inflammation and pain. Fever is triggered by inflammatory and infectious diseases. Cytokines are produced in the central nervous system (CNS) during an inflammatory response. These cytokines induce COX-2 production that increases the synthesis of prostaglandin, specifically prostaglandin E2 which adjusts hypothalamic temperature control by increasing heat production. Because nabumetone decreases PGE2 in the CNS, it has an antipyretic effect. This drug is administered as an intramuscular or intravenous injection.

Anisotropine methylbromide is a quaternary ammonium compound. Its use as treatment adjunct in peptic ulcer has been replaced by the use of more effective agents. Depending on the dose, anisotropine methylbromide may reduce the motility and secretory activity of the gastrointestinal system, and the tone of the ureter and urinary bladder and may have a slight relaxant action on the bile ducts and gallbladder. In general, smaller doses of anisotropine methylbromide inhibit salivary and bronchial secretions, sweating, and accommodation; cause dilatation of the pupil; and increase the heart rate. Larger doses are required to decrease motility of the gastrointestinal and urinary tracts and to inhibit gastric acid secretion. Quaternary ammonium compounds such as anisotropine methylbromide inhibit the muscarinic actions of acetylcholine on structures innervated by postganglionic cholinergic nerves as well as on smooth muscles that respond to acetylcholine but lack cholinergic innervation. These postganglionic receptor sites are present in the autonomic effector cells of the smooth muscle, cardiac muscle, sinoatrial and atrioventricular nodes, and exocrine glands. By being an antagonist of the M2 receptor on the smooth muscle of the GI tract, this drug inhibits the Gi signalling pathway leading to decreased intracellular calcium levels and muscle relaxation, therefore decreasing the motility of the GI tract. Possible side effects of using anisotropine methylbromide may include constipation, dry mouth, urinary retention, and headache.

Vilazodone selectively inhibits serotonin reuptake in the central nervous system as well as acting as a partial agonist of 5HT-1A receptors. The exact mechanism for how these effects translate to its antidepressant effects are not known though there is an association between these effects and anti-depressive activity.

Procyclidine is an antispasmodic drug used to treat parkinsonism of various types and in the treatment of extrapyramidal symptoms. A muscarinic antagonist that crosses the blood-brain barrier and is used in the treatment of drug-induced extrapyramidal disorders and in parkinsonism. Procyclidine has an atropine-like action on parasympathetic-innervated peripheral structures including smooth muscle. Its antispasmodic effects are thought to be related to the blockage of central cholinergic receptors M1, M2 and M4. It is used to treat symptomatic Parkinsonism and extrapyramidal dysfunction caused by antipsychotic agents. The mechanism of action is unknown. It is thought that Procyclidine acts by blocking central cholinergic receptors, and thus balancing cholinergic and dopaminergic activity in the basal ganglia. Many of its effects are due to its pharmacologic similarities with atropine. Procyclidine exerts an antispasmodic effect on smooth muscle, and may produce mydriasis and reduction in salivation. By blocking the M1 receptor, the action of acetylcholine is blocked. Procyclidine is administered as an oral tablet. Possible side effects of using procyclidine may include flushing, pupil dilation, blurred vision, and dry mouth.

Verapamil, known as the brand names Calan, Isoptin, Tarka, and Verelan, is a non-dihydropyridine calcium channel blocker used in the treatment of angina, arrhythmia, and hypertension. It is used for the treament of vasopastic angina, unstable angina, chronic stable angina, treat hypertension, for the prophylaxis of repetitive paroxysmal supraventricular tachycardia,and atrial fibrillation or atrial flutter in combination with digoxin. It is normally given intravenously, so it has a rapid release with a short duration of action. Verapamil acts on smooth muscles and cardiac muscles. Verapamil is an L-type calcium channel blocker with antiarrhythmic, antianginal, and antihypertensive activity. The inhibition of L-type calcium channels prevents the influx of calcium in vascular smooth muscle myocytes and the heart's cardiomyocytes, which prevents contraction of vascular smooth muscles and heart muscles. Preventing the contraction of vascular smooth muscles causes relaxation or dilation of peripheral blood vessels. This reduction in vascular resistance also reduces the force on the heart, decreasing myocardial energy consumption and oxygen requirements. Verapamil's mechanism of action in the treatment of cluster headaches is unclear, but is thought to be involved with its effect on calcium channels.

Bethanechol is a muscarinic agonist used to treat postoperative and postpartum nonobstructive functional urinary retention and neurogenic atony of the bladder with retention. It can be found under the brand name Duvoid. Bethanechol is a synthetic ester that was initially synthesized in 1935. As a cholinergic agent, bethanechol is similar in structure and pharmacological function to acetylcholine and is used in specific cases when stimulation of the parasympathetic nervous system is necessary. For example, bethanechol is readily used to treat postoperative or postpartum urinary retention. An advantage of bethanechol is that in contrast to acetylcholine, bethanechol is not degraded by cholinesterase allowing its effects to be longer-lasting. When taken orally or administered by injection, Bethanechol binds to and activates these muscarinic receptors. By doing so, it mimics the effects of acetylcholine, a neurotransmitter that naturally activates these receptors. The activation of M2 and M3 receptors leads to several physiological responses, including increased smooth muscle tone and contraction. Bethanechol is commonly used to stimulate bladder contractions in individuals with urinary retention or certain bladder disorders. By activating the M3 receptors in the bladder, it increases the tone of the detrusor muscle and causes the bladder to contract, thereby promoting urination. In addition to its effects on the urinary system, Bethanechol can also affect smooth muscles in other organs, such as the gastrointestinal tract. It can increase the muscular contractions of the gastrointestinal tract, which may be beneficial in certain conditions involving reduced motility, such as postoperative ileus or constipation. Possible side effects of using bethanechol may include belching, blurred vision, dizziness, and headache.

Dabigatran etexilate is an anticoagulant used to prevent venous thromboembolism, it is a prodrug that is administered orally and hydrolyzed via first-pass metabolism into the competitive thrombin inhibitor dabigatran. Dabigatran competitively binds and inhibits thrombin by doing so stops the formation of fibrin and therefore the meshwork for a thrombus. When administered orally, the capsule should not be tampered with in any way prior to administration. The highest concentration of the drug within the body peaks one hour after consumption. The maximum concentration can be prolonged to two hours if a high-fat meal is consumed prior, afterwards the drug is then primarily eliminated through urine and feces. This drug does interact with food, herbs and supplements with anticoagulant and antiplatelet activity should be avoided such as garlic, ginger, bilberry, danshen, piracetam and ginkgo biloba. St. John's wort should also be avoided as it induces an enzyme that can reduce the concentration of active dabigatran. Dabigatran etexilate should be taken with a full glass of water and can be taken with or without the consumption of food.

Fesoterodine is an antimuscarinic agent used in the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. It can be found under the brand name Toviaz. Muscarinic receptors have long been the target receptors for treatment of patients with overactive bladder (OAB). These patients experience symptoms of urgency, urinary frequency and nocturia, with or without urge incontinence (the involuntary leakage of urine associated with urge). Fesoterodine, a pro-drug, structurally and functionally related to tolterodine, is the newest agent developed for the treatment of OAB. Fesoterodine is broken down to the active metabolite, 5-hydroxy-methyl-tolterodine (5-HMT) by non-specific esterases. This metabolism results in the complete breakdown of the parent compound and is responsible for dose related improvements in clinical efficacy and health related quality of life. Like other antimuscarinic agents including tolterodine, fesoterodine is associated with improvements in clinical variables related both to bladder filling (decreasing micturition frequency and increasing mean voided volume) and urgency (urgency and urge incontinence episodes). Fesoterodine, once converted to its active metabolite, 5-hydroxymethyltolterodine, acts as a competitive antagonists at muscarinic receptors. This results in the inhibition of bladder contraction, decrease in detrusor pressure, and an incomplete emptying of the bladder. Possible side effects of using fesoterodine may include dry mouth, constipation, dry eyes, and back pain.