Phenytoin is an anti-epileptic drug. Phenytoin has been used with much clinical success against all types of epileptiform seizures, except petit mal epilepsy. Phenytoin is a available for oral administration (tablets, capsules, suspension). CEREBYX® (fosphenytoin sodium injection) is a prodrug intended for parenteral administration; its active metabolite is phenytoin. CEREBYX should be used only when oral phenytoin administration is not possible. Although several potential targets for phenytoin action have been identified within the CNS (Na-K-ATPase, the GABAA receptor complex, ionotropic glutamate receptors, calcium channels and sigma binding sites) to date, though, the best evidence hinges on the inhibition of voltage-sensitive Na channels in the plasma membrane of neurons undergoing seizure activity.

Lisdexamfetamine (LDX) is a d-amphetamine (d-AMPH) pro-drug used to treat Attention Deficit and Hyperactivity Disorder (ADHD) and Binge Eating Disorder (BED). After oral administration, lisdexamfetamine dimesylate is rapidly absorbed from the gastrointestinal tract and converted to dextroamphetamine, which is responsible for the drug’s activity. Amphetamines are thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. Most common adverse reactions in children, adolescents and/or adults with ADHD were anorexia, anxiety, decreased appetite, decreased weight, diarrhea, dizziness, dry mouth, irritability, insomnia, nausea, upper abdominal pain, and vomiting. Agents that alter urinary pH can alter blood levels of amphetamine. Acidifying agents decrease amphetamine blood levels, while alkalinizing agents increase amphetamine blood levels. Needs to adjust Lisdexamfetamine dosage accordingly.

Progesterone is indicated in amenorrhea and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids of uterine cancer. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Progesterone is a naturally occurring steroid that is secreted by the ovary, placenta, and adrenal gland. In the presence of adequate estrogen, progesterone transforms a proliferative endometrium into a secretory endometrium. Progesterone is necessary to increase endometrial receptivity for implantation of an embryo. Once an embryo is implanted, progesterone acts to maintain a pregnancy. Progesterone shares the pharmacological actions of the progestins. Progesterone binds to the progesterone and estrogen receptors. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progesterone will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge. In women who have adequate endogenous estrogen, progesterone transforms a proliferative endometrium into a secretory one. Progesterone is metabolized primarily by the liver largely to pregnanediols and pregnanolones. Pregnanediols and pregnanolones are conjugated in the liver to glucuronide and sulfate metabolites. Progesterone metabolites that are excreted in the bile may be deconjugated and may be further metabolized in the gut via reduction, dehydroxylation, and epimerization. Common progesterone side effects may include: drowsiness, dizziness; breast pain; mood changes; headache; constipation, diarrhea, heartburn; bloating, swelling in your hands or feet; joint pain; hot flashes; or vaginal discharge.

Cholecalciferol (/ˌkoʊləkælˈsɪfərɒl/) (vitamin D3) is one of the five forms of vitamin D. Cholecalciferol is a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, in mineralization of bone, and for the assimilation of Vitamin A. The classical manifestation of vitamin D deficiency is rickets, which is seen in children and results in bony deformities including bowed long bones. Most people meet at least some of their vitamin D needs through exposure to sunlight. Ultraviolet (UV) B radiation with a wavelength of 290–320 nanometers penetrates uncovered skin and converts cutaneous 7-dehydrocholesterol to previtamin D3, which in turn becomes vitamin D3. In supplements and fortified foods, vitamin D is available in two forms, D2 (ergocalciferol) and D3 (cholecalciferol) that differ chemically only in their side-chain structure. Vitamin D2 is manufactured by the UV irradiation of ergosterol in yeast, and vitamin D3 is manufactured by the irradiation of 7-dehydrocholesterol from lanolin and the chemical conversion of cholesterol. The two forms have traditionally been regarded as equivalent based on their ability to cure rickets and, indeed, most steps involved in the metabolism and actions of vitamin D2 and vitamin D3 are identical. Both forms (as well as vitamin D in foods and from cutaneous synthesis) effectively raise serum 25(OH) D levels. Firm conclusions about any different effects of these two forms of vitamin D cannot be drawn. However, it appears that at nutritional doses, vitamins D2 and D3 are equivalent, but at high doses, vitamin D2 is less potent. The American Academy of Pediatrics (AAP) recommends that exclusively and partially breastfed infants receive supplements of 400 IU/day of vitamin D shortly after birth and continue to receive these supplements until they are weaned and consume ≥1,000 mL/day of vitamin D-fortified formula or whole milk. Cholecalciferol is used in diet supplementary to treat Vitamin D Deficiency. Cholecalciferol is inactive: it is converted to its active form by two hydroxylations: the first in the liver, the second in the kidney, to form calcitriol, whose action is mediated by the vitamin D receptor, a nuclear receptor which regulates the synthesis of hundreds of enzymes and is present in virtually every cell in the body. Calcitriol increases the serum calcium concentrations by increasing GI absorption of phosphorus and calcium, increasing osteoclastic resorption, and increasing distal renal tubular reabsorption of calcium. Calcitriol appears to promote intestinal absorption of calcium through binding to the vitamin D receptor in the mucosal cytoplasm of the intestine. Subsequently, calcium is absorbed through formation of a calcium-binding protein.

Quinidine is a pharmaceutical agent that acts as a class I antiarrhythmic agent (Ia) in the heart. It is a stereoisomer of quinine, originally derived from the bark of the cinchona tree. The drug causes increased action potential duration, as well as a prolonged QT interval. Like all other class I antiarrhythmic agents, quinidine primarily works by blocking the fast inward sodium current (INa). Quinidine's effect on INa is known as a 'use-dependent block'. This means at higher heart rates, the block increases, while at lower heart rates, the block decreases. The effect of blocking the fast inward sodium current causes the phase 0 depolarization of the cardiac action potential to decrease (decreased Vmax). Quinidine also blocks the slowly inactivating, tetrodotoxin-sensitive Na current, the slow inward calcium current (ICA), the rapid (IKr) and slow (IKs) components of the delayed potassium rectifier current, the inward potassium rectifier current (IKI), the ATP-sensitive potassium channel (IKATP) and Ito. Quinidine is also an inhibitor of the cytochrome P450 enzyme 2D6 and can lead to increased blood levels of lidocaine, beta blockers, opioids, and some antidepressants. Quinidine also inhibits the transport protein P-glycoprotein and so can cause some peripherally acting drugs such as loperamide to have central nervous system side effects, such as respiratory depression if the two drugs are coadministered. Quinidine can cause thrombocytopenia, granulomatous hepatitis, myasthenia gravis, and torsades de pointes, so is not used much today. Torsades can occur after the first dose. Quinidine-induced thrombocytopenia (low platelet count) is mediated by the immune system and may lead to thrombocytic purpura. A combination of dextromethorphan and quinidine has been shown to alleviate symptoms of easy laughing and crying (pseudobulbar affect) in patients with amyotrophic lateral sclerosis and multiple sclerosis. This drug is marketed as Nuedexta in the United States. Intravenous quinidine is also indicated for the treatment of Plasmodium falciparum malaria. However, quinidine is not considered the first-line therapy for P. falciparum. The recommended treatments for P. falciparum malaria, according to the Toronto Notes 2008, are a combination of either quinine and doxycycline or atovaquone and proguanil (Malarone). The drug is also effective for the treatment of atrial fibrillation in horses.

The alkaloid L-(-)-scopolamine [L-(-)-hyoscine], a belladonna alkaloid, competitively inhibits muscarinic receptors for acetylcholine and acts as a nonselective muscarinic antagonist, producing both peripheral antimuscarinic properties and central sedative, antiemetic, and amnestic effects. Scopolamine acts: i) as a competitive inhibitor at postganglionic muscarinic receptor sites of the parasympathetic nervous system, and ii) on smooth muscles that respond to acetylcholine but lack cholinergic innervation. It has been suggested that scopolamine acts in the central nervous system (CNS) by blocking cholinergic transmission from the vestibular nuclei to higher centers in the CNS and from the reticular formation to the vomiting center. Scopolamine can inhibit the secretion of saliva and sweat, decrease gastrointestinal secretions and motility, cause drowsiness, dilate the pupils, increase heart rate, and depress motor function. Scopolamine is used for premedication in anesthesia and for the prevention of nausea and vomiting (post operative and associated with motion sickness).

Apomorphine (brand names: Apokyn, Ixense, Spontane, Uprima) is indicated for the acute, intermittent treatment of hypomobility, “off” episodes (“end-of-dose wearing off” and unpredictable “on/off” episodes) in patients with advanced Parkinson’s disease. Apomorphine has been studied as an adjunct to other medications. It is a non-ergoline dopamine agonist with high in vitro binding affinity for the dopamine D4 receptor, and moderate affinity for the dopamine D2, D3, and D5, and adrenergic α1D, α2B, α2C receptors. The precise mechanism of action as a treatment for Parkinson’s disease is unknown, although it is believed to be due to stimulation of post-synaptic dopamine D2-type receptors within the caudate-putamen in the brain.

Cocaine is an alkaloid ester extracted from the leaves of plants including coca. Cocaine is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Cocaine is addictive due to its effect on the reward pathway in the brain. After a short period of use, there is a high risk that dependence will occur. Its use also increases the risk of stroke, myocardial infarction, lung problems in those who smoke it, blood infections, and sudden cardiac death. Cocaine sold on the street is commonly mixed with local anesthetics, cornstarch, quinine, or sugar which can result in additional toxicity. Following repeated doses, a person may have decreased the ability to feel pleasure and be very physically tired. Cocaine acts by inhibiting the reuptake of serotonin, norepinephrine, and dopamine. This results in greater concentrations of these three neurotransmitters in the brain. It can easily cross the blood-brain barrier and may lead to the breakdown of the barrier.

Piperonyl butoxide (PBO) is an organic compound used as a component of pesticide formulations. It is a waxy white solid. It is a semisynthetic derivative of safrole. It is used for the treatment of head, pubic (crab), and body lice. Piperonyl butoxide is a synergist. It has no pesticidal activity of its own, but acts to increase the activity of pesticides such as carbamates, pyrethrins, pyrethroids, and rotenone. PBO acts as an insecticide synergist by inhibiting the natural defense mechanisms of the insect, the most important of which is the Mixed Function Oxidase system, also known as the cytochrome P-450 system. The MFO system is the primary route of detoxification in insects, and causes the oxidative breakdown of insecticides like pyrethrins and the synthetic pyrethroids - thus when PBO is added, higher insecticide levels remain in the insect to exercise their lethal effect. An important consequence of this property is that, by enhancing the activity of a given insecticide, less may be used to achieve the same result. PBO does not appear to have a significant effect on the MFO system in humans. Skin Sensitization PBO has a low acute toxicity by oral, inhalation and dermal routes. It is minimally irritating to the eyes and skin. It is a not a dermal sensitizer. No evidence suggests that PBO disrupts the normal functioning of the endocrine system. This includes the recently developed data to assess the possible interaction of PBO with the endocrine system.

Miconazole is a synthetic imidazole derivative, a topical antifungal agent for use in the local treatment of vaginal, and skin and nail infections due to yeasts and dermatophytes. It is particularly active against Candida spp., Trichophyton spp., Epidermophyton spp., Microsporum spp. and Pityrosporon orbiculare (Malassezia furfur), but also possesses some activity against Gram-positive bacteria. It binds to the heme moiety of the fungal cytochrome P-450 dependent enzyme lanosterol 14-alpha-demethlyase. Inhibits 14-alpha-demethlyase, blocks formation of ergosterol and leads to the buildup of toxic methylated 14-a-sterols. Miconazole also affects the synthesis of triglycerides and fatty acids and inhibits oxidative and peroxidative enzymes, increasing the amount of active oxygen species within the cell.