Part B Q1. The normal dose of paracetamol is very safe to use and it is not over 4g per 24 hours; however, when the patient take more than 6g per 24 hours of paracetamol, the liver necrosis will happen within 10 to 12 hours and liver damage may occur within 24 to 48 hours. For the metabolism, most of the paracetamol is converted to nontoxic metabolites by the phase II conjugation of glucuronide and sulfate and a small amount of paracetamol is oxidized by the Cytochrome P450 (CYP) enzymes in the phase I metabolism. In this phase, CYP1A2 and CYP2E1 enzymes convert paracetamol to N-acetyl-p-benzoquinoneimine (NAPBQI) which is highly toxic substances.…
Minoxidil is important for future studies because it can be used to treat high blood…
The bioavailability or clearance can commonly be altered by a pathophysiologic change or co-administration of a second drug? Give an example of a disease/drug, drug/drug, or drug/food interaction with your molecule. Concurrent use of Fluconazole and Losartan changes the bioavailability of Losartan. Bioavailability of Losartan increases since fluconazole is a potent inhibitor of the cytochrome P450 2C9, which metabolizes Losartan.…
This will prevent additional injury to the skeletal muscle. • Since Saskia is currently taking Enalpril for hypertension, it may need to be discontinued due to risk of kidney complications. The prescriber must ensure blood pressure if monitored during this time to ensure harmful effects do not occur. OBJECTIVE #7 – Strategies for addressing potential pharmacokinetic and pharmacodynamic drug-drug interactions in professional practice • It is important to always be aware of metabolic pathways that medications follow throughout the body to help prevent drug interactions from occurring (Delafuente, 2003, p. 141).…
Should significant resources be expended in order to phase out the use of animals in preclinical testing? Topic Preclinical animal testing is an outdated research method which is inaccurate, unethical, and extremely costly; sponsor companies should expend the necessary resources to begin adopting non-animal testing models as they become available in order to progressively reduce, and ultimately discontinue their use of animals. The contents of this paper will discuss supporting ethical, scientific, and economic evidence, in addition to evaluating possible opposing arguments, and proposing a relevant plan of action. Background Preclinical animal testing has been a boiler plate topic for nearly a century.…
What is Lipitor? Lipitor is a brand name for drug atorvastatin, which is a newer selective and competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase that belongs to a group of drugs known as statins. Atorvastatin was synthesized in 1985 and its development was mostly based on molecular comparisons of fungal metabolites and other synthetic inhibitors. Atorvastatin is approved for the reduction of elevated total cholesterol, LDL cholesterol, apo B and triglyceride levels, but its usage also leads to an increase of HDL cholesterol in individuals with primary hypercholesterolemia and mixed dyslipidemia.…
By 1970, although classification of varying β-receptors was yet to be announced, practolol was known to selectively target β-adrenoceptors in the heart, but not occupy receptors in the bronchi or peripheral vasculature (Whelton et al 1970). Lipid solubility was suggested as the mechanism for this action at the time and practolol was found to be an effective therapeutic for arrhythmias, particularly for asthma sufferers (Whelton et al 1970). Unfortunately 27 patients (Table 1) suffered Oculomucocutaneous syndrome as a consequence of its use (Wright, 1975). Systemic lupus erythrematosis syndrome was also linked to the drug, which was removed from clinical use in the UK in 1975 (Raftery and Denman, 1973; Cobert,…
P450-GloTM bioluminescent CYP assay Three concentrations of PTV (1, 10, 100 µM) were conducted to detect the luciferin PPXE activity against recombinant CYP3A4 and CYP3A5. A significant decrease in the luminescene activity in both recombinant CYP3A4 and CYP3A5 was observed in 10 µM and 100 µM of PTV (Fig 1). It seems that PTV is a candidate drug for metabolism against CYP3A4 and CYP3A5 enzymes. Metabolite profiling and Identification After incubating PTV with HLMs in the presence of a NADPH regenerating system, a metabolite (M2) of PTV was profiled, characterized, and identified by LC-MS/MS. A representative chromatograms are provided in Fig 2 (a) and (b).…
Peak antihypertensive effects of lisinopril are reached at approximately six hours after administration which correlates with peak serum levels (Gomez, Cirillo, & Moncloa, 2005, S27). Lisinopril has a half-life of approximately 12 hours. Mechanism of Action. Lisinopril’s mechanism of action occurs through the inhibition of angiotensin-converting…
whatever the process, the goal is to make the drug easier to excrete. Individual drug metabolism rates are influenced by genetic factors, coexisting disorders and drug interactions (inhibition and induction). For many drugs, metabolism occurs in 2 phases. Phase 1 reaction involves the formation of a new or modified functional group or cleavage (oxidation, reduction etc); these reactions are nonsynthetic.…
The same results from in-vitro study were found for haloperidol (Kudo S ). In order to verify the first simulation it was decided to focus on several aspects of QSAR modeling for human cytochrome P450. The research was accomplished in the OCHEM platform All the descriptors, datasets and models which were used are publicly available. The OCHEM platform based on two parts – the experimental databases and the QSAR framework, so it is easy to make manipulations in it, upload and download different QSAR data.…
Synthetic drugs are a common source of acute injury of the liver. Compared with 30 years ago, the average patient today was older, has more Co morbidity and is exposed to more diagnostic and therapeutic procedures with the potential to harm liver function. Drug Cisplatin (cis-diamminedichloroplatinum) shown to cause hepatotoxic, is an effective against solid tumors as an anti-tumor drug for the treatment of several human affected by cancer to exert their toxic effects by one or more common pathogenic mechanism. Cisplatin is a very effective and an important anticancer drug used for the cancer patients, but, the studies for drug induced liver injury (C-DILI) in In-vitro and In-vivo, shown the adverse effect of cisplatin as both hepatotoxic and nephrotoxic. 1, 2-4 Drug-induced…
As individuals age, it is likely that they will require some form of medication to treat the development of health conditions. Health conditions, such as cardiovascular disease, stroke, diabetes and high cholesterol, are more likely to occur. Most of these conditions require the administration of pharmacology. Geriatric patients are therefore more likely to be on medications, and often on multiple medications at once, a condition called polypharmacy. Age-related changes in the human body makes it more susceptible to the medications.…
g) Solubility: soluble in methanol, slightly soluble in water (13.4 mg/ml) and very slightly soluble in dichloromethane h) Route of administration: Oral i) Excretion: kidney j) Therapeutic category: Antiretroviral drug k) Metabolism: The cytochrome P450 enzyme system is not involved with the metabolism of Tenofovir disoproxil or Tenofovir. l) pKa value: 3.75 m) Trade Name: Viread 2.2.5 Drug profile of Efavirenz: Efavirenz is an antiretroviral drug and it belongs to the class of Non-nucleoside reverse transcriptase inhibitor (NNRTI). It is used for the treatment of HIV type 1.…
Enantiomeric purity The enantiomeric purity is an important issue to produce pharmaceutical products of acceptable quality. The mobile phase was optimized to discriminate ESO and S-NAP from their chiral impurity (R-isomer). For checking the method ability to separate the chiral impurities from the active isomers of each drug, spiking of the prepared pure S-NAP and ESO isomers with their corresponding racemic mixtures at 1%, 2% and 5% levels of the main peak was done. Method optimization was done in order to achieve sufficient resolution and detecting the R isomer at low levels of the main peak, S isomer.…