QUESTIONS IN PHARMACOLOGY

 

 

 

How to Avoid Drug In

teractions 

by admin on: February 22nd, 2012

Harmful drug interactions are a major problem all around the world. For example, many people do not realize that eatingeating chocolate, aged cheese, pepperoni, or salami when taking an MAO, monoamine oxidase, inhibitors, like the prescription drugs Nardil or Parnate, could cause a dangerous rise in blood pressure. While doctors and pharmacists are constantly on the lookout for potential problems with the medicines they prescribe, it is still very important for patients to get involved in the discussion....

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Tips for Using OTC and Prescriptions Drugs Safely

by admin on: February 20th, 2012

Consumers have a responsibility when it comes to using over-the-counter drugs (OTC) and prescription drugs safely. This responsibility can be discharged by following a few simple tips. Always tell your doctor and pharmacist about the drugs you’re currently taking to avoid a drug interaction. Bring a list of drug allergies, dietary supplements, OTC drugs and prescription drugs you take on a regular basis with you to doctors appointments. When you pick up your medications at the pharmacy be sure...

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Tips for Uneventful Pharmacy Visits

by admin on: February 17th, 2012

When you visit a pharmacy, there are some healthy guidelines you should follow to get the most out of your visit. Remember, you may be sitting or standing in a group of other people all waiting for their medications. The pharmacist is multi-tasking by filling prescriptions, speaking with customers about their medicine and overseeing the two or three pharmacy techs. It is important, therefore, to know what to do in order to have as uneventful a visit as possible. Chances are, you’ll stand in...

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Hints for Older Adults on Prescribed Medication

by admin on: February 15th, 2012

Older Americans have the most difficulty of any age group with taking daily medications. Whether they forget a dose, take too much, or don’t understand the food and beverage interactions, the results can be dangerous. Here is a list of factors that contribute to errors when taking medication and some possible solutions. 1. Speaking with a Pharmacist can be frustrating for an older adult with a hearing aid. However, by asking for a written statement of how, and when, to take the medication an...

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Safety with Pain Medications

by admin on: February 13th, 2012

Using pain medication in a safe manner is of utmost importance. For, while these drugs are vary effective at controlling pain, pain medication is highly addictive if not taken properly. Always use prescription Pain medication exactly as the label on the prescription bottle indicates. Do not take your medication at the pharmacy unless someone else is driving you immediately home. Some pain drugs work very quickly on an empty stomach.You may feel sleepy, dizzy, lightheaded or drowsy with the medication...

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Your Child’s Medications

by admin on: February 9th, 2012

Most children are not responsible enough to take their medication on their own, so it is up to the caregiver to deliver the medication on time and at the right dose. There are four important reasons why an adult should maintain control on daily prescribed medications. 1. A child will stop taking the medication if they feel better, not realizing that the illness could come back if they do not complete the regimen. 2. Children may take too much if the medication is in liquid form or a sweet chew-able...

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Stop Smoking with the Community Pharmacist

by admin on: February 8th, 2012

Pharmacists have been answering important questions about the over-the-counter and prescribed medications to quit smoking for decades. Your local pharmacist is available to advise you on Nicotine Replacement Therapy (NRT) and guide you to the treatment that will work best for you. However, until that enlightening conversation with your pharmacist, here are some hints and tips to assist you in your attempt to quit smoking. First, make sure to get your medications in order before you actually stop...

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Using Medicare at the Pharmacy

by admin on: February 6th, 2012

If you are old enough to qualify for Medicare and its prescription program, then you are probably old enough to appreciate some hints about how to use this new privilege. This is your time to enjoy the world on your own terms, and the last thing you want is to be delayed at the pharmacy. Your Medicare card will show, among other things, which of the Medicare programs you chose. Therefore, when you visit the pharmacy, make sure you have your Medicare card with you. You will also need the Medicare...

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You and Your Pharmacist are a Team

by admin on: February 1st, 2012

Pharmaceutical companies often change the color, shape, and dosage of medications. It is the pharmacist’s job is to keep up with these changes so he or she can dispense your medication quickly and accurately. Help you pharmacist by being proactive about your health and following these easy steps: 1. Always ask your doctor why you are being prescribed a given medication. Know the purpose, food and beverage interactions, and potential problems with any of the other drugs you may be taking. 2....

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Save Big at the Pharmacy

by admin on: January 30th, 2012

Just because you need a prescription medication, doesn’t mean you can’t shop around to get the best price. Shopping around is particularly valuable if you are on a given medication for an extended period of time. However, these tips and tricks can be used to save money any time you get a prescription: 1. Always check for prescription transfer coupons. Some pharmacies offer as much as $20-$30 in bonus cards if you transfer all your drugs to their pharmacy. However, make sure all your drugs...

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Drug metabolism

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Drug metabolism is the biochemical modification of pharmaceutical substances by living organisms, usually through specialized enzymatic systems. This is a form of xenobiotic metabolism. Drug metabolism often converts lipophilic chemical compounds into more readily excreted polar products. Its rate is an important determinant of the duration and intensity of the pharmacological action of drugs.
Drug metabolism can result in toxication or detoxication - the activation or deactivation of the chemical. While both occur, the major metabolites of most drugs are detoxication products.
Drugs are almost all xenobiotics. Other commonly used organic chemicals are also xenobiotics, and are metabolized by the same enzymes as drugs. This provides the opportunity for drug-drug and drug-chemical interactions or reactions.

Contents  [hide]  1 Phases 1.1 Phase I 1.1.1 Oxidation 1.1.2 Reduction 1.1.3 Hydrolysis 1.2 Phase II 2 Sites 3 Factors that affect drug metabolism 4 References

[edit] Phases

Phases I and II of the metabolism of a lipophilic drug.

[edit] Phase I

Phase I reactions (also termed nonsynthetic reactions) may occur by oxidation, reduction, hydrolysis, cyclization, and decyclization addition of oxygen or removal of hydrogen, carried out by mixed function oxidases, often in the liver. These oxidative reactions typically involve a cytochrome P450 monooxygenase (often abbreviated CYP), NADPH and oxygen. The classes of pharmaceutical drugs that utilize this method for their metabolism include phenothiazines, paracetamol, and steroids. If the metabolites of phase I reactions are sufficiently polar, they may be readily excreted at this point. However, many phase I products are not eliminated rapidly and undergo a subsequent reaction in which an endogenous substrate combines with the newly incorporated functional group to form a highly polar conjugate.
A common Phase I oxidation involves conversion of a C-H bond to a C-OH. This reaction sometimes converts a pharmacologically inactive compound (a prodrug) to a pharmacologically active one. By the same token, Phase I can turn a nontoxic molecule into a poisonous one (toxification). Simple hydrolysis in the stomach transforms , which are comparatively innocuous. But Phase I metabolism converts acetonitrile to HOCH₂CN, which rapidly dissociates into formaldehyde and hydrogen cyanide, both of which are toxic.
Phase I metabolism of drug candidates can be simulated in the laboratory using non-enzyme catalysts.^[1] This example of a biomimetic reaction tends to give products that often contains the Phase I metabolites. As an example, the major metabolite of the pharmaceutical trimebutine, desmethyltrimebutine (nor-trimebutine), can be efficiently produced by in vitro oxidation of the commercially available drug. Hydroxylation of an N-methyl group leads to expulsion of a molecule of formaldehyde, while oxidation of the O-methyl groups takes place to a lesser extent.

[edit] Oxidation

• Cytochrome P450 monooxygenase system
• Flavin-containing monooxygenase system
• Alcohol dehydrogenase and aldehyde dehydrogenase
• Monoamine oxidase
• Co-oxidation by peroxidases

[edit] Reduction

• NADPH-cytochrome P450 reductase

Cytochrome P450 reductase also known as NADPH:ferrihemoprotein oxidoreductase, NADPH:hemoprotein oxidoreductase, NADPH:P450 oxidoreductase, P450 reductase, POR, CPR, CYPOR, is a membrane-bound enzyme required for electron transfer to cytochrome P450 in the microsome of the eukaryotic cell from a FAD- and FMN-containing enzyme NADPH:cytochrome P450 reductase The general scheme of electron flow in the POR/P450 system is: NADPH → FAD → FMN → P450 → O2

• Reduced (ferrous) cytochrome P450

During reduction reactions, a chemical can enter futile cycling, in which it gains a free-radical electron, then promptly loses it to oxygen (to form a superoxide anion).

[edit] Hydrolysis

• Esterases and Amidase
• Epoxide hydrolase

[edit] Phase II

Phase II reactions — usually known as conjugation reactions (e.g., with glucuronic acid, sulfonates (commonly known as sulfation), glutathione or amino acids) — are usually detoxicating in nature, and involve the interactions of the polar functional groups of phase I metabolites. Sites on drugs where conjugation reactions occur include carboxyl (-COOH), hydroxyl (-OH), amino (NH₂), and sulfhydryl (-SH) groups. Products of conjugation reactions have increased molecular weight and are usually inactive unlike Phase I reactions which often produce active metabolites.

Mechanism	Involved enzyme[2]	Co-factor[2]	Location[2]
Methylation	Methyltransferase	S-adenosyl-L-methionine	Liver, kidney, lung, CNS
Sulphation	Sulfotransferases	3'-phosphoadenosine-5'-phosphosulfate	Liver, kidney, intestine
Acetylation	N-acetyltransferases Bile acid-CoA:amino acid N-acyltransferases	Acetyl coenzyme A	Liver, lung, spleen, gastric mucosa, RBCs, lymphocytes
Glucuronidation	UDP-glucuronosyltransferases	UDP-glucuronic acid	Liver, kidney, intestine, lung, skin, prostate, brain
Glutathione conjugation	Glutathione S-transferases	Glutathione	Liver, kidney

|- ! Glycine conjugation | Acetyl Co-enzyme As || Glycine || Liver, kidney |}

[edit] Sites

Quantitatively, the smooth endoplasmic reticulum of the liver cell is the principal organ of drug metabolism, although every biological tissue has some ability to metabolize drugs. Factors responsible for the liver's contribution to drug metabolism include that it is a large organ, that it is the first organ perfused by chemicals absorbed in the gut, and that there are very high concentrations of most drug-metabolizing enzyme systems relative to other organs. If a drug is taken into the GI tract, where it enters hepatic circulation through the portal vein, it becomes well-metabolized and is said to show the first pass effect.
Other sites of drug metabolism include epithelial cells of the gastrointestinal tract, lungs, kidneys, and the skin. These sites are usually responsible for localized toxicity reactions.

[edit] Factors that affect drug metabolism

The duration and intensity of pharmacological action of most lipophilic drugs are determined by the rate they are metabolized to inactive products. The Cytochrome P450 monooxygenase system is the most important pathway in this regard. In general, anything that increases the rate of metabolism (e.g., enzyme induction) of a pharmacologically active metabolite will decrease the duration and intensity of the drug action. The opposite is also true (e.g., enzyme inhibition). However, in cases where an enzyme is responsible for metabolizing a pro-drug into a drug, enzyme induction can speed up this conversion and increase drug levels, potentially causing toxicity.
Various physiological and pathological factors can also affect drug metabolism. Physiological factors that can influence drug metabolism include age, individual variation (e.g., pharmacogenetics), enterohepatic circulation, nutrition, intestinal flora, or sex differences.
In general, drugs are metabolized more slowly in fetal, neonatal and elderly humans and animals than in adults.
Genetic variation (polymorphism) accounts for some of the variability in the effect of drugs. With N-acetyltransferases (involved in Phase II reactions), individual variation creates a group of people who acetylate slowly (slow acetylators) and those who acetylate quickly, split roughly 50:50 in the population of Canada. This variation may have dramatic consequences, as the slow acetylators are more prone to dose-dependent toxicity.
Cytochrome P450 monooxygenase system enzymes can also vary across individuals, with deficiencies occurring in 1 - 30% of people, depending on their ethnic background.
Pathological factors can also influence drug metabolism, including liver, kidney, or heart diseases.
In silico modelling and simulation methods allow drug metabolism to be predicted in virtual patient populations prior to performing clinical studies in human subjects.^[3] This can be used to identify individuals most at risk from adverse reaction.

Clinical pharmacology

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This article does not cite any references or sources. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (October 2008)

Clinical pharmacology is the science of drugs and their clinical use. It is underpinned by the basic science of pharmacology, with added focus on the application of pharmacological principles and methods in the real world. It has a broad scope, from the discovery of new target molecules, to the effects of drug usage in whole populations.
Clinical pharmacology connects the gap between medical practice and laboratory science. The main objective is to promote the safety of prescription, maximise the drug effects and minimise the side effects. It is important that there be association with pharmacists skilled in areas of drug information, medication safety and other aspects of pharmacy practice related to clinical pharmacology.
Clinical pharmacologists usually have a rigorous medical and scientific training which enables them to evaluate evidence and produce new data through well designed studies. Clinical pharmacologists must have access to enough outpatients for clinical care, teaching and education, and research as well be supervised by medical specialists. Their responsibilities to patients include, but are not limited to analyzing adverse drug effects, therapeutics, and toxicology including reproductive toxicology, cardiovascular risks, perioperative drug management and psychopharmacology.
In addition, the application of genetic, biochemical, or virotherapeutical techniques has led to a clear appreciation of the mechanisms involved in drug action.

[edit] Branches

• Pharmacodynamics - finding out what drugs do to the body and how. This includes not just the cellular and molecular aspects, but also more relevant clinical measurements. For example, not just the biology of salbutamol, a beta2-adrenergic receptor agonist, but the peak flow rate of both healthy volunteers and real patients.
• Pharmacokinetics - what happens to the drug while in the body. This involves the body systems for handling the drug, usually divided into the following classification:
  • Absorption
  • Distribution
  • Metabolism
  • Excretion.
• Rational Prescribing - using the right medication, at the right dose, using the right route and frequency of administration for the patient, and stopping the drug appropriately.
• Adverse Drug Effects
• Toxicology
• Drug interactions
• Drug development - usually culminating in some form of clinical trial.