Pharmacology 101
By HAWLEY HOLMAN
Pharmacology is the study of pharmaceuticals and their effects-is the fundamental science of drug development.
The filed of pharmacology has two branches: pharmacokinetics and pharmacodynamics.
Pharmacokinetics examines what your body does to a drug, including how a drug gets where it needs to go and how
your body gets rid of it. It can explain adverse events when drugs interact.
Pharmacodynamics studies the drug’s effect on your body: for example, how a pill works its therapeutic effect. It
can describe adverse events resulting from the response from the body’s response to a drug.
A drug gets into the body in several ways such as pills, capsules, etc. Once in your stomach it must cross the stomach or intestinal
wall and then enter the bloodstream to reach its treatment target.
Pharmacokinetics considers four areas:
(1) Absorption - The size and chemical properties of a drug molecule determines how easily the body can absorb it. Drugs pas through a membrane in several ways. By diffusion and others use transport proteins. How readily a drug is absorbed affects how much is available to exert therapeutic (or toxic) effect. Stomach acidity can affect absorption. Food in the stomach may affect absorption. Absorption affects the percentage of a dose the body will take up and how quickly. Absorption is key to determining the amount of drug needed, the timing of the doses, and the way the drug is administered. Researchers developing a new drug must consider its absorption rate and corresponding dosage in assessing the risk of side effects.
(2) Distribution - Some drugs travel throughout the body while others target a specific organ. When a drug enters the bloodstream the first organ it encounters is the liver and some drug’s chemicals remain there which can be advantageous but also cause adverse reactions. For example, cholesterol-lowering drugs can cause liver damage because they concentrate there and become toxic. People taking these drugs require periodic liver function tests. Protein-binding also affects drug distribution. Most drugs bind to proteins and when this occurs the drugs are no longer floating around free so they may not be able to cross membranes and exert their intended effect. When many drugs are in the bloodstream at once, they may compete to bind with proteins and this may cause a drug interaction. For example, many people with hear disease take/Warfarin which has a very narrow window where it is beneficial-i.e. there is a small range between the dose that is helpful and the dose that can cause serious problems, including bleeding .If another drug is present with more protein-binding power this can send more Warfarin into the bloodstream placing the patient at risk for bleeding or hemorrhage.
(3) Metabolism - Drugs are foreign to our bodies .and our system attempts to expel them not discriminating between the helpful and harmful ones. Manu drugs must be changed or transformed- metabolized-before they can be removed. If your body didn’t eliminate a drug it would remain in your system and if you kept taking it this could lead to toxic levels in your bloodstream. Generally, your body metabolizes the drug to make it inactive or turn it into a molecule that can be easily eliminated fro the body. However, in some cases metabolism actually makes a drug more active. Thus, some drugs are inactive when administered and become active after a certain change takes place inside the body. The most common way the body metabolizes drugs is by using a family of proteins known as the cytochrome P450 pathway. The enzymes of the P450 family are proteins that help our bodies remove drugs. These individual proteins are called isozymes. There are many of them but all perform similar functions. If one enzyme is metabolizing two drugs being taken together, the enzyme may not metabolize them as quickly as it would if only one were present. This is called affect dosing. Drug interactions are the reasons some drugs removed from the market. This is why it is critical for drug company to study how a compound is metabolized along with other pharmacokinetic effects, in order to identify potential harmful interactions with other commonly used drugs. For example, Posicor was withdrawn when it was shown that certain drugs rose to dangerous levels when administered with Posicar. Baycol- used to treat high cholesterol- was also withdrawn after ti showed increased risks of inducing a severe muscle adverse reaction.
(4) Elimination or Excretion - The body typically expels drugs through the urine or feces. Some leave unchanged while others leave after they are metabolized. This process usually occurs in the kidneys which filters the drug or drug metabolites into the urine. Because drugs filter through the kidneys and ultimately concentrate there, these organs are susceptible to drug-induced toxicity. Since a patient with kidney disease who may experience symptoms which may be caused by adverse drug effect physicians must carefully monitor patients with renal failure and other kidney diseases when using medications
HOW DRUGS DO WHAT THEY DO
Drugs generally bind to a cellular receptor or enzyme where they initiate a series of biochemical reactions which is separate and distinct from the protein-binding process discussed above. A drug does not initiate any biological response when it bonds to a protein in the blood; but, when a drug binds to a receptor or enzyme that a pharmacologic effect can occur. A cellular receptor is a protein with a specific biological function that a drug can enhance or disrupt. When a drug turns receptors “on” or “off”, it starts or stops certain biochemical reactions that alter the cell’s physiology and yield a certain effect. Some drugs block or enhance the function of enzymes and proteins within cells, including statins, which stop the enzymes they bind with from producing more cholesterol which lowers the level of cholesterol in the blood. Because a cell contains only a limited number of receptors to which a drug can bind, the drug’s effect is limited. This is why it is not always better to take more of a drug. There may be a large increase in toxicity with a small increase in therapeutic benefit. A drug’s effect depends upon how well it fits into a specific receptor site. The receptor or enzyme is the lock; the molecule is the key. Thus, the lock-and-key model.
EFFICACY AND POTENCY
“Potency” refers to a drug’s strength; “efficacy” refers to the degree to which it can produce a certain effect. Efficacy means the degree to which a drug is able to induce an effect. Potency is typically used to compare drugs within a class or group that work by the same mechanism. Efficacy is used to compare drugs that have different mechanisms. Drugs that are more potent may also pose higher risk of toxic side effects and drug companies must be aware of these potential risks. Drugs can also have more than one effect. Many locks can be opened by more than one key. Also, many drugs treat the same conditions thus creating a class of drugs. Conversely, keys can look alike and open more than one lock allowing a drug to work on more than one receptor. This secondary activity may lead to new treatment or to unwanted side effects. For example, Rogaine was developed to treat hypertension but one side effect was hair growth and today it is marketed as remedy for hair thinning. Some drugs have unexpected side effects that are toxic.
A drug company is supposed to design a clinical trial according to the principals of pharmacokinetics and pharmacodynamics. However, in litigation with drug companies you must determine what the company was looking for and what it should have been looking for. You must also ask if the company ignored obvious signs of adverse effects. Were the trials thorough enough to detect potential problems? These are just a few questions which may need to be answered when investigating a drug claim.