Essay on Pharmacology: Basic Principles

by: Archimedes O. Bayquen, RPh, MPH

Pharmacology is the study of drugs or in laymen’s term more commonly referred to as medications. Drugs are any substances that can alter the physiological functioning of the body. The official and more complete definition of drugs can be found in United States Pharmacopeia.

Brief History

Drugs are beneficial to the society. As old as man himself, drugs were used a very long time ago. During the very early times, incantations/ prayers by shamans and spiritual healers were employed as treatment of disease. In the ancient civilization, herbs, plant extracts, natural chemicals, biologic products were used by the Egyptians, Sumerians, Chinese and many others. Paracelsus, the Father of Pharmacology is recognized for his many contributions in the field. Many personalities like Galen and Dioscorides, Alexander Fleming, Paul Erhlich, Jenner, etc have also contributed much to the field of pharmacology from herbal formulation of ointments, creams to developing biologic products such as vaccine, development of antibiotic, demonstrating selective toxicity and so on.

At this present day and age, drugs have evolved employing recombinant DNA, nanotechnology, nanocapsules, complicated drug designs are applied. Pharmaceuticals have greatly advanced with newer drug delivery systems, better and safer drugs along the way.

Pharmacokinetics

Kinetics is how the body responds to the drug. It involves ADME (Abosorption, Distribution, Metabolism and Excretion. It is how the body processes the drug so that it reaches the target cell and effects a response. Some drugs can not be given orally due to extensive metabolism by liver enzymes termed as first pass effect. Others take advantage of this mechanism as they are given as inactive preparations only to be activated once it passes thru the liver known as “prodrugs”. Most of the drugs in the market are weak acids and weak bases as they are more readily absorbed. This is governed by the Henderson-Hasselbach equation. Meanwhile, the Fick’s Law of Diffusion predicts the rate of movement of molecules across a barrier so that absorption is faster in organs with larger surface area as in the small intestine and is also faster in organs with thinner membranes such as  the lungs.

Some drugs require energy and special transport carriers to be absorbed. Distribution is achieved when the drug is now in the circulation and enters the target organ. Highly-perfused organs such as the heart, brain, kidneys have higher concentration of drugs. Albumin is also a special protein where weakly acidic drug binds to and serves as a buffer or reservoir of drug materials. Only the free active form of the drug has a biological effect. Bioavailability is also an important concept in Pharmacology. It refers to the amount of drug that reaches the systemic circulation (blood stream) so that a higher bioavailability is desired.

Elimination refers both to metabolism and excretion. Metabolism/ biotransformation/ detoxification primarily occurs in the liver where thousands if not millions of enzymes reside. They help convert the parent compound into a less lipid or more water soluble form for easier excretion. But not all of the time this happen because some are converted to a more active component (malathion to malaoxon, enalapril to enalaprilat), or are converted to still an active metabolite (codeine to morphine).

Excretion in the kidneys are usually enhanced by protonation or conversion to an ion so that acidic drugs are more excreted by a basic urine and vice versa. This is the principle of administering ammonium chloride, a urine acidifier, in cases of amphetamine (basic drug). Drugs can also be excreted in sweat, breast milk (mammary products), seminal fluid, saliva and expired air. That is why the chico smell of alcohol can be detected in intoxication since ethanol is excreted as the person expires.

Zero order elimination occurs when the rate of elimination is constant regardless of concentration as demonstrated by warfarin, heparin, aspirin, phenytoin, ethanol and the like. It has no true half life and can happen due to saturation of the enzymes when given in high doses. Meanwhile, first order kinetics has a true half life and can be calculated mathematically using an equation. It occurs when the elimination rate is proportionate to the drug concentration and is demonstrated by exponential decrease over time. this is the most common type of elimination as many drugs are disposed off this way.

Pharmacodynamics

Dynamics take into account mechanism of action of drugs, receptor-drug interaction, binding affinity, antagonism, tolerance and the like. Specific molecules in a biological system known as receptors interact with drugs to alter biological functions. For example when a long-acting beta-agonist such as Salmeterol interact with Beta-2 receptors in the lungs, bronchodilation occurs. This is why salmeterol is clinically useful in the management of airway obstructions such as asthma and COPD. Interaction with receptors may be achieved by different mechanism and is very selective and specific.

The efficacy of a specific drug is determined in a graded dose response curve as the minimum dose when the maximal effect of an agonist is achieved. Take into consideration that an agonist both have an intrinsic activity and affinity whereas an antagonist do not have an intrinsic activity but has strong affinity to the receptor. A partial agonist such as labetalol and carvedilol on the one hand has a weak intrinsic activity at intermediate to high doses. An antagonist can be further classified into physiological, chemical, pharmacologic (reversible/ competitive inhibition or non-reversible/ non-competitive type). A physiologic antagonist can be classically demonstrated by the bronchoconstriction effect of histamine is being reversed by epinephrine via beta-2 agonist effect. A chemical antagonist is noted when tetracycline interacts directly with milk/ alkali-containing antacids/ calcium supplement, inactivating and de-stabilizing its chemical structure leading to inactive/ ineffective drug product. Both tetracycline and Calcium supplement will neither exert its intended therapeutic effect in this manner. A pharmacologic agonist occurs when a drug either competitively or non-competitively compete with the same receptor or another allosteric site.

The therapeutic index of the drug can be determined by Quantal dose curved where the Lethal Dose 50 and Effective Dose 50 are plotted. A wide margin of safety is better tolerated even at higher doses and is an ideal characteristic of a drug. A narrow therapeutic index such as digoxin and lithium should be carefully monitored due to its potential toxicity. Potency can either be derived by quantal/graded dose response curved. It is defined as the minimum dose producing a therapeutic effect. A small dose of Drug X producing the same biologic activity as larger dose of Drug Y is said to be more potent.

Summary

In marketing a generic product, pharmacokinetics and pharmacodynamic parameter must be shown to be identical or at least near-identical. Bioequivalence studies conducted in Quality Control section are important.  It is the property of  a drug product with the same active formulation to elicit the same level of response at the site of action and so must achieve the same level of drug concentration in the blood. It is more of a pharmacokinetic application but the pharmacodynamics of the drug is still important with this respect.