Pharmacology is the biomedical science of drugs and their effects on living systems
Pharmacology is the biomedical science of drugs and their effects on living systems. The study encompasses everything ranging from the composition and properties of the drugs, to its chemical and biological mechanisms or effects on the human anatomy, and the medical applications of such drugs. Pharmacology is omnipresent in today’s society, and its knowledge if often pivotal or crucial in saving the lives of many all across the world. It helps in developing new drugs when the older ones start to become less effective, and it is also responsible for determining the proper forms of administration of the drugs for optimal effects, be it in terms of mode of administration or dosage. Essentially, pharmacology is the branch of medicine concerned with the uses, effects and modes of action of the drugs.
The 2 main areas of pharmacology are pharmacodynamics and pharmacokinetics and the effect of the drug against the human body depend on the different pharmacological class of drug. Pharmacological class is classified in a set of medications and other compounds that have similar chemical structures, similar characteristics, the same mechanism of action and a related mode of action and/or are used to treat the same disease.
There are various pharmacological classes such as Beta Blockers, Angiotensin-Converting Enzyme (ACE) inhibitors and NonSteroidal Anti-Inflammatory Drugs (NSAIDs). Beta blockers, also known as beta-adrenergic blocking agents, are medications that lower blood pressure. Their primary function is to block the effects of the hormone epinephrine, also known as adrenaline from binding to receptors. Examples of Beta Blockers are Atenolol, propranolol etc. Angiotensin-converting enzyme (ACE) inhibitors are heart medications that enlarge or dilate blood vessels that increases the amount of blood a heart pumps and lower the blood pressure. They also increase blood flow, which helps to lower a heart’s workload. ACE inhibitors help to prevent, treat or improve symptoms in conditions such as high blood pressure, coronary artery disease, heart failure, diabetes etc. Examples of ACE inhibitors are Benazepril, Moexipril, Sulfonylureas, Meglitinides etc. NSAIDs is a drug class that are more than pain relievers. They also help to reduce fever, averts blood clots and reduces inflammation. Examples are aspirin, ibuprofen and naproxen, mefenamic acid etc.
Pharmacodynamics of Aspirin
Pharmacodynamics is the relationship between drug concentration and pharmacological response at the site of action and the resulting effect which include the time course and intensity of therapeutic and adverse effects. It is important to know that the change in drug effect is not correspond to the change in drug dose or concentration. The effect of a drug present at the site of action is determined by that drug’s binding with a receptor. Receptors are proteins on the cell wall which bind to ligands and the binding reactions convert into a signal to the cell and cause responses in the immune system. The concentration at the site of the receptor determines the intensity of a drug’s effect for most of the drug. It may be present on the neurons in the central nervous system in the part of the body to depress pain sensation, on heart muscle to affect the intensity of contraction, or even within bacteria to disorder the maintenance of the bacterial cell wall.
Aspirin is effective in reducing fever and inflammation, in thinning of blood to prevent blood clots, and as a pain reliever. It does so by inhibiting the action of enzymes in the body, such as prostaglandin synthesis which induces analgesic effects. Prostaglandins are made at sites of tissue damage or infection, where they cause inflammation, pain and fever as part of the healing process. When a blood vessel is injured, it stimulates the formation of a blood clot and tightens the muscle in the blood vessel wall to prevent blood loss and try to heal the injury. Prostaglandins can also relax the muscle in the blood vessel to cause the vessel to be widen and control the amount of blood flow and regulate response to injury and inflammation. The mechanism of action of the drug aspirin act on the Central Nervous System of the brain. The substances in the mechanism of actions of aspirin works by stopping prostaglandin being made and aspirin molecules enter the cell and chemically modify the enzyme to prevent prostaglandin being made. Aspirin molecules that enter the cell to stop an enzyme is knowns as cyclooxygenase, COX-1 and COX-2, which is involved with the ring closure and addition of oxygen t arachidonic converting to prostaglandins. The acetyl group on aspirin is known as hydrolyzed and then bonded to the alcohol group of serine as an ester. This has the effect of preventing the channel in the enzyme and obstructing arachidonic from entering the active site of the enzyme. By preventing or obstructing this enzyme, the synthesis of prostaglandins is blocked, which in turn relives some of the effects of pain and fever. Aspirin also works to prevent heart attacks and strokes by reducing the production of thromboxane, a chemical that makes platelets sticky and it produce less thromboxane and are less likely to form a blood clot that could block an artery.
Routes of administration
There are two general methods of drug administration, enteral and parenteral administration. For enteral administration solid and liquid dosage form are normally used and its comprises the esophagus, stomach, and small and large intestines (i.e., the gastrointestinal tract). The methods of administration include oral, (swallow by mouth) sublingual (dissolving the drug under the tongue), and rectal (supporities). As for parenteral routes, which do not involve the gastrointestinal tract, subcutaneous (injection under the skin), include intravenous (injection into a vein), intramuscular (injection into a muscle), transdermal (absorption through intact skin) and inhalation (infusion through the lungs),
Introduction of Pharmacokinetics
Pharmacokinetics is the study with what the body does to the different dosage form of drugs after the different routes of administration. For drugs to produce their therapeutic effects, they must bind with the receptor in the body. The processes that occur after drug administration can be broken down into four district area (ADME), Absorption of the drug, Distribution of the drug molecules, Metabolism of the parent drug and Excretion or elimination of the drug and its metabolites.
Drug absorption is determined by the drug’s physicochemical properties, formulation, and route of administration. A drug in a solid dosage forms is administered orally through the mouth and moves through the GI tract and disintegrates into small particles and dissolve in GI fluid before absorption process. Majority of oral drugs, after they enter the portal venous system and pass through the liver before gaining access to the systemic circulation. Drugs that are administered by buccal, sublingual or rectal routes bypass the liver (first pass metabolism), avoiding the gastric acid, binding to food and metabolism by gut wall or liver enzymes. As for parenteral administration, absorption will directly into the circulatory system through the small pores in the capillary walls thus bioavailability is 100%.
Distribution is the process of the reversible movement of drug from the blood into the tissues. After absorption into the bloodstream, drug molecules must cross capillary walls to enter the tissues, reach cell membranes and enter the cells. Many drugs are bound to plasma proteins and is unable to leave the blood circulation due to its large molecular size and fraction is inert, thus it reduces the overall potency of a drug. The drug fraction freely diffuses out of the vascular system and distributes to the tissues and effects are reduced. The drug might also bind to non-target receptors, producing unwanted effects.
Metabolism is the process by which drugs are chemically transformed from a lipid-soluble form suitable for absorption and distribution to a more polar form that is suitable for excretion out from the body. The reactions are catalysed by enzymes in the liver and though some changes in the lungs, gut wall and blood plasma are known as metabolites. Producing metabolites that consist of polar molecules which can be excreted in the body fluids such as bile and urine. Metabolism if divided in to two phases:
Phase 1 metabolism involves the conversion of patent drug molecules into more polar molecules for excretion, via chemical processes such as oxidation, reduction or hydrolysis. These reactions are primarily aided by the cytochrome 450 family enzymes commonly found in the smooth endoplasmic reticulum of the liver cells. Most products are pharmacologically inactive and one or more of the metabolites are pharmacologically active but lower than original the drug. The original substances are not pharmacologically active and known as Prodrug.
Phase 2 metabolism, the Phase 1 metabolite or the original drugs are conjugated with an endogenous substrate to form highly polar products, increasing their solubility in water such that it is able to be excreted.
Excretion is the removal of drugs and/or its metabolites from the body by biliary system (kidney), urinary tract, sweat, tears, saliva or exhalation. Urinary excretion is the usual route for the elimination of small drugs which are water-soluble. While drugs bound to plasma proteins are not filtered by the glomeruli, small molecules that are free are filtered and enter the renal tubules. These small molecules with low molecular mass can include drugs that have not been metabolised, as well as the metabolites which have entered the bloodstream after metabolism in the liver or other organs. After entering the tubules, the molecules may be reabsorbed if they are still lipid-soluble and excreted otherwise.
On the other hand, for larger, heavier molecules, faecal excretion is the preferred route of elimination. These include those that are conjugated with glucuronide in the liver via Phase 2 metabolism, and any drugs that are not absorbed. Molecules of drugs or metabolite that enter the bile after metabolism in the liver are carried into the intestinal lumen, passed down the gut and subsequently excreted in the faeces. Similarly to urinary excretion, the lipid-soluble molecules may be reabsorbed back through the tubules and the re-enter the bloodstream, namely the portal vein. This recycling between the liver, bile, gut and portal vein is known as the entero-hepatic circulation.
Pharmacokinetics of Aspirin
Aspirin is acidic drug that will be better absorbed in the stomach and intestine by passive diffusion and is transformed into salicylate in the stomach, in the intestinal mucosa, in the blood and mainly in the liver. Aspirin take a short time to metabolise and eliminate from the bloodstream (short half- life) as such, salicylate is mainly metabolized by the liver, occurs primarily by hepatic conjugation with glycin or glucuronic acid. The prevalent pathway is the conjugation with glycin which saturable and salicylate metabolites is excreted in the urine.
All patients have very different immune system, absorption, distribution, elimination characteristics. The mechanisms of a drugs that cause variable responses to medications in different patients will affect the bioavailability. Pharmacology is the study of medicine in regard with the uses, effects and modes of action of the drugs. Due to more medicines in the market, it has become more important in determining the potential interactions caused by patients taking multi prescribed, over the counter and even homeopathic medications.