What is pharmacology?

Pharmacology comes from two Greek roots: “pharmakon” meaning drug, and “logos” meaning study of — so pharmacology means the study of drugs.

Definition: Pharmacology is a branch of science which deals with the study of drugs — their origin, nature, properties and effects. Put another way: the study of how a drug affects a biological system, and how the body responds to the drug.

A drug, defined

A drug is a medicine or other substance used for the purpose of diagnosis, prevention, relief, or cure of disease in man or animals.

Branches of pharmacology

Pharmacodynamics and Pharmacokinetics are the two main divisions of pharmacology.

• Pharmacodynamics
• Pharmacokinetics
• Pharmacotherapeutics
• Clinical pharmacology
• Chemotherapy
• Toxicology

Pharmacodynamics

What the drug does to the body (effect). Includes the effects of a drug on organ systems and their mechanism of action — molecular, biochemical and physiological. Example: adrenaline (epinephrine) binds to its receptor (the adrenoceptor / adrenergic receptor) present in the kidney, heart etc., causing stimulation — an increase in heart rate, force of contraction, cardiac output and blood pressure.

Pharmacokinetics

“Pharmaco” (drug) + “kinetics” (movement) — what the body does to the drug (respond). The study of the movement of drugs in the body.

Pharmacotherapeutics

The branch of medicine concerned with the cure of disease or relief of symptoms.

Clinical pharmacology

Study of the effects of drugs in human beings; includes pharmacodynamic and pharmacokinetic investigation in healthy volunteers as well as in patients.

Chemotherapy

Use of a proper clinical dose to have the maximum effect — chemical treatment for the treatment of systemic infection or cancer, with a drug that has selective toxicity for the infective organism or malignant cell and a minimum effect on the human (host) cell.

Toxicology

Study of poisons — the study of the poisonous or adverse effects of drugs, and the practice of diagnosing and treating poisoning. A drug used in overdose (poisoning) shows its side effects; the same side effects used for another disease can become a treatment.

Example: cardiac arrest in a person is a loss of the heart’s pumping flow. The adrenaline drug binds to the adrenergic receptor, causing cardiac stimulation and an increase in heart rate — a pharmacodynamic action.

Historical landmarks

It is of intellectual interest to know how drugs are discovered and developed. In the past, intelligent observation became the reason for the discovery of many drugs, like cinchona (quinine) and penicillin (antibiotics that kill bacteria), used to treat malaria and infection respectively. Ancient civilisations discovered that extracts from plants, animals and minerals had a medicinal effect on body tissue — these discoveries became the foundation of pharmacology.

Scope of pharmacology

Disease / disorder

To study pathophysiology.

Pharmacodynamics

Study of what the drug does to the body (effect).

Pharmacokinetics / ADME

Study of what the body does to the drug (respond).

Clinical pharmacology & therapeutics

Making a drug’s efficacy / effect increase and its side effects decrease, for use against different diseases or symptoms. Includes posology (deciding the dose of a drug for age) and bioavailability (how much drug reaches the systemic circulation to show its effect).

Toxicology

Study of drug use in poisoning — showing side effects; a side effect used for another disease can become a treatment; finding the drug dose/time to inject or the drug present in the body.

Forensic science

Preventing / detecting drug misuse in the body.

Nature and source of drugs

A drug is the single active chemical entity present in a medicine that is used for the diagnosis, prevention, treatment or cure of a disease.

Classification by chemical nature

Classification by physical nature

Source of drugs

A closer look at plant and animal sources

Concept of essential drugs

Essential drugs (also known as essential medicines) are, according to WHO, those drugs that satisfy the health-care needs of the majority of the population. Essential medicines should always be available in the health system, at all times, in adequate amounts, in the appropriate dosage form, with assured quality and adequate information, and at a price the individual and the community can afford.

WHO criteria for selecting a medicine for a country’s EML

• To meet the needs of the majority of people, priority should be given to medicines of proven efficacy and safety (unnecessary duplication of medicines should be avoided).
• Each selected medicine must meet the prescribed standard of quality, including shelf life in the local climate and storage conditions.
• When two or more drugs appear to have similar efficacy and safety, preference should be given to the medicine with the more favourable pharmacokinetic data.
• Cost of the total treatment should be considered a major selection criterion for including a medicine in the list.
• The proposed medicine should preferably be a single-dose compound; a fixed-dose combination of two medicines is acceptable only when both medicines meet the requirement of the pharmacokinetic criteria.

Routes of drug administration

A route of administration is the path by which a drug comes into contact with the body.

Local routes

The simplest mode of administering a drug at the site (a particular area) where the desired action is required.

Topical route

The drug is applied to the external / outer surface of the skin, at various sites, for local action. This includes administering drugs to any mucous membrane — eye, nose, ear, vagina, lungs, urethra.

Inhalation

The drug is inhaled in the form of a gas, volatile agent or aerosol. Example: bronchodilators used in a nebulizer are inhaled to show their effect on the respiratory tract — e.g. salbutamol, a medication that relaxes and opens the airways (bronchi) in the lungs.

Rectal route

Administering a drug in the form of a suppository, or as an enema, into the rectum — used to treat constipation by injecting a liquid solution into the rectum.

Systemic routes

Enteral route: oral

Drugs given by an enteral route pass through the GIT and reach the blood to show a systemic effect. Oral administration is the most common and acceptable route for drug administration (drug taken by mouth). Dosage forms for oral administration: tablet, capsule, syrup, emulsion, suspension. Example: paracetamol tablet for fever.

Buccal and sublingual route

Placing the drug under the tongue, or between the gums and cheek, inside the mouth. Some drugs are taken as small tablets that are held in the mouth or under the tongue — these are buccal or sublingual dosage forms. Buccal tablets are often harder (about a 4-hour disintegration time), designed to dissolve slowly. Sublingual tablets are softer (about a 2-minute disintegration time) and dissolve rapidly.

Parenteral route

First-pass metabolism of the drug does not occur, because the drug does not pass through the intestine or liver — it goes directly into the blood, showing a systemic effect.

Intravenous (IV)

The drug is injected directly into the bloodstream through a vein, either as a slow IV injection or an IV infusion.

Subcutaneous (SC)

The drug is injected into the subcutaneous tissue of the thigh, abdomen or arms. Example: adrenaline, insulin.

Intramuscular (IM)

The drug is injected deep into the belly of a large skeletal muscle (e.g. triceps), at a 90° angle.

Intracardiac (IC)

An injection given directly into the heart muscle or ventricles; can be used in emergencies.

Intra-arterial (IA)

Administration of a drug into an artery. Considered more dangerous than IV and should be done by an expert.

Receptors, agonists and antagonists

Receptor

A macromolecule or binding site, located on the surface of or inside a cell, that recognises a drug and initiates its action.

Agonist

A chemical that binds to a receptor and activates it to produce a biological response. Receptors can be activated by an endogenous agonist (a hormone or neurotransmitter, e.g. adrenaline / acetylcholine in the body) or an exogenous agonist (a drug, e.g. an adrenaline / acetylcholine drug).

Antagonist

A chemical / drug that prevents an agonist from binding to the receptor site and blocks the biological response.

Competitive antagonist

Has the same structure as the agonist, and binds to the receptor at the same binding site (active site) as the agonist — but without activating the receptor.

Non-competitive antagonist

Has a different structure from the agonist. It may act in one of two ways: binding to the active site of the receptor, or binding to an allosteric site of the receptor. If it binds an allosteric site, it is called an allosteric antagonist.

Spare receptors

Receptors that are not occupied by the drug molecule in producing a pharmacological action / response. They are the same as normal (non-spare) receptors — they are not hidden.

Addiction, dependence, tolerance and tachyphylaxis

Addiction

A psychological and physical inability to stop consuming a chemical, drug or substance, even though it is causing psychological and physical harm. The term isn’t limited to substances such as heroin or cocaine — anyone who can’t stop taking a particular drug or chemical has a drug addiction. Example: amphetamines, cocaine, cannabis and LSD are drugs that produce addiction.

Drug dependence

A state in which an organism functions normally only in the presence of a drug. Dependence develops when neurons adapt to repeated drug exposure and only function normally when the drug is present.

Drug tolerance

A state in which an organism no longer responds to a drug — i.e. a higher dose is required to achieve the same effect or response. Tolerance is the diminishing effect that results from repeated administration of a given dose.

Tachyphylaxis

The rapid development of tolerance, seen when some drugs are administered repeatedly within a short time. Also known as acute tolerance.

Idiosyncrasy and drug allergy

Idiosyncrasy

A condition in which a side effect of a drug is seen only in a few people in a population after the drug is taken. Example: a barbiturate drug taken by a group of people causes excitement or mental confusion in only a few of them.

Drug allergy (hypersensitivity)

The abnormal reaction of the immune system to a medication. Any medication — over-the-counter, prescription, or herbal — is capable of inducing a drug allergy.

The most common signs and symptoms of a drug allergy: rash, fever, shortness of breath, facial swelling, joint swelling, tender lymph nodes.

Types of allergic reaction

What is pharmacokinetics? (ADME)

Pharmacokinetics is the study of the movement of drugs in the body — what the body does to the drug. It is the study of how drugs are Absorbed, Distributed, Metabolised (biotransformed) and Excreted from the body — hence pharmacokinetics is also known as ADME.

Example: a paracetamol tablet is taken orally → it moves into the GIT → it is completely absorbed in the GIT within 30–60 minutes → it is then distributed throughout the body via the blood → the liver then helps metabolise (biotransform) it → it is then excreted via the kidney.

All of these processes involve the passage of the drug molecule across various barriers, such as the intestinal epithelium, the capillary barrier, and the cell membrane.

Drug transport across the cell membrane

The cell membrane is made up of two layers of phospholipids. The hydrophilic (water-attracting) heads face outward on both sides, and the hydrophobic (water-repelling) tails face inward, with fluid present both inside and outside the cell.

Lipophilic drugs cross the cell membrane easily, i.e. they have a faster rate of absorption. Hydrophilic (hydrophobic-to-water) drugs do not cross the cell membrane easily — they need a protein channel to cross, i.e. they have a lower rate of absorption.

Transport types

Passive transport

(i) simple diffusion, (ii) filtration — the drug moves across the cell membrane without any need for energy. About 95% of drugs move by passive transport.

Carrier-mediated transport

(i) active transport, (ii) facilitated diffusion.

Endocytosis / pinocytosis

A separate mechanism for engulfing larger material.

Simple diffusion

The transfer of a drug across the cell membrane in the direction of its concentration gradient. The speed of diffusion depends on (i) the concentration gradient and (ii) the lipid solubility of the drug.

Filtration (aqueous diffusion)

The passage of drugs through aqueous pores to cross the cell membrane. A hydrophilic (water-soluble) drug can cross the biological membrane by filtration this way — e.g. urea.

Active transport

The transfer of a drug against its concentration gradient, which needs energy; it is carried by a special carrier protein. Example: levodopa, sugar.

Facilitated diffusion

A unique form of carrier transport, different from active transport — it needs no energy, and movement occurs in the direction of the concentration gradient.

Endocytosis / pinocytosis

A process in which small droplets of a substance are engulfed by a fold of the cell membrane, which makes a pocket-like structure that then moves across the cell membrane.

Absorption and the factors affecting it

Drug solubilisation

If a drug is lipid-soluble in nature, it crosses the cell membrane easily and has fast solubility / absorption. If a drug is water-soluble (hydrophilic in nature), it cannot easily cross the cell membrane and has less solubility / absorption.

Formulation factor

Materials added to a drug during processing can affect its solubilisation: excipient + fillers + API + disintegrators + binder + lubricant. Fillers add bulk to the drug; disintegrators cause the tablet to break down into granules; binders hold the tablet together; lubricants prevent the tablet from sticking. Depending on the formulation, the absorption rate increases or decreases.

Concentration of drug at the absorption site

More liquid / fluid flow means the drug concentration is higher, so the absorption rate increases; less fluid flow means the concentration is lower, so absorption is lower.

Surface area

If the surface area at the absorption site increases, more of the drug is absorbed — e.g. the stomach has less space so less absorption, whereas the intestine has more surface area for faster absorption.

Route of administration

The intravenous route has 100% bioavailability and faster absorption of the drug, since it goes directly into the blood. The oral route has less absorption because some drugs undergo first-pass metabolism.

Blood flow

Where blood flow at the absorption site is faster, absorption of the drug increases; where blood flow is slower, absorption is lower.

Gastric emptying

The time taken for food to empty from the stomach and enter the intestine. Faster gastric emptying means faster absorption of the drug; slow gastric emptying means slower absorption.

Food

Some food increases the absorption rate of some medicines, while other food (fatty food) decreases the absorption rate of some medicines.

Intestinal motility

The movement / passage of food in the intestine. Faster intestinal motility means faster gastric emptying, and so faster absorption.

Bioequivalence

Two products of the same drug, often from different companies (e.g. Glaxo vs Cipla), can differ in their making, active agents, strength, dosage form and route of administration, yet still be considered bioequivalent if given orally with a similar bioavailability (e.g. 80%).

Bioavailability

Bioavailability means the fraction of a drug that enters the systemic circulation and then reaches its site of action.

Oral drugs, due to first-pass metabolism, have lower bioavailability. Example: a 100 mg tablet, after first-pass metabolism, leaves only 60 mg of active drug — 60% bioavailability. An intravenous injection goes directly into the systemic circulation — 100% bioavailability. Example: a 100 mg IV injection puts 100 mg in the blood — 100% bioavailability.

Distribution

Once a drug is absorbed into the systemic circulation, it can be carried throughout the body’s cells — this process is called distribution.

When a drug is absorbed into the blood, it binds to plasma protein, which is present in the blood; some drugs are not bound to plasma protein. A drug bound to plasma protein distributes more slowly; a drug not bound distributes faster. Example plasma proteins: albumin, lipoprotein, α₁-acid glycoprotein.

Factors affecting distribution

Regional blood flow

Tissues / organs with a high blood flow have a rapid distribution of drug. Approximate perfusion rate (mL/min/100 g tissue): lung 400, kidney 350, muscle 3, skin 1, adipose tissue — low.

Capillary permeability

If capillary size is high, there is faster / more distribution of the drug. Example: the liver has large capillary junctions — fast distribution of drug.

Rate of transfer from interstitial fluid into tissue

By passive diffusion (most common, works in the direction of the concentration gradient — high concentration in blood vessel to low concentration in tissue), active transport, and endocytosis.

Binding to plasma protein

Albumin: works as the drug’s primary binding site, with the strongest affinity for weak acid and hydrophobic drugs. Lipoproteins: a drug binds a lipid-soluble drug, and the binding capacity depends on their lipid content. Binding ability of lipoproteins, from high to low: VLDL > LDL > HDL (very low density → low density → high density lipoprotein).

Barriers to drug distribution