Introduction to Pharmacology

The word "Pharmacology" derives from Greek word:

• Pharmacon = drug
• Logos = discoursein

Pharmacology is the branch of medicine that studies how chemical substances that are not consumed by the body interact with it at the level of live cells, tissues, organs, or systems.

The two main divisions of pharmacology are:

• Pharmacokinetics
• Pharmacodynamics

Branches of Pharmacology

Pharmacokinetics: Pharmacokinetics is the study of how a drug interacts with the body. It is described as the procedure by which the body assimilates, distributes, metabolizes, and excretes a drug.

Pharmacodynamics: The study of a drug's effects on the body is known as pharmacodynamics. It is the study of how a drug enters the body from the point of administration, travels to various body regions, is metabolized, and then is released through specific organs in the excretory system.

Terminology Related to Pharmacolory Pharmaceutical

Drug:
According to WHO (1996), "Drug is any substance or product that is used or is intended to be used to modify or explore physiological states for the benefit of the recipient." Chemical substances employed in the diagnosis, prevention, and treatment of disease are also referred to as drugs.

Pharmacy:
The goal of pharmacy is to ensure the safe, efficient, and cheap use of medications. Pharmacy is the art and science of compounding, distributing, reviewing, or producing appropriate dosage forms for administration of medications in humans or animals.

Clinical Pharmacology:
It covers every facet of the interaction between drugs and people. It is emphasizing the efficient, safe, and cost-effective use of medications. It is a broad field that both preserves and improves the very finest medical care.

Pharmacotherapeutics:
It is the use of pharmacodynamic knowledge and disease knowledge for disease prevention, control, or treatment.

Toxicology:
It is the study of poisonous effect of drugs and other chemicals with emphasis on detection, prevention and treatment of poisonings.

Hospital Pharmacist:
The hospital's pharmacist oversees all drug-related issues and administrative management. He handles all drug-related tasks in hospitals, including dispensing, manufacturing, teaching, and making medications.

Medication:
It is a substance that is given to a person in order to diagnose, treat, prevent, relieve, or otherwise improve their health. One of a nurse's main duties is to provide medication in a safe and correct manner. Nurses are therefore required to be familiar with the name, classification, mode of action, indication, dosage, contraindication, side effect, and nursing responsibilities of all medications. while dispensing medicines

Dose:
It is the quantity to be administered at one time, or the total quantity administered during a specified period. For example Amoxycillin 500mg tid for 7 days. 500mg dose of Amoxycillin. Dosage implies a regimen; it is the regulated administration of individual doses and is usually expressed as a quantity per unit of time.

Poison:
It is a substance which endangers life by severely affecting one or more vital functions.

Indication/Use:
It is the strong reason for believing that a particular course of action is desirable. Eg: High fever patient, anti-pyretic drugs are indicated.

Contraindication:
Any factor in a patient's condition that makes it unwise to pursue a certain line of treatment is known as contraindiction. Example: Aspirin is contraindicated in peptic ulcer disease

Pharmacogenetics:

Pharmacogenetics is the study of how the actions of and reactions to drugs vary with the patient's genes

Therapeutics:
Treatment and care of a patient for the purpose of both preventing and combating disease or alleviating pain or injury. The term comes from the Greek therapeutikos, which means "inclined to serve."

Chemotherapy:
The effect of drugs on infected micro-organisms and parasites in a living organism is called chemotherapy. It also includes the treatment of cancer.

Pharmacopeia & Formulary:
Drug compendia refers to the collection of guidelines for pharmaceuticals and medical equipment, also known as pharmacopeia and formularies. A pharmacopeia, also known as a formulary, is a book that contains a list of medicinal substances (drugs) and articles (devices), chosen by a reputable authority, together with descriptions, tests, and formulas for their creation. In the majority of nations, government is the acknowledged authority that provides these criteria. Official drug compendia are accepted as benchmarks for strength, quality, and purity by a national government body.

Prescription:
It is a written directive given to a pharmacist by a licensed medical professional (AHW/CMA, HA, Sr. AHW, or Dr.) to formulate and dispense a certain prescription for the patient. A medical prescription is a written directive from a physician to a pharmacist that specifies the preparation and distribution of medications to patients. Latin terms or abbreviations are commonly utilized in prescriptions even though they are typically written in English to save time. The usual Latin phrases and abbreviations used by prescribers when writing prescriptions or cardexes must therefore be familiar to nurses and pharmacists.

Handling of prescriptions:
Pricsriptions should always be handled in the following manners:

• Receiving
• Reading and checking
• Numbering and dating
• Preparing the prescription:
  • Collecting and weighing of material
  • Compounding, labeling, and packing
• Rechecking
• Delivering and patients counseling
• Recording and filing
• Pricing the prescription

Drugs:

Any substance or product that is utilized or intended to be employed to alter physiological functions or investigate pathological disorders for the benefit of the recipient is referred to as a drug.
Drugs are those compounds that alter the pathophysiological systems of patients' or living beings' bodies, emotions, and behaviors. The body's systems and their cyclical interconnections must all be taken into account for medication treatment to be effective in the end.

Stages of drug use:

• Experimental
• Recreational drug use
• Dependent drug use
• Abstains (not taking any drugs)

The types of medicines that have mental effects and how they relate to cerebral function: Almost every medication in the pharmacopeia has the potential to cause mental effects in specific situations. For example, the hallucinogens or psychotomimetic substances LSD and mescaline are examples of this. The majority of medications work like a key lock system on the receptors that are of concern and block those receptors in order to make other medications work as well (see Pharmacodynamics as a drug's mode of action in Le.

Nature of drugs:

Pharmacodynamics:

• Stimulate the CNS eg. Cocaine, caffeine
• Depress the CNS eg Phenobarbitone, Alcohol
• Irritation the intestine eg Castor oil, Bisacodyl irritates the intestine fo laxative.
• Replacement e.g ORS, Insulin
• Modifying immune system e.g Ascorbic acid

Nature of drugs, our National regulatory body, DDA has classified into three parts:

• Group Ka: Narcotic and psychotropic drugs: Morphine, Zolpidem, Diaepam etc
• Group Kha: Antibiotic e.gAmoxycillin, Tetracycline 3.
• Group Ga: All OTC drugs come under OTC drugs. E.g Paracetamol, Albendazole, Cough expectorant etc

Prescription Drug vs nonprescription drugs

• Prescription drug:
  • Especially antibiotic should not be dispensed without doctor's prescription
• General drugs:
  • OTC drugs can be sold even by retailers

Principle of drug action

• Antagonism e.g Naloxone is given where there is overdose for Opioids.
• Therapeutic Index e.g Digoxin has the narrow therapeutic window/Index whereas Penicillin has the broad therapeutic index
• Combined drug effect:
  • If there are two drugs with the same purposes, the action is somehow enhancing. i.e drug A =1, drug B = 2(value) the resultant therapeutic value will be more than 3
• Receptor/ key lock system:
  • As per this system, concern drug block to the receptor e.g. Histamine H1 causes the itching or urticarial. If we take antihistamine that works by blocking the receptor.
• Factor modifying the drug action:
• Food also alter the absorption of drugs as well. Similarly, the particles size of Albendazole, Griseofulvin and Antacid should be smaller to show up the good absorption of drugs. The lesser particle sizes the better the absorption.

Characteristics that any drug can have:

• Effectiveness: Effectiveness is the most important property a drug can have
• Selectivity: There is no such thing as a safe drug. All the medicines can show the side effects
• Safety: A safe drug is defined as one that cannot produce harmful effects. E.g. Side effects of Opioids is respiratory failure.

Source of Drugs

Drugs are mainly obtained from plants, animals, microbes and minerals sources, but majorities of the drugs are obtained from synthetic or semi-synthetic chemicals products. The various of sources of drugs are:

• Plant sources:
  • Morphine, Codeine = opium- fruit
  • Quinine = Cinchona - bark Atropine = Belladona - any part
  • Resterpine = Serpentine - roots
  • Digoxin = Digitalis - leaves
• Animal sources:
  • Heparin, Gonadotropins, Insulin, Latgut,
  • Antiserum, Thyroid extract
• Micro-organism source:
  • Penicillin, Cephalosporins, Streptomycin iv. Minerals sources:
  • Liquid paraffin, Magnesium sulfate, Kaolin, Iron, Calcium, Sodium, Potassium, Zinc
• Semi synthetic sources:
  • Amoxycillin, Quinidine, Doxycycline
• Synthetic source:
  • Aspirin Paracetamol, Diclofenac, Atenolol, Salbutamol, Methotrexate, Isoniazid
• Genetic engineering technology:
  • Human Insulin, Immunoglobulin, Human growth hormone

The Important Routes of Drugs Administrstion:

Drugs are administered by different routes so that it can reach the site of action and initiate pharmacological action. Route of administration of drugs modify the action and absorption of the drugs. The important routes of administration are:

• Local route
  • Skin: lotion, Cream, Ointments, Gel, transdermal patches.
  • Mucous membrane: Gel, Enema, Suppositories, Pessaries, Douches, Mouth wash, Irrigations.
• Systemic routes
  • Oral: Tablet, Capsule, syrup, Powder.
  • Parenteral: Intra venous, Intra muscular, intra dermal, intra spinal, intra medullary, Sub cutanous.
• Others routes
  • Lungs: inhalation (local or systemic effect).
  • Vaginal: usually local
  • Eye/ear: usually local
• Topical
  • Skin: ointment, cream, lotion, paste, powder etc.
  •  Mucous membrane: Mouth - gargles, mouth washes, paints Eye, ear and nose as drops, ointments, nasal spray
  • Vagina as vaginal tablets, creams, powders
  • Anal canal = as ointment, suppositories
• Systemic routes
  The drugs administered through systemic routes (orally or parenterally), are absorbed into the blood, distributed along through the circulation and produce their desirable effects.

  • Oral:
    It is an oldest and commonest route of drug administration. Both solid dosage forms (tablets, capsules, powder) and liquid dosage forms (syrups, emulsions, mixtures, elixirs) can be given orally.

    • Advantages:
      • Safe
      • Convenient: self administered, pain free, noninvasive & easy to take.
      • Economical: compared to other parenteral route.
      • Usually good absorption: takes place along the whole length of the GI tract.
      • No need for sterilization.
    • Disadvantages:
      • Drug action is slow and thus not suitable for emergency condition
      • Unpalatable and other irritant drugs cannot be administered
      • Cannot be used for unconscious and uncooperative patients
      • May not be useful in presence of vomiting and diarrhoea
      •  Drugs likely to be destroyed by digestive juices can't be administered orally e.g. penicillin, insulin
      • The absorption of some drugs are negligible e.g. streptomycin
      • May cause nausea and vomiting

    • Sublingual (S.L.) or buccal:
      The drugs containing tablet is placed under the tongue or crushed and spread over the buccal mucosa. Buprenorphine, Nitroglycerine drugs given by this route.

      • Advantages:
        • Rapid absorption and effect.
        • Fast pass metabolism is avoided.
      • Disadvantages:
        • Inconvenient for frequent use.
        • Large dose cannot be given.
        •  It may cause mucosal irritation and excessive salivation.
    • Rectal routes:
      Certain irritant and unpleasant drugs can be put into rectum as suppositories or retention enema for systemic effect. Some of the drugs used in these routes are paraldehyde, diazepam, paracetamol etc.
      • Advantages:
        • Can be used in patient who can't take orally
        • Can be used in patient who is having recurrent vomiting
      • Disadvantages:
        • Inconvenient
        • Embarrassing
        • Absorption is slow, irregular and often unpredictable
    • Inhalation:
      It is a method of introducing drug through the respiratory tract to produce rapid effects. Bronchodilator, inhaler general anaesthesia are administered by this route.
      • Advantages:
        • Drugs as gases/aerosols can be rapidly taken up or eliminated.
      • Disadvantages:
        • Special apparatus is requird.
        • Irritant vapours can cause inflammation & increased secretion.
  • Parenteral route:
    Administration of medicine by injection into the body tissue is called parenteral administration.
    • Advantages:
      • Drug action is very rapid and accuracy of dose is ensured
      • Can be administered in unconscious and uncooperative patients
      • Can be use in case of vomiting and diarrhoea
      • Drugs likely to be destroyed by digestive juices can be administered by this route e.g. penicillin Can be used in patient who are unable to swallow
    • Disadvantages:
      • Less safe
      • More expensive
      • Inconvenient and painful for the patient .Self medication is difficult
      • Chances of local injury at the site of injection
    • The important parenteral routes are:
      • Intravenous injection (i.v.): into veins.
        • It should be given at 25 degree angle.
      • Intramuscular injection (i.m.): into skeletal muscle.
        • It should be given at 90 degree angle.
        • It should be given into large skeletal muscle like deltoid, gluteus, triceps, maximus, rectus femoris.
      • Intradermal injection (i.d): into skin
        • It should be given at 10-15 degree angle.
      • Subcutaneous injection(s.c.): into subcutaneous tissue.
        • It should be given at 45 degree angle.
      • Intra-arterial injection (i.a.): into arteries 
      • Intraspinal injection: into subarachroid space
      • Intramedullary injection: into a bone marrow
      • Intracardiac injection: into a heart
      • Intraperitoneal injection: into a peritoneal cavity

Three Phases of Drug Action

The Three Phases of Drug Action from dose to effect are:

• Drug Administration Phase
• Pharmacokinetic Phase
• Pharmacodynamic Phase

Branches of Clinical Pharmacology

The two main branches of pharmacology are:

1. Pharmacokinetics
2. Pharmacodynamics

Pharmacokinetics (Greek: Pharmakon-drug, Kinesis-movement):

It is the study of absorption, distribution, metabolism and elimination of drugs. It is the study of what happens to the drug after entering the living system. It means 'WHAT THE BODY DOSE TO THE DRUG'.

• Absorption of Drug
  Absorption of a drug is the transfer of the drug from the site of administration to the blood circulation.
  Passage of drugs across cell membrane:
  Drugs can pass through cell membrane by two processes. They are:
  • Passive transfer:
    • Simple diffusion
      Diffusion refers to the net movement of molecules from higher to lower concentration. Simple diffusion is bi-directional process: polar, water soluble and non-polar, lipid- soluble substances can be transported by this process. Majority of drugs are absorbed by this process.
    • Filtration
      Only water soluble and low molecular weight drugs can be transported by this process. It involves passage through pores present in the cell membranes.
  • Specialized transport:
    • Active transport
      It is a selective process which require energy. It also requires a carrier and so is called a carrier transport. Eg. methotrexate, 5-flurouracil.
    • Facilitated diffusion
      If transport follows from higher to lower concentration then it is called. It does not require energy. Eg. Vitamin.
    • Endocytosis
      Proteins and macromolecules are transported by this process. It is similar to phagocytosis where cells engulf fluid or macromolecule from the surroundings. E.g insulin.
  • Factors affecting drug absorption:
    • Route of administration
    • Concentration
    • Particle size
    • Area of absorbing surface
    • Solubility & physical state
    • Dissolution rate vii. Vascularity of the absorbing surface
    • Disease states
    • Physiological factors
    • G.I. transit time
    • Presence of other agents
    • Metabolism of drug
• Distribution of Drugs
  Drug disrtibution is the process by which a drug reversibly leaves the blood stream and enters the intestinal, and the cells of the tissue, the rate or the extent being dependent on its lipid solubility, ionization at physiological pH, extent of binding to plasma and tissue protein and differences in regional blood flow.
  The delivery of drug from plasma to intestitium depends on:
  • Blood flow
  • Capillary permeability
  • Binding of drugs to protein
• Metabolism (Biotransformation) of Drug
  • Chemical alteration of a drug in a living organism is known as bio- transformation. It is also known as "fate of drug".
  • Metabolism of drug in the intestinal wall or portal circulation before reaching systemic circulation, so the amount reaching systemic circulation is less than the amount absorbed.
  • Metabolism sites are:
    • Liver
    • Intestinal wall
    • Intestinal lumen etc.
• Elimination
  Elimination is the removal of active drug from the body and has two components, biotransformation and excretion. Drugs are excreted via different routes.
  Drugs and their metabolites are excreted by:
  • Urine (Kidney): kidney is the most excretory organ for drugs. Excretion to drugs & their metabolites into the urine involves three processes eg glomerular filtration, active tubular secretion & passive tubular reabsorption. e.g. Penicillin, streptomycin, gentamycin & most of the drugs
  • Faeces (intestine): e.g. Heavy metals, ampicillin, Erythromycin, Tetracycline
  • Exhaled (lungs) e.g. alcohol, Aneasthetics
  • Milk (breast) e.g. Pethidine, Morphine, anti- cancer drugs
  • Salive (mouth) e.g. Metallic salt, Rifampicin
  • Sweat (skin) e.g. Arsenic & Mercury

Pharmacodynamics (Greek: Pharmakon-drug, Dynamics-power)

It is the study of the biological and therapeutic effect and mechanism of action of a drug. This study is done at the molecular level of the living system. It means "WHAT A DRUG DOSES TO THE BODY".

Principles of drug action:

• The receptor theory
• Anti-metabolites
• Enzyme action
• Action on cell membranes
• Replacement of deficiencies
• Cytotoxic effect

The receptor theory:

The receptor theory is defined as "a component of a cell that interacts selectively with an extracellular compound to initiate a cascade of biochemical events that culminate in the observed effects of the compound."

• Receptors
  • It is a special constituent of the cell that binds with the drug and mediates its pharmacological actions. Is a special constituent of the cell that binds with the drug and mediates its. Examples: Adrenergic, cholinergic receptors
  • Agonistic and antagonistic drug action
  • Agonists activate receptors to produce a response.
  • Antagonists bind with receptors but do not activate them or cause a response. They can block the activation of receptors.
  • Partial agonists produce a response. However, this is less than would be expected by a full agonistic drug. Inverse agonists are drugs which can reduce the normal activity of the cell.
  • Competitive antagonists are drugs that prevent activation of the cell by their normal agent.
  • Non-competitive antagonists are drugs that may block the receptor but not in a permanent way.
• Anti metabolites: These drugs closely resemble substances which are used by cells for nutrition and, when absorbed, the cells cannot use them and so fail to multiply. Several drugs used in the treatment of cancer act in the way. E.g. methotrexate (anti-cancer), which is similar to folic acid, a normal cell constituent, competes with folic acid for a vital step in the build-up of nuclear material within the cell and blocks the process so that the cancer cell dies.
• Enzyme action: Enzymes are substances which speed up many chemical processes within the body.
  • Stimulation of enzyme; some drugs stimulate enzymes to show its action e.g. adrenaline stimulates adenyl cyclase.
  • Inhibition of enzyme; certain drugs have the property of inhibiting their action and thus interfere with some of these processes. E.g.Captopril inhibits angiotensin converting enzyme (ACE)
• Cytotoxic effect: Drugs may be used to kill bacteria or malignant cells without undue change to the patient's cells. Selective cytotoxic action for invading parasites or cancer cells, without significantly affecting the host cells is utilized for cure or prevention of infection & neoplasm. E.g. Antibiotics like tetracycline, penicillin, Amoxicillin etc.
• Action on cell membranes: The function of nerves and muscles depends on ions passing across the across the membranes surrounding these cells. Certain drugs interfere with the movement of these ions and thus prevent nerve or muscle functions, as demonstrated by local anesthetics which block impulses passing up a sensory nerve.

Factors affecting the drug action

Variation in response to the same dose of drug between different patients and even same patient can occur.

• Size of the patient
• Age
• Sex
• Nutritional factors
• Species & races
• Genetics
• Tolerance
•  Drug tolerance
• Pathological conditions
• Routes & time of administration
• Other drugs