Introduction to Pharmacology

Introductory Pharmacology

Introduction to Pharmacology

• Pharmacology is the science of drugs, derived from the Greek words pharmacon (drug) and logos (discourse in).
• Can be defined as the study of the interactions of exogenously administered chemical molecules (drugs) with living systems.
• Encompasses all knowledge about drugs, especially related to their effective and safe medicinal use.

Scope of Pharmacology

• Understanding drugs scientifically can help predict the pharmacological effects of new chemicals for therapeutic purposes.
• Over the last decade, the scope of pharmacology has expanded to include new approaches.
• These include computer-assisted drug design, genetic screens, protein engineering, and novel drug delivery using viruses and artificial cells.
• There is a need for society to have pharmacologists who comprehend modern therapeutics and can contribute to academic, pharmaceutical, and governmental research.

Historical Perspectives of Pharmacology

• Pharmacology was established as an experimental science by Rudolf Buchheim, who founded the first pharmacology institute in Germany in 1847.
• Oswald Schmiedeberg, regarded as the 'father of pharmacology', along with J Langley, T Frazer, P Ehrlich, AJ Clark, and JJ Abel developed fundamental pharmacology concepts in the late 19th century.
• Since then, drugs have been purified, chemically characterized, and developed into highly potent and selective forms.
• Interest in pharmacology expanded in the 20th century, dividing the subject into separate, yet mutually dependent disciplines.
• The two primary divisions of pharmacology are pharmacodynamics and pharmacokinetics.

Pharmacodynamics

• Originates from the Greek word dynamis (power).
• Can be summarized as "what the drug does to the body."
• Concerns drug's physiological and biochemical effects and their mechanisms of action at the organ, system, subcellular, and macromolecular levels.
• Adrenaline interacts with adrenoceptors, stimulating G-protein-mediated adenylyl cyclase, increasing intracellular cyclic 3',5'AMP, leading to cardiac stimulation, hepatic glycogenolysis, and hyperglycemia.

Pharmacokinetics

• The term kinesis is movement in Greek.
• Can be summarized as "what the body does to the drug".
• Refers to the movement of the drug in, and alteration of the drug by, the body.
• Includes absorption, distribution, biotransformation (metabolism), and excretion, collectively known as ADME.
• Paracetamol: It is quickly and almost completely absorbed orally, reaching peak blood levels in 30-60 minutes with 25% bound to plasma proteins. The volume of distribution is about 1L/kg. It undergoes extensive liver metabolism, and is excreted in urine. The plasma half-life (t½) is 2-3 hours, and clearance is 5 ml/kg/min.

Other Divisions of Pharmacology

• Clinical pharmacology: Scientific study of drugs that includes investigations of pharmacodynamics and pharmacokinetics in healthy volunteers and patients. Also includes safety and efficacy evaluations, comparative trials, and adverse effects surveillance.
• Clinical Pharmacology Aims: Generates data for optimizing drug use and evidence-based medicine practice.
• Pharmacotherapeutics. This is the application of pharmacological information along with the disease knowledge for prevention or cure, by selecting appropriate drug, dosage ,and treatment duration . Patient is also considered.

Subdivisions of Pharmacology

• Toxicology: The study of the poisonous effects of drugs and other chemicals, with a focus on detection, prevention, and treatment of poisoning; it includes consideration for adverse drug effects.
• Pharmacogenetics: A relatively new field that studies genetic variations in drug response; heredity's role in drug responses.
• Biochemical Pharmacology: Studies the influence of drugs on biochemical activity in the cell.
• Pharmacogenomics: Overlaps with pharmacogenetics; it uses genetic information to guide drug therapy decisions on an individual basis.
• Pharmacogenomics Principle: Individual therapeutic drug responses can be predicted genetically, primarily through polymorphisms of drug-metabolizing enzymes or receptors.
• Pharmacogenomics Goal: To allow therapeutic choices based on an individual's genotype, by linking variations in specific genes to variations in a particular drug's therapeutic effect.
• Pharmacovigilance: Focuses on impact of drug effects on patient safety. Includes the assessment, detection, and understanding of adverse events associated with drug administration, like drug reactions, toxicities, and side effects from short/long-term drug use.
• Adverse drug reactions, including drug-drug interactions, are a main cause of mortality, leading to longer hospitalizations.
• No drug doesn't cause any toxicity; some side effects can be trivial, serious, or fatal.
• Pharmacoepidemiology: Is the study of drug effects at a population level. It examines variability of drug effects between individuals and across populations. Regulatory authorities consider this when licensing drugs for therapeutic use.
• It takes into account patient compliance and is used to review drug use under real-life conditions.
• Pharmacoeconomics: This branch of health economics aims to quantify, in economic terms, the costs and benefits of drugs used therapeutically.
• Concerned with the rising costs of healthcare, it raises questions about what procedures best represent value.
• Regulatory authorities require economic analysis alongside evidence of individual benefit to license drugs.

Drugs

• The properties of drugs, medicines, and poisons were originally studied by medicament purveyors and poisoners.
• Plants were the primary source of drugs until the end of the last century. Botany was closely linked to collection and preparation.
• Safe usage of drugs requires a good understanding of :mode of action, side effects, toxicity, dosage, rates and routes of excretion, and interactions with other drugs.

Sources of drugs

• Drugs are obtained from six major sources
• Plant
• Animal
• Mineral/ Earth
• Microbiological
• Semi synthetic/ Synthetic
• Recombinant DNA technology.

Plant Sources

Animal sources

• Pancreas: Insulin is used to treat diabetes mellitus.
• Urine of Pregnant Women: Provides human chorionic gonadotropin (hCG) for treating infertility.
• Sheep thyroid: Provides thyroxine for treating hypothyroidism.
• Cod Liver: Source of vitamin A and D.
• Blood: Used in preparation for vaccines.
• Stomach tissue: Pepsin and trypsin digestive enzyme for treatment of peptic diseases.

Mineral Sources

Microbiological Sources

• Penicillium notatum: A type of fungus that produces penicillin.
• Actinobacteria: Give rise to streptomycin.
• Aminoglycosides: Consist of the tobramycin and gentamicin streptomycis.

Routes of Drug Administration

• Most drugs have a variety of routes in which they can be administered through.
• The chosen route depends on drug factors and patient factors.

Factors Governing Route Choice

• Physical and Chemical Properties: This includes solid/liquid/gas form solubility, stability, pH, and irritancy.
• Action Site: Either for localized or systemic effect.
• Absorption Rate: The rate and extent of drug absorption.
• Digestive Effects: Considering digestive juices and first-pass metabolism.
• Response Speed: How quickly is a response needed.
• Dosage Accuracy: IV and inhalation can be regulated.
• Patient State: Unconscious / Vomiting.

Routes of Drug Administration

• Routes are divided into: Local, Systemic, Topical, Intra-articular, Intrathecal, Enternal (through GIT), Oral, Rectal, Parenteral, Subcutaneous, Intramuscular, Intravenous, Sublingual, Transdermal, Nasal, Inhalational.

Local Routes

• Local routes are suitable for localized lesions at accessible sites. Drugs must have minimal or no systemic absorption.
• The desired site attains high concentrations without exposing the rest of the body.
• Toxicity from systemic side effects are absent/minimal.
• Some Drugs: Can have minimal systemic absorption, like glyceryl trinitrate (GTN) on the skin as ointment or transdermal patch.

Topical

• Topical drug application is for localized action.
• It is often more convenient and patient compliance is more likely.
• Topical medication can be the form of lotions, ointments, creams, rinses, paints, drops, sprays, pessaries, and suppositories.
• Action drugs are Non-absorbable for G.I mucosa, inhalation for on bronchi, and irrigating solutions for urethra.

Deeper Tissues

• Certain Deep Areas- can be approached using a needle and syringe, the drug should be slow in systemic absorption. E.g. intra-articular injection, infiltration, and retrobulbar injections.
• Arterial supply: For angiography contrast media can be used, for limb malignancies, it can be used to infuse femoral or brachial injection.

Systemic Routes

• The drug administered through a systemic route is absorbed into the bloodstream.
• Oral Ingestion is the oldest and commonest.
• Safer, convenient, and cheaper.
• Can be used through dosage forms such as emulsions, capsules, syrups, tablets, powder, etc.

Limitations of Oral Route of Administration

• Action is typically slower, not good for emergencies.
• If a drug is in a bad taste, then it can be made into a capsule instead.
• Other limitations can be causing vomiting and not safe for vomiting patients.
• Absorption of certain drugs cannot be achieved while others are destroyed.

Sublingual or Buccal

• A tablet/pellet with the drug is in the mouth under the tongue or crushed on the buccal mucosa.
• Only administer soluble-lipid drugs.
• Absorption takes a few minutes but is convenient.
• By-passes the liver, with high first pass metabolism.
• Medications: nitroglycerin/buprenorphine/Nifedipine,

Rectal

• For drugs that are irritant, suppositories can be injected into the rectam for a systemic effect.
• When the patient is vomiting, this can be used.
• Can be inconvenient and embarrassing.
• External hemorrhoidal veins bypass the liver, internal veins do not.
• Rectal inflammation can result from irritant drugs.
• Medications: Diazepam/Indomethacin/Paraldehyde/Ergotamine etc.

Cutaneous

• Highly soluble lipid drugs on the skin = slow, prolonged administration.
• Liver by-passed.
• Made incorporated into the ointments.
• Absorption is applied in specified areas and by rubbing the the skin followed by a dressing of oil.

Transdermal Therapeutic Systems

• Devices are patches of different shapes and sizes that are deliver a continues amount throuh circulation from corneum.
• Delivery by diffusion for circulation.
• Rate of absorbtion for absorption offset.
• The site is delivered in constant rate = chest, abdomen, upper arm, lower back butt, regions of the mastoid,

Transdermal Patches

• Meds available isosorbide denitrate, estradiol, nicotine and diclofenac are available in Nigeria.
• Should last 1-7 days for different drugs that provide plasma with little affect of side effects.
• Many patients prefer patches over oral methods with patient compliance better.
• Rotating the side of application can reduce irritation and erythema.

Inhalation

• Liquid and gases are by inhalation for systemic action e.g. anesthetics.
• Absorption from Alveoli = Rapid Reaction.
• If administration is discontinued, substance is rapidly reduced and eliminated.
• Moment adjustment is possible.
• Irritant vapors can cause inflammation/more secretion.

Nasal

• Mucous of the nose absorbs any drugs without needing digestive juices.
• Meds used: GnRH agonists and desmopressin.
• Trying peptide drugs.

Parenteral

• Administration through injection without crossing the intestinal.
• Oral administration are not needed.
• Useful for unconscious, vomiting patients
• Preparations are sterile
• tissue can be harmed and risky through this method.

Subcutaneous

• Is deposited into rich nerve tissue but less vasular (Slows intake)
• Self injections becaus e not needed.
• Patients who are shock needs delayment.