Introduction to Pharmacology Basic Concepts PDF

Introduction to Pharmacology Basic Concepts Dr.Oğuzhan Aydemir E mail: 1st of October, [email protected] 2024  Pharmacology - Science of Drugs Pharmacology is a branch of science that investigates...

Introduction to Pharmacology Basic Concepts Dr.Oğuzhan Aydemir E mail: 1st of October, [email protected] 2024  Pharmacology - Science of Drugs Pharmacology is a branch of science that investigates the interaction of drugs and biological systems in vitro or in vivo, depending on the purpose and pharmaco n (drug) situation, and provides education on this subject. It enables the identification of the most suitable chemical substance for the diagnosis, treatment, Pharmacolo prevention of diseases, and other medical gy purposes and for the development of it as a drug. It covers a wide range of information about medicines, logia including their origins, how they are obtained, their (knowledg effects on the body, side effects, poisoning and their e) treatment, and the changes that drugs undergo in the body. 2  The Branches of Pharmacology 1- 2- Pharmacokinetic Pharmacodynamic s s 3- 4- Toxicology & Pharmacotherap Pharmacovigilance y (Applied Pharmacology) 5- Clinical Pharmacy 6- Pharmaceutical technology 7- Pharmacogenetics 8- Pharmacoeconomi 3 Pharmacokine tics Pharmacokinetics focuses on; Absorption Distribution Metabolism (biotransformation) Elimination (excretion) of drugs quantitatively and especially in time dimensions. The blood or plasma «It focuses on what the body does to the drug.» concentration-time curve reveals the pharmacokinetic profile of the drug. 4 Pharmacodyn amics Pharmacodynamics focuses on the basic effects of drugs on physiological events in the human body and their mechanisms. «It focuses on what the drug does to the body.» 5  Pharmacotherap y Pharmacotherapy focuses on the clinical conditions in which drugs are used (indication), conditions in which they should not be used (contraindication), and drug interactions. It examines the usage of drugs in treatment to achieve the desired effect with minimal side effects. Chemotherapy Chemotherapy treats diseases caused by bacteria, other microorganisms, and various parasites that invade the human body. 6  Toxicology Toxicology = The science of poison. Toxicology focuses on the poisonous (toxic) effects of drugs and chemicals used in our daily lives or in agriculture, industry, and other fields of endeavor. Poison: It refers to a chemical substance with a nonselective or persistent effect that cannot be used as a medicine. Side effect: Undesirable effects of medicines, even when used at usual doses, in addition to their intended effects. Toxic effect: An effect that is unpleasant for the patient, causes discomfort and uneasiness, prevents him/her from working, requires hospitalization, sometimes endangers the patient's life, and even leads to death. 7  Pharmacovigil ance pharmacon (drug) + vigilance (wakefulness) 1972 World Health Organization (WHO): Pharmacovigilance: Any attempt to identify possible causal relationships between adverse effects from the use of medicines in a given population; drug monitoring. Pharmacovigilance in "daily clinical practice" - collection of clinical data on the safety of medicines, - monitoring of problems in drug administration, It is defined as; identifying, recognizing, investigating, recording, announcing, and taking necessary actions to address the responsible causes. 8 Clinical Pharmacology It focuses on drug studies in humans. It aims to find and develop new drugs. Pharmaceutical Technology Medicines need to be formulated into appropriate pharmaceutical forms (such as tablets, pills, capsules, elixirs, oral suspensions, suppositories, syrups, ampoules, or vials containing solutions for injection). Pharmaceutical technology ensures that the medicine is put into the appropriate pharmaceutical form. Pharmacogenetics It examines the differences in the drug effect between individuals due to genetic differences in individuals. Pharmacoeconomics Analyzes and defines the costs of drug treatment to the health system and society. 9 BASIC CONCEPTS Dose: The amount of medicine given at one time. Drog: It is a raw material obtained from animals and plants by drying or collecting them by special methods and used in pharmacy and industry. Daily dose: The recommended amount of medicine to be given throughout the day. Side effect: Undesirable effects of medicines, even at usual doses, in addition to their desired effects. Toxic effect: It is an unpleasant, uncomfortable, and even fatal effect for the patient due to the exacerbation of the pharmacodynamic effects of drugs. Benefit/risk ratio: The benefit of medication must be superior to the harm in drug treatment. Safety interval: The distance between the therapeutic dose of the drug 10 and BASIC CONCEPTS Indication: The effects of a medicine for its intended use. Contraindication: Conditions in which the medicine should not be used. Resistance: It is the development of resistance to drugs depending on the characteristics of microorganisms and the ineffectiveness of drugs as a result. Tolerance: A progressive decrease in the effect of medication in the case of continuous medication use. Half-life of a drug: The time it takes for the amount of a drug's active substance in the body to reduce by half. Pharmacopoeia: A book containing formulas and recipes for making medicines. Prospectus: A brochure with introductory information about the medicine. 11 MEDICINE/DRUG: A pure chemical substance used in medicine that has biological activity (bioactive) or an equivalent natural mixture of plant or animal origin containing a standardized amount of active substances. 12  Drug definition according to WHO; A substance or product used for the purpose of modifying or investigating physiological systems and pathological conditions for the benefit of the field or intended to be used. There are 3 ways that drugs have their effects: They replace active They excrete or destroy substances, salts, and pathogenic microbes, They have an effect on fluids, deficiency of which parasites, or certain body functions or mental causes disease, which are harmful substances that functions. produced in the human enter the body and cause body or must be taken disease. from outside. 13  Selectivity: The drug should act on the cells and structures related to its intended use and the biological events there, and should not affect other structures and events. This is called the selectivity of a drug. This feature is Key Features of found in medicines relatively, not completely. For example, digitalis glycosides have the highest effect on the heart muscle. Drug Action Temporary: This means that the effect should disappear after a short time when the medication is stopped. A lasting effect on the body is often a characteristic of poisons. Dose dependent 14 How Are Diseases Treated With Medication? Symptomatic Radical (Palliative) Empiric Treatment: Treatment Treatment It is a method that It does not Treatment given allows the disease eliminate the cause based on to be cured by of the disease but experience, completely partially prevents without precise eliminating the the pathological knowledge of the cause of the event or corrects Substitutioncause or nature of disease. Prophylactic the symptoms and Treatment a disorder. signs of the disease. Treatment It is called A medication or replacement treatment therapy. It ensures designed and that substances used to prevent a such as vitamins, disease from hormones, occurring. For enzymes, etc. that example, are deficient in the vaccines. body reach normal 15  Sources of Medicines Medicines are derived from natural sources or prepared synthetically. However, nowadays, many of the drugs from natural sources are produced synthetically or semi-synthetically in order to be more economical. Natural sources Plants Animals Microorganisms Minerals 16  Medicines of plant origin They are usually found in a specific part of plants (such as sap, leaves, rhizomes, roots, seeds, or bark) and obtained as a pure substance by extraction. Medicines of animal origin They are obtained either in pure form or prepared as extractive forms containing concentrated active substances. Some hormones and enzymes, notably insulin. Microorganisms: Microorganisms are the source of antibiotic drugs. Minerals: Some drugs such as sodium chloride, magnesium salts, potassium chloride, and kaolin are obtained from minerals by purifying them. 17  DNA Recombination - Human interferons, insulin, growth hormone, and some vaccines have been prepared with this technique. 18  Classification of Drugs By Chemical Structures: Choline esters, organic nitrates, tetracyclines, beta-lactam antibiotics, etc. By Site of Action: Autonomic nervous system drugs, hematopoietic drugs, cardiac drugs, etc. By Clinical Conditions and Purposes of Use: Antihypertensive drugs, analgesic drugs, antiemetic drugs, anesthetic drugs, diuretic drugs, etc. 19  Names of Drugs Common Commercial Chemical Name (Generic Name Name Name) The name standardized (Brand It is the special name It is the name given by the WHO to facilitate that companies give according to the rules communication in Name) to their own products. of the International publications in medicine, (For example: Union of Pure and pharmacy, and health- Coraspin, Parol) Applied Chemistry related education. (IUPAC) and identifies (For example: the chemical structure. Acetylcysteine) (For example: Acetyl salicylic acid) 20 New Drug Development 1. (Bio)Synthesis Structure-Activity Relationship (SAR) is an Phase 1, Phase 2, (Bio)Synthesis Preclinical Investigations Licensing Phase 0 Phase 3 Post Marketing Trials: Phase 4 Clinical Trials: (Screening tests): approach designed to find relationships between chemical structure (or structural-related properties) and biological activity (or target property) of studied compounds. New candidate molecules are synthesized based on 21 New Drug 2. Preclinical Development Investigations (Screening tests): Phase 0 First, substances synthesized or extracted from natural sources or Phase 1, Phase 2, (Bio)Synthesis Preclinical Investigations Licensing Phase 0 Phase 3 Post Marketing Trials: Phase 4 Clinical Trials: (Screening tests): recombinant products are subjected to screening tests. Simple in vitro assay systems or screening models are used to demonstrate the basic effects or potential toxicity of the drug being developed that match its predicted therapeutic effect. In which medium is it done? In culture cells In isolated organ preparations In experimental animals 22  3. Clinical Trials: Phase 1, Phase 2, Phase 3 Phase 1 It is performed with 20-80 healthy volunteers. In this phase, the drug is given in increasing doses to determine human tolerance to the investigational drug, the safety of the drug, the Phase 1, Phase 2, (Bio)Synthesis Preclinical Investigations Licensing Phase 0 Phase 3 Post Marketing Trials: Phase 4 Clinical Trials: (Screening tests): safe dose range, its pharmacokinetics in humans, and the relationship between plasma levels and pharmacodynamic effects. Phase 2 It is performed in 150-300 patients with the disease for which the drug is being developed. The optimal dose and therapeutic dose range, the degree of therapeutic effect, and the side effect profile are determined. Phase 3 Multi-center, multi-national coordinated trials with the same protocol in many centers in a large number of patients over a prescribed period of time. The therapeutic efficacy of the new investigational drug is compared with placebo. 23  4. Licensing An application file is prepared for the licensing and marketing Phase 1, Phase 2, (Bio)Synthesis Preclinical Investigations Licensing Phase 0 Phase 3 Post Marketing Trials: Phase 4 Clinical Trials: (Screening tests): authorization of the new investigational drug found suitable in Phase III trials and a license application is submitted to the TİTCK (Türkiye İlaç ve Tıbbi Cihaz Kurumu). Phase 3 trials continue after the application. For this reason, it is divided into two as pre-license Phase 3a and post- license Phase 3b. The drug whose application is approved and licensed is offered for medical use through pharmacies in the form of preparation. 24  5. Post Marketing Trials: Phase 4 Medicines that are licensed, marketed, and prescribed by physicians need to be monitored for Phase 1, Phase 2, (Bio)Synthesis Preclinical Investigations Licensing Phase 0 Phase 3 Post Marketing Trials: Phase 4 Clinical Trials: (Screening tests): clinical efficacy and side effects, i.e. safety, under routine medical use. Trials and epidemiological studies are conducted to compare the drug with other drugs used in the same indications in terms of clinical efficacy, side effect profile, and pharmacoeconomics. *** Studies investigating high doses, new indications, new age groups, new routes of administration, and new side effects of the licensed drug are included in the scope of Phase 25 3.***  Pharmaceutical equivalents Pharmaceutical Equivalence Two different preparations are pharmaceutically equivalent if they contain; the same active substance or substances in the same amounts, and in identical or comparable pharmaceutical forms (such as tablets and capsules or ampoules and vials). 26 Bioequivalence Two preparations that are pharmaceutical equivalents, their bioavailability (rate and extent of absorption), and thus their therapeutic effects are similar enough to ensure that they are identical in terms of both efficacy and safety after administration of the same molar dose. The objective of bioequivalence studies is to prove that the generic drug product is bioequivalent to the original product. *** It is the most clinically important indicator of drug valency.*** 27 Bioavailability The rate and extent to which a drug enters the systemic circulation given by a non-intravenous route (im, oral...). In bioavailability studies, Cmax, tmax, and AUC (area under the curve) parameters of the drug are measured. Two drugs with these parameters in the range of 80 - 125% are considered bioequivalent. Factors affecting bioavailability: ✓ Disintegration of the drug ( degradation in the stomach) ✓ Dissolution of the drug (dissolution in the stomach contents) ✓ Dietary pattern ✓ Tablet size ✓ Quality control in manufacturing and formulation 28 Therapeutic Equivalence Approved drug products are considered to be therapeutic equivalents if they are pharmaceutical equivalents for which bioequivalence has been demonstrated, and they can be expected to have the same clinical effect and safety profile when administered to patients under the conditions specified in the labeling. Proving therapeutic equivalence of two pharmaceutically equivalent preparations is much more difficult than proving bioequivalence. ***If two pharmaceutically equivalent medicines are bioequivalent, they are also considered therapeutically equivalent and can replace each other in the treatment of diseases.*** 29 Therapeutic Alternatives Sometimes drugs with different pharmacological properties and different mechanisms of therapeutic action are used to treat the same disease. These are called therapeutic alternatives, not equivalent. (Example: Diuretics, beta-blockers, ACE inhibitors, angiotensin receptor blockers etc. used in the treatment of hypertension). 30 Original Drugs: It is an international term for new medicines; that have been proven to have a positive effect on a particular disease as a result of long research and clinical trials, that are based on a patented molecule, and that have no previous analogues. Generic Drugs: After the legal protection period of the original medicine expires, pharmaceutical companies may launch generic drugs similar to the original medicine. These medicines are called generic drugs. 31 Generic Drug; It must contain the same active substance as the original drug in the same amount. It must be in the same formulation and pharmaceutical form. Bioequivalence to the original medicine must be proven. 32 Pharmaceutical Forms of Drugs A pharmaceutical Solid Pharmaceutical Forms form is a specially molded form of a drug that can be Orally administered to a Administered Applied from Other Routes patient. Drugs are classified according to their physical properties and 33 Oral Forms Tablet: It is obtained by mixing powdered medicines with binding agents and compressing them in machines. It can be in half cylinder, round, etc. shapes. Disintegrates in water. There are different forms such as chewable tablets, effervescent tablets, and sublingual tablets. Dragee: A form of medicine formed by coating tablets with sweeteners such as sugar to make them easier to take. Pilule: It is the flat or round shape of the powdered medicine after it is combined with adhesive substances such as honey. Capsule: A cylindrical, flat, and olive-shaped form of medicine prepared in interlocking gelatin protectors for easy ingestion of powdered or liquid medicines with unpleasant taste and smell. Cachet: A pharmaceutical form made of starch in an oval or cylindrical shape with two interlocking lids containing powdered medicine. Powder: The powdered form of the drug. Package: A one-time dose of the powdered drug in special paper packets. Pastil: A form of medicine that is dissolved in the mouth and is generally used in the treatment of 34 diseases in the oral cavity. Pharmaceutical Forms Used by Other Routes Suppository: A suppository, the main ingredient of which is cocoa butter and glycerinated gelatin, is a cylindrical medicine that can easily enter body cavities or entrances. It is a form of medicine that is solid at room temperature but melts easily at body temperature. It is administered rectally. Ovule: An oval or cylindrical form of medicine that dissolves quickly at body temperature. It is used vaginally. Transdermal Therapeutic System (TTS): It is used for rapid absorption of small amounts of potent drugs through the skin. It is a pharmaceutical form prepared by applying the active drug substance on a special patch and applied on the skin. 35 Semi-Solid Pharmaceutical Forms Ointment (pomade): Used as an ointment for the treatment of skin and mucous membrane diseases. Ointment with a thicker consistency is called paste. The form of drug with more water content and softer than ointment is called cream. It is applied externally to the skin and mucosa. 36 The Liquid Pharmaceutical Forms Solution: A form of medicine prepared by dissolving active drug substances in water or other solvent. The form applied to the mouth is called mouthwash. There are forms that are applied to the eyes, nose, and ears as drops and administered parenterally as ampoules. Tincture: A pharmaceutical drug form prepared by mixing the active drug substance in alcohol. It is used externally or orally. Elixir: It is a solution of the active drug substance prepared with water, alcohol, sugar, and sweeteners. It is used orally. Syrup: Preparations are obtained by mixing the active drug substance with water and 60% sugar or sweeteners. It is used orally. Drops: It is a pharmaceutical drug in the form of a solution in small quantities, counted in drops, and applied to the ear, eye, nose, and mouth. Suspansion: It is obtained by dispersing the solid drug substance in small particles in a liquid. The solid substance settles to the bottom when left to stand, it should be shaken before use. There are oral and parenteral forms. Emulsion: It is a form of drug obtained by mixing the active liquid drug substance in a dissolving liquid. Used orally and parenterally. Enema: A pharmaceutical drug in the form of a solution or suspension prepared for rectal use. Aerosol: A form of pharmaceutical drug prepared in a special liquid that can dissolve the active substance. It is applied by inhalation. Ampoule, vial: Ampoule, vial, vial: A glass-contained pharmaceutical drug form containing powder or liquid active substance prepared under sterile conditions. It is administered parenterally. Ampoules and vials contain liquid or powdered medicine. Lostion: Preparations in the form of a solution or suspension. Shake before use. It is used by applying it on the skin. 37