Pharmacology and pharmacokinetics

• Study notes covering basic pharmacology and pharmacokinetics

Introduction

• The study guide aims to provide a basic understanding of pharmacology and pharmacokinetics.
• A strong foundation in pharmacology is essential for healthcare professionals to safely prescribe, dispense, administer, and monitor medications.
• Basic pharmacology encompasses the principles of how drugs interact with the body to treat diseases.

Instructions

• The study guide is divided into chapters and sections for sensible study planning
• Use a systematic approach by working through prescribed topics in detail
• The pharmacology course is multidisciplinary, requiring knowledge of anatomy, physiology, biochemistry, and microbiology.

Study Feedback and Evaluation

• The modular educational system uses continuous assessments, tests, and exams.
• Instructors can offer help with specific concepts or questions.
• The course is designed to be interesting and foster a more scientific interest in pharmacology.

Chapter I: Introductions

1. Key Definitions

• Pharmacology is the science of the effects of drugs and chemicals on biological systems.
• Pharmacology studies how drugs/chemicals exert their effects on biological/living systems.
• Pharmacology focuses on drug/chemical interactions with living systems through chemical processes, especially binding to regulatory molecules.
• Pharmacology is the activation or inhibition of normal body processes
• Drugs/chemicals are administered to achieve a beneficial therapeutic effect.

Pharmacology vs. Pharmacy

• Pharmacology is a discipline to study how drugs produce their effects on the body.
• Pharmacy deals with preparing, preserving, dispensing drugs, and ensuring their proper utilization and delivery
• Clinical Pharmacy is a health specialty that promotes the rational and appropriate use of medicinal products and devices.

Evolution of Pharmacology

• Pharmacology has evolved from traditional therapeutics using magical potions and herbal remedies, to modern approaches integrating biomedical sciences and chemistry.

2. Division and Disciplines of Pharmacology

• Pharmacokinetics describes what the body does to drugs, including absorption, distribution, metabolism, and elimination (ADME).
• Pharmacodynamics defines what the drug does to the body, referring to the biochemical and physiologic mechanisms of drug action, involving interactions with cellular proteins like receptors or enzymes.

Divisions: Pharmacokinetics-Pharmacodynamics

• Pharmacokinetics involves Absorption, Distribution, Metabolism & Excretion
• Pharmacodynamics involves the pharmacologic effect and clinical response.

Disciplines of Pharmacology

• Clinical pharmacology focuses on medication effects in humans.
• It provides an overview of clinical actions and indications across organ systems.
• Pharmacotherapeutics involves using drugs to prevent and treat diseases/disorders.
• Pharmacogenetics is the study of genetic influences on drug responses (drug metabolism).
• Pharmacogenomics uses genetic information to guide drug therapy on an individual basis.
• Pharmacoepidemiology studies drug effects at the population level, addressing drug effect variability between individuals and populations.
• Pharmacoeconomics is a branch of health economics that quantifies the costs and benefits of drugs used therapeutically.
• Medical pharmacology is science of substances used to prevent, diagnose, and treat disease.
• Experimental pharmacology studies biological and therapeutic properties of new or synthetic substances
• Experimental pharmacology uses systematic testing on living systems with techniques specific to pharmacology or borrowed from physiology and biology.
• Social Pharmacy combines social sciences and pharmacy.
• Toxicology is the study of harmful effects of drugs.

3. Drugs and Drug Discovery Process

• A drug is a chemical substance that interacts with a living system through chemical processes.
• Drug binding and regulatory molecules produce biological effects by activating or inhibiting normal body function.
• The word drug is often associated with addictive, narcotic, or mind-altering substances, leading to negative connotations.
• Medicine is defined as a drug delivery system.
• According to the legal definition, a drug is a synthetic or natural chemical used to treat, cure, prevent, diagnose, restore, correct, or modify physiological, physical, or psychological functions in humans or animals
• Examples include curative drugs (antibiotics), preventive drugs (vaccines), reliever drugs (analgesics), diagnose drugs (contrast products), and modifier or corrector drugs (contraceptives).

Pro-Drug & Drug Precursor

• A pro-drug is a pharmacologically inactive medication converted to an active form through metabolic processes like hydrolysis of an ester

• An example is Chloramphenicol-palmitate ester converting to chloramphenicol.

• A precursor is an inactive molecule converted to an active form in the body through normal metabolic processes like oxidation or decarboxylation

• An L-Dopa converting to Dopamine is an exmaple.

• Prodrugs are classified into bioactivated inside cells (Type I) or outside cells (Type II)

• An example of of Type I is anti-viral nucleoside analogs requiring phosphorylation

• An example of of Type II is sulfasalazine, which the gut bacteria needs to convert to aminosalicylic acid (5ASA) and sulfapyridine

Sources of Drugs

• Drugs can be sourced from minerals, animals, herbs/plants, and synthetic/biological methods.
• Examples:
• Iron is found in FeSO4
• Sodium Bicarbonate is found in NaHCO3
• Lithium Carbonate is found inLi2CO3
• Aluminum Hydroxide is found in Al(OH)3
• Insulin is a animal drug.
• Morphine (pavot) and Quinine (quinquina) are herbal.
• Pethidine and Amodiaquine are synthetic.
• Erythropoietin (EPO) is biotech-derived thanks to DNA Recombinant technology

Sources of Drugs: 1. Plants/Herbs

• Digitalis Purpurea leaves give Digitoxin and Digoxin, which are cardiac glycosides.
• Tobacco leaves give nicotine.
• Atropa belladonna gives atropine.
• Senna pods give anthracine, a purgative ingredient (used in constipation medications)
• Calabar beans give physostigmine, a cholinomimetic agent.

Sources of Drugs: 2. Animals/Humans

• The pancreas is a source of Insulin used to treat Diabetes.
• Sheep thyroid is a source of thyroxin used to treat hypothyroidism.
• Cod liver is a vitamin A and D source.
• The anterior pituitary gland is a source of pituitary gonadotropins to treat infertility.
• Animal blood is used to prepare vaccines.
• Pregnant women's urine gives human chorionic gonadotropin (hCG) to treat infertility.

Sources of Drugs: 3. Minerals

• Iron treats iron deficiency anemia.
• Mercurial salts treat Syphilis.
• Zinc is used as a zinc supplement; zinc oxide paste is used in wounds, eczema, and diarrhea.
• Iodine is an antiseptic with supplements used.
• Gold salts treat rheumatoid arthritis.
• Fluorine offers antiseptic properties
• Selenium used in selenium sulphide is used in anti dandruff shampoos.

Sources of Drugs: 4. Semi synthetic

• Synthetic Sources:
• Synthetic drugs are prepared by chemical reactions from raw materials
• Examples: Amodiaquine and Paracetamol
• Semi Synthetic Source:
• The nucleus of the drug is obtained from natural sources but altered chemically.
• Examples: Diacetyl morphine, Ethinyl Estradiol, and Methyl testosterone.

Sources of Drugs: 5. Microbiological

• Penicillium notatum is a fungus source of penicillin.
• Actinobacteria gives Streptomycin.
• Aminoglycosides like gentamicin and tobramycin are obtained from streptomycis and micromonosporas.
• Recombinant DNA technology uses enzymes to cleave DNA, releases desired gene
  • The desired gene is inserted to to create vast amounts.
• Example: Erythropoietin.

Advantages of Recombinant DNA technology

• Large quantities of drugs that can be produced.
• Drugs can be obtained in pure form.
• Less antigenic.
• Well equipped lab is required.

Disadvantages;

• Highly tramed staff is required.
• A complex and complex technique that has to be used.

Drug Discovery & Process Development

• A new drug goes through chemical discovery, animal pharmacological testing, clinical investigations, marketing, and post-marketing stages.

Chemical Discovery Phase

• Find new molecules.
• Modify existing drugs.
• Use sources from plants.
• Use total syntheses.
• Use partial syntheses.
• Use the researcher companies spent big amounts of money to discover new molecules.
• Synthesis results in thousand of molecules, but very few will satisfy animal experiments.

Animal Testing Phase

• Determine pharmacological action and effects.
• Estimate acute toxicity.
• Estimate subacute and chronic toxicity.
• Assess for teratogenesis effect.
• Assess for mutagenesis effect.
• Assess for carcinogenesis effect.
• If a molecule is somehow active and with acceptable toxicity, the researcher company will request authorization to proceed to a clinical trial (IND).

Clinical Trial Phases

Clinical Trial Terms

• Placebo refers to "dummy" medications to resemble the active version as much as possible.
• A placebo effect refers to the positive therapeutic response due to psychological reasons.
• A single-blind study investigates the subjects receiving active medicine and placebos.
• Double-blind the medication in a clinical trial is a blind crossover

Clinical Term: IND and NDA

• Investigational New Drug (IND) Exemption is the FDA approval needed to carry out trials on humans, and requires animal data.
• New Drug Application (NDA) is FDA approval to market for ordinary use.
• Clinical trials typically follow three parts: I, II, and III.
• Once NDA to fully evaluate the safety.
• A possitive control, a used standard therapy or an alternative.
• Orphan drug has the potential to develop disease for in which the expert's US patients list is very high.