Pharmacology Notes Lecture 1 PDF

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2060: Pharmacology Notes 1 MODULE 1: CHEMISTRY OF PHARMACOLOGY Introduction Pharmacology: the word pharmacology is derived from the Greek words pharmakon meaning remedy and logos meaning study, generally pharmacology is considered the study of drugs The study of drugs can include various aspects, so...

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2060: Pharmacology Notes

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MODULE 1: CHEMISTRY OF PHARMACOLOGY Introduction Pharmacology: the word pharmacology is derived from the Greek words pharmakon meaning remedy and logos meaning study, generally pharmacology is considered the study of drugs The study of drugs can include various aspects, some of which include: 1. How a drug is delivered (its route of administration) 2. How a drug works (it’s mechanism of action) 3. The therapeutic effect of drugs on patients 4. The adverse effects of drugs on patients Classification of Therapeutics 1. Drugs – traditional drugs (i.e. chemical agents) 2. Biologics – antibodies and hormones 3. Natural Health Products – herbals, vitamins, and minerals Canadian Drug Legislation Therapeutic Products Directorate Food and Drugs Act & Regulation

Health Canada

Health Canada Products and Food Branch

Biologics & Genetics Therapies Directorate Natural Health Products Directorate

Drugs Drugs have 3 types of names: - Chemical Name - describes the chemical structure of the molecule; used by chemists only - Generic Name – a unique name that identifies a drug and is most commonly used in pharmacology (note: often there are very many names for the same drug if many companies make it) - Trade Name – the name assigned by the drug company, it is easy to remember and marketable Example: - Chemical name: 7-chloro-1,3-dihydro-1-methyl-5-phenyl-1,4-benzodiazepin2(2H)-one - Generic name: Diazepam - Trade name: Valium Approval of Marketed Drugs in Canada 1. Drug Discovery/Preclinical Testing a. In cultured cells, living tissue or experimental animals b. Evaluate the biological effects, pharmacokinetics and toxicity of the drug c. Time: ~ 6.5 years 2. Clinical Trial Application a. Submitted to Health Canada prior to any human studies b. Involves a lot of paper work detailing all the pre-clinical data found c. Time: Health Canada responds within 30 days of receipt 3. Phase 1 Clinical Trial a. 20-100 healthy volunteers (NOT patients that the drug is for) b. Evaluation of pharmacokinetics and pharmacodynamics c. Time: ~ 1 year

2060: Pharmacology Notes 4. Phase 2 Clinical Trial a. 300-500 patients with the target disorder b. Therapeutic effectiveness of the drug, side effects and dosing information is gathered c. Time: ~ 2 years 5. Phase 3 Clinical Trial a. 500-5000 patients with the target disorder b. Therapeutic effectiveness verified and long term side effects are assessed c. Time: ~ 4 years 6. New Drug Submission (NDS) a. A report that details therapeutic effectiveness and safety, and includes results from pre-clinical and clinical studies b. If approved, Health Canada issues a Notices of Compliance (NOC) and a Drug Identification Number (DIN) both of which are required to market the drug c. Time: ~1.5 years 7. Phase 4 Clinical Trial a. Post marketing surveillance; Health Canada monitors the efficacy and safety of the drug after its been marketing b. Time: unknown, this continues long after the drug has been put on the market Basic Physiology and the Cell Membrane Physiological Barriers to Drug Transport  Our body has many well-developed barriers to help protect us  Intestinal villi form a barrier against ingested drugs, toxins and nutrients  Some cells have tight junction which prevent molecules from passing between cells  To exerts its effect then a drug must have the right chemical properties to pass through these barriers Components of the Cell  Nucleus: contains genetic material (i.e. DNA)  Smooth Endoplasmic Reticulum: metabolizes drugs, carbohydrates and steroids  Rough Endoplasmic Reticulum: synthesizes proteins  Golgi Apparatus: processes and packages proteins and lipids  Mitochondria: produces ATP (cell’s source of energy)  Cell Membrane: separates the intracellular and extracellular environments The Cell Membrane  Composed of phospholipids which have a polar (water soluble) phosphate containing head and two fatty acid (lipid soluble) tails.  Also, called the lipid bilayer because of the phospholipid arrangement  Fluid; the phospholipids are flexible allowing them to undulate back and forth  The cell membrane also contains proteins embedded in the phospholipids How do Drugs Cross the Cell Membrane?

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2060: Pharmacology Notes

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Direct penetration of the cell membrane o To directly penetrate cell membranes, drugs must be lipid soluble (lipophilic) o Remember that cell membranes are composed of primarily lipid, therefore drugs must be able to dissolve into the lipids of the cell membrane to pass through it o Molecules that are not lipophilic cannot pass through cell membranes Through ion channels and pores o Ion channels and pores are very small and so only very small compounds (molecular weight...