SAMUEL AGUAZIM ( MD)

 The study of the interaction between chemicals and living systems  Pharmacology is the science that deals with the study of therapeutic agents.

 A drug is broadly defined as any chemical agent that affects biologic systems

What is Pharmacology ? Pharmacology Pharmacokinetics Pharmacodynamics What the body does to drug What the drug does to body Pharmacotherapeutics Pharmacocognosy The study of the use of drugs Identifying crude materials as drugs Toxicology

 Pharmacokinetics- describes “ what the body does to the drug.” this includes topics such as absorption, distribution, metabolism and excretion of drugs.

 Pharmacodynamics- describes “ what the drug does to the body.” specifically, it deals with the biochemical and physiological effects of drugs and their mechanisms of action

 Pharmacotherapeutics- describes the use of drugs for the prevention, diagnosis and treatment of disease.  Toxicology- describes the undesirable effects of therapeutic agents, poisons and pollutants on biologic systems

 Pharmacokinetics describes actions of the body on drugs, including the principles of drug absorption, distribution, biotransformation (metabolism) and excretion

 Absorption is the rate at which and extent to which a drug moves form its site of administration

 Route of administration- the intravenous route is most effective.  Blood flow- highly vascularized organs such as the small intestine have the greatest absorbing ability  Surface area available- absorption of a drug is directly proportional to the surface area available

 Solubility of a drug- the ratio of hydrophilic to lipophilic properties that a drug has will determine whether the drug can permeate cell membranes  Drugs-drugs interaction- when given in combination, drugs can either enhance or inhibit one another’s absorption.  pH- a drug’s acidity or alkalinity affects its charge which affects absorption

 Many drugs are either weak acids or weak bases. Acidic drugs are uncharged when protonated while  Basic drugs are charged when protonated

 Generally, a drug will pass through cell membranes more easily if it is uncharged. Therefore, the amount of drug absorbed depends upon its ration of charged to uncharged species, which is determined by the ambient pH at the site of administration and the pKa(negative log of dissociation constant) of the drug

 The fraction of administered drug that gains access to its site of action or a biologic fluid that allows access to the site of action.

 What is the bioavailability of an intravenously injected drug?  100%- because all of the drug enters the systemic circulation  what is the bioavailability of any drug that is not intravascularly injected?  Less than 100%- because some of the drug may not be absorbed or it may become inactivated.

 1. first pass hepatic metabolism  2. all of the factors that affect absorption (i.e., blood flow, drug solubility, drug-drug interactions, route of administration)

Parenteral (IV) Inhaled Oral Transdermal Rectal Topical Parenteral (SC, IM)

 Alimentary  Parenteral  Inhalation  Topical  Transdermal  subcutaneous

 Oral -commonest route  Advantages: convenience/patient compliance and the utilization of the small intestine, which is specialized for absorption because of its large surface area.

 Buccal( between gum and cheeks).  Advantages: allows direct absorption into the venous circulation  Sublingual( under the tongue)  Nitroglycerin is often given by this route.  Advantage: allows the drug to drain into the superior vena cava, thus bypassing hepatic first-pass metabolism

 Rectal (suppository)-useful when the oral route is unavailable due to vomiting or loss of consciousness:  Advantages: approximately 50% of drug absorbed from the rectum will bypass the liver

 1. intravenous- direct injection into the vascular system.  Advantage: most rapid and potent mode of administration, because 100% of drugs enters circulation

 Intramuscular  Advantages: usually more rapid and complete absorption than with oral administration.  Minimizes hazards of intravascular injection  Location important  Deltoid - rapid  Thigh - moderate  Buttocks - slowest  Difference in blood supply & distance

 Subcutaneous-under skin  Advantages: same as intramuscular  Intrathecal- under sheath of nerve fibers, spinal cord, or brain  Advantage: in cases of acute CNS infections or spinal anesthesia, drugs can be more effective if injected directly into the spinal subarachnoid space.

 What category of drugs is commonly administered by inhalation?  Answer: pulmonary agents  How are inhaled drugs administered?  By machine aerosolization or vaporization

 When is topical administration used?  Usually for treatment of localized disease( e.g psoriasis, acne, eye infections)  When is transdermal administration used?  For sustained release of a drug- for example nicotine patches.

 Is define as the process by which a drugs leaves the bloodstream and enters the interstitium or the cells of the tissue

 1. Passive diffusion: it is the most common mode of drug transport which makes a drug move from higher concentration to one of low concentration  2. Transport by special carrier proteins-  3. Active transport. The energy for this mechanism comes from dephosphorylation of adenosine triphosphosphate

 Blood flow  Capillary permeability- the structure of capillaries varies depending on the organ. E.g. in the brain the junction between cells is very tight. In the liver and spleen, the junction between endothelial cells is wide. Which allows large molecules to pass through.  Binding to plasma proteins such as albumin- this will limit access to cellular compartments

 Drug structure- small lipophilic molecules will be able to distribute to more compartments than will large polar molecules

 Why does the body biotransform drugs?  The lipophilic properties of drugs that allow them to pass through the cell membranes hinder elimination. Therefore, drugs are modified to become more polar so that elimination can occur more quickly.

 Two main modification occur in biotransformation:  Phase 1: oxidation, reduction(dehydrogenation) and hydrolysis  occur in endoplasmic reticulum  Phase 2: formation of a covalent linkage between functional groups on the parent drug and another substrate(i.e glucuronate, acetic acid, glutathione and sulfate)  Occur in cytosol  they both occur in the LIVER

 Genetic differences  Induction of the cytochrome P-450( increase biotransformation)  Inhibition of the cutochrome P-450 system  Disease of the liver  Age and gender

 Yes. In general, drugs will be inactivated or biotransformed according to one of two general chemistry principle.  First order kinetics  Zero-order kinetics

 Process by which a constant percentage of substrate is metabolized per unit time.  The higher the concentration of drug, the greater the absolute amount of drug biotransformed or excreted per unit of time

 Process by which a constant amount of drug is metabolized per unit of time regardless of the drug concentration.  Alcohol is metabolized according to zero order kinetics.

 Is define as the process by which a drug or metabolite is removed from the body

 Excretion is the removal of a drug from the body  Secretion occurs when the drug is actively transported from one compartment into another.  ( for example: drugs are secreted into the renal tubule from the medullary capillaries)

 Renal- urine is one of the most common routes of elimination  Fecal  Respiration- primarily for anesthetic gases and vapors  Breast milk  skin