BASIC PHARMACOLOGY

Pharmacology Greek pharmakon drug and Logo science deals with study of drugs and their actions on living organism Is the science which is concerned with the history, sources, physical and chemical properties of the drugs as well as the ways in which drugs affect living system. THERAPEUTIC METHODS Approaches to therapy Drug therapy Diet therapy Physiotherapy Psychological therapy Drug chemical substances that have an effect on living organism

United State Pharmacopeia (USP) National Formulary(NF) Standardization to ensure drug products produce by different manufacturer, will be uniformly pure and potent United state Adopted Name (USAN) USP Dictionary of USAN and International Drug DEFINITION OF TERMS Posology The study of dosage or amount of drugs given in the treatment of diseases. Pharmacist A person licensed to prepare and dispensed drugs. DRUG DEFINITION AS TO CLASSIFICATION As to the Body System they Affect As to Therapeutic Use or Clinical Indication As to Physiologic or Chemical Action As to Prescription or Non prescription drugs Prescription Drugs Non Prescription Drugs or Over The Counter Drugs Illegal or Recreational Drugs

Therapeutic Drugs or Medicines drugs used for the prevention or treatment of disease Prescription written direction for the preparation and administration of drug. DRUG DEFINITION AS TO NOMENCLATURE Official Name The name after which the drug is listed in one of the official publications (US Food and Drugs Administration). Chemical Name The name which describes the constituents of drugs precisely. Generic Name Common or non proprietary name The name given to a drug before it becomes official. Given by USAN Brand Name trademark or proprietary name The name given to a drug by the manufacturer (also, Trademark) Chemical name (+/-)-2-(p-isobutylphenyl) propionic acid Generic name ibuprofen Trade name Motrin DRUG DEFINITION AS TO NOMENCLATURE (canada) Official Name Any drug for which a standard is described either specifically in the Food and Drug Regulations or in any publications named in the Food and Drug Act as satisfactory. ProperName Non proprietary (generic name) used to decribe an official drug in Canada. SOURCES OF DRUG STANDARDS

Regulated drugs Drugs with potential abuse Drug abuse- excessive self administration of a drug that could result in addiction and that could be detrimental to the individuals health Addiction- drug seeking behavior in which the abuser is unable to control the desire for the drug Withdrawal- physical effects resulting when drug is discontinued in an individual who is addicted to a drug Physical dependence-withdrawal of the drug produces physical effects on the individual. Psychological dependence(habituation) Intense desire or craving for the drug when it is not available(no physical or withdrawal effects)

Controlled Substance Schedule Schedule 1: drugs with high abuse potential,no accepted medical use.mj,h Schedule II: high potential for drug abuse,can lead to strong physical and psychological dependency. meperidine,Morphine,Amphetamine Schedule III: medically-accepted drugs, potential abuse is less than 1 & II. may cause dependence,ex.codeine Schedule IV: medically-accepted drugs,may cause dependence diazepam,Phenobarbital Schedule V: medically- accepted drugs Very limited potential for dependence Ex. Opioid-controlled substance for diarrhea or cough,lomotil,robitussin Classes of Drug Abuse CNS Depressant Relieves anxiety and induce sleep,dilatepupils, decrease temp. Ex. Alcohol, sleeping pills Stimulants Increase alertness Flushing, dry mouth, inc HR, inc BP Hallucinogens Hear, see , feel something that is not there Lysergic acid diethylamide,MESCALINE Opiates Relieves pain

ex. Morphine, heroine,codeine Consrict pupil Volatile solvents Ex. rugby Pharmacologic Principles Pharmaceutics Pharmacokinetics Pharmacodynamics Pharmacotherapeutics Pharmacognosy Pharmaceutics The study of how various drug forms influence pharmacokinetic and pharmacodynamic activities

Is the study of how drugs may best be used in the treatment of disease, i.e. which drug would be most or at least appropriate to use for a specific disorder, what dose of the drug would required

Pharmacognosy The study of natural (plant and animal) drug sources Subdivision Of Pharmacology Toxicology Is the study of poisons and poisonings. Since almost all drugs are capable of being toxic under some circumstances, toxicology is an essential part of the study of all drugs. PHARMACOKINETICS ABSORPTION The process by which a drug is transferred from its site of entry into the body to the circulating body fluid for distribution The rate at which a drug leaves its site of administration, and the extent to which absorption occurs. Bioavailability Bioequivalent Bioavailability-fraction of administered drug that gains access to the systemic circulation in a chemically unchanged form. For ORAL route- less than 100% (Usually 20-40%) IV route- 100%

Pharmacokinetics The study of what the body does to the drug: Absorption Distribution Metabolism Excretion Deals with the absorption, distribution, biotransformation and excretion of drugs. Each of these factors is related to the concentration of drug and/or its chemical byproducts in various body sites as well as the time required for these drug concentrations to develop and/or change.

Factors

That Affect Absorption Administration route of the drug Food or fluids administered with the drug Dosage formulation Status of the absorptive surface Rate of blood flow to the small intestine Acidity of the stomach Status of GI motility

Drug Absorption of Various Oral Preparations Liquids, elixirs, syrups Fastest Suspension solutions v Powders v Capsules v Tablets v Coated tablets v Enteric-coated tablets Slowest Rate depend on several factors Route of administration Blood flow through the tissue site of administration Solubility of the drug Note Administer oral drug with an adequate amount of fluid Give parenteral form properly Reconstitute and dilute drug with recommended diluent Categories of drug administration Enteral Oral, rectal, nasogastric Must be dissolve in body fluids Conversion process involved if administrating drug with or without meal

Pharmacodynamics The study of what the drug does to the body: The mechanism of drug actions in living tissues Is the study of biochemical and physiological effects of drugs as their mechanisms of action Pharmacotherapeutics The use of drugs and the clinical indications for drugs to prevent and treat diseases

Parenteral Subcutaneous (subQ), intramuscular (IM), intravenous (IV) Rate of blood flow to the tissue Cooling the site of injection is afactor Percutaneous Inhalation, sublingual, topical Factors (topical) Drug concentration Length of drug contact time Hydration of tissue Degree of skin disruption Factors (inhalation) Depth of inhalation Fineness of droplet particles Available surface area of mucous membrane Contact time Hydration Blood supply Concentration of drug

Topical

Route Skin (including transdermal patches) Eyes Ears Nose Lungs (inhalation) Vagina

DISTRIBUTION Refers to the way in which the drug are transported by the circulating body fluids to the site of action (receptor), metabolism and excretion The transport of a drug in the body by the bloodstream to its site of action. Factors Chemical property of drug Fat lipid soluble drugs Protein protein binding drugs Affected by blood and tissue in contact GENERAL SELECTIVE Protein-binding Water soluble vs. fat soluble Blood-brain barrier Areas of rapid distribution: heart, liver, kidneys, brain Areas of slow distribution: muscle, skin, fat

First-Pass Effect The metabolism of a drug and its passage from the liver into the circulation. Routes that bypass the liver: Sublingual Buccal Rectal* Intravenous Intranasal Transdermal Vaginal Intramuscular Subcutaneous Inhalation

METABOLISM BIOTRANSFORMATION Is a process by which the body inactivates the drug Primary site of metabolism= LIVER Other site WBC, GIT tract, Lungs The biologic transformation of a drug into an inactive metabolite, a more soluble compound, or a more potent metabolite. Liver (main organ) Kidneys Lungs Plasma Intestinal mucosa Factors Factors that decrease metabolism: Cardiovascular dysfunction Renal insufficiency Starvation Obstructive jaundice Slow acetylator Erythromycin or ketoconazole drug therapy that increase metabolism: Fast acetylator Barbiturates Rifampin therapy

*Rectal route undergoes a higher degree of first-pass effects than the other routes listed. A drug given via the oral route may be extensively metabolized by the liver before reaching the systemic circulation (high first-pass effect). The same druggiven IVbypasses the liver, preventing the first-pass effect from taking place, and more drug reaches the circulation.

Delayed drug metabolism results in: Accumulation of drugs Prolonged action of the effects of the drugs Stimulating drug metabolism causes: Diminished pharmacologic effects EXCRETION Elimination of drug metabolite and active drug The elimination of drugs from the body Kidneys (main organ) Liver Bowel Biliary excretion

Parenteral Route Intravenous* Intramuscular Subcutaneous Intradermal Intrathecal Intraarticular *Fastest delivery into the blood circulation

Enterohepatic circulation Secretions from skin, lungs, mouth and breast

HALF- LIFE The amount of time required for 50 % the drug to be eliminated from the body The measure of time required for elimination Determined by an individual patient to metabolized and excrete a particular drug The time it takes for one half of the original amount of a drug in the body to be removed. A measure of the rate at which drugs are removed from the body. Example: Digoxin 36 hrs Aspirin 5 hrs

PHARMACODYNAMICS The study of what the drug does to the body The mechanism of drug actions in living tissues Is the study of biochemical and physiological effects of drugs as their mechanisms of action Drug actions The cellular processes involved in the drug and cell interaction Drug effect The physiologic reaction of the body to the drug Onset Peak The time it takes for the drug to elicit a therapeutic response The time it takes for a drug to reach its maximum therapeutic response

Duration The time a drug concentration is sufficient to elicit a therapeutic response Mechanisms of Action The ways by which drugs can produce therapeutic effects: Once the drug is at the site of action, it can modify the rate (increase or decrease) at which the cells or tissues function. A drug cannot make a cell or tissue perform a function it was not designed to perform. Mechanisms of Action Receptor interaction Enzyme interaction Nonspecific interactions DRUG ACTION Desired Action expected response Adverse Effect or Side Effect drugs have potential to affect more than one body system simultaneously producing a response

ADVERSE DRUG REACTION (ADR) any noxious, unintended and undesired effect of a drug, which occurs at doses used in human prophylaxis, diagnosis and therapy (WHO) Predictable had to be measured Parameter (therapeutic action, side effect, adverse effect, drug interaction) Most common reaction rash, nausea, itching, thrombocytopenia, vomiting, hyperglycemia and diarrhea Class of medicine with large account Antibiotics, cardiovascular drug, chemotherapy drugs, analgesics and anti-inflammatory Idiosyncratic Reaction occurs when something unusual or abnormal happens when drug is first administered Overresponse happens in patients inability to metabolized the drug (genetic defect) Allergic Reaction occurs to patient who has been previously exposed to a drug and have developed antibodies to it from the immune system Anaphylactic Reaction severe life threatening reaction that causes respiratory distress and cardiovascular collapse Carcinogenecity the ability of a drug to induced living cells to mutate and became cancerous Teratogen a drug that induced birth defect Variable factors influencing drug action Age Body Weight Metabolic Rate Illness Psychological Aspect Tolerance Dependence Cummulative Effect Psychological Aspect Placebo effect patients positive expectation about treatment and care received can positively affect the outcome Placebo A drug dosage form with no pharmacologic activity Nocebo Effect patients negative expectation about treatment and care received TOLERANCE occurs when person begins to require a higher dosage to produce the same effects that a lower dosage once provided DEPENDENCE Addiction/ habituation, occurs when a person is unable to control the ingestion of drugs Physical and Psychological Dependence Cumulative Effect A drug may accumulate in the body if the next dose is administered before the previously administered dose has been metabolized or excreted.

Excessive Drug Accumulation may result to Toxicity

DRUG INTERACTION Occurs when the action of one drug is altered by the action of another drug 2 ways Increase the action of one or both drugs Decrease the effectiveness of one or both drugs Categories of Drug Interaction altering: Absorption Distribution Metabolism Excretion Additive Effect Two drug with similar action are taken for a doubled effect Synergistic Effect Combined effect of two drugs are greater than the sum of the effect of each drug given alone Antagonistic Effect One drug interfere with the action of another Displacement Displacement of the first drug by a second drug increases the activity of the first drug Interference First drug inhibits the metabolism or excretion of the second drug, causing increase activity of the second drug. Incompatibility The first drug is chemically incompatible with the second drug, causing deterioration when both drug are mixed in the same syringe or solution Drug Action Across the Life Span Gender- specific Study of the difference in the normal function of men and women and how each sex perceive and experience disease Pharmacogenetics Study how drug response may vary according to inherited differences in drug metabolism Polymorphism Naturally occurring variation in the structure of gene and product Absorption Age consideration Medications Topical Transdermal Enteric tablet/ capsule/ chewable tablets GI absorption Passive diffusion Drug destroyed by gastric (ampicillin and penicillin) Acidic environment(phenobarbital and acetaminophen) Absence of enzyme needed for HYDROLYSIS Intestinal Transit Gender consideration Slower Gastric emptying Greater gastric acidity Lower gastric enzyme (alcohol dehydrogenase)

Body weight

Distribution Factors ph body water concentration, quantity fat tissues, protein binding cardiac output regional blood flow Metabolism / Excretion Factors Genes Diet Age Maturity of enzyme system Gender CYP3A4 component of of cytochrome p450 (erythro, predn, verapamil and diazepam) Excretion AGE 15% premature 35% term 50% 4wks 100% 9-12 months therapeutic Drug Monitoring Blood , saliva, urine Epilepsy, arrythmia, heart failure and antimibrobial Timing PHARMACOTHERAPEUTICS Types of Therapies Acute therapy Maintenance therapy Supplemental therapy Palliative therapy Supportive therapy Prophylactic therapy Pharmacotherapeutics: Monitoring The effectiveness of the drug therapy must be evaluated. One must be familiar with the drugs intended therapeutic action (beneficial) and the drugs unintended but potential side effects (predictable, adverse drug reactions). Therapeutic index The ratio between a drugs therapeutic benefits and its toxic effects Therapeutic Index = TxD50 ED50

Medication Misadventures Adverse drug events ALL are preventable Medication errors that result in patient harm Adverse drug reactions Inherent, not preventable event occurring in the normal therapeutic use of a drug Any reaction that is unexpected, undesirable, and occurs at doses normally used Some adverse drug reactions are classified as side effects Expected, well-known reactions that result in little or no change in patient management Predictable frequency The effects intensity and occurrence is related to the size of the dose

Adverse Drug Reaction An undesirable response to drug therapy Idiosyncratic Hypersensitivity reactions Drug interactions Factors Altering Drug Responses Age Pediatric or geriatric Immature or decreased hepatic, renal function Weight Big patients spread drug over larger volume Gender Difference in sizes Difference in fat/water distribution Environment Heat or cold Presence or real or perceived threats Fever Shock Pathology Drug may aggravate underlying pathology Hepatic disease may slow drug metabolism Renal disease may slow drug elimination Acid/base abnormalities may change drug absorption or elimination Influencing factors Genetic effects Lack of specific enzymes Lower metabolic rate Psychological factors Placebo effect Pediatric Patients Higher proportion of water Lower plasma protein levels More available drug Immature liver/kidneys Liver often metabolizes more slowly Kidneys may excrete more slowly Geriatric Patients Chronic disease states Decreased plasma protein binding Slower metabolism Slower excretion Dietary deficiencies Use of multiple medications Lack of compliance

Drug concentration Patients condition Tolerance and dependence Side effects/adverse drug effects Interactions may occur with other drugs or food Drug interactions: the alteration of action of a drug by: Other prescribed drugs Over-the-counter medications Herbal therapies

Interactions Additive effect Synergistic effect Antagonistic effect Incompatibility