Week 2 Biopharmaceutics - Basic Principles of Pharmacology PDF

Pharmacology& Venipuncture RDSC 2014 Stephanie Mullings, EdD o Outline briefly the history of Pharmacology o Define terms, including: Pharmacology Pharmacokinetics Pharmacodynamics Dependence Bioavailability Venipuncture o Describe various routes...

Pharmacology& Venipuncture RDSC 2014 Stephanie Mullings, EdD o Outline briefly the history of Pharmacology o Define terms, including: Pharmacology Pharmacokinetics Pharmacodynamics Dependence Bioavailability Venipuncture o Describe various routes of administration of drugs. What is Pharmacology?  Pharmacology oDerived from two Greek words: pharmakon – ‘medicine’ and logos – means ‘study’. Thus pharmacology simply means the study of medicine. oIt is the biomedical science concerned with the interaction of chemicals with living cells, tissues, and organisms.  Pharmacology oThe study of substances that interact with living systems through chemical processes, especially by binding to regulatory molecules and activating or inhibiting normal body processes.  Pharmacology oThese substances are chemicals administered either; to achieve a beneficial therapeutic effect on some processes within the patient. for their toxic effects on regulatory processes in parasites infecting the patient.  Brief history of Pharmacology o Since the beginning people search to treat illness and cure disease. The first or earliest phase of drug usage o Primitive people through the Egyptian period believe that evil spirit living in the body caused the illness. o 5000 years ago – the oldest known prescription found on a clay. Included salves containing thyme. o 4000 years ago – people attempted to treat diseases with substances derived from noxious plants, animals and minerals.  Historical Trends in Pharmacology The second phase of drug usage oHippocrates (fifth century) – Idea that disease resulted from natural causes. oThe selection and use of drugs were based mostly on experience (empiricism) – substances that were actually beneficial in relieving particular disease symptoms. oThe first effective drugs were probably simple external preparations such as cool mud or a soothing leaf.  Historical Trends in Pharmacology The second phase of drug usage oOver the years people learned the therapeutic value of natural products through trial and error (use of castor oil, opium, other medicinal plants). oMonasteries (site of learning) – Christian monks cultivated and studied the use of herbal medicines. oThe Arabs' interest in medicine, pharmacy and chemistry was reflected in hospitals and schools.  Historical Trends in Pharmacology oIn 1240 AD – Frederick declared pharmacy to be separate from medicine. oParacelsus (1541) – denounced humoral pathology, introduced new remedies.  Historical Trends in Pharmacology oCordus wrote the first pharmacopeia (the total of all authorized drugs available within the country) 1618: The first London pharmacopeia including opium, tincture 1818: The first pharmacopeia – the French codex 1820: US pharmacopeia  Brief history of Pharmacology The third phase of drug usage oThe rational or scientific phase – gradually evolved over the past century with important advances in chemistry and physiology (pharmacology). oA more rational understanding of disease mechanisms provided a scientific basis for employing drugs whose physiologic actions and effects were understood.  Historical Trends in Pharmacology Science of pharmacology is less than 150 years old. 20th century developments o 21st century emphasis: include: providing quality health use of insulin for diabetes care. discovery of antimicrobial administering medication and antineoplastic drugs in health care agency, recent advances in molecular community and home care biology, genetics and setting nanotechnology → further teaching client safe and developments. effective self administration.  Goal of Pharmacology To understand the mechanisms by which drugs interact with biological systems so as to enable the rational use of effective agents in the diagnosis and treatment of the disease.  What is a Drug? oA natural product, chemical substance, or pharmaceutical preparation intended for administration to a human or animal for use in the diagnosis, cure, mitigation, treatment, or prevention of a disease.  What is a Drug? oAfter a drug is administered it is called a medication. oDrugs are given in a variety of dosage forms or delivery systems (tablets, capsules, ointments, liquids, etc) to the site of action to produce the desired systemic or local therapeutic activity.  Pharmacology -Definitions Formulary Lists of drugs and drug recipes commonly used by pharmacists. Pharmacopoeia Medical reference summary indicating standards of drug purity, strength, and directions for synthesis.  Pharmacology -Definitions Pathophysiology The study of diseases and the functional changes occurring in the body as a result of diseases. Therapeutics The branch of medicine concerned with the treatment of disease and suffering.  Pharmacology- Definitions Therapeutic effect: the primary effect intended that is the reason the drug being prescribed (such as morphine sulfate is analgesia). Side effect: secondary unintended effect of the drug side effects are usually predictable and may or may not be harmless  Pharmacology Definitions Drug toxicity: deleterious effect of the drug on an organism or tissue, result from overdose or external use. Drug allergy: is immunological reaction to a drug. Drug interaction: occur when administration of one drug before or after alter effect of one or both drug.  Pharmacology Definitions Drug misuse: Is the improper use of common medications in a way that leads to acute and chronic toxicity for example laxatives, antacids, and vitamins. Drug abuse: is an inappropriate intake of substances either continually or periodically.  Pharmacology Definitions Drug dependence: is a person’s reliance on or need to take a drug or substance there are two types of dependence: Physiological dependence: is due to biochemical changes in the body tissue that these tissues come to require for normal function.  Pharmacology Definitions Psychological dependence: is emotional reliance on a drug to maintain a sense of wellbeing accompanied by feeling of need. Drug habituation: denotes a mild form of psychological dependence. Other Related Sciences Toxicology: The science of poisons and toxicity. oConcerned with the relationship between the dose of an agent and the resulting tissue concentration and biologic effects that the agent produces. Other Related Sciences Toxicology focuses on: oharmful effects of drugs and other chemicals. omechanisms by which toxic agents produce pathologic changes, diseases, and death. oantidotes  Other Related Sciences Pharmacotherapeutics: The medical science concerned with the use of drugs in the treatment of disease (clinical use). Clinical trials Human studies used to determine the efficacy and safety of drug therapy. Pharmacy Concerned with the preparation, storage, dispensing, and proper utilization of drug products.  Other Related Sciences Pharmacy Related Sciences – include pharmacognosy, medicinal chemistry, and pharmaceutical chemistry. Pharmacognosy: The study of natural drug sources Isolation and characterization of drugs from plants (e.g. digitalis, vincristine), microbes (e.g. Streptokinase), animal tissues (e.g. epinephrine, insulin, ACTH), and minerals (e.g. iron, iodine, zinc).  Other Related Sciences Medicinal chemistry: A branch of organic chemistry that specializes in the design and chemical synthesis of drugs. Pharmaceutical chemistry or pharmaceutics: The science of preparing and dispensing drugs Deals with the formulation and chemical properties of pharmaceutical products (e.g. tablets, liquid solutions, suspensions, aerosols).  Pharmacology Subdivisions oTwo major subdivisions – pharmacokinetics and pharmacodynamics. oPharmacokinetics – the processes that determine the concentration of drugs in the body fluids and tissues over time. It includes: oAdministration/absorption oDistribution oMetabolism (Biotransformation) ADME oExcretion Pharmacology Subdivisions oPharmacodynamics o– the study of the actions of drugs on target organs. o Particularly concerned with: o the biochemical mechanisms by which drugs produce their physiologic effects and; o the dose-response relationship (the relationship between the concentration of a drug in a tissue and the magnitude of the tissue’s response to that drug).  Plasma Site of Dosage Effects Concen. Action Pharmacokinetics Pharmacodynamics What the body What the does to the drug does to drugs the body Pharmacokinetic Processes  Importance of Pharmacokinetics o Pharmacokinetics tell us: What dose to give How often to give it How to change the dose or route in certain medical conditions How some drug interactions occur  Pharmacokinetics of Drugs Site of action Other storage tissues Pharmacological effects AR A+R AT A+T Plasma Distribution Absorption Unchanged Drug (A) Free drug [A] A Administration Distribution Excretion Metabolism A’ Systemic circulation Drug metabolite (A’) A+P AP Plasma protein-bound drug (AP) Protein-drug complex Routes of Drug Administratio n o List as many different routes of drug administration as you can think of… Routes of Drug Administratio n o List as many different routes of drug administration as you can think of… Name four (4) routes of administration State two (2) advantages and two (2) disadvantages of each route. Pharmacokinetics - Routes of Administration o Enteral administration (via GIT) o Parenteral (by injection) o Transdermal o Inhalational Pharmacokinetics - Routes of Administration o Topical o (There are subsets within each broad category) o Drugs require transport by circulation to the intended site of action. o The rate and efficiency of absorption differ depending on the route of admin.  Routes of Administration oThe amount of drug adsorbed into circulation may be only a small fraction of the dose administered when given by certain routes. The amount of drug absorbed = bioavailability The amount administered oThe amount of intact drug reaching the blood stream is affected by oEnzyme activity in the gut or liver oGastric pH or intestinal motility Bioavailability (F) Diagram – First-pass Effect  Routes of Drug Administration Enteral Routes (via GIT) Oral (PO): drug administration by mouth (swallowed); most common and most variable route Buccal: in the pouch between the gums and cheek Sublingual (SL): placement under tongue Rectal (PR): used when oral ingestion impossible, such as children or unconscious patients Enteral Administration  Routes of Drug Administration oIf a drug is taken by mouth (orally): The pharmaceutic (dissolution) phase. o In GIT drugs need to be in solution to be absorbed. o Disintegration: the breakdown of a tablet into smaller particles. o Dissolution: dissolving of smaller particles in the GI fluid before absorption. Routes of Drug Administration  Routes of Drug Administration Oral – Features Offers maximum convenience, relatively safe and economical – most popular. Drug absorbed from stomach/small intestine. Absorption may be slower and less complete than when parenteral routes are used  Routes of Drug Administration Oral – Features Ingested drugs are subject to first-pass effect in gut wall and/or in the liver before it reaches the systemic circulation. Some drugs therefore have low bioavailability when given orally. Drugs may be activated/inactivated in the liver.  Routes of Drug Administration Oral Administration – Advantages: Safe, convenient and economical Disadvantages: Onset of action is slow Oral administration cannot be used – in comatose or unconscious patients – sedated patients – patients suffering from nausea and vomiting.  Routes of Drug Administration Oral Route – Disadvantages Limited absorption Metabolized by first-pass effect Digestive enzyme Low gastric pH in GI tract Emesis as result of gastric irritation  Routes of Drug Administration Oral Route – Disadvantages Presence of food or other drugs or low GI motility affects drug absorption Absorption is slow with food for tetracyclines and penicillin Propranolol bioavaliability is higher after food.  Routes of Drug Administration Buccal – Features Permits direct absorption into the systemic venous circulation. Bypasses the hepatic portal circuit and first-pass metabolism. The process may be fast or slow depending on the physical formulation of the product. Routes of Drug Administration Sublingual – Features Offers same features as the buccal route Diffuses into the capillary network Bypass first pass effect Used for potent drug e.g., Drug must have good solubility in water and lipid membranes Examples (buccal/sublingual) – Nitroglycerin (for treating ischemic heart disease) – hyoscyamine (for treating bowel cramps) Routes of Drug Administration Rectal (suppository) – Features Drug placed in the rectum diffuses across mucosa and enters systemic circulation. Used when oral ingestion is impossible children/infants (e.g. diazepam for status epilepticus) Patients in unconscious states Patients with protracted vomiting and are unable to take drugs by oral route.  Routes of Drug Administration Rectal (suppository) – Features May be administered for local effect e.g. anti-inflammatory drugs for ulcerative colitis Offers partial avoidance from the first-pass effect (though not as completely as the sublingual route). Routes of Drug Administration Rectal (suppository) – Features About 50% of the drug absorbed from the rectum will bypass the liver depending on site of rectal mucosa from which drug is absorbed. Fecal matter retards drug absorption Aspirin, paracetamol, theophylline, antiemetic dugs. Routes of Drug Administration Bioavailability Advantages Disadvantages  Routes of Drug Administration Parenteral routes (by Injection – needle and syringe or with an intravenous infusion device) Intravenous (IV) bolus or infusion most common parenteral route  Routes of Drug Administration Intramuscular (IM): Injected into the muscle; used for aqueous solution or non-aqueous suspension (in oil vehicles) Subcutaneous (SC): Injected underneath the skin; used only for drugs that are not irritating to tissues Intravenous (IV) Administration  Routes of Drug Administration Intravenous (IV) – Features Injection of drug directly into vein. Bypasses the process of drug absorption, instantaneous. By definition, bioavailability = 100% Provides the greatest reliability and control over the dose of drug reaching the general circulation.  Routes of Drug Administration Intravenous (IV) – Features Often preferred for administration of drugs that have short half-lives and drugs whose dosage must be carefully titrated to the physiologic response, such as agents used to treat hypotension, shock and acute heart failure.  Routes of Drug Administration Intravenous (IV) – Features Widely used to administer antibiotics and antineoplastic drugs to critically ill patients. Potentially the most dangerous route, because rapid administration of drugs by this route may cause serious toxicity.  Routes of Drug Administration Intravenous (IV) – Features Immediate desired drug concentration – rapid onset of action Dosage can be readily adjusted Bypass first pass effect Solution for certain irritations (GI tract)  Routes of Drug Administration Intravenous (IV) – Features Irreversible side effect or overdose Bacterial contamination – infection, inflammation, abscess at injection site Must maintain patent vein – repeated IV Drugs in oily vehicles, extremely lipid soluble drugs that precipitate in blood, or drugs that may cause hemolysis, cannot be given by this route Intramuscular Administration  Routes of Drug Administration Intramuscular (IM) – Features Injection of drug into large skeletal muscle. Absorption from an intramuscular injection site is often (not always) faster and more complete (higher bioavailability) than with oral administration.  Routes of Drug Administration Intramuscular (IM) – Features Large volumes may be given (e.g. >5mL into each buttock. First-pass metabolism is avoided Solutions are absorbed more rapidly than particle suspensions. Drug absorbed more rapidly than SC because of greater circulation of blood in the muscle. Subcutaneous (SC) Administration Routes of Drug Administration Subcutaneous (SC) – Features Drug injected directly under skin Drug has direct access to skin capillaries. Rate of absorption = blood flow in area of injection. Absorption improved by massage, heat Routes of Drug Administration Subcutaneous (SC) – Features Drug injected directly under skin. Drug has direct access to skin capillaries. Rate of absorption = blood flow in area of injection. Absorption improved by massage, heat Absorption is slower than I.M. Irritant drugs may cause tissue damage. Small volumes are administered First-pass metabolism is avoided  Routes of Drug Administration Intrathecal – Features Refers to injection of drug through the theca of the spinal cord and into the subarachnoid space. In cases of meningitis, the intrathecal route is useful in administering antibiotics that do not cross the blood brain barrier. Intra-articular – Features Less commonly used Administration of drugs used to treat arthritis. Routes of Drug Administration  Routes of Drug Administration Other routes Transdermal: Most drugs that are incorporated into creams or ointments are applied to the skin for local effect Inhalation and Intranasal: Gases, liquid droplets or solid particles  Routes of Drug Administration Transdermal – Features Application of drugs to the skin for absorption into the circulation. Application may be via a skin patch, or less commonly via an ointment. Bypasses first-pass hepatic inactivation.  Routes of Drug Administration Transdermal – Features Reliable route for drugs that are effective when given in a relatively low dosage and that are highly soluble in lipid membranes. Usually slow absorption through skin Prolonged duration of action Examples of transdermal preparations – estradiol transdermal patches – nitroglycerin ointment.  Routes of Drug Administration Topical – Features Refers to the application of drugs to the surface of the body to produce a localized effect. Drug administered directly to mucosal layer or the skin for local effect. Used for treating disorders of the skin, eyes, nose, mouth, throat, rectum, and vagina. Rate of absorption varies with drug formulation and area of application.  Routes of Drug Administration Inhalation – Features Ideal route for lipid-soluble, readily volatized drugs required to reach systemic circulation in high concentrations. Quick absorption and produce rapid local and systemic effects. Local effect: Bronchodilators Systemic effect: General anesthesia By pass first pass effect  Routes of Drug Administration Local effects –Treating asthma (e.g. salmeterol) or rhinitis Systemic effects – General anesthetics e.g. halothane Almost instant absorption by diffusion - Large surface area, limited thickness of pulmonary membrane and high blood flow in lungs Avoid first pass effect  Routes of Drug Administration Administration is cumbersome - must use specific machines or equipment Patients must be able to inhale with certain timing and depth in order to get full effects of drug Impaction may occur, if drug particles size is too large to pass through the bronchi and reach the alveoli Routes of Drug Administration Bioavailability Advantages Disadvantages Quiz A patient with a history of episodic attacks of coughing, wheezing, and shortness of breath is being evaluated in the asthma clinic. Several drug treatments with different routes of administration are under consideration. Which of the following statements about routes of administration is most correct?  Quiz A. Blood levels often rise more slowly after intramuscular injection than after oral dosing B. The ‘first-pass’ effect is the result of the metabolism of a drug after administration and before it enters the systemic circulation. C. Administration of anti-asthmatic drugs by inhaled aerosol is usually associated with more adverse effects than administration of these drugs by mouth. D. Bioavailability of most drugs is greater with rectal (suppository) administration than with sublingual administration. E. Administration of a drug by transdermal patch is often faster but is associated with more first-pass metabolism than oral administration. References Katzung, B. G., Trevor A. J. (2002). Basic and Clinical Pharmacology. Lange Medical books/ McGraw-Hill Medical Publishing Division. Rosenfeld, G. C., Loose-Mitchell D. S., Jones J.B. (2003). Board Review Series Pharmacology (3rded.). Karch, A. M. (2007). Focus on Nursing Pharmacology (4thed.). Brunton, L. L., Parker, K. L., Lazo, J. S. (2005). Goodman and Gilman’s: The Pharmacological Basis of Therapeutics (11thed.). McGraw-Hill Professional. References Rang, H. P., Dale, M. M. (2012). Pharmacology (7thed.). Grahame-Smith, D. G., Aronson, J. K. (2002). Clinical Pharmacology and Drug Therapy. Craig C. R., Stitzel R. E. (2004). Modern Pharmacology. Lippincott, Williams and Wilkins (2006). Pharmacology (3rded.). Lippincott’s Illustrated Reviews.