Fundamentals of Pharmacolgy 2-kinetics.pdf

Pharmacokinetics Camille Marie B. Urbano Components of Pharmacology Pharmacotherapeutics: The clinical purpose or reason for the medication Pharmacokinetics: The movement of the drug through the body -What the body does to the drug Pharmacodynamics: T...

Pharmacokinetics Camille Marie B. Urbano Components of Pharmacology Pharmacotherapeutics: The clinical purpose or reason for the medication Pharmacokinetics: The movement of the drug through the body -What the body does to the drug Pharmacodynamics: The physiological response of the body to the drug. -What the drug does to the body Pharmacokinetics Derived from the root words Pharmacon – medicine;drug Kinetikos – putting in motion The study of the the movement of the drugs into, within and out of the body. (ADME) 3 Factors that paly a role in Pharmacokinetics Onset of action – the time it takes for the drug to elicit a therapeutic response. Peak concentration – blood concentration level when the absorption rate equals the elimination rate Duration of action – the length of time a drug produces a therapeutic effect.  Process of Pharmacokinetics 1. L iberation the release of a drug from its dosage form. 2. A bsorption the movement of drug form the site of administration to the blood circulation. 3. D istribution the process by which drug diffuses from the intravascular to the extravascular space. 4. M etabolism the chemical conversion of drugs into compounds. 5. E xcretion the elimination of unchanged drug (metabolite) from the body via renal, biliary or pulmonary process. LIBERATION - the way that a drug is released from its administered form. For oral administration, important liberation processes include the disintegration of tablets or the dissolving of soluble coatings of tablets and capsules.  Routes of Administration 1.Enteral -the most common, convenient, and economical method of drug administration by mouth. 2.Parenteral -the administration of drugs directly into the systemic circulation. 3.Inhalation -provide rapid delivery of drug across the large area of the RT(mucous membranes) and the pulmonary epithelium.  Routes of Administration 5.Topical -application of medication when a local effect of the drug is desired. (skin, eye, intravaginal, intranasal) 6.Transdermal -application of drug to the skin for systemic effect via a transdermal patch. 7.Rectal -administration of drugs through the rectum. 8.Intrathecal/ -administration of drugs directly into the CSF. Intraventricular Ommaya reservoir -a dome- shaped container that is placed under the scalp during surgery; it holds the drugs as they flow through a small tube into the brain. Enteral Administration a. Oral a) Tablets – dried powdered drugs compressed into small disks b) Enteric-coated tablets– a chemical envelope protects the drug from the stomach acid, delivering it to the less acidic intestine , where the coating dissolves and releases the drug. c) Extended-release preparations – special coated drugs that control drug release, allowing slower absorption and prolonged duration of action. *common abbreviations (ER, XR, XL, SR) d) Capsules – small, cylindrical gelatin containers that hold dry powder or liquid medicinal agents. e) Lozenges – sweetened and flavored medicated material that is designed to be held in the mouth for slow dissolution. (pastille or troche) Enteral Administration f) Elixir – clear liquids made up of drugs dissolved in alcohol and water; used primarily when the drug will not dissolve in water alone. g) Emulsion – stabilized oil(active ingredient)-in-water dispersions. h) Suspension – liquid dose forms that contain solid, insoluble drug particles dispersed in a liquid base. i) Syrup – sugar-based liquid medication b. Sublingual - placement of a drug under the tongue. c. Buccal – placement of drug between the cheek and gum. Parenteral Administration a. Intravenous - most common parenteral route. b. Intramuscular c. Subcutaneous d. Intradermal Topical Administration a. Suppository – solid but readily meltable cone or cylinder designed for introduction into a body orifice; at body temperature, the substance dissolves and is absorbed by the mucous membranes; should be stored in a cool place to prevent softening. b. Lotions – aqueous preparations that contain suspended materials. c. Ointments – semisolid preparations of medicinal substances in an oily base such as lanolin or petroleum. d. Transdermal patch – provides controlled release of prescribed medication through a semi-permeable membrane for several hours or weeks when applied to intact skin. e. Creams- semisolid emulsions for external application. ACTIVITY Instructions: - Name and illustrate drugs/medications based on the given administration routes and identify its form. - Give at least two (2) from each form of drug. a.Enteral b.Parenteral c. Inhalation d.Topical e.Transdermal f. Rectal ABSORPTION -Process that occurs from the time a drug enters the body to the time it enters the bloodstream to be circulated. Mechanism of Absorption of drugs form the GI tract a.Passive diffusion b.Facilitated diffusion c.Active transport d.Endocytosis and Exocytosis ABSORPTION Factors Influencing Absorption a.Effect of pH on drug absorption b.Blood flow to the absorption site c.Total surface area available for absorption d.Contact time at the absorption surface ABSORPTION Factors Influencing Absorption a.Effect of pH on drug absorption Ionized drugs are poorly absorbed while unionized drugs are lipid soluble and are well absorbed. Acidic drugs remain unionized in acidic medium of the stomach and are rapidly absorbed e.g. aspirin, barbiturates Basic drugs are unionized when they reach the alkaline medium of intestine from where they are rapidly absorbed e.g. pethidine, ephedrine. strong acid and bases are highly ionized and therefore poorly absorbed e.g. heparin, streptomycin. ABSORPTION Factors Influencing Absorption a.Effect of pH on drug absorption b.Blood flow to the absorption site The intestines receive much more blood flow than the stomach, so absorption from the intestine is favored over the stomach. The greater the blood flow, the faster the absorption. ABSORPTION Factors Influencing Absorption a.Effect of pH on drug absorption b.Blood flow to the absorption site c.Total surface area available for absorption The intestine has a surface area about 1000-fold that of the stomach, making absorption of the drug across the intestine more efficient. ABSORPTION Factors Influencing Absorption a.Effect of pH on drug absorption b.Blood flow to the absorption site c.Total surface area available for absorption d.Contact time at the absorption surface Gastric-emptying time : If gastric emptying is faster, drug absorption is faster. Intestinal motility : If a drug moves faster through the GI tract very quickly, absorption is reduced. e.g. severe diarrhea Anything that delays transport of drug from the stomach to the intestines delays the rate of absorption. e.g. food in the stomach ABSORPTION Bioavailability - the rate and extent to which an administered drug reaches the systemic circulation. When drug is given orally, only part of the administered dose appears in the plasma. e.g. If 100 mg of a drug is administered orally and 70 mg is absorbed unchanged, the bioavailability is 0.7 or 70%. In IV administration, 100% of the drug rapidly enters the circulation. ABSORPTION First-pass hepatic metabolism Mechanism wherein the liver may metabolize much of the drug before it enters the circulation. It is also called presystemic metabolism or first pass effect. A drug given via the oral route may be extensively metabolized by the liver before reaching the systemic circulation - - high-pass effect. The same drug given IV bypasses the liver, preventing the first-pass effect from taking place, and more drug reaches the circulation. DISTRIBUTION - the process by which the drug is delivered from the systemic circulation to body tissues and fluids Factors Affecting Distribution Blood flow Solubility Protein binding DISTRIBUTION Factors Affecting Distribution Blood flow Drug is quickly distributed to organs with large supply of blood such as the heart, liver and kidneys DISTRIBUTION Factors Affecting Distribution Blood flow Solubility Lipid-soluble drugs easily cross through cell membranes, through the blood brain barrier and enter the brain During pregnancy and lactation, drug distribution is unique as most drugs cross the placenta or in the case of lactation, pass into breast milk. DISTRIBUTION Factors Affecting Distribution Blood flow Solubility Protein binding The portion of the drug that gets “protein-bound” is inactive while it is bound, but the portion of the drug that escapes initial protein binding becomes immediately “free” to bind to the target tissue and exert or block an action. METABOLISM (Biotransformation) - the process by which the body changes a drug from its dosage form to a more water-soluble form that can be excreted. Drugs can be metabolized in several ways: Into inactive metabolites which are then excreted Into active metabolites which are capable of exerting their own pharmacologic action. Most drugs are metabolized by the Cytochrome P450 (CYP450) enzymes in the liver; also plasma, kidneys and membranes of the intestines. METABOLISM Delayed drug metabolism results in: Accumulation of drugs Prolonged action of the drugs Stimulating drug metabolism causes diminished pharmacologic effect. EXCRETION - the elimination of drugs from the body. Kidneys Liver Bowel Biliary excretion -involves active secretion of drug molecules or their metabolites from hepatocytes into the bile. The bile then transports the drugs to the gut, where the drugs are excreted. Enterohepatic circulation -refers to the substances metabolized in the liver, excreted through this bile to get into the intestinal lumen, and then reabsorbed and returned to the liver through the portal circulation. EXCRETION Most drugs are excreted by the kidneys and leave the body through urine. Drugs can also be excreted through the LUNGS, EXOCRINE GLANDS, SKIN and INTESTINAL TRACT. Half-Life (t ½) – half of the drug The time it takes for one half of the drug to be eliminated by the body. Factors affecting drug half-life: Rate of absorption Metabolism Excretion Knowing how long a drug remains in the body helps determine how frequently it should be administered. A drug that is given only once is eliminated from the body almost completely after 4 to 5 half-lives.