Dental Pharmacology PHT 350 Past Paper PDF

Pharmacology 1-Pharmacokinetics Pharmacology deals with the knowledge of drugs, their sources, 2-Pharmacodynamics biochemical and physiological effects, mechanism of a...

Pharmacology 1-Pharmacokinetics Pharmacology deals with the knowledge of drugs, their sources, 2-Pharmacodynamics biochemical and physiological effects, mechanism of action, and therapeutic uses of drug. Pharmacology comprises two main branches: 3. Cholinergic ANS 4-Adrenergic ANS 5-Antihypertensives MY Pharmacokinetics Pharmacodynamics what body does a to what drug does to drug body Dental Pharmacology G (B-→ D) (D-→ B) PHT 350 Quiz 1 1443 1 2 ADMÉ Pharmacokinetics Pharmacodynamics Pharmacokinetics of Drugs of Drugs: of Drugs: FI H First, drug absorption from the site of 1 (Absorption) administration (Absorption) permits entry of the therapeutic agent into plasma Absorption Drug actions me 2 Second, the drug may then reversibly leave the blood stream and distribute into the interstitial Distribution Mechanism of It 6 (Distribution). and intracellular fluids (Distribution). fm.am action active Third, the drug may be metabolized by the liver, Metabolism and Adverse 3 (Metabolism). kidney, or other tissues effects of drugs in in side e ffects Finally, the drug and its metabolites are Excretion 4 (Elimination). removed from the body in urine, bile, or feces (Elimination). 3 Kidny sweat 4  ok Absorption em Absorption is the transfer of a drug from Schematic C its site of administration to the blood stream. representation of drug absorption, distribution, metabolism, and Commonly used routes of elimination. drug administration. IV = intravenous; is IM = intramuscular; SC = subcutaneous. 6 5 Mechanisms of transport of drugs across cell 1. Passive diffusion: membranes: Characteristics 1- Along concentration gradient. ; the drug moves from a region of high Passive concentration to one of lower I Facilitated Active concentration. diffusion diffusion Endocytosis transport 2- NO carrier. 3- NO energy. The vast majority of drugs gain access to the s body by this mechanism. Schematic representation of Lipid-soluble drugs readily move across most drugs crossing a cell biologic membranes due to their solubility in membrane of an epithelial cell of the the membrane bilayers. gastrointestinal tract. 7 wishes TdHÉpid 8  saturation of it 2. Facilitated diffusion: 3. Active transport: Through the protein channel in the cell Characteristics membrane; facilitate the passage of large 1. Against concentration gradient; molecules. from a region of low drug Characteristics concentration to one of higher If drug concentration. 1. Along concentration gradient 2. Needs Carrier → Site for 44 2. Needs Carrier → Site for Saturation 3. No energy Saturation & Competition (Interaction) 3. Need Energy A few drugs that closely resemble the a Schematic representation of structure of naturally occurring metabolites Schematic representation of drugs crossing a cell drugs crossing a cell membrane of an epithelial are actively transported across cell membrane of an epithelial i iI cell of the membranes using these specific carrier cell of the gastrointestinal tract. proteins. gastrointestinal tract. The process shows saturation ATP = adenosine triphosphate; kinetics for the carrier. ADP = adenosine diphosphate. 9 10 4. Endocytosis: This type of drug delivery transports drugs of exceptionally large size across the cell membrane. Endocytosis involves 11 engulfment of a drug molecule protien carrineyes by the cell membrane and transport into the cell by pinching off the drug-filled 9to vesicle. waterf.li Schematic representation of For example, vitamin B is drugs crossing a cell membrane of an epithelial transported across the gut wall cell of the by endocytosis. gastrointestinal tract. 12 11 wa f vescle si  SIT A fraction of Most drugs binds Reversibly to Drug Distribution Binding of plasma proteins Mainly albumin. a Drugs To The Bound fraction of the drug → Drug distribution is the process by which a drug reversibly leaves the 1) Blood flow, Pdistrition Plasma NOT Active NOT Filtered bloodstream interstitium and enters (extracellular the fluid) Proteins NOT Metabolized NOT Excreted → and/or the cells of the tissues. Depot Form. 2) Capillary The delivery of a drug from the plasma blood M permeability, More binding = More Depot = Longer duration. 1 se Ii capillaryPermiblity to the interstitium primarily depends fi on: 3) The degree of binding i iff of the drug to plasma The Free fraction of the drug → Edith j and tissue proteins, and Albumin main Active, Metabolized Excreted. There equilibrium between the free makethebenititactive 4) The relative hydrophobicity of the bound & the free fractions of the drug. fromAlbumn drug. Tstration Yasmin storage notactive 13 14 Binding of Class I and Class II drugs to Clinical importance of drug albumin when drugs are administered alone (A and B) or together (C). displacement: This assignment of drug classification assumes importance when a patient taking a Class I drug, such as warfarin, is given a Class II drug, such as a sulfonamide antibiotic. A low aunt alotalbumin loweffect Warfarin is highly bound to albumin, and only a small fraction is free. This means that most of the drug is sequestered on albumin and is inert in highaiunt lowalbumin high effect terms of exerting pharmacologic actions. is together displacement.fm f wm is If a sulfonamide is administered, it displaces warfarin from albumin, leading to a rapid increase in the concentration of free warfarin in in i plasma, because almost 100 percent is now free, compared with the initial small percentage. [Note: The increase in warfarin concentration may lead to increased therapeutic effects, as well as increased toxic effects, such as bleeding.] 15 16 class dk.it  dasI umlfnmide themain sideof metabolism liver to Metabolism a us Chemical alteration of the drug AIMING to convert: Drugs (Active, an chemical Non-ionized & Lipid soluble) → Metabolite (Inactive, Ionized & water soluble) → Easily excreted in urine & bile. Site Of Biotransformation metabolism tw 11 a- Liver (Hepatic) is the main site for biotransformation inactive b- Lung → Nicotine, Prostaglandins & Angiotensin (ACE). ionized nin iiized c- Kidney → Vitamin D lipidsoulble The biotransformation of drugs. d- G.I.T. & Gut flora → Tyramine & Histamine watersoulble e- Skin → Vitamin D tmetabolis inaoire f- Plasma (Cholinesterase) → Succinylcholine [Note: Some agents are initially administered as inactive 18 compounds (pro-drugs) and must be metabolized to their active forms.] activwwtwsdim.hu 17 Oxidation Factors Affecting Hepatic Microsomal 9911 Phase I reactions Reduction Phase activitiative Enzymes µ Hydrolysis I A) Hepatic Microsomal Enzyme Inducers (Activators): db.ME 94 a tinswwsix Edf Examples: Phenytoin, Testosterone, Cortisol & Tobacco smoking. They  Metabolism of other drugs e.g. Oral anti-coagulants, Oral PDose Conjugation with sulfate, glycine, or C c hypoglycemics & Oral contraceptives →  Their duration of action. glucuronic acid to increase drug w They  Their own metabolism (Auto-induction) → Tolerance. Pid Phase II polarity. reactions The conjugates are ionized, and the as charged molecules cannot back- B) Hepatic Microsomal Enzyme Inhibitors: diffuse out of the kidney lumen. Specific: Grapefruit, Estrogen, Cimetidine, Chloramphenicol, Ciprofloxacin. Non-specific (General): toxic live.atworkliver 1 a- Hepato-toxic drugs: Carbon monoxide, Carbon tetrachloride & Ozone. 41 111 adf.ie b- Drugs  Hepatic blood flow: -Blockers (Propranolol) & H2-Blockers (Cimetidine) 19 C) Age: iii a Elimination H.M.E. Activity is inhibited in extremities of age. soulble Premature neonate can NOT conjugate chloramphenicol → Fatal Grey Baby Syndrome. D) Liver disease & Cancer →  H.M.E. Activity inactiv Kissing E) Genetic Abnormality (Idiosyncrasy): Favism & Abnormal Pseudo-Ch.E. Removal of a drug from the body F) Starvation vitamin, protein or calcium deficiency impairs drug metabolism occurs via a number of routes, the decreased activity of the microsomal enzymes of the liver most important being through the G) Pregnancy kidney into the urine. I) Hormonal effects Other routes include the bile, Thyroidectomy reduces the metabolism of a number of drugs like barbiturate induced sleeping time is prolonged in thyroidectomized animals. intestine, lung, or milk in nursing mothers. Alloxan or streptozotocin induced diabetes in rats also reduced the metabolism of hexobarbitone thus prolonging the sleeping time. 22 Drug elimination by the kidney: A drug passes through several processes in the kidney before elimination: Glomerular filtration Renal elimination of a drug Active tubular secretion, Effect of drug metabolism on reabsorption in the distal tubule. Passive i tubular reabsorption. 24 23 THAT’S THAT’SIT!! IT!!