1 - Introduction to Pharmacology.pdf

Faculty Of Medicine and Health Sciences Department Of Dentistry and Dental Surgery Dental Pharmacology and Therapeutics 7503318 g...

Faculty Of Medicine and Health Sciences Department Of Dentistry and Dental Surgery Dental Pharmacology and Therapeutics 7503318 g Dr. Thikrayat Yahya DDS, ID MSc [ "122 = +mi +2) 4 First Semester 2023-2024 Basic Principles in General Pharmacology Lecture Content: Introduction and Definitions Sources of drugs Sources of drug information Routs of Drug Administration and dosage forms. Drug nomenclature Pharmacokinetics Pharmacodynamics  Intended Lecture Outcomes At the end of this lecture, students should develop a comprehensive understanding of the foundational principles of pharmacology and be able to: Define general principles in pharmacology. Describe various routes of drug administration (oral, parenteral, topical..) and their advantages and disadvantages. Apply the acquired knowledge to differentiate between Pharmacokinetics and pharmacodynamics. Explain the processes of drug absorption, distribution, metabolism, and elimination (ADME), and the factors influencing drug pharmacokinetics. Describe the principles of drug-receptor interactions. Explain dose-response relationships and concepts like efficacy and potency.  Introduction and Definitions  Pharmacology · jyd Pharmacology) :  Pharmacy living systems /I Baile 103/997  Drug Absorption Metabolism ↑ Pharmacy * S's  Pharmacokinetics (ADME) , g Pharmacokinetics distribution "excretion E  Pharmacodynamics & 11961ju Pharmacodynamics s : ↳ bin; -  Therapeutics - - Eny17 P So9)- Therapeutics : +100,5, 1559 jese ! 1 9618 2505 /  Chemotherapy -living systems /151si59  Clinical pharmacology JB1 % Chemotherapy : bir & anti-neoplasmic /1 + antimicrobial /I s Sources of drugs and dosage forms Drugs have three major sources: ① Natural - jigny... ② Semisynthetic > - nature rig su # ③ Synthetic > - y is ga Natural sources Micro- Plants organisms Morphine -: J Penicillin-1- Minerals ferrous sulfate :5 Animals Insulin-: 5  morphine (115-m & Semisynthetic: like Hydromorphone > - Y. % 13745 - Synthetic :like Aspirin , Paracetamol  Sources Of Drug Information Official Compendia (Pharmacopoeia, Formulary) Unofficial Compendia Text Books Periodicals, and Websites.  - is-25 99 * Formulary& Pharmacopoeia 50) 55g(0 [ & pjxS1] - - 2 Eggs ajsyia zi... Istalojjjessi/Sa -G  Routes of Drug Administration & Skigde A Route : Parenteral Enteral Routes Routes Miscellaneous Routes  Enteral Routes % GT tracts /1605/-oral Drugs * absorption Oral route GI mulosa /1 Jx Y Sublingual route = y+ j s(g)mj4 sublingual route =- -8 * Rectal route (Suppositories, Enemas) Jxin Rectal route * (00/1/8-1  Parenteral Routes 1. Injections: Liquid formulations intended for injection into the body via various routes: Intravenous: Drugs are injected directly into a vein for rapid systemic distribution. Intramuscular: Drugs are injected into a muscle. Subcutaneous: Drugs are injected into the fatty tissue under the skin. Intradermal: Drugs are injected into the top layer of skin (e.g. for skin testing) 66 e # 2. Infusions: Solutions administered intravenously over a specific period, (PICC line, intraosseous line, Porta Cath..)  des um Infusion & sY Injections 0 : $500 · j 1951 - Liquid formula go ja - Injection ① -jja jjdt - Intravenous @ &% j Intramuscular def -= < subcutaneous @ < Kin(1-1) - Intradermal ⑪ & solutions Infusions & jij is s -  Other Routes 1. Topical Route:  Dermal: Drugs are applied to the skin's surface and absorbed through the skin.  Ophthalmic: Drugs are applied (e.g. eye drops, ointments, or gels) for ocular conditions.  Otic (auricular): Drugs are applied (e.g. ear drops) for ear-related conditions.  Subgingival: delivery of medications or therapeutic agents directly into the gingival crevice.  exce nurcourtes :- skin surface /10 1 - Dermal : -vyp5-1 - Ophthalmic :· &yes did Wiggin Otic : gingival jy M -1 - subgingival minary um route. - MIS/10- lungs/1545 g 58 in Inhalers : & 561j jS - Nebulizers : mumransdermal route 5515= Jillian p je  Other Routes 2. Pulmonary (Inhalation) Route: Inhalers: Drugs are inhaled into the lungs through devices like metered-dose inhalers (MDIs). Nebulizers: Liquid medications are converted into a fine mist for inhalation 3. Transdermal Route: E.g. Transdermal Patches: Adhesive patches applied to the skin deliver drugs gradually over time.  Other Routes El subarachnoid space (4) Intrathecal 4. Intrathecal and Epidural Routes: : /5/1s/5xNBs-brain/JS5 & --- Intrathecal: Drugs are administered into the subarachnoid space, often for anesthesia, pain management, or treatment of infections like meningitis Epidural: Drugs are injected into the epidural space around the spinal cord for pain relief during childbirth or surgery. & - Topical Lozenge Gel Suppositories/Enema Patches Drug Dosage Forms Solution Mouth Rinse - JerisIgS1 Syrup Gargle 584 S75470s1 / Suspension 0 solid drug particle > - /I Paste ↓ Sel : 500 5 ; Ampoules & 9) 8 100 Eye/Ear/Nasal Drops. j + + y : Vials Aerosol Spray  muffing mu Dosage form Tablets ⑪ J G (06 Kisss. + Enteric coated - = + sublingual - Jestibule/Ig cheek /1-5 buscal space (425) - buccal [. &jin 1- chewables * is -1- sustained-released · sign lji is & acidity (0y "shill" g. - Capsules & Stomach 1 strepsil (10% 1 - Lozenges & )/k- 9 suppositories G  Drug Nomenclature Chemical Name: describes the drug molecular structure and chemical composition. It is complex and not suitable for everyday use. For example, the chemical name for Paracetamol is N-acetyl-p-aminophenol, and Aspirin is acetylsalicylic acid. Generic Name (Nonproprietary Name): it is a non-proprietary name given to a drug by an organization like the United States Adopted Names (USAN) Council. It is less complex than the chemical name. E.G., Paracetamol and Aspirin are generic names. Proprietary Name (Brand Name): The brand name, also known as proprietary name, is the name under which a pharmaceutical company markets a specific product. Brand names are often short and easy to recall. For example, the brand name for the generic drug Paracetamol is Tylenol, Aspirin is Disprin, Ibuprofen is Advil  5 :s structure (15 rid y 1 - Chemical Name * sig · iii * Generic Name * Paracetamol /19-0X , 5-Y > : - Paracetamol /1 : 1- 1, e591). - Brand Name *.... Tyleno &S %  Pharmacokinetics Pharmacokinetics (PK) is derived from the two words: Pharmakon (means drug) and kinesis (means movement) Pharmacokinetics: explains movement of a drug over time through the body. & eyes 0 j 1 g) insigh -Pharmacokinetics : - A It helps us understand how drugs are absorbed into the bloodstream, how D they are distributed to various tissues, how they are metabolized and how > - ↓ they are eventually eliminated. E > - M ADME(1b T * Pharmacokinetics Absorption Distribution Metabolism Elimination  Absorption It is the transfer of a drug from its site of administration into systemic circulation To reach the bloodstream, a drug molecule needs to cross various biological membranes, using one of the following mechanisms: Passive Transfer Specialized Transfer Simple diffusion Active transport Filtration  testation ① (Plasma) systemic circulation) 1 & site of administration /10005 11 gd/De 5 skin/ & topical route) ? 26 GI mucosal I enteric route /? site of administration /1 : systemic circulation & site administration /1 - of methods & 9) absorption sty * - S : zX administration Passives 1 : absorption 5 1551 y : · ziespecialized / > - jS9 Passive Transfer/1.. 2: 554915)1jjj5191j5 515 Deji , - concentration /I& --- simple diffusion O Sig Xg & · S * simple diffusion) %25 16. j , 1: 3 a concentration gradient - & concentration / & absorption / / &151 - : ✓ Molecular weight absorption) (j52)(150 ✓ Drug dose nej drug Jose (1/** concentration (18 70 + ✓ Local effect of drug , BV N constriction adrenaline(11-1801 ✓ Drug combination : & Yabsorption (1054216 site of injection ↓ ✓ Dosage form absorption /I j. De Molecular weight /100: ✓ Route of administration < /1d iron /15-sdrug combination /160; Vitamin : ✓ Available surface area. Calle iron (18 combination /11596 absorption (1) - ✓ Blood flow to the absorption sitesublingual/1990-111 absorptions 1-1,4 , G, route of administration /10: ✓ Contact time at absorption site +  Absorption... &-S & , Factors Affecting Absorption sustained-release tablets /1 1 Dosage form /1 Drug Related Factors: densed layers j- : Jg" Tod absorption /55w> ✓ Molecular weight tablets (1 ✓ Drug dose 1 release 9%.9 of Beiji sustained release - Note * : /I doe joy1 109 as i : ·ssis dose 11 9. % ✓ Local effect of drug systemic circulation/1& ✓ Drug combination Soy surface area (1-55- intestines) ! - surface area / d : ✓ Dosage form absorption /1- (jSI microvilli/1S ✓ Route of administration (2) & absorption site /j 151 : 50 absorption ✓ Available surface area. diarrhea 975155 516 contact time , /%: ✓ Blood flow to the absorption site gol absorption (1-5 ✓ Contact time at absorption site contact time less absorption less = :  Absorption ✓Lipid solubility: combines two factors ❖Lipophilicity of the drug (ability to dissolve in lipids) ❖Ionized (charged) drug molecules Lipid solubility depends on the pH of the surrounding environment: Acidic drugs (HA) in basic environment will become charged A- Basic drugs (B) in acidic environment will become charged BH+  * j5, oxg 939 * lipid solubility (1 absorption /1: 3961 , 81 ,/19811.. lipicts %%2. i & substance Noj = lipid solubility : - : j & lipid solubility) * &jes more lipophilic sigd1s # Lipid /1, 55gd sIgblog - lipophilicity & je" 195 CHA) Ionization of drug molecule ② ↑ - -Acidic BodyujpH/ & linid solubility /1 : (A-)5/55 basic environment J d es acid /11559 ge,2 as /1299 ↳ & · 10/2) (H +  Distribution What Is The Importance of Plasma Protein Binding Highly bound drugs to plasma proteins have low volume of distribution Binding to plasma proteins delays the bounded drug metabolism. Highly protein-bound drugs have a longer duration of action. & jo de actively= 10j183-5, bound drugs albumin se active 19 /%s albumin /% vibj,Sin * - Alduration of action /15 2% bis-metabolism I bounded drugs /16  Distribution What Is the Clinical Significance of Plasma Protein Binding?  Distribution Redistribution of drugs (like thiopentone used for induction of general anesthesia) adipose tissue /95% thispentine 10: tissue is is release a Blood Brain Barrier (endothelial cells in brain capillaries are tightly joined-only uncharged lipid-soluble drugs can reach the brain) Some drugs accumulate in body tissues or organs, this may lead to toxicity on chronic use ·posi (i) in endothelial cells /Is BBBJ45 lipophilic drugs /l bjo ijs6 j 9)g1pj y & Si will Gil 9 metabolism/ - S Metabolis 4.. : - a, Metabolism I livery A term that describes the biotransformation of a drug in the body so it can be easily eliminated Major site of metabolism is the liver Biotransformation may convert a drug as following: active inactive a active drug yyox T Active Inactive Cobaine(15-13 active - die active drug /105 * & - sl metabolism morphines I' , Active Active active Prodrug: is an inactive form of a drug that is converted to an active form after metabolism Inactive Active (prodrug) "Prodrugs"active 2157 metabolism/120 inactive I'd gi * Drug Toxin metabolism (19 toxin ( =& *  Metabolism Metabolism phases: Phase I: aims to convert lipophilic molecules into more polar molecules either by adding or unmasking a polar functional group ( -OH, -NH3,..) Phase I involves reactions like Oxidation, Reduction, Hydrolysis, Addition of oxygen and/or Breakdown/ removal of hydrogen Removal of oxygen or cleavage of the (the most important metabolic addition of hydrogen compound by adding reaction) water Phase II : conjugation reactions that adds endogenous groups (like: glucuronic acids, acetic acids, etc.) to the functional group (-OH,-NH3,- COOH)  ?? metabolism liversi * polar molecules lipophilic drug dig Phase 1 -molecule oiji juse's Phase o Polar functional group 5555 : hydrolysis /1 g reduction," exidation/lis 2 -scleavage 54 10 e GHz wigiozdi ↳ HedjI gl 02 water Soluble :5% /"Sa conjugation reaction & Phase 11 * sight functional groups je glucuronic acid--water soluble (11250 -- : bile 14 E Kidney E. (2) 15 Gbz , conjugation reaction ( 1 :  Metabolism Drug-Metabolizing Enzymes Microsomal enzymes: mainly present in the endoplasmic reticulum of the hepatocytes (e.g.CYP450), and catalyze most of phase I reactions, and glucuronide conjugation reaction (one of phase II reactions) Non-microsomal enzymes: found in the cytoplasm, hepatocellular mitochondria, etc., and catalyze all phase II reactions (except glucuronide acid conjugation)  livery u> Phase I reaction /121si-99 9 oxidation 11 * microsomal enzymes (1 (1-u hepatocytes/1 os -endoplasmic reticulum//i1 m& 55 1- microsomal enzymes : & j , CVP is oidation 1 dg jls-se Phase It - - glucuronide conjugation reaction /I dis144 Sign 455 Non-microsomal enzymes. - glucuronide cojugation /I sitis ! Phase 11 I s  Metabolism Cytochrome P450 System Most of phase 1 reactions are catalyzed by microsomal isozymes system: CYP450 Divided into families, each family is indicated by a number, and followed by a capital letter to indicate the subfamily, another number is added to indicate the specific isozyme. E.g. & CYP3A4 This isozyme is responsible for metabolizing approximately 60% of - Family Number drugs Subfamily Letter A drug may be a substrate for more than one CYP450 isozymes Isozyme Number isozymes 5515 ? metabolism /S1gS =&:  Metabolism CYP450 INDUCERS: some drugs increase the synthesis of one or more CYP isozymes, thus increasing the degradation of other administered drugs that are substrates for the same isozyme or the inducer drug itself , e.g. rifampin is considered CYP450 inducer, and decrease the plasma concentration of HIV proteas inhibitors thus dimensioning their ability to suppress HIV virion maturation CYP450 INHIBITORS: some drugs inhibit one or more CYP450 isozyme (e.g. competition for the same isozyme or inhibiting other drug-isozyme reactions) this leads to accumulation of other drugs, e.g. omeprazole or erythromycin inhibits warfarin metabolism CYP isozymes, this will increase warfarin levels in the blood leading to increased risk of hemorrhage.  =jus 3549 : jg one islymes eiejpylene - pinducers : & jjls & metabolism Sle N degradation (15) isozymes /1155 degradation effect /I. 2 5.5 %9 HIV protease inhibitors & bj1j5 dis Cyp inducer & rifampin 1- * control a sg5b9 9. jus Se : HIV drugs/1dG0 9 Des , i55. (P / _ vej llsa C inhibitor : JgY,je hemorrhage 3 -2015 ge warfarin metabolism /1 = erythromycin /19-- *  & e.g Je Phase 11 gr : metabolism 19 i pjj I'd li * hydrolysis &.99 Phase 1 % 5cj e> INH(15ng)15 acetylation , 86 Metabolism water soluble is hard drugs jg Reversal of order of metabolizing phases: The antituberculosis drug isoniazid (INH) is first acetylated (Phase II conjugation reaction) then hydrolyzed (Phase I reaction) Few drugs do not need metabolism as they are already water soluble. The overall aim of drug metabolism is to produce more water soluble compound to be excreted easily in body fluids  Metabolism INH hard drugs DRUG DRUG DRUG DRUG DRUG PH1 PH 2 PH 2 PH1 PH 2 PH 1 EXCRETION  immitass metabolism first pass metabolism 2005" site of siministrations" J liver /1951-816 Bioavailability circulation (9/196/ijjj9k ↑ & 751. 1996 first Pass (1% 24 % (1991, 119 - Amy Yes *** 951 &Y IV She we first pass metabolism B livery * locally  Metabolism Kinetics of metabolism First order metabolism: a constant ratio of drug is metabolized per unit of time (this unit of time is called half life) Zero order metabolism: a constant amount of drug is metabolized per unit of time. (Few drugs eliminated by zero order) Half life: the time needed to eliminate 50 % of the drug from the plasma *Determination of the inter-dosage interval *Determine the duration of drug action *Estimate the time required to reach the steady state plasma concentration  i - tim 150 Jig # sight n constant ration / 01- first order metabolism * 100 Jigslsdl n constantamont - ple zer order metabolism * First order () Zero order (2) - L 100 - & 100 = 50 % - -911gd1 * 100g/1 - j/jg59% * 40 constant dose 39 jos 80- 25 %12 5 50. 6 25 ⑨. 3 125. - N I 2 ↓ · 6j > Time - jjy 1: Zerorder (1 * i stilg slisis J 80 is N Nest slo , yo 50 / 21095195144/5(515695jy1 elimination , & (11) )5 time interval 5% %1164: %11 sy concentration S 151 : - : 9 ?/1 259:. 219 %j4 5915 1904  187 3. Real< &- 300/200 400 20 · 19 x)x · ~ o = 59>4 8 ↑ - > 25 2 93 Too -. -. j 150 100 87 3 S - Y. & I - ⑮ j 2 constant ·. 75 ↳ Truff > " I ! j I ↳ half lifes - first order metabolism-531%>in elimination j2'0 * seusi toxic another Jose I d So-z//. 9 S/, * unaffective yo half life Js"? & Is, tissue spaces) infection NJ 5/1/9% Ug swelling is edontogenic infection is used * loading dose /1561 1009 Yee] leading rose/11 - Ye & dose n double [constant 5 j51dosef1 s half life % and 2009 bjys451951 50 % / elimination Spyis19 -half life ↓ : > 1g duration of action /115% ② Gose /1561 Pix --1]Q-. 100 steady state plasma concentration no 51 jis1 ,  elimination /1 & &Y 1s & 51 * Elimination - Kidneys /1. 9 The most important route of elimination is through kidneys into the urine. Other routes include: bile, intestines, milk in nursing mothers, skin, saliva.. Renal elimination of the drug occurs through 1. Glomerular filtration >>> drugs with small molecular size, not bound to plasma protein are filtered into Bowman’s space. 2. Proximal tubular secretion>>> energy requiring-carriers one for anions and one for cations. ACTIVE SECRETION 3. Distal tubular secretion: drugs concentrated in distal tubule, if uncharged it will be reabsorbed into the systemic circulation  ? drugs Nelimination & 1 = excretion &g Bowman's capsules 2 solution / Glomerular filtration Q - & gj be1 active -5 excretion /1 - > proximal tubulesI & / my distal tubules81 - / & uncharged 1s reabsorption sig/59s - &  Elimination Manipulating urine pH to increase the ionized form and minimize the amount of reabsorption 41)9 * Ion trapping  3195)- Pharmacodynamics > - , Derived from the two words: Pharmakon (means drug) and Dynamis (means power). This term covers all the aspects relating to the effect of the drug on the body: how the drug interacts with its target, drug mechanism of action, drug adverse effects. ↑ 1961j 39610 like effects)9 & j + Pharmacodynamics # receptors (119511961m +- / Drugs are considered signal molecules that deliver messages to different body compartments through interaction with receptors (key and lock) receptors (4 basis eij Sij Y * Other drugs do not need receptors to exert their effect, like antiacids that chemically alter the excess gastric acids. receptors ( % * antiacids/18  Pharmacodynamics Receptor: Biologic molecules to which a drug binds to and produces a response. Major receptor families:  Pharmacodynamics Drug-receptor interaction Drug-receptor Interaction depends on the type of chemical pond between the receptor and the drug molecule. The ability of the drug to get bound to a receptor via chemical bonds is called Affinity affinity - receptor As i drug Jose : The ability of a drug to produce a pharmacological response after combining with the receptor is called Intrinsic activity & i intracellulareffect us il drug /10 ( : intrinsic activity - receptors ? A drug that has both Affinity and Intrinsic activity is called : AGONIST & A drug that has Affinity but does not have Intrinsic activity is called: ANTAGONIST --  Pharmacodynamics /155 concentration 55 receptor Dose –Response related Relationships: &/ & iss wir : /effect The magnitude of the drug effect depends on the concentration at the receptor site Potency: a measure of the amount of a drug necessary to produce an effect of a given magnitude Efficacy: maximum effect gained by the drug (it depends on the number of drug-receptor complexes formed) 734925  Pharmacodynamics Drug A and B show similar efficacy Drug A is more potent than drug B, as a lower dose is needed to induce the safe efficacy.  i i,jet B drug A 5 drug 9 I * substance Jjs41 l efficacy & ju, effects /i is &· jj S i j5959w gijjj1y so J & Drug A * B &1 drug 2 effect /1 & gl use & Dis efficacy) * intracellular effect i receptors & syste = Potency /1 * intracellular effect /I Yes i  & 7 Theraputic index Pharmacodynamics : Xj5slgsi -jj! Therapeutic index: is an index of drug safety Drugs with a narrow TI have a narrow window between their minimum effective doses and those at which they produce toxicity (e.g. digitalis, phenytoin) Therapeutic Drug Monitoring (TDM) is an important tool to keep the patient safety. The wider the value of Therapeutic Index the safer is the drug. jes"Thepatic index/ 15005 : i spil narrow theraputic index slid"Y :· josslg5/ &" pixic toxic Jose /1 & %s: effective Jose /I also monitoring References: Pharmacokinetics, Lippincott’s Illustrated Reviews in Pharmacology, (Fifth edition), Karen Whalen, Carinda Feild, Rajan Radhakrishnan, 2011. Drug-Receptor Interaction and Pharmacodynamics, Lippincott’s Illustrated Reviews in Pharmacology, (Fifth edition), Karen Whalen, Carinda Feild, Rajan Radhakrishnan, 2011 General Pharmacology, Pharmacology for Dentistry, Second Edition, Tara V. Shanbhag, Smita Shenoy, Veena Nayak, 2014. Pharmacology and Therapeutics for Dentistry, Seventh edition. Angelo Mariotti, Bart Johnson and Frank J. Dowd. 2017.