dr. mahmoud h. taleb 1 course description: it consists of course concerning the action of drugs on...

Dr. Mahmoud H. TalebDr. Mahmoud H. Taleb 11

Course Description:Course Description:

It consists of course concerning the action of It consists of course concerning the action of drugs on physiological and pathological drugs on physiological and pathological processes with special emphasis on agents of processes with special emphasis on agents of special importance in the practice of dentistry.special importance in the practice of dentistry.

الرحيم الرحمن الله الرحيم بسم الرحمن الله بسم

Pharmacology I for dental studentsPharmacology I for dental students


Educational Objectives:Educational Objectives:

The student will gain knowledge in the principles of The student will gain knowledge in the principles of general pharmacology. The objectives will be for the general pharmacology. The objectives will be for the student to be able to describe (1) Different families of student to be able to describe (1) Different families of therapeutic agents taken by or prescribed to dental therapeutic agents taken by or prescribed to dental patients in terms of clinical pharmacology, patients in terms of clinical pharmacology,

(2) indication, usage, precautions, (2) indication, usage, precautions, (3) adverse reactions, (3) adverse reactions, (4) over dosage absorption, (4) over dosage absorption, (5) metabolic rate, (5) metabolic rate, (6) distribution, (6) distribution, (7) excretion(7) excretion


Competencies Addressed/Assurance of Competencies Addressed/Assurance of Competencies:Competencies:

This course is designed to assure that This course is designed to assure that students are familiar with the mechanisms students are familiar with the mechanisms of action and potential druginteractions/ of action and potential druginteractions/ contraindications of the medications that contraindications of the medications that their patients are most likely to be taking their patients are most likely to be taking when they seek dental care. when they seek dental care.


Course outlineCourse outline

Unit I . general principles of pharmacologyUnit I . general principles of pharmacology

**** Definitions and history of PharmacologyDefinitions and history of Pharmacology** Drug nature, sources and dosage forms .** Drug nature, sources and dosage forms .

** Receptors** Receptors ** Signal transmission and signal transduction** Signal transmission and signal transduction ** Dose response curve and pharmacokinetics** Dose response curve and pharmacokinetics ** Pharmacogenetics** Pharmacogenetics ** Adverse effects and drug toxicity.** Adverse effects and drug toxicity. ** Mechanism of drug action and factors affecting on it.** Mechanism of drug action and factors affecting on it. ** Dug laws and prescription writing** Dug laws and prescription writing


UNIT II. ANTI-INFECTIVES UNIT II. ANTI-INFECTIVES - - Sulfonamides Sulfonamides - - Penicillins Penicillins - - Cephalosporins and relatedCephalosporins and related antibiotics antibiotics

- -Tetracyclines, Macrolides, andTetracyclines, Macrolides, and Lincosamides Lincosamides - - Fluroquinolones and aminoglycosidesFluroquinolones and aminoglycosides - - Miscellaneous Anti-infectives Miscellaneous Anti-infectives - - Antitubercular Drugs Antitubercular Drugs - - Leprostatic Drugs Leprostatic Drugs - - Antiviral Drugs Antiviral Drugs - - Antifungal Antifungal Drugs - - Antiparasitic DrugsDrugs


UNIT III. DRUGS USED TO MANAGE PAIN

- Nonnarcotic Analgesics: Salicylates and Nonsalicylates-Nonnarcotic Analgesics: NonsteroidalAnti-inflammatory Drugs -Narcotic Analgesics -Narcotic Antagonists


UNIT IV. DRUGS THAT AFFECT THERESPIRATORY SYSTEM

Antihistamines and Decongestants Bronchodilators and Antiasthma Drugs Antitussives, Mucolytics, Expectorants


UNIT V. DRUGS THAT AFFECTTHE CARDIOVASCULAR SYSTEM

- Cardiotonics Drugs - Antiarrhythmic Drugs -Antianginal and Peripheral Dilating Drugs-Antihypertensives-Antihyperlipidemic Drugs


UNIT VII. DRUGS THAT AFFECT THE HEMATOLOGICAL SYSTEM

UNIT VI. DRUGS THAT AFFEC THE GASTROINTESTINALAND URINARY SYSTEMS

Anticoagulant and Thrombolytic Drugs

Agents Used in the Treatment of Anemia

-Diuretics -Drugs That Affect the Gastrointestinal

System


References References Pharmacology and Therapeutics for Dentistry, Needle and Pharmacology and Therapeutics for Dentistry, Needle and

Yagilla Yagilla Lippincott's Illustrated Reviews: Pharmacology, 4th EdLippincott's Illustrated Reviews: Pharmacology, 4th Ed Basic and clinical pharmacology; Bertam KatzungBasic and clinical pharmacology; Bertam Katzung annual review article published in the Journal of the American annual review article published in the Journal of the American

Dental Association on the top 50 prescription medications Dental Association on the top 50 prescription medications dispensed in pharmacies for the previous year.dispensed in pharmacies for the previous year.

Color atlas of pharmacology, 2nd Ed. (by H. Lullmann et al., Thieme 2000, Color atlas of pharmacology, 2nd Ed. (by H. Lullmann et al., Thieme 2000, ISBN 0865778434)ISBN 0865778434)


Unit I. General principlesUnit I. General principles

What is pharmacology? What is pharmacology? Pharmacology Pharmacology can be defined as the study of substances can be defined as the study of substances

that interact with living systems through chemical that interact with living systems through chemical processes, especially by binding to regulatory molecules processes, especially by binding to regulatory molecules

and activating or inhibiting normal body processes. and activating or inhibiting normal body processes.

These substances may be chemicals administered to These substances may be chemicals administered to achieve a beneficial therapeutic effect on some process achieve a beneficial therapeutic effect on some process within the patient or for their toxic effects on regulatory within the patient or for their toxic effects on regulatory

processes in parasites infecting the patient. processes in parasites infecting the patient. Such deliberate therapeutic applications may be Such deliberate therapeutic applications may be

considered the proper role of considered the proper role of medicalmedical..


Pharmacology is not concerned primarily Pharmacology is not concerned primarily with what the drug may be used for, but with what the drug may be used for, but with what actions it has , and what fate it with what actions it has , and what fate it encounters in the living organism.encounters in the living organism.


Such deliberate therapeutic applications Such deliberate therapeutic applications may be considered the proper role of may be considered the proper role of medical pharmacology,medical pharmacology, which is often which is often defined as the science of substances defined as the science of substances used to prevent, diagnose, and treat used to prevent, diagnose, and treat disease. disease.


ToxicologyToxicology is that branch of is that branch of pharmacology which deals with the pharmacology which deals with the undesirable effects of chemicals on living undesirable effects of chemicals on living systems, from individual cells to complex systems, from individual cells to complex ecosystems.ecosystems.


WHAT IS A DRUGWHAT IS A DRUG??

A drug can be defined as A drug can be defined as a chemical a chemical substance of known structure, other than a substance of known structure, other than a nutrient or an essential dietary ingredient, nutrient or an essential dietary ingredient, which, when administered to a living which, when administered to a living organism, produces a biological effect. organism, produces a biological effect. e.g. Vit C, penicillin, LSD, hydrocortisonee.g. Vit C, penicillin, LSD, hydrocortisone


Drugs may be ( Plant sources, animal sources, Drugs may be ( Plant sources, animal sources, mineral sources or synthetic) mineral sources or synthetic)

-- -- synthetic chemicalssynthetic chemicals,e.g. aspirin ,e.g. aspirin - - chemicals obtainedchemicals obtained from plants or animals. from plants or animals.

- - products of genetic engineeringproducts of genetic engineering..

A A medicinemedicine is a chemical preparation, which is a chemical preparation, which usually but not necessarily contains one or more usually but not necessarily contains one or more drugs, administered with the intention of drugs, administered with the intention of producing a therapeutic effect. producing a therapeutic effect.


DrugDrug NomenclatureNomenclature

- - Chemical nameChemical name - Nonpropietary drug name( generic name).- Nonpropietary drug name( generic name). Propietary drug name ( trade name).Propietary drug name ( trade name). Common name.Common name.


Medicines usually contain other substances Medicines usually contain other substances (excipients, stabilisers, solvents, etc.) besides (excipients, stabilisers, solvents, etc.) besides the active drug, to make them more convenient the active drug, to make them more convenient to use. To count as a drug, the substance must to use. To count as a drug, the substance must be administered as such, rather than released be administered as such, rather than released by physiological mechanisms. Many substances, by physiological mechanisms. Many substances, such as insulin or thyroxine, are endogenous such as insulin or thyroxine, are endogenous hormones but are also drugs when they are hormones but are also drugs when they are administered intentionally. administered intentionally.


Figure 1.1 Schematic representation of drug absorption, distribution, metabolism, and elimination.


The chief aspects of pharmacology The chief aspects of pharmacology includesincludes::

*** Pharmacokinetics: kinetics of ADME*** Pharmacokinetics: kinetics of ADME *** Pharmacodynamics: study biochemical, *** Pharmacodynamics: study biochemical,

pharmacological effect of drugs & their pharmacological effect of drugs & their mechanism of action.mechanism of action.

*** Pharmacotherapeutics: proper selection *** Pharmacotherapeutics: proper selection &use of drugs ( pharmacology of drugs----- &use of drugs ( pharmacology of drugs----- physiology & pathology of disease).physiology & pathology of disease).


Dose of drugADMEADME Drug conc in

target organReceptor bindingReceptor binding

Mechanism & Therapeutic effect of drug


Mechanism of drug actionMechanism of drug action

1- physically e.g. 1- physically e.g. adsorptionadsorption 2- chemically e.g. neutralization2- chemically e.g. neutralization 3- Action on enzymes e.g. acetozolamide3- Action on enzymes e.g. acetozolamide 4- action on cell membrane e.g. procaine4- action on cell membrane e.g. procaine 5- Interferance with normal metabolic 5- Interferance with normal metabolic

pathway e.g. sulphonamidepathway e.g. sulphonamide 6- Action on cell receptor e.g. most 6- Action on cell receptor e.g. most

common drugscommon drugs


The dosage of drugsThe dosage of drugs

Therapeutic dose.Therapeutic dose. Maximal tolerated dose.Maximal tolerated dose. Initial dose.Initial dose. Maintenance doseMaintenance dose Lethal or fatal dose.Lethal or fatal dose.


Drug standard & referencesDrug standard & references

The definition and standardization of drugs The definition and standardization of drugs are regulated by law in term of name, are regulated by law in term of name, purity, potency, preparation and purity, potency, preparation and disribution to the public.disribution to the public.

The standards are published in The standards are published in pharmacopoeias.pharmacopoeias.

A drug listed in pharmacopoeia is termed A drug listed in pharmacopoeia is termed an “ official”.an “ official”.


Other sources of informationOther sources of information

There are other sources of information as There are other sources of information as scientific journalsscientific journals

* Drugs* Drugs * Pharmacological Reviews* Pharmacological Reviews * British Journal of Pharmacology* British Journal of Pharmacology *Biochemical Pharmacology*Biochemical Pharmacology * Pharmacy & Pharmacology* Pharmacy & Pharmacology


Factors modifying the dosage and Factors modifying the dosage and action of drugsaction of drugs

1-Age, weight & BSA1-Age, weight & BSA

Child require smaller dose.Child require smaller dose.

2- Sex2- Sex- Female require smaller doseFemale require smaller dose- Female pass during pregnancy, labour and lactation.Female pass during pregnancy, labour and lactation.

3- Route of administration.3- Route of administration.

4- Time of administration4- Time of administration

5- Drug intolerance5- Drug intolerance

6- Drug allergy6- Drug allergy

7- Tolerance7- Tolerance


8- Pathological state8- Pathological state

9- Accumulation9- Accumulation

10- Emotional factors10- Emotional factors

11- Genetic abnormalities11- Genetic abnormalities

12- Drug interactions12- Drug interactions

13- Drug toxicity13- Drug toxicity

14- Drug dependence14- Drug dependence


Drug ToxicityDrug ToxicityKnowledge of toxic effects of drug is of importance inKnowledge of toxic effects of drug is of importance in

determining their safety. Before a new drug is introduced determining their safety. Before a new drug is introduced clinically, it is usually subjected to a variety of a animal clinically, it is usually subjected to a variety of a animal

toxicity teststoxicity tests..

Animal toxicity studiesAnimal toxicity studies

The acute toxicity of drugs is usually measured by the The acute toxicity of drugs is usually measured by the median lethal dose or LDmedian lethal dose or LD5050 will vary according to many will vary according to many

factors.factors.

Therapeutic indexTherapeutic index

This is the ratio of LDThis is the ratio of LD5050/ED/ED50 . 50 . The therapeutic index is a The therapeutic index is a

good guide to the safety of a drug.good guide to the safety of a drug. The higher the The higher the index, the safer is the drug.index, the safer is the drug.


Toxic effect of drug in manToxic effect of drug in man

The toxicity of therapeutic agents in man The toxicity of therapeutic agents in man may be due to any of the following causes:may be due to any of the following causes:

1- overdose1- overdose2- Allergy2- Allergy3- Teratogenicity3- Teratogenicity4-Intolerance4-Intolerance5- Secondary effects5- Secondary effects6- Production of disease6- Production of disease7- Iodiosyncrasy7- Iodiosyncrasy


8- 8- HepatotoxicityHepatotoxicity

9- Nephrotoxicity9- Nephrotoxicity

10- Nerve damage10- Nerve damage

11- Hematological toxicity11- Hematological toxicity

12- Drug dependance12- Drug dependance13- Carcinogenesis13- Carcinogenesis

14- Drug interaction14- Drug interaction


Drug dependenceDrug dependenceIt is a phenomenon which is related to tolerance , It may It is a phenomenon which is related to tolerance , It may

either take the form of habituation or addiction. either take the form of habituation or addiction.

Where continued presence of the drug is required for Where continued presence of the drug is required for normal function is called physical dependence, which is normal function is called physical dependence, which is defined as signs& symptoms make withdrawal defined as signs& symptoms make withdrawal symptoms or abstinence syndrome.symptoms or abstinence syndrome.

Addiction. e.g. Addiction. e.g. morphine, tramadol, barbituratesmorphine, tramadol, barbiturates

Habituation e.g. Habituation e.g. tea tea


Drug interactionDrug interaction

1- Synergism1- Synergism

2- Potentiation2- Potentiation

3- Addition3- Addition

4- Antagonism4- Antagonism


Classification of drug interactionClassification of drug interaction

ConsequenceConsequence1- Beneficial ( enhancement of therapeutic 1- Beneficial ( enhancement of therapeutic

effectiveness , or diminished of toxicity).effectiveness , or diminished of toxicity).

2- Adverse ( diminished of therapeutic 2- Adverse ( diminished of therapeutic effectiveness or enhancement of toxicity0.effectiveness or enhancement of toxicity0.


Site of interactionSite of interaction ExternalExternal ( Physicochemical incompatibility ( Physicochemical incompatibility InternalInternal This can be a body site or system This can be a body site or system

e.g. GIT, Liver) or the site of drug action e.g.e.g. GIT, Liver) or the site of drug action e.g. cell membrane, receptor.cell membrane, receptor.


MechanismMechanism

Pharmacodyanmic interactionPharmacodyanmic interaction: refers to : refers to drug-induced changes in the effects of drug-induced changes in the effects of other drugs.other drugs.

Pharmacokinetic interactionPharmacokinetic interaction: change in : change in the pharmacokinetics of one drug the pharmacokinetics of one drug introduced by another drug ADMEintroduced by another drug ADME


AbsorptionAbsorptionPhysicochemical interactionPhysicochemical interactionAltered gastrointestinal motilityAltered gastrointestinal motilityChange in bacterial floraChange in bacterial floraMucosal damageMucosal damage

DistributionDistributionBlood flowBlood flowSerum bindingSerum bindingTissue bindingTissue binding


Drug ReceptorDrug Receptor and and PharmacodynamicsPharmacodynamics

Definition of receptors:Definition of receptors: A range of different biological components that A range of different biological components that

may serve as binding sites , mediating the may serve as binding sites , mediating the actions of drugs or chemical reactive area on actions of drugs or chemical reactive area on cell and as a result produce biological action cell and as a result produce biological action e.g. e.g. enzymesenzymes

They are targets of drug action that may be protein They are targets of drug action that may be protein in nature, and these include lipids, ions, and in nature, and these include lipids, ions, and water.water.


Receptor Mechanistic conceptReceptor Mechanistic concept1- Receptors are membrane protein, have 1- Receptors are membrane protein, have

more one subtypes of binding site. more one subtypes of binding site. 2- Binding of compound for the receptor 2- Binding of compound for the receptor

result in activation of the receptor and result in activation of the receptor and transmission of a signal to intracellular transmission of a signal to intracellular side.side.

3- The magnitude of transmembrane signal 3- The magnitude of transmembrane signal may depend on the % of available may depend on the % of available receptor that are occupied or rate of receptor that are occupied or rate of occupancy.occupancy.


Drug interaction with specific Drug interaction with specific receptorsreceptors

** Intetaction of a drug with a receptor involve ** Intetaction of a drug with a receptor involve various types of chemical forces various types of chemical forces ( electrostatic forces, hydrogen bonds. ( electrostatic forces, hydrogen bonds. Vandervals forces)…. withVandervals forces)…. with molecular molecular complementarily with fitness of molecular shape complementarily with fitness of molecular shape and location.and location.

** Minor alteration of the drug molecule , alter the ** Minor alteration of the drug molecule , alter the ability of the drug to bind to the receptor ability of the drug to bind to the receptor ( Stereoselective). ( Stereoselective).


Drug receptor bindingDrug receptor bindingAffinity of a receptor for a drug can be measured Affinity of a receptor for a drug can be measured

and the index of this affinity referred to and the index of this affinity referred to association constantassociation constant Ka Ka

D + R → DR → effectD + R → DR → effect

KK1 1 → rate of binding→ rate of binding

kk2 2 →→ rate of dissociation rate of dissociation

Association constant = KAssociation constant = K1/ 1/ kk2 =2 =KaKa

DissociationDissociation constant =constant = KK2/ 2/ kk1 =1 =Kd Kd The value of Kd can be used to determine the affinity of a drug for

its receptor. Affinity describes the strength of the interaction (binding) between a ligand and its receptor. The

higher the Kd value, the weaker the interaction and the lower the affinity.


Effect of drug on receptorEffect of drug on receptor

Agonists: If a drug binds to a receptor and produces a biologic response that mimics the response to the endogenous ligand, it is known as an agonist. For example, phenylephrine is an agonist at α1-adrenoceptors,

because it produces effects that resemble the action of the endogenous ligand,norepinephrine.


Upon binding to α-adrenoceptors on the membranes of vascular smooth muscle, phenylephrine mobilizes intracellular Ca2+, causing contraction of the actin and myosin filaments. The shortening of the muscle cells decreases the diameter of the arteriole, causing an increase in resistance to the flow of blood through the vessel. Blood pressure therefore rises to maintain the blood flow.

All of these actions are attributable to interaction of the drug molecule with the receptor molecule.

In general, a full agonist has a strong affinity for its receptor and good efficacy.


Antagonists: Antagonists are drugs that decrease the actions of another drug or endogenous ligand. Antagonism may occur in several ways.

Many antagonists act on the identical receptor macromolecule as the agonist.

Antagonists, however, have no intrinsic activity and, therefore, produce no effect by themselves. Although

antagonists have no intrinsic activity, they are able to bind avidly to target receptors because they possess strong affinity.

If both antagonist and agonist bind to the same site on the receptor, they are said to be competitive


Figure 2.2 Transmembrane signaling mechanisms .A. Ligand binds to the extracellular domain of a ligand-gated channel.

B. Ligand binds to a domain of a serpentine receptor, which is coupled to a G protein.

C. Ligand binds to the extracellular domain of a receptor that activates a kinase enzyme. D. Lipid-soluble ligand diffuses across the membrane to interact with its intracellular receptor.


Drug solubility and AbsorptionDrug solubility and Absorption

Routes of drug administration.Routes of drug administration.

Choice of route…. Must depend on Choice of route…. Must depend on therapeutic objectives therapeutic objectives

dr. mahmoud h. taleb 1 course description: it consists of course concerning the action of drugs on...

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