PHARMACOLOGY LEC (June 15, 2011) Pharmacology – study of drugs Drugs – any chemical substance that affects the biological

system Drug molecule – bind to receptor site (protein molecule) Routes Enteral – enteric; anything that passes through the GIT Parenteral – given through injection, needles, or hypodermic route Branches 1. Pharmacodynamics – mechanical action of the drug − what the drug does to the body 2. Pharmacokinetics – fate of the drug − how the body is going to react to the drug − (ADME) absorption, distribution, metabolism, excretion Pharmacotherapeutics – study of giving cure and treatment

150 100
Efficacy (%)

50 0 0 10 mg 15 mg
Potency

50 mg 100mg Meperidine HCl

Morphine HCl

Morphine is more potent because only 10 mg can produce an action thus, it is stronger. Increase dosage means increase potential for toxicity Both are efficacious Drug Nomenclature Chemical Name – first name of the drug convey the chemical structure of the drug Generic Name – second name − also called non-proprietary name − official name − universal name of the drug − doctors are required to write prescription using generic name Republic Act 6675 (Generic Act of 1988) − promote , require, and ensure that there will be an adequate supply of drug for use and distribution *prevent monopoly from manufacturers *promote healthy competition among drug companies *cost (Something to do with the cost, make the drug cheaper) 1 generic name = thousand drugs NSAID – Non-steroidal Anti-inflammatory Drug/Agent analgesic Superscription – doctor and patients information Rx – you take, take them Inscription – body of the prescription (500mg Brand name/Commercial name) Subscription – instruction to pharmacist (q.6h #8 cap) Transcription – signature (1cap 4x/d for pain prn) PRN – prorenata (if necessary) not in antibiotics (June 22, 2011) Pharmacotherapeutics – drug therapy Pharmacokinetics – how the body handles the drug Areas Absorption – the process of a substance entering the body and movement of a drug into the blood stream Distribution – dispersion or dissemination of substances throughout the fluids and tissues of the body to target point (blood) Metabolism – irreversible transformation of a parent compound into daughter metabolites (liver) Excretion – elimination of substance from the body (kidney) Aim/Goal − Adequate drug doses must be delivered to the target tissues so that therapeutic yet non-toxic levels are obtained − To have sufficient amount of action of drug Underdose - no sufficient amount, useless Elicit significant dose of drug Pharmaceutical Process In the GIT, drugs need to be in solution to be absorbed

3.

Importance of pharmacology to dentists: for dentists to be familiar with drugs Posology - study of dosage Aspirin (Acetylsalicylic Acid) − Anti-pyretic − Pain reliever − Has anti-platelet properties − Maintenance drug − Prevent clotting of the blood − Aggravate gastric bleeding (ulcer) Common Adverse Reaction − gastric disturbance − diarrhea Adverse Reaction − less severe − severe − allergic reaction *less severe and severe are predictable and dose related Measure of Drugs Activity : Potency And Efficacy Potency – strength; amount of drug capable of producing the desired action/effect Efficacy – maximum/inherent intensity/potential of the drug Threshold Dose – minimum amount of drug capable of producing an action Example: Morphine HCl 10 mg Meperidine HCl 100 mg Both are strong analgesic

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A drug in solid form must disintegrate into smaller particles in order for it to dissolve

Disintegration − breakdown of solid form of drug into smaller parts Dissolution disintegration of smaller particles in the GIT fluid for absorption Rate Limiting time it takes for the drug to disintegrate and become available for absorption Bioavailabitlity fraction of administered drug that reaches the circulation in a chemically unchanged form Ex. If 100mg of a drug is administerd orally and 70 mg of the drug is absorbed unchanged, the bioavailability is 70% Oral Route − most common , most complicated route − the absorption of drug is slower Factors for Easy Absorption  Coating Material o Enteric-coated drugs resists disintegration in the gastric acid of the stomach but occurs only when the drug reaches the alkaline environment of the intestine  Absorption o Process by which drug molecules are transferred from ite of administration in the body to … bodily fluids? o Principal Mechanisms (involved in the passageway of drugs)\ Mechanisms:  Simple diffusion  Aqueous diffusion  Specific carrier mediated transport system - Active transport - Passive transport (most common) Simple Diffusion Lipid Diffusion Like dissolves like Lipid soluble A steady state is achieved when the concentration of the non-ionized species is the same on both sides of the membranes Aqueous Diffusion filtration through pores Drug should be lipophilc and hydrophilic Active Transport − A substance is transported against a concentration gradient − a drug moves from lower to higher concentration − energy dependent − concentration gradient − involves specific carriers Passive Transport − Facilitated diffusion − drug moves more rapidly − higher to lower concentration − vast majority of drugs gain access to the body by this process Factors Affecting Absorption 1. physico-chemical factors 2. site of absorption/blood flow at the site 3. drug solubility 4. effects of food (blood flow, gastric emptying)

1. Physic-Chemical Factors -lipid solubility -degree of ionization -effect of pH -molecular weight, size and shape -chemical stability Lipid Solubility (simple diffusion) degree of lipid solubility of the drug determines the total amount of drug being transferred Non-ionized are lipid soluble Most drugs are partially ionized at physiologic pH and only non-ionized species… Degree of ionization Most drugs are weak electrolytes either weak acids or weak base Drugs that are weak electrolytes dissociate in solution as both non ionized and ionized form Ionized portion being less lipid soluble Non-ionized portion behaves as a non-polar lipid soluble compound which… Non-Ionized Ionized Non-Polar Polar Lipid Soluble Lipid Insoluble

Effect of pH Dissociation constant indication measure of the strength.. Clinical Significance: knowing the pKa of a drug gives the patient the idea as to the extent to which it ionizes at any pH − pKa compound is the same as the pH at which it would be half dissociated and half ionized Example: ASA (aspirin)- pKa 3.5 Stomach- pH 1.0-1.5 At the pH of 3.5, ASA is 50% ionized Decrease pH below 3.5 Decrease ionization to less than 50% thus increase the amount of un-ionized form – greater drug absorption  Ionization  Lipid Solubility Absorption Aspirin pKa 3.5 Blood pH 7.0  Ionization  Lipid Solubility  Absorption 2. Site of Absorption total surface area available for absorption intestine has a surface area about 1000 times larger than the stomach intestine surface is very rich in microvilli

Blood Flow to the Site of Absorption blood flow from the intestine is much greater than the stomach 3. 4. Drug Solubility Effects of Food Food influences the amount of…

Blood Flow Liquid glucose meal o Decreases blood flow Meal rich in protein o Increases blood flow Decrease Absorption in the Presence Of Food Aspirin Penicillin

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Acetaminophen

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Site of drug loss or storage

Gastric Emptying Food that delays gastric emptying also delay the absorption of orally administered drugs Transfer of food from stomach to intestines Delay Gastric Emptying Low pH or high fat solutes Hot meals Solution rich in fats and CHO Rule of Thumb If food reduces absorption of drug, giving the drug at least 1 hour before meals will minimize this effect If foof enhances drug absorption, the drug is given with meals  Distribution o Circulating fluid to target site o Blood, plasma, water o Process by which the drug becomes available to the whole body…

Affinity Tissues May be sites of Action or Areas of Transient Storage Fat, bone, liver, eye, muscle Guamethidine – heart and skeletal muscle Quinacrine – liver and skeletal muscle Tetracycline – bone and enamel Thiopental – adipose tissue Oral Route Most convenient Most complicated First Pass. / Presystemic Metabolism/ Effect Rapid deactivation of drug Less percentage will be absorbed

Primary Purpose of D. Trans. Allow drug to reach its site of action at specific tissue sites Forms of Drug inside the Body Free/unbound State (50%) Active form Plasma H2O Biologically active Bound State (50%) Inactive form Albumins and globulins Transient/storage depot 50-50% - help prolong the action of the drug Only free drugs are biologically active and can cause a pharmacologic response As the free drug in the tissues [decreases], more bound drug is released from the protein to maintain the balance of the drug Biologic Half-Life (t½) Time necessary for the body to eliminate half the quantity of the drug present in the circulation Determine dosing and time interval It takes several half-lives before more than 90% of the drug is eliminated in the system Short half-life (4-8 hours) Long half-life (24 hours or longer) ASA (apirin) = 650mg T½ 1 2 3 4 5 6 t½ = 3 hours Time of Elimination 3 6 9 12 15 18 Dosage Remaining 325 162 81 40.5 20 10 % Left 50 25 12.5 6.25 3.1 1.55

Without tissue storage sites (Affinity tissue), many drugs would rapidly be metabolized and eliminated from the body, having little time to exert any effect Storage Depot (Non-Specific Site) Areas for transient storage It may prevent or prolong the action of drugs

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