_.. 21.8.2024 Introduction to pharmacology.pdf

Nursing Pharmacology: Introduction Mohamed M. Abdel-Daim; Ph.D. Professor of Pharmacology 0580192142 [email protected] Nursing Pharmacology: Introduction Nursing Pharmacology: Introduction Chapter 1 INTRODUCTION TO...

Nursing Pharmacology: Introduction Mohamed M. Abdel-Daim; Ph.D. Professor of Pharmacology 0580192142 [email protected] Nursing Pharmacology: Introduction Nursing Pharmacology: Introduction Chapter 1 INTRODUCTION TO NURSING PHARMACOLOGY PART 1 Nursing Pharmacology: Introduction MEDICINES Sources of drugs Nursing Pharmacology: Introduction Sources of drugs 227%20Foxglove,%20Digitalis%20purpurea Plant products Plants Fox Glove Digoxin Poppy Opium opium Belladonna Atropine Coffee Caffeine Tobacco Nicotine tobacco coffee%20plant  Nursing Pharmacology: Introduction Animal products Hormones: Premarin (conjugated Oestrogen) from Pregnant Mares cow Insulin from pigs & cows Heparin: from pigs & cows pig  Nursing Pharmacology: Introduction Inorganic compounds (compounds with no Carbon) puratronic_inorganics Sodium + Chloride ions: Sodium Chloride Zinc + Sulphate ions: Zinc Sulphate (Calamine lotion) Aluminium +Hydroxyl: Aluminium hydroxide Nursing Pharmacology: Introduction Synthetic sources (Laboratory Derived Products) Human Insulin (genetically engineered, biosynthetic human insulin or recombinant or DNA-derived insulin, Drug Names Three types of drug names 1. Chemical name (N-acetyl-para-aminophenol) long & complex 2. Generic name (Paracetamol) Only 1 generic name Usually more complicated than the trade name Lower case 3. Trade name (Tylenol) brand names marketing name created by drug company easier to remember and pronounce may be multiple companies and thus multiple names must be approved by the FDA Upper case The drug ⚫ TRADE NAME: – Benadryl ⚫ CHEMICAL NAME: – 2(Diphenylmethoxy)-N,N-dimethylethylamine hydrochloride ⚫ CHEMICAL STRUCTURE: ⚫ GENERIC NAME: – diphenhydramine hydrochloride Drugs and Nursing Understanding drugs is essential for nursing practice Nurses need to: 1. Anticipate patient responses to drugs 2. Apply principles of pharmacology to patient care  Goal of drug therapy To obtain the maximum therapeutic effect and minimize adverse drug reactions Nursing Role: 1. Collect baseline data 2. Identify high risk patients 3. Administer right drug, right route, right time, right dose, to the right patient. 4. Minimize adverse drug effects and interactions 5. Manage prn decisions 6. Manage drug toxicities Properties of Ideal Drug Effectiveness: A drug that elicits the response it was meant to (FDA approved with appropriate experiments) Safety: Safe even at high concentrations and for long periods of administration (no such thing) –Reduced by proper administration (iv, ip, im, sc, etc…) –No habit forming aspects –No side effects (resp. failure, immune reaction, etc…) Selectivity: Selective for specific reaction with no side effects –Cramps, fever, nausea, depression, anemia, etc… Additional Properties of Ideal Drug: Reversible action- removal w/i specific time (1/2 life is short but potent during that time) Predictability- know how patient will respond Ease of Administration- number of doses low and easy to administer (inc. compliance & decrease errors) Freedom from drug interactions- should not augment or decrease action of other drugs or have adverse combined effects Low Cost- easy to afford (especially with chronic illness) Chemical Stability- no lose of effectiveness with storage Possession of a simple generic name- easy to remember and pronounce (No drug is ideal!)  Sources of individual variation: Each patient is unique in ability to respond and to how they each respond, but formation of “IDEAL DRUG” will lessen this variation –Age- very important factor –Gender due to hormonal differences –Weight- less effective and longer lasting in obese individuals (storage in fat) –Kidney & liver functions - elimination of drug –Genetic variables- tolerance, allergy (though not always genetic)  The Development of Pharmacokinetics Absorption, Distribution, Medicines Metabolism & Excretion of drugs Pharmacodynamics Action Mechanisms of drug action Science of Pharmacology Pharmacotherapeutics Toxicology Evidence based approach to the toxicity & adverse use of drugs to treat disease effects of drugs Development of new drugs Preclinical trials New drugs or treatment approaches are often tested first on animals or live human cells in test tubes and Petri dish. Scientists identify an approach that is most likely to succeed, and then carry out preliminary research into safety and effectiveness. _959324_mouse300  Phase 1 studies: Early Clinical Trials These first trials usually involve a small number of individuals (less than 100) who are healthy. The objective= to find out if the new drug is safe. Phase 2 Continuing Clinical Trials If the new compound is considered safe on human, testing is expanded to see if it is effective. Trials include people who have the disease or condition against which the researchers think a new compound will be effective. Safety testing continues and is expanded & animal testing also  people Phase 3 studies A drug is tested in several hundred to several thousand subjects. This large-scale testing provides more information about the drug's effectiveness, possible side effects, and safety in a broader range of people. Pharmacology It is the science dealing with drugs and includes, Pharmacokinetics, Pharmacodynamics, ….. Pharmacokinetics (ADME) Defined as study the effect of body on the drugs (the study of drug absorption, distribution, metabolism and excretion) Pharmacodynamics (Action + mechanism of action) It involves study of the effects of the drug on the body & its mechanisms of action. Pharmacotherapy The use of drugs to treat disease and include assessment implementation, monitoring and reassessment up-pill Adverse reactions: Study the toxicity of the drugs predictable & unpredictable, iatrogenic (caused by practitioners), carcinogenic (causing cancer) & teratogenic (causing embryonic deformities) Apply Your Knowledge Matching: ___ Study of adverse effect of drugs A. Pharmacokinetics ___ Study of what the body does to drugs B. Drugs ___ Used to prevent, diagnose, or treat disease C. Toxicology ___ Study of what drugs do to the body D. Pharmacodynamics Apply Your Knowledge Matching: C Study of adverse effect of drugs A. Pharmacokinetics A Study of what the body does to drugs B. Drugs B Used to prevent, diagnose, or treat disease C. Toxicology D Study of what drugs do to the body D. Pharmacodynamics  Apply Your Knowledge 1. What is the role of pharmacology in nursing? 2. What is the difference between pharmacodynamics and pharmacokinetics? Pharmacokinetics The study of drug absorption distribution, metabolism and excretion ADME ◦ Absorption ◦ Distribution ◦ Metabolism ◦ Elimination  ADME determine: ◦ The speed of onset of drug action ◦ The intensity of the drug effect ◦ The duration of drug action Absorption: The drug absorption from the site of administration which permits the entry of the therapeutic agent into the plasma Distribution: Reversible process, the drug leaves the bloodstream and distributes into the interstitial and intracellular fluids Metabolism: Biotransformation of the drug into metabolites by the liver or other tissues Elimination: The drug and its metabolites are eliminated into urine, bile or feces  Enteral ◦ Oral ◦ Sublingual  Parenteral ◦ Intravenous (IV) ◦ Intramuscular (IM) ◦ Subcutaneous (SC)  Other routes ◦ Inhalation ◦ Intrathecal/Intraventricular ◦ Topical ◦ Transdermal ◦ Rectal Lippincott's Illustrated Reviews 6th edition  Oral administration: ◦ Advantages  Easily self-administered  Low risk of systemic infections (compared to parenteral)  Easier to manage toxicity ◦ Disadvantages  Inactivation of drugs due to first pass effect or stomach acidity  Drugs irritant to stomach  Drugs not stable in GIT  Drugs did not absorb from GIT  Leads to food drug interaction  Sublingual: Drug diffuses into the capillary network to the systemic circulation ◦ Advantages  Excellent absorption for non-ionized drug (Example Nitroglycerin, apomorphine)  It has high absorption rate close to intravenous injection  Avoid hepatic first pass metabolism  Direct administration of the drug across body barriers into the systemic circulation ◦ Used for: 1. Drugs with poor GI absorption (e.g., heparin) 2. Drugs unstable in GI (e.g., insulin) 3. Unconscious patients 4. Rapid onset of action 5. High bioavailability ◦ Advantage: no first pass metabolism ◦ Disadvantages: Risk of infection  Intravenous (IV) ◦ Bolus: Immediate delivery of full amount ◦ Infusion: Delivery over a longer time  Intramuscular ◦ Aqueous solution (Rapid absorption) ◦ Depot preparation in nonaqueous vehicle ◦ It is suitable for insoluble drugs such as pellets and suspension  Subcutaneous ◦ Less risk of hemolysis ◦ May provide sustained slow effect  Inhalation ◦ Oral or nasal ◦ Rapid delivery across the large surface area of mucous membranes  Intrathecal/intraventricular ◦ Direct injection into the cerebrospinal fluid ◦ Rapid delivery ◦ To avoid the blood brain barrier  Topical: application ◦ Skin, for local effect.  Transdermal ◦ Sustained delivery of drugs (e.g. nicotine patches)  Rectal ◦ Avoids first pass metabolism ◦ Rapid delivery ◦ Used when oral administration is not possible (antiemetic)  Absorption is the transfer of a drug from the site of administration to the bloodstream via one of several mechanisms Rate and efficiency of absorption of a drug depend on: ◦Chemical characteristics of the drug ◦Route of administration  Absorption Rate: how rapidly does the drug get from its site of administration to the general circulation ?  Absorption Extent: How much of the administered dose enters the general circulation ? ( % bioavailability )  Bioavailability: The fraction of administered drug that reaches the systemic circulation  Example 100 mg of a drug were administered orally; 70 mg of the drug were absorbed unchanged. ◦ The bioavailability of this drug is 70%  For IV drugs, absorption is complete ◦ (100% bioavailability)  Drug administration by other routes may result in partial absorption and lower bioavailability  Factors that influence oral bioavailability ◦ First-pass hepatic metabolism (Metabolism by liver enzymes prior to reaching the systemic circulation) ◦ Solubility of the drug ◦ Chemical instability ◦ Decomposition in acidic gastric juices ◦ Decomposition by hydrolytic gut enzymes (eg, proteases, lipases) ◦ Degradation by gut microorganisms ◦ Food in the gut may alter absorption rate and amount (interact or form a complex)  When an oral drug is absorbed across the GI tract, it first enters the portal circulation before the systemic circulation  If the drug is rapidly metabolized, less of the active ingredient will reach the systemic circulation  Example: nitroglycerine (90% is cleared through passage through the liver) ◦ It is Given sublingually  Solubility of the drug ◦ Very hydrophilic drugs can not cross lipid-rich cell membranes, and so they are poorly absorbed ◦ Extremely hydrophobic drugs are poorly absorbed because they’re insoluble in aqueous body fluids ◦ For good absorption, the drug needs to be hydrophobic with some water solubility ◦ Most drugs are weak acids or bases  Chemical instability ◦ Insulin is destroyed in the stomach by degradative enzymes ◦ Penicillin G. is instable in gastric pH   Passive diffusion:  Facilitated diffusion:  Active transport:  Endocytosis and exocytosis:  Movement of drug molecules across membranes from a region of high concentration to a region of lower concentration  Most drugs are absorbed through this mechanism  No carrier involved  Non saturable  Entry to the cell through specialized transmembrane carrier proteins  Movement occurs from the area of the high concentration to the area of low concentration  Does not require energy  Can be saturated and inhibited by compounds that compete for the carrier  Involves specific carrier proteins  Requires energy  Moves the drugs against the concentration gradient (from low concentration to high concentration regions)  Selective Saturable, can be inhibited by co-transported substances  Transport of exceptionally large drugs  Endocytosis: engulfment of a molecule by the cell membrane  Exocytosis: the reverse process that leads to the release of molecules Example: Vitamin B12 transport across the gut wall by endocytosis 1. pH ◦ Most drugs are weak acids or weak bases HA H+ + A- BH+ B + H+ ◦ Drugs pass through membranes easier when uncharged ◦ pH < pKa protonated form predominates ◦ pH > pKa deprotonated form predominates How does charge affect a drug’s ability to permeate a cell membrane? Generally, a drug will pass through cell membrane more easily if it is uncharged. Therefore, the amount of drug absorbed depends on its ratio of charged to uncharged species, which is determined by the pH and pKa of the drug. Pka = the drug present in form of 50% of uncharged form and 50% of charged form 2. Blood flow to the absorption site ◦ Because blood flow is much greater in the intestines than the stomach, absorption is greater in the intestines. 3.Total surface area available for absorption ◦ Intestines have large surface area 4.Contact time at the absorption surface ◦ Absorption is affected by changes in gastric motility (e.g., diarrhea) 5.Expression of P-glycoprotein ◦ Drug transporter (reduces absorption) ◦ In liver, kidney, brain, intestines  It is expressed throughout the body, and its functions include: ◦ In the liver: transporting drugs into bile for elimination ◦ In kidneys: pumping drugs into urine for excretion ◦ In the placenta: transporting drugs back into maternal blood, thereby reducing fetal exposure to drugs ◦ In the intestines: transporting drugs into the intestinal lumen and reducing drug absorption into the blood ◦ In the brain capillaries: pumping drugs back into blood, limiting drug access to the brain  High expression of P-gp reduces absorption  Distribution of drugs  Distribution: the process by which a drug reversibly leaves the blood stream and enters the interstitium and then cells For an IV drug; No absorption occurs Distribution occurs immediately after administration Adams et al. 2008 Distribution depends on: 1.Cardiac output and regional blood flow 2.Capillary permeability 3.Tissue volume 4.Drug-protein binding in plasma and tissues 5.Hydrophobicity of the drug  Due to unequal distribution of cardiac output, the rate of blood flow to tissue capillaries is variable  Blood flow to the brain, liver and kidney is greater than that to skeletal muscles  Adipose tissue, skin and viscera have lower rates of blood flow  Example: thiopental, highly lipid soluble ◦ Initially rapidly moves into the brain due to high blood flow and produces anesthesia ◦ A slower distribution into skeletal muscles and adipose tissues lowers plasma concentration, and CNS concentration ◦ Consciousness is regained   Depends on ◦ Capillary structure ◦ Chemical nature of the drug The structure of capillaries varies depending on the organ. For example, in the brain, the junction between cells is very tight. In the liver and spleen, the junction between endothelial cells is wide, which allows large molecules to pass through. 3.  Binding to plasma proteins ◦ Nonselective ◦ Albumin ◦ Protein bound drug Free drug Distribution Metabolism Excretion  Binding to tissue proteins ◦Drugs can accumulate in tissues due to tissue protein binding extending their effects or causing local toxicity  Hydrophobicity ◦Hydrophobic drugs cross cell membranes ◦Hydrophilic drugs need to pass through the slit junction Vd= Amount of drug in the body C0 Vd: Apparent volume of distribution C0:Plasma concentration at time zero  Vd has no physiologic basis It can be used to compare the distribution of a drug in the water compartments of the body Plasma (4L) large molecular weight or highly protein bound drugs g. Heparin Extracellular fluid (14L) Low molecular weight but hydrophilic and can not cross cell membranes Total body water (42 L) Low molecular weight and hydrophobic  Apparent volume of distribution (Vd) ◦ A drug rarely associates with one water compartment ◦ Usually, drugs are bound to cellular compartments like  Proteins in plasma and cells  Lipids in adipocytes and cell membranes  Nucleic acids in nuclei of cells  Vd is useful for calculating the loading dose of a drug  Length of time needed to decrease drug plasma concentration by one half  The greater the half-life of the drug, the longer it takes to excrete  Determines frequency and dosages  Elimination depends on the amount of the drug delivered to the liver or the kidney per time unit  The greater the Vd the less drug that is available to the excretory organ  The greater the Vd the higher the half life of the drug, and the longer the duration of action  Once the drug enters the body, elimination begins  Routes of elimination include: 1. Hepatic metabolism 2. Elimination in bile 3. Elimination in urine  Metabolism leads to products with increased polarity which allows drug elimination  Clearance (CL) the amount of drug cleared from the body per unit time ◦ CL= 0.693 X Vd/t1/2 t1/2: elimination half life for the drug Vd: apparent volume of distribution 1. First-order kinetics The rate of drug metabolism and elimination is directly proportional to the drug concentration 2. Zero-order kinetics (nonlinear kinetics) e.g. aspirin, ethanol, phenytoin The rate of metabolism or elimination is constant and does not depend on drug concentration.  Kidney cannot efficiently eliminate lipophilic drugs as they get reabsorbed in distal convoluted tubules.  Lipid soluble agents must be metabolized into more polar (hydrophilic) substances in the liver 1.Phase I reactions Oxidation, Reduction, Hydrolysis 2.Phase II reactions Conjugation  Not all drugs undergo Phase I and Phase II metabolism in that order, sometimes the order is reversed.  Conversion of lipophilic molecules into more polar molecules by unmasking or adding a polar group like –OH or –NH2 ◦ Involve P450 enzymes (most frequent for Phase I drug metabolism) ◦ Not involving P450: e.g. Esterases and Hydrolysis  Factors affecting drug biotransformation  Genetically variable The capacity to metabolize a drug through a given pathway varies in each individual patient  Inducers (increase metabolism) (Drug Interactions) ◦ Decrease plasma concentration ◦ Decrease therapeutic effect ◦ Decrease drug activity if metabolite is inactive ◦ Increase drug activity if metabolite is active Factors affecting drug biotransformation  Inhibitors: ◦ P450 inhibitors cause drug interactions ◦ Can cause adverse reactions ◦ Example: Grapefruit and its juice can inhibit CYP3A4 leading to increased levels of drugs metabolized by this enzyme causing higher therapeutic or toxic effects   Conjugation reactions  If Phase I metabolite are still too lipophilic then they undergo conjugation reactions with endogenous substrates like: ◦ Glucuronic acid (most common) ◦ Sulfuric acid ◦ Acetic acid ◦ Amino acid  The most important route for drug removal from the body is through the kidney into the urine  Drugs need to be polar enough for efficient excretion  Elimination of drugs into the urine involves 3 processes: 1.Glomerular filtration 2.Proximal tubular secretion 3.Distal tubular reabsorption Drugs enter the kidney through renal arteries which divide to form a glomerular capillary plexus Free drug (non-protein bound) flows into Bowman’s space as part of the glomerular filtrate  Glomerular filtration rate is 125mL/min  Lipid solubility and pH do not influence glomerular filtration rate  Secretion occurs in the proximal tubules by 2 energy requiring active transport systems ◦ One for anions (deprotonated forms of weak acids) ◦ One for cations (protonated forms of weak bases)  Competition between drugs on the transport systems can occur As a drug moves toward DTC its concentration becomes higher than in the perivascular space  Uncharged drugs will diffuse out of the nephric lumen to the systemic circulation  Increasing the ionized form of the drug in the lumen by changing the pH of the urine can minimize the back-diffusion and increase clearance {Ion Trapping} ◦Elimination of weak acids can be increased by alkalinization of the urine  e.g. phenobarbital (weak acid) overdose Alkalinization of urine with bicarbonate keeps the drug ionized ◦Elimination of weak bases can be enhanced by acidification of the urine  e.g. overdose of amphetamine (weak base) Acidification of urine with NH4Cl causes the protonation of the drug and enhancement of its excretion  Most drugs are lipid soluble  Without chemical modification drugs would diffuse back from the kidney lumen when their concentration is higher there  To minimize reabsorption , drugs are modified (mainly in liver) to more polar compounds  Liver  Intestine  Bile  Lungs  Milk in nursing mothers To a small extent in sweat, tears, saliva, hair and skin  Liver ◦ contributes to drug loss through metabolism and/or excretion into the bile ◦ patients with renal failure may benefit from drugs excreted through this route  Feces ◦ Elimination of unabsorbed orally ingested drugs ◦ Elimination of drugs that are secreted directly into the intestines or bile  Lungs ◦ Elimination of anesthetic gases  Breast milk ◦ Source of undesired effects to the infant Case Base Analysis Important Pharmacokinetic Principles Differences between a 25 year old fit healthy adult ,an elderly adult & an Infant  Absorption of drugs-infant Gastric Cells are immature until approx. 3 years of age, therefore gastric pH is less acid than an adults gastric pH Emptying is slowed because of slow and irregular peristalsis Immaturity of liver and reduced levels of (microsomal) liver enzymes means that first pass elimination is limited Proportionately greater body surface and thin skin layers means that topical absorption is greater Intramuscular absorption is faster and unpredictable because of proportionately greater mass and lack of maturity of vaso control Distribution of drugs-infant Total Body Water is much greater: 65%-75% more in infants than adults Fat content is less because of greater TBW content Protein binding is less because of less protein is produced within immature liver Blood brain barrier immaturity means that more drugs can enter the brain. Metabolism of drugs-infant Liver immaturity means that microsomal enzymes are low in number Older children have an increased metabolism Excretion of drugs-infant Immaturity of kidney (i.e. possible immature glomeruli, renal tubules and a shorter loop of Henle) means that filtration, tubular reabsorption and secretion is decreased due to initial low perfusion rates. This leads to a reduced renal function and a decreased ability to concentrate urine.  Absorption of drugs- Elderly adult A gradual reduction in gastric cells results in a reduction in gastric pH = less acid than and younger adult Emptying is slowed because of gradual decline in muscle tone and motor activity Peristalsis is also slowed because of a decline in muscle tone and motor activity Blood flow to the GI tract is reduced by 40%-50% because of decreased Cardiac Output and decreased blood flow Liver (microsomal) enzymes decrease by approx. 1.5% for each year after the age of 25 years and this ultimately effects reduction in first pass elimination The GI absorptive surface area is decreased as the villi both blunt Distribution of drugs- Elderly adult Body composition changes with age: TBW is decreased and the ratio of fat to water increases Fat content increases because of a decease in lean body mass The ageing liver is less able to manufacture adequate levels of protein resulting in a reduction in protein binding sites. Metabolism of drugs- Elderly adult The ageing liver is less able to produce microsomal enzymes Liver blood flow is decreased by 1.5% per year after the age of 25 years.  Sites for Administration of Drugs Topical: Skin, eyes (eye lids/conjunctiva), ears Oral (or naso/oral: tube) Nasal Rectal Vaginal Injections: S/C, IM, Intra Venous, intrathecal, intra abdominal, etc.  Apply Your Knowledge Which one of the following illustrates the ideal meaning of pharmacology The study of the formulation of drugs The study of diagnosis techniques The study of drugs including their actions and effects in living systems The study of preparation and development of drugs. A drug from micro-organisms sources is Morphine Insulin Aspirin Pencillin The generic name of a drug can be defined as The name used to market the drug A precise description of the drug’s chemical composition and molecular structure The official drug name or scientific name assigned by the manufacturer A name that is protected by copyright Which one of the following define the meaning of pharmacokinetics Describes what the body does to a drug. Describes what the drug does to the body It deals with the biochemical and physiological effects of drugs It deals with the mechanisms of action of drugs  The correct sequence of pharmacokinetic phases of a drug may pass through is Administration, inhalation, absorption and excretion Formulation, absorption, metabolism and excretion Disintegration, absorption, elimination and expiration Absorption, distribution, metabolism and excretion Which of the following is correct about sublingual route of administration Low rate of absorption Avoid hepatic first pass metabolism Used for drugs with poor GI absorption Inactivation of drugs due to hepatic first pass metabolism Bioavailability is defined as: Proportion of the dose reaching the receptor intact Proportion of the dose reaching the systemic circulation intact Proportion of the dose metabolized by the liver Proportion of the dose excreted by the kidneys  The rectal route of administration Provides nearly 100 percent bioavailability Is suitable for persons with nausea and vomiting Is subject to a high degree of first-pass metabolism Is used for administration of nitroglycerin A drug given by which route could theoretically reach high plasma concentrations and have 100% bioavailability? Oral Inhalation IV Injection Topical administration If a drug exhibits zero-order kinetics, then The rate of drug elimination is constant Plasma drug concentration is constant Drug half-life is constant Drug clearance is constant If a drug has a half-life of 4 hours The drug will exhibit its maximum effect after 4 hours The plasma concentration of the drug will fall to 50% of the peak plasma concentration in 4 hours. The initial dose of drug administered will be eliminated in 4 hours Steady state will be reached in 4 hours.  Phase II drug metabolism Includes hydrolytic reactions Produces low molecular weight products Usually forms inactive and water soluble metabolites Takes place mainly in the kidneys Which of the following is correct about drugs of first-order drug kinetics The rate of elimination is constant The rate of metabolism is constant Drug clearance is directly proportional to plasma drug concentration The rate of metabolism & elimination is directly proportional to drug concentration What type of drug could potentially have a large volume of distribution (present in total body water) Water soluble drugs Lipid soluble drugs High molecular weight drugs Drugs bounded to plasma proteins  A drug of large molecular weight or highly protein bound drug is likely to be found mainly: In the plasma In the central nervous system In extracellular compartments In intracellular compartments Concerning the effect of pH on the urinary excretion of drugs, it can be correctly stated that Urinary acidification accelerates excretion of weak acids and base drugs Urinary alkalization accelerates excretion of weak acids and base drugs Urinary acidification accelerates excretion of weak acid drugs Urinary alkalization accelerates excretion of weak acid drugs  Go to a pharmacy and check the ingredients of four or five different OTC drugs for comparison and to familiarize yourself with the difficulty a layperson may encounter while trying to find this information. Bring the detail of these products into the classroom for comparison in future studies & discuss this with your mentor. Give rationale for why some drugs need to be kept under lock and key on the hospital unit. Discuss this with your mentor. Familiarize yourself with 4 or 5 drugs that are often prescribed & administered in your placement setting. Outline the role of the nurse in the safe administration these drugs. Discuss this with your mentor & your clinical teacher.  Saudi Food & drugs Authority Pregnancy categories Controlled substances Generic drugs Orphan drugs Over-the-counter (OTC) drugs Paracetamol Prescription Only Medicines (POM) Warfarin Nurse Prescriber’s Extended Formulary Sources of drug information Data Sheets General Pharmacology Chapter 1 GENERAL PHARMACOLOGY Pharmacodynamics Pharmacodynamics Pharmacodynamics is the study of the biological and therapeutic effects of the drugs as well as the mechanism of action of the drugs Pharmacodynamics (Action + Mechanism of action)  Mechanisms of action Physical action: (Adsorption), Eg: Kaolin adsorbs the Toxins during diarrhea Chemical action: (Neutralization), Eg: Sodium bicarbonate neutralizes the action of hydrochloric acid in the stomach during gastritis Action of different drugs:  Action on enzymes: Stimulation Inhibition Irreversible Reversible - Long lasting - Short lasting - Requires new enzyme synthesis Eg: Neostigmine E.g.: Organophosphorous compounds Drug Receptors  Drug Receptors Affinity: Tendency of a drug to bind to the receptor Potency: How much drug is required to elicit a response? Efficacy: Biological response Competitive Antagonism: Displaced by an excess agonist Non-Competitive Antagonism: Not displaced by an excess agonist Partial Agonist: Stimulates and Blocks receptors Eg; benzodiazepines → Agonist of Benzodiazepine receptor → Produces sedation, Anxiolytic activities  Factors modifying the dosage and action of drugs Age: Newborn infants are premature and more susceptible to drug’s effects due to: Underdevelopment of microsomal enzymes, Reduced excretion Underdeveloped BBB Adult dose X Weight in Kgs For infants: Clark’s formula =----------------------------------------------- 70 Adult dose X Age in years For children: Young’s formula = ------------------------------------------- Age + 12 Children metabolise ‘Digitalis’ fast, hence they may require a high dose of ‘Digitalis’ Elderly: a) Between 60 – 70 years of age → ¾ of the adult dose b) Above 70 years of age → ½ the dose of adult This is due to, 1) Aging of liver microsomal enzymes 2) Underweight 3) Reduced renal function II) Body weight and surface area: a) The bigger the body weight, the larger the dose b) Increase in body weight due to Oedema or Fat is not taken into consideration In the case of obese patients: Increase the dose of fat-soluble drugs Decrease the dose of water-soluble drugs Surface area is most accurate parameter for dose calculation 2) SEX/GENDER Women need smaller doses of drugs than Men. This is due to: Fat Content more in females Enzyme inhibition effect of female sex hormones Enzyme induction effect of male sex hormones During menstruation, avoid: Salicylates and caster oil During pregnancy, avoid: Teratogenic drugs and uterine stimulants During lactation, avoid: Chloramphenicol, Anticoagulants, Phenolphthalein 3) ROUTES OF ADMINISTRATION IV > Sublingual & Inhalation > IM > SC > Oral The action of the drug is also affected by the route of drug administration: E.g.: magnesium sulfate: Orally → Purgative Rectally → Dehydrating agent IV → Anticonvulsant 4) Drug Intolerance: Because of super sensitivity, hence decrease the dose of the drug 5) Tolerance: Failure of response to the usual dose of a drug is known as tolerance May be due to, a) Congenital reasons: Racial, Species, Individual variations b) Acquired reasons: Repetitive drug administration Eg, Morphine, Ethyl alcohol, Nitrates, Ephedrine Special types of tolerance: a) Tachyphylaxis: rapidly diminishing response to successive doses of a drug, E.g., Ephedrine in BP b) Cross tolerance: Tolerance between related drugs E.g., Ethyl alcohol and general aesthetics 6) HYPERSENSITIVITY – Allergic reactions: It is because of the exaggerated immune response, May does not occur in the first dose but surely occurs in the second dose It is not dependent on the dose or concentration of the drug 7) IDIOSYNCRASY = PHARMACOGENETICS Abnormal effect to a drug because of genetics or enzyme effect Eg: Peripheral neuritis with slow Isoniazid metabolizers 8) DRUG DEPENDENCE Habituation: Emotional or psychological dependence on the drug If the habituation is stopped, emotional distress develops Ex: Cigarette smoking Addiction: Psychic craving for or physiological dependence If the addicted drug is stopped, Severe withdrawal reactions are seen Ex: Marijuana, Amphetamine 9) PATHOLOGICAL STATE Aspirin lowers the temperature to normal but not less than normal. 10) CUMULATION If the rate of drug administration is more than the drug elimination, the drug undergoes cumulation and adverse drug reaction, drug interactions are seen Eg: Digitalis. 11) EMOTIONAL STATE – PLACEBO EFFECT Placebo are inert dosage forms that produce their effect psychologically: They are used in testing new drugs 12) DRUG COMBINATIONS: Addition or summation: 1 + 1 = 2 Synergism: 1 + 1 = 3 Potentiation: 1 + 1 = 2 Antagonism: 1 + 1 = 0  Drug Toxicity Toxicity of drugs: Adverse drug Reactions (Unwanted) a) Unpredictable: Eg, Idiosyncrasy Allergic reactions (Hypersensitivity reactions) b) Predictable 1) Overdose toxicity 2) Teratogenic effect 3) Long-acting sulphonamides can produce jaundice in babies 4) Chloramphenicol – blood complications 5) Smoking and radiation – Carcinogenic effect 6) Streptomycin can produce 8th cranial nerve damage 7) Prolong use of antibiotics – Superinfection and Vit B and Vit K deficiency  DOSAGE OF DRUGS: Therapeutic dose: The average adult dose required to produce a therapeutic effect Maximum tolerated dose: largest safe dose that can be taken Lethal dose: Dose that produces death Loading dose: The dose that is given at the onset of therapy to produce a rapid increase in plasma concentration to reach drug concentration within the therapeutic range Maintenance dose: It is the dose needed to keep the plasma drug concentration constant at the steady state Type A: Predictable and dose-dependent (Augmented) Extension of pharmacological action Ex: Hypoglycemia by insulin Excess bleeding by warfarin Bronchoconstriction by Propranolol Pupil constriction by Prazosin Type B: Unpredicted and dose-dependent (Bizarre) Usually, the opposite reaction due to genetic abnormalities Ex: Benzodiazepines induced excitement in females Isoniazid-induced peripheral neuritis Succinyl choline-induced apnea Primaquine-induced hemolysis Anaphylactic reaction with penicillin Type C: Continuous leading to cell damage Ex: Bleomycin-induced pulmonary fibrosis Cyclosporine-induced Nephrotoxicity Paracetamol-induced Hepatotoxicity Anti-cancer agents induced decreased sexual characteristics in males and females Type D: Delayed after long use of drugs Ex: Thalidomide induced phocomelia Phenytoin caused cleft lip and cleft palate. Valproate-induced spina bifida Warfarin caused microcephaly Thank you