Pharmacology: The word pharmacology is derived from two Greek words: Y Pharmacon, which means “medicine or active principle,” and ¥ Logos, which means “study.” Thus, pharmacology is most simply defined as the study of medicine or drug. Pharmacy: The science which deals with the preparation, compounding and dispensing of medicine.> Routes of Drug Admi Medicines are available in tablet, injection, spray, and cream form; So four routes are as follows: Medicines can be given to patient by Enteral, Parenteral, Inhalation or Topical routes. Details are as follows; The route of administration (ROA) for drug delivery is 1 of the substance. Three sub-types are 1. Oral (Giving medicine by mouth) : this is usually the safest, most convenient, and cheapest route but not suitable in emergency. 2. Sublingual: These drugs are given buccally (in the pouch between the cheek and gum), sublingually (under the tongue), or trans-lingual (on the tongue) to speed their absorption. 3. Rectal and vaginal: suppositories, ointments, creams, gels, and tablets may be administered into the rectum or vagina for local or systemic effects.1. Intravenous: the |.V. route allows injection of substances (drugs, fluids, blood or blood products, and diagnostic contrast agents) directly into the bloodstream through a vein. 2. Intramuscular: this route allows drugs to be injected directly into various muscle groups at varying tissue depths. Ask patient to relax muscle and insert needle rapidly to reduce pain. 3. Subcutaneous: Subcutaneous injection is delivered under the dermis. Insulin, heparin, vitamins, some vaccines, and other medications are given in patient’s upper arm, thigh, or abdomen. 4. Other types of parenteral route: Intradermal (just below skin), Intracardiac (injection in heart in emergency), Intrapleural (injection to lungs directly), Intrathecal (injection into sub-arachnoid space in lumbar puncture in spinal cord) Intra- articular Injections (joint injections). 1. Inhaler: It can be self-administered at anywhere.2. Endotracheal tube: Drugs can be administered directly into the lungs through in emergency situations and in Intensive Care Unit (ICU). 1. Epidermic route: Applying lotions and creams on skin 2. Instillation: Putting drops in Ear Nose and Throat (ENT) 3. Insertion: Putting suppositories in rectal cavity and pessaries in vagina and boogies in urethra. Advantages and disadvantages of IV route : ADVANTAGES OF IV DISADVANTAGES ROUTE OF IV ROUTE Onset is very fast (15-30 More risk of seconds) addiction and abuse Bioavailability is 100% Strict asepsis is required Can deliver continuous High risk of HIV medication (Morphine and other ‘for pain, Saline as Fluid infectious replacement) diseases if needles are shared Suitable for drugs that Expensive than cannot be given via gut like tablets anticancer medicines. In cases when patient is Can cause unable to take medicine, potentially fetal unconscious pt. air bubblesPHARMACOKINETICS Definition: “Pharmacokinetics is the study of: The movement of drug molecules: Passive Diffusion ii. Carrier Mediated transport: iii. | Endocytosis. Water and Lipid Solubility: 1. Solubility: Many drugs are weak acids or weak bases, so their charged form (ionization state) or uncharged form (no- ionized state) depends on pH of medium. If we know the pH of medium and pKa of a drug, we can predict the charge by: Henderson Hassel Balch | SS ee equation: Unprotonated form ) ~ P*=~ PI Use: we can treat an overdose by decreasing absorption from the gut and reabsorption from the tubular urine by making the drug less lipid-soluble. |onization attracts water molecules and decreases lipid solubility2. lonization: Weak Bases are lonized = more water soluble Weak Acids are non-lonized = Less water Soluble For example Tolbutamide is anti-diabetic drug, is a weak acid with pH 5.3. If a child ingests it, we can treat this toxicity by giving NaHCO; that will alkalinize urine so Tolbutamide will now be ionized and hence water soluble so it goes out of body in urine. Definition: The process by which a drug is transferred from the site of entry to the circulating fluids. Factors affecting absorption of drugs: Drug formulation and dose. Size of the drug molecule. Surface area of the absorptive site. Digestive motility or blood flow. Lipid solubility. Degree of ionization. Acidity or alkalinity (pH). Interactions with food and other medications. ee cateDefinition. Distribution involves the transport of drugs throughout the body. The simplest factor determining distribution is the amount of blood flow to body tissues. The HEART, LIVER, KIDNEYS, AND BRAIN receive the most blood supply so more drug is received. SKIN, BONE, AND ADIPOSE TISSUE receive a lower blood supply so less drugs is received. The BRAIN AND PLACENTA possess special anatomic barriers that prevent many chemicals and medications from entering. These barriers are referred to as the blood-brain barrier and fetal—placental barrier. Some drugs prove TOXIC IN PREGNANCY and are teratogen (cause abnormal child) given to pregnant ladies in 3 Trimester (7"", 8th and 9" month) and can be dangerous to fetus for example antibiotics like Tetracycline, pain killer drugs like Morphine, epilepsy and sleep medicine like Diazepam and Goiter medicine like carbimazole.When we take medicine, our Liver makes it soluble in water by metabolizing it; this is called biotransformation, by which the liver converts a drug to inactive compounds, so finally it can be removed from body by urine. Definition: Biotransformation is The process of chemically converting a drug to a form that is usually more easily removed from the body. 1. Drugs reach our Liver and metabolized by Enzymes called Cytochrome P450. 2. Also drugs are metabolized by our Gut, Lungs and Kidneys. 3. The drug is made more water soluble. Remember: Lipid soluble drug absorb in body much faster and water soluble drugs are excreted by body thru kidneys much faster. Reactions in Liver: These transform drug taken by patient, it occurs in 2 Phases; Phase 1 Reactions: 1. Oxidation 2. Reduction 3. Hydrolysis.Phase 2 Reactions: it CONJUGATION occur with 1, Glucuronide 2. Glutathione 3. Aceticacid or 4. Sulfate First pass effect: The process of first-pass effect applies to drugs absorbed across the cell membranes of the small intestines that are first transported to the liver via portal circulation where they undergo liver metabolism before release into the systemic circulation. The first-pass effect can decrease bioavailability of the drug. Only drugs administered orally undergo the first-pass effect. Factors affecting biotransformation of Drugs: 1. Age: Slow metabolism in newborn and old age people. 2. Nutrition: Slow metabolism in poor nutrition cases. 3. Diseases: Slow metabolism in patients with liver disease when P 450 enzymes are damaged. 4. Route of Administration: Oral drugs go to Liver before reaching body cells for action this is called first- pass effect in which much drug is metabolized by Liver. 1.V injection drugs reach site of action without going to liver first so these are less metabolized. 5. Sex and Genetic differences: More drug quantity is metabolized by males.Effect of Drugs, on Drug Metabolism: These include the following: 1. Addition: The action of drugs taken together as a total. 2. Synergism: The action of drugs resulting in a potentiated (more than total) effect. 3. Antagonism: Drugs taken together with blocked or opposite effects. 4. Displacement: When drugs are taken together, one drug may shift another drug at Plasma protein binding site to change its effect. There are 2 rates of drug removal: - First order kinetics - Zero Order Kinetics Drug elimination with First order kinetics is constant and with Zero order kinetics it is not constant. ’ The process by which a drug is removed from the body’. Routes of excretion: 1. Kidneys Fecal excretion Respiratory excretion Brest milk excretion Skin excretion WRWNBIOAVAILABILITY Definition? The proportion of the active drug that reaches the systemic circulation (blood flow throughout the body) in unchanged form, after administration of its pharmaceutical preparation. v Drugs given by I.V route have 100% Bioavailability ¥ The systemic circulation distributes drugs to various body tissues or target sites. v Bioavailability depends on following factors: 1. Quality of Drug making 2. Route of Administration First Pass metabolism: After we take drug by mouth, its metabolism is started in Mouth, Stomach, Intestine, then in Liver. In liver where most of drug is metabolized and Liver make it Water soluble by biotransformation, so from liver it goes by blood to whole body and kidneys. In body it starts its action, but kidneys start to waste it because it is now water soluble, so it comes out of body in urine. That is why if a drug has more First pass effect; we give it by injection — so that it can go to site of action directly and not through mouth, gut and liver pathway. Factors affecting drug absorption from GIT: 1) pHin gut and 2) Blood flow of gut 10Volume of DISTRIBUTION (vp) Definition: A hypothetical volume of fluid into which a drug is dispersed is called vol. of distribution or Vd. It relates amount of drug in the body to the plasma concentration. The volume of distribution is equal to the dose of medication administered, divided by the measure of plasma concentration. Use of VD is to calculate the dose of medicine which is amount of drug in the body, and also to measure Clearance of drug from the body. Formula: VD = Pari SonceuaConoran If VD is greater, there will be less plasma concentration of the drug, because if VD is greater, it shows that the drug is more diluted than it should be, meaning more of it is distributed in tissue. In simple words drugs with high lipid solubility, have high Vd. Factors affecting VD: 1. Pregnant Person: The fetus may take up the drug 50 VD is more in pregnant ladies. 2. Fat person: Lean person has less VD and person with increased body weight has more VD. 3. Blood flow: Rapid blood flow increases VD. 11PLASMA HALF-LIFE (t 4) An example is as follows; Time 0 1 2 3 4 5 (Hour): Plasma 100 50 25 12.5 6.25 | 3.12 Conc, (mg): It shows that 100 - 3.12 = 96.8% of drug is eliminated after five half-lives. _ 07xVd cr Formula: th% ¢ Vd is Volume of distribution and CL is Clearance. e Plasma Half-life is a parameter that denotes how quickly a drug is removed from the plasma by biotransformation (metabolism) or excretion. e It indicates Duration of Action of Drugs e It determines Frequency of administration of the therapeutic drug doses Factors affecting Half Life: Half Life Decrease when there is increased metabolism by P450 in Liver, and when GFR and Renal blood flow increases. Half-life is increased when renal blood flow is decreased as in shock. 1213 PHARMACODYNAMICS Definition: Pharmacodynamics is the study of biochemical and physiological EFFECTS of drugs and their mechanism of action (MOA). Mechanism of Drug Action i.e. dynamics of drug can be studied with understanding of; Affinity: The tendency of a drug to combine with receptor is called affinity. Intrinsic Activity: Capacity of a drug to initiate a chain reaction resulting in its effect is called intrinsic activity or efficacy. Agonist: A drug that produces a pharmacological effect when it combines with a receptor. It has affinity as well as intrinsic activity. For example Acetylcholine, noradrenaline etc.Full Agonist: A drug when bound to receptor produces 100% of the maximum response. Partial Agonist: Drugs when bound to receptor produce less than 100% of the maximum response; no matter how high is their concentration Antagonist: (blockers) Drugs that bind to receptors and inhibits the effect of an agonist. An antagonist has affinity but no intrinsic activity. For example Atropine (muscarinic antagonist), and Propranolol (beta antagonist). Antagonist can bind reversibly (Competitive antagonist) or irreversibly (noncompetitive antagonist) Types of Antagonism: It is of three types; 1) Chemical antagonism: (NAHCO; antagonizes HCL) 2. Physiological antagonism: In it, two drugs act independently on different receptors like Histamine- Adrenaline antagonism. 3) Pharmacological antagonism: In it, an antagonist prevents an agonist from acting upon its receptors to produce an effect. 14DRUG INTERACTIONS Definition: Modification of the action of a drug in the body, by another drug given together or after the first drug given, is called Drug Interaction. When two or more drugs are given at the same time, they may exert their effect independently or they may interact i.e. one drug may influence the action of the other drug. The drugs mostly involved in serious interactions are those drugs with small therapeutic index like Phenytoin and those where the dose must be carefully controlled according to response like anti-diabetics, anti-epileptics, antihypertensive, and antiarrhythmic drugs. Examples of drug interactions: a. If we take milk with antifungal medicine, the medicine effect will not occur. b. Liquid Paraffin interferes with the absorption of Vitamin D. c. Oral Contraceptives interfere with the absorption of Folic Acid. d. Phenobarbitone increases the metabolism of Warfarin. e. Sodium bicarbonate increases the excretion of Aspirin and Barbiturates. a5Additive effects: Alcohol, and antiallergic tablets and cough syrup if taken in combination can lead to deep , sleep stop respiration and . Some important Drug Interactions (Table) Drug Causing | Examples of Drugs the Affected Interaction Alcohol CNS depressants | Additive CNS depression, sedation, ataxia, MAO Catecholamine Increased inhibitors releasers norepinephrine in (amphetamine, sympathetic nerve ephedrine endings released by the interacting drugs Rifampin ‘Azoles, Warfarin, | Reduced effect of Corticosteroids, other drugs Methadone, because of sulfonylureas, induction of metabolism Salicylates | Heparin, Warfarin | Increased bleeding tendency 16