Pharmacology Lecture (9) PDF

INTROODUCTION TO PHARMACOLOGY PHL229 Lecture (9) Chapter 3 Pharmacokinetics & Pharmacodynamics   Pharmacodynamics is the study of actions of the drugs on the body and their mechanisms of action.  Principles of drug acti...

INTROODUCTION TO PHARMACOLOGY PHL229 Lecture (9) Chapter 3 Pharmacokinetics & Pharmacodynamics   Pharmacodynamics is the study of actions of the drugs on the body and their mechanisms of action.  Principles of drug action  Drugs do not produce new functions for any cells/tissues/organs; they just change their Pharmacodynam specific functions. ics  The basic types of drug action are classified as: o Stimulation o Depression o Irritation o Replacement o Cytotoxic action  Stimulation is the increase in the activity of specialized cells/tissues/organs. Examples 1. CNS Stimulants: as Methylphenidate (Ritalin), Amphetamine 1- (Adderall).  These drugs mainly target the brain and spinal cord  They are commonly used to treat conditions such as narcolepsy. Stimulati 2. Cardiovascular Stimulants: as Dopamine, Dobutamine, and Epinephrine on  These drugs mainly target the cardiovascular system and can increase heart rate, blood pressure, and cardiac output.  They are used to treat conditions such as low blood pressure and heart failure. 3. Respiratory Stimulants: as Doxapram  These drugs mainly target the respiratory system and are used to improve respiration or breathing rate.  Depression is the decrease in the activity of specialized cells/tissues/organs Ex: Quinidine depresses the heart. 2- Barbiturates depresses the CNS. Depressi NOTE Some drugs may stimulate an organ and depress another. Ex: on Acetylcholine stimulates intestinal smooth muscles but depresses the heart. Morphine stimulates the vagus center but depresses the CNS.   Irritants are substances that cause a burning sensation to the skin, the eyes or airways after a single exposure.  They produce an inflammatory response at the site of application or administration. Ex: 1. Topical irritants: 3-  Some drugs are applied to the skin or mucous membranes to produce a localized irritation or inflammation. Irritation  For example, certain creams or ointments containing menthol or salicylates may be used for pain relief, as they create a sensation of heat or coolness that can help relieve pain. 2. Irritant laxatives:  Certain laxatives, such as anthraquinone derivatives (e.g., Senna), work by irritating the mucous membranes of the gastrointestinal tract, which stimulates intestinal motility and promote the elimination of stool.   Drugs that act by replacement are drugs that replace or substitute a deficient substance in the body.  These drugs help the body's organs to restore their normal physiological functions. 4- Examples 1. Hormone replacement therapy  It is commonly used to replace or substitute hormones that Replace are deficient in the body.  For example, o Estrogen and progesterone replacement therapy is ment often prescribed to relieve symptoms of menopause in women. o Thyroid hormone replacement is used to treat hypothyroidism. 2. Insulin:  Used in people with type 1 diabetes to compensate for insufficient insulin production by the pancreas.  3. Iron supplements:  Used in case of iron deficiency anemia 4. Vitamin and mineral supplements: 4-  such as vitamin D, vitamin B12, calcium, magnesium, and others can be prescribed to restore appropriate nutrient levels in the body. Replace ment  Cytotoxic action  It is the toxic action of drugs on cancer cells or on the infective organisms without significantly affecting the host cells. Ex: Antibiotics as penicillin - Anticancer drugs as 5-  cyclophosphamide Cytotoxic ity INTROODUCTION TO PHARMACOLOGY PHL229 Lecture (10) Combined effect of drugs and Adverse Drug reaction   When two or more drugs are given together, they may show synergism or antagonism. Drug synergism  Synergism (Greek: Syn-together; ergon-work) Combined effect  Synergism is the enhancement of the effect of one drug by another when given together of drugs  Types of Synergism a. Additive effect (summation) b. Supra-additive effect (Potentiation)  a. Additive effect (summation)  It is the use of two drugs that have similar actions in which each drug adds some benefits Additive to the other: o In this case, the effect of the combination is effect equal to the sum of their individual actions. o Effect of drugs (A + B) = Effect of drug (A) + (summatio effect of drug (B) when used separately n) Examples o Aspirin & Paracetamol as Analgesics o Ephedrine & theophylline as bronchodilator o Glibenclamide & Metformin as antidiabetics  b. Supra-additive effect (Potentiation) Supra-  It is the use of two drugs together, one of them does NOT have an effect when given alone but additive enhances the effect of the other drug when used together effect o In this case, the effect of the combination is greater than the sum of their individual actions. (Potentiati o Effect or drug (A + B) > effect of drug (A) + effect of drug (B) when used separately on)  Examples:  Trimethoprim & Sulphamethoxazole (bacteriostatic)  The effect of the combination is bactericidal   It is the use of two drugs together, where one of them antagonizes or inhibits the effect of the other  Types of antagonism Antagonis Physical antagonism Chemical Antagonism m Physiological Antagonism Pharmacological Antagonism (Antagonism at the receptor level) 1- Competitive antagonism o Reversible o Irreversible 2- Non-competitive antagonism.  Physical antagonism  It is a type of antagonism that is based on the physical property of the drug.  In this case, the antagonist can bind to the agonist and prevent its action without any chemical reaction. Example Physicalan  Activated charcoal adsorbs alkaloids and can prevent their absorption _ used in alkaloidal poisoning d Chemical Chemical antagonism  Chemical antagonism occurs when two drugs react chemically antagonism and form an inactive product Examples o KMnO4 oxidizes alkaloids _ used for gastric lavage in poisoning. o Tannins precipitates alkaloids forming insoluble alkaloidal tannate. o Antacids like aluminum hydroxide neutralize gastric acid in case of hyperacidity  Physiological antagonism  In this case, 2 endogenous substances bind to 2 different receptors to produce opposite effects on the same physiological function Physiologic (both of them are agonists) al Examples antagonism o Histamine and adrenaline on bronchial muscles and on BP. o Acetylcholine and norepinephrine on BP o Glucagon and insulin on blood sugar level. Pharmacological Antagonism  Pharmacological antagonists are further divided into two types: 1- Competitive antagonist  It is a type of pharmacological antagonism  In this case, the agonist and antagonist compete with each other for the same binding site of the receptor.  If the antagonist binds to the receptor, it will prevent the agonist from binding to the same receptor.  There are 2 types of competitive antagonists, depending on the type of bond formed between the antagonist and the receptor. Reversible competitive antagonism (A) Reversible competitive antagonism  Both agonist and antagonist interact with their receptors by weak bonds (ionic bond or Hydrogen bond) So, the increase in concentration of either one of these drugs can displace the other from receptor binding sites. Example o Acetylcholine and atropine compete for the muscarinic receptors. o The antagonism can be overcome by increasing the concentration of acetylcholine at the receptor. (B) Irreversible competitive antagonism  In this case, the antagonist bind strongly to the receptor through covalent bonds.  Thus it blocks the action of the agonist and the blockade cannot be overcome by increasing the dose of the agonist and hence it is irreversible antagonism Example  Adrenaline and phenoxybenzamine at alpha adrenergic receptors Non-competitive antagonism 2- Non-competitive antagonism  In this case, the agonist and the antagonist act on different sites, so there is no competition between them.  In contrast to a competitive antagonist, the effect of a non-competitive antagonist cannot be reversed by increasing the concentration of the agonist Example,  Verapamil blocks the calcium channels in the cardiac muscle and inhibits the entry of Ca+2 during contraction. It thereby antagonizes the effect of cardiac stimulants like adrenaline  There are several terms commonly used to describe the adverse effects of drug treatment:  An adverse effect  It is an unexpected harmful response that occurs after administration of normal dose of drugs.  A side effect  It is unwanted effects unrelated to the main pharmacological actions of the drug but due to other normal actions of the drug.  Drug toxicity  It is the adverse effect of a drug that occurs by using high dose Adverse Drug or due to high plasma concentration, either unintentionally or intentionally. Reactions (ADR) Classified into:  Type A reactions (Augmented)  Type B reactions (Bizarre)  Type C reactions (Continuous)  Type D reactions (Delayed)  Type E reactions (Ending Use)  Type F reactions (Failure of Efficacy)  Type A reactions (Excessive therapeutic effect)  Type A reactions are predictable, very common, dose dependent unwanted effects that are related to the pharmacological actions of the drug.  Type A reactions occur when the normal dose of a drug produces greater therapeutic effect than is necessary.  Type A reactions are reversible _ Disappears after dose reduction or cessation of therapy  Examples : o Bleeding with warfarin (Anti-coagulant). o Hypotension with antihypertensives o Hypoglycemia with insulin o Mydriasis in tropicamide  Type B reactions (Bizarre)  Type B reactions are non-predictable responses that are not related to the known pharmacological actions of the drug  These reactions are less common, not dose dependent and often serious.  They developed on the basis of : o The immunological response to the drug (Allergy) o Genetic susceptibility of person (Idiosyncratic reactions)  Mostly require immediate withdrawal of the drug.  Forms of Type B reactions  Hypersensitivity _ Allergic reactions: It is an abnormal response to the drug due to antigen-antibody reactions. For example o Skin rashes with antibiotics. o Anaphylaxis in response to penicillin o Aplastic Anemia caused by Chloramphenicol  Idiosyncrasy _ Genetic disorders: It is an abnormal response to the drug due to genetic disorders. For example: o Malignant hyperthermia  Type C reactions (Continuous reaction)  Occur due to the long term use of a drug or due to dose accumulation.  Type C reactions are uncommon, dose dependent and time dependent  The reactions persist for a relatively long time. Examples o Nephropathy due to long term use of NSAIDs o Hepatotoxicity associated with paracetamol  Type D reactions (Delayed adverse reactions)  Type D reactions are reactions which occur due to prolonged use of a drug which doesn't tend to accumulate.  Type D reactions are uncommon, and usually dose dependent, difficult to detect due to long time between administration of drug and symptoms appearing.  Forms of Type D reactions 1- Carcinogenesis  It is the ability of some substances to induce cancer.  Bladder Carcinoma after treatment with cyclophosphamide is another example. 2- Teratogenesis  It is a congenital malformations occurring in the fetus due to exposure to drugs during pregnancy  e.g. Thalidomide causes Phocomelia  Type E reactions (end-of-use’ reactions)  Type E reactions are associated with the sudden withdrawal of a drug  These are uncommon and occur soon after the withdrawal of the drug. Examples o Sudden withdrawal of long term therapy with -blockers can induce rebound tachycardia and hypertension o Sudden withdrawal of long term therapy with anticonvulsant drugs can induce Seizures  Type F reactions (failure)  Type F reactions are characterized by the unexpected failure of therapy, where the expected response to treatment is not achieved.  These reactions are common, dose-related and often caused by drug interactions.  Examples o The decreased effect of antibiotics due to bacterial resistance o Failure of oral contraceptives in presence of enzyme inducers INTROODUCTION TO PHARMACOLOGY PHL229 Lecture (11) Drug compendia and Drug nomenclature  Drug Compendia are collections of information about drugs  Some drug compendia are produced by governments and are called official compendia (Pharmacopoeias and Formularies).  On the other hand, some drug compendia are produced by non-governmental professional bodies and are called non-official compendia. Pharmacopoeias Drug Compendia  They are official compendia  They contain description of chemical structure, molecular weight, physical and chemical characteristics, solubility, and assay methods, standards of purity, and dosage forms of officially approved drugs in a country.  They are useful to drug manufacturers and regulatory authorities, but not to doctors.  Ex: British pharmacopoeia (BP), European pharmacopoeia (Eur P), United States pharmacopoeia (USP).  Formularies  They are official compendia  Generally produced in easily carried booklet form.  They list indications, dose, dosage forms, contraindications, and adverse effects of selected drugs that are available for medicinal use in a country. Ex : o British National Formulary (BNF) Drug Compendia o National Formulary of India (NFI) Martindale - The Extra Pharmacopoeia  It is a non-official compendium  It published every 2–3 years by the Royal Pharmaceutical Society of Great Britain,  It lists an updated information on drugs used all over the world.   There are several different types of drug names including: o Chemical name o Non-proprietary name – Generic name ‫اس@م غ@ير مس@جل‬ ‫الملكية‬ o Proprietary name - Brand or trade name ‫اس@@م مس@@جل‬ ‫ العالمة التجارية‬/ ‫الملكية‬ Drug Chemical name nomenclature  Chemical names describe the exact chemical composition of a drug. (Drug names) o The chemical name of aspirin is acetylsalicylic acid (2- (acetyloxy)benzoic acid). o The chemical name of propranolol is 1-(Isopropylamino)-3- (1-naphthyloxy) propan-2-ol  These chemical names are usually complex and not easy to use.  Non-proprietary name -‫اسم غير مسجل الملكية‬ Generic or common name - ‫اسم عام‬  A generic name is the standard name of a drug that is approved by an official organization within each country such as : Drug o The United States Adopted Name (USAN) council o Drug’s British Approved Name (BAN). nomenclature (Drug names)  A generic name is a short name that is usually derived from the chemical structure of the drug  It is usually not owned by any specific pharmaceutical company.  It is always NOT capitalized  Non-proprietary name -‫اسم غير مسجل الملكية‬ For example, The generic name of the popular analgesic PANADOL is paracetamol The generic name of the popular antidiabetic Drug GLUCOPHAGE is metformin nomenclature NOTE A generic name is the name by which the drug is described (Drug names) in scientific literature and in official books like pharmacopoeias e.g., paracetamol, metformin.  Proprietary name ‫اسم مسجل الملكية‬ Brand or trade name ‫العالمة التجارية أو االسم التجاري‬  A brand name of a drug is the name that is created by the pharmaceutical company that developed it and approved by official organizations within each country (such as USFDA). Drug  A brand name of a drug is given on a proprietary nomenclature (copyright) basis. ‫حق الملكية‬  Brand names are designed to be attractive, short, easy (Drug names) to remember  The brand name is always CAPITALIZED.  This name is often followed by the symbol ® which indicates that the name is registered to a specific manufacturer.  One particular drug could have multiple brand name.  Proprietary name ‫اسم مسجل الملكية‬  Example:  Brand names of Sildenafil are: o VIAGRA®, REVATIO®  Brand names of Omeprazole are: Drug o OMEZ®, OCID® nomenclature  Brand names of Metformin are: (Drug names) o GLUCOPHAGE®, GLUMETZA®  These brands are manufacture by different companies Brand Name Drugs vs Generic Drugs  Innovator drugs (Brand drugs) ‫األدوية المبتكرة‬  Innovator drug is the first drug in the market to be approved with a specific active ingredient.  When a pharmaceutical company develops a new drug, it gives that drug a unique brand name (Brand drug) o The brand name is usually attractive, short, easy to remember  The innovator drug is protected by a patent, which gives the company the exclusive right to manufacture and sell the drug for a certain period of time, usually 20 years. o During the patent period, other companies cannot produce or sell the same drug until the patent expires.  Once the patent expires, other drug manufacturers can apply to produce the same drug under a different name (Generic drugs) o A generic drug is a legal copy of a brand name drug Similarities between generic and brand name drugs  The pharmacological effect of the generic drug must be exactly the SAME as that of its innovative counterpart. o They both have the SAME active ingredient. o They both have the SAME dosage form o They both share the SAME pharmacokinetic and pharmacodynamic properties in the body.  Differences between generic and brand name drugs  They usually have DIFFERENT names  They may have DIFFERENT inactive ingredients (such as flavours or preservatives).  They may have slightly DIFFERENT colours or smell.  Brand-name drugs are more expensive than generic drugs - because of the cost of research, clinical trials and marketing.