PHARMACOLOGY.pptx IUIU. 20224.pptx by dr admola

pharmacology

1. INTRODUCTION TO PHARMACOLOGY SULAYMAN ADEMOLA B.Pharm.,PGD (HSE), Msc (Pharm.),MPH, LLB, Ph D , MCPAN FPCPharm,FIAPH HOD-PHARMACOLOGY SENIOR LECTURER/CONSULTANT PSYCHIATRIST ISLAMIC UNIVERSITY IN UGANDA, UGANDA. [email protected] [email protected] [email protected] [phone],[phone]

2. PHARMACOLOGY WHAT IS PHARMACOLOGY It is the Science of drug action on biological systems in its entirety. It has to do with the knowledge of the sources, chemical properties, biological effects and therapeutic uses of the drugs. It is broadly divided into Pharmacokinetics and Pharmacodynamics

3. SCOPE OF PHARMACOLOGY History - It is of intellectual interest to the physician to know how drugs are discovered and developed. Often in the past, this was based on folklore or intelligent observation (e.g. digitalis leaf, penicillin). Nowadays, new drugs are mostly developed by the organic chemist working with a pharmacologist, increasingly from basic knowledge about key molecular targets. Usually some sort of biological screen is used to select among organic molecules for optimum pharmacological activity. 1 . Francois Magendie (1783-1855) , a French physiologist laid down the dictum "Facts and facts alone are the basis of science." Experimental procedures with animals are the testing grounds for determination of drug action. 2 . Claude Bernard (1813-1878 ) worked in Magendie's lab, investigated the plant extract curare and proposed a site of action for this agent. 3 . Rudolph Buchheim (1820-1879) . In 1847 Buchheim established the first laboratory devoted to experimental pharmacology in the basement of his home in Dorpat which is known as the cradle of experimental pharmacology . .

4. 4. Oswald Schmiedeberg (1838-1921 ). In 1872 Schmiedeberg set up an institute of pharmacology in Strasbourg, France (Germany at that time) which became a mecca for students who were interest in pharmacological problems. 5. J.N. Langley (1852-1925) and Sir Henry Dale (1875-1968) pioneered pharmacology in England, taking a physiological approach. 6. John J. Abel (1857-1938) established the first chair of pharmacology in the U.S.A. (U. Michigan, 1891) after training in Germany. Able went to Johns Hopkins in 1893, and trained many U.S. pharmacologists. He is known as "The Father of American Pharmacology". 7. The second world war was the impetus for accelerated research in pharmacology (the war time antimalarial program) in the U.S., and introduced strong analytical and synthetic chemical approaches

5. Chemistry - Chemical structures of drugs can provide information about mechanism of action, pharmacokinetics, stability, and metabolic fate. 1. Structure-Activity Relationship - A modification of the chemical structure of a drug may accentuate or diminish its pharmacological effects, often providing clues as to the mechanism of action. A picture of the biological reactive site (the receptor) can be developed in such studies. Also, drugs are metabolized by body systems, which may convert the parent drug to a more active or a less active form. The drug structure can be modified to enhance or diminish the rate of metabolic conversion. 2 . Sites of Action - The organ or cellular target of drug action. 3 . Drug Receptors - Macromolecules in cells or cell membranes with which drugs interact to exert their effects. Usually the interacting forces are reversible ionic and Van der Waals bonds of relatively low energy, but sometimes covalent bonds are formed (e.g. organophosphate insecticides).

6. Pharmacodynamics - The effect of the drug on the body. Pharmaco -dynamics is the study of the relationship of drug concentration and the biologic effect (physiological or biochemical ). For most drugs it is necessary to know the site of action and mechanism of action at the level of the organ, functional system, or tissue . For example, the drug effect may be localized to the brain, the neuromuscular junction, the heart, the kidney, etc. Often the mechanism of action can be described in biochemical or molecular terms.

7. Pharmacokinetics - The effect of the body on the drug. To produce its characteristic effects, a drug must be present in appropriate concentrations at its sites of action . Thus, it is important to know the inter relationship of the absorption, distribution , binding, biotransformation, and excretion of a drug and its concentration at its locus of action.

8. Clinical Pharmacology and Therapeutics 1 . Indications and Therapeutic Uses - Emphasis is placed on the therapeutic use of drugs for the treatment of disease in clinical pharmacology, internal medicine and therapeutics. There are specific clinic disorders or disease entities for which a given drug may be prescribed and the physician must weigh the potential benefit of drug use against the risks of adverse effects. 2 . Contraindications and Factors (e.g., liver disease)May Modify Drug Action - where detoxification of the drug by the liver is important. It is important to know that the presence of disease or organ pathology may influence the actions of a drug. Conditions such as age, pregnancy, concomitant administration of other drugs and disease may alter the patient's response to a given drug. 3 . Posology - Is an archaic term describing dosage regimens. Consideration of dosage schedules is a part of pharmacokinetics .

9. 4. Bioavailability - The fraction of drug administered which is actually absorbed and reaches the systemic circulation following oral dosing. Preparations of the same drug by different manufacturers may have a different bioavailability. 5. Prescription writing - It is important that the physician write clear, error-free directions for the drug provider (pharmacist) and for the patient. Physicians must guard against prescribing too many drugs, or preparations of little value. Drugs of unproven clinical value should be avoided, as well as potentially toxic agents if drugs equally effective but less dangerous are available. Risk-benefit and cost-benefit should be considered. Drugs may be prescribed by generic name, since often a less expensive drug product can be obtained in this way. A particular manufacturer may be specified if the physician has reason to believe a better or more reliable preparation is available from that manufacturer. 6. Drug Nomenclature - In addition to its formal chemical name, a new drug is usually assigned a code name by the pharmaceutical manufacturer. If the drug appears promising and the manufacturer wishes to place it on the market, a United States Adopted Name (USAN) is selected by the USAN Council

10. Toxicology - That aspect of pharmacology that deals with the adverse effects of chemical agents. Toxicology is concerned not only with drugs used in therapy but also with the other chemicals that may be responsible for household, environmental or industrial intoxication. 1 . Forensic Toxicology - Addresses medicolegal aspects of the use of chemicals that are harmful to animals or man. Analytical chemistry and fundamental toxicological principles are hybridized to underlie this aspect of toxicology. Nonetheless accidental poisoning with drugs is a health problem of major significance. More than 1/4 of the fatalities and about 1/2 of all poisonings occur in children under 5 years of age. All common household articles that are poisonous should be made unavailable to children, and poisonous rodenticides and insecticides should not be placed in the home or keep out of reach. 2 . Clinical Toxicology - Focuses on toxic events that are caused by or are uniquely associated with drugs or other chemicals.

11. Pharmacovigilance - The area of pharmacology that focuses on the effects of drugs on patient safety. It involves the characterization, detection, and understanding of adverse events associated with drug administration, including adverse drug reactions, toxicities, and side effects that arise as a consequence of the short- or long-term use of drugs. Adverse drug reactions, including drug-drug interactions , are estimated to be a major cause of mortality of in-patients and also lead to significant increases in duration of hospitalization. No drug is free of toxic effects . Some untoward effects of drugs are trivial, but others are serious and may be fatal. Side effects often are predictable from a knowledge of the pharmacology of a particular drug. Examples of chemicals or drug-induced toxicities are given below : 1. Allergic reactions - The number of serious allergic reactions to drugs involving antigen-antibody reactions is low but when they occur the physician must have sufficient knowledge to manage these problems. 2 . Blood dyscrasias - These are very serious and sometimes fatal complications of drug therapy. They include: agranulocytosis, aplastic anemia , hemolytic anemia , thrombocytopenia and defects in clotting factors . 3 . Hepatotoxicity and nephrotoxicity - Because many chemicals and drugs are eliminated and metabolized by the liver and kidney, damage to these organs is seen commonly .

12. 4. Teratogenic effects - The thalidomide tragedy dramatically emphasized that drugs may adversely influence fetal development. 5. Behavioral toxicity - This is a term used to describe suppression of normal anxiety, reduction in motivation, impairment of memory and learning, distortion of judgement, impairment of reflexes, adverse effects on mood, etc. 6. Drug dependence and drug abuse - The repeated administration of some chemicals may lead to drug dependence. Drugs likely to be abused and upon which drug dependence may develop are the various psychopharmacological agents such as opiates, barbiturates, amphetamines, nicotine and ethanol. Dependence on tobacco (nicotine) is also well known. 7. Carcinogenesis - Carcinogenesis is a delayed type of toxicity with a latency of many years. 8. Pharmacogenetic toxicities - Certain genetically-predisposed individuals have a markedly toxic reaction to certain otherwise safe drugs. Examples are prolonged apnea after succinylcholine, or malignant hyperthermia associated with anesthetics .

13. Basic introduction to units and conversions Physicians need to be able to make accurate drug calculations in order to safely prescribe or administer drugs to their patients . It is therefore important that medical students begin to engage with mathematics early in their education. This brief introduction is aimed at motivating you to engage and help you develop your skills to the required level.

14. Equivalencies of weight UNIT SYMBOL EQUIVALENT SYMBOL 1 kilogram (kg)= 1000 grams (g) 1 gram (g) = 1000 milligrams mg 1 milligram (mg) = 1000 micrograms (mcg or μ g) 1 microgram (mcg) = 1000 nanograms (ng)

15. Before performing many drug calculations you will need to convert the numbers you use in the calculation so that they all appear in the same units. You should be familiar with the units as above ,they are the most common in drug calculation. To convert from a smaller unit (e.g. a gram) to a larger unit (e.g. a kilogram), divide by 1000, so: 5000g ÷ 1000 = 5kg To convert from a larger unit (e.g. a gram) to a smaller unit (e.g. a milligram), multiply by 1000, so: 5g × 1000 = 5000mg It is important to be comfortable with unit conversions before progressing to using a drug calculation formula . Basic formula There is more than one way to do a drug calculation, but the simplest and most widely used method This isthe basic formula : D × Q⁄H = X Where: D = desired dose H = strength available

16. What is a drug A drug is any substance other than food that when inhaled, injected, smoked, consumed, absorbed via the skin or dissolved under the tongue causes physiological changes in the body. It is usually intended for diagnosis, prevention, treatment or management of diseases or conditions.

17. ROUTES OF DRUG ADMINISTRATION A route of drug administration is the path by which a drug, fluid, poison or other substance is taken into the body. They are generally classified by the location at which the substance is applied or gained entry.

18. Factors Influencing the Route of Administration A route of administration is a way of getting a drug onto or into the body Drugs come in many different forms: designed by pharmaceutical scientists for administration or application Many factors determine the choice of route of administration

19. Ease of Administration Prescribers assess characteristics to determine route of administration some patients are unable swallow very young or older adult patients might have difficulty swallowing avoid solid, oral dose forms in favor of liquid dose forms or nonoral routes of administration oral route of administration is inadvisable for a patient experiencing nausea and vomiting

20. Site of Action Choice of route of administration is influenced by desired site of action The term local use refers to site-specific applications of drugs The term systemic use refers to the application of a drug to the site of action by absorption into the blood and subsequent transportation throughout the body even drugs meant for systemic administration are usually targeted to a specific site of action

21. Onset of Action Onset rate varies with route of administration: Oral medications for systemic use must proceed through a series of steps before they exert their therapeutic effect ( desired pharmaceutical action on the body) Liquid solutions or suspensions work faster than oral tablets or capsules medication is more readily available for absorption

22. Onset of Action Tablets placed under tongue or between cheek and gums work quickly medication bypasses stomach and liver, goes directly into bloodstream Drugs injected/infused directly into bloodstream are carried immediately throughout the body Topical medications work quickly localized therapeutic effects, especially those applied to the skin • inhaled into the lungs instilled into the eye

23. Duration of Action The duration of action is the length of time a drug gives the desired response or is at the therapeutic level Controlled- /extended-release tablet may last for 12 to 24 hours compared with 4 to 6 hours for same drug in immediate-release formulation Transdermal patches deliver small amounts of a drug steadily over many hours or even days Sustained-duration effect can be achieved by means of intravenous (IV) infusion Injections into the muscle and skin last longer than injections directly into the bloodstream

24. Quantity of Drug Sometimes route of administration is chosen because of the amount of a drug a tablet containing a lot of filler (diluent) might be preferred for a drug containing a very small amount of active ingredient IV infusion is an excellent method for systemic delivery of large quantities of material rapidly diluted in the bloodstream IV injections and infusions can deliver a higher dose of medication to the target site important in serious illnesses

25. Metabolism by the Liver or Excretion by the Kidney Liver metabolism breaks down active drug to inactive metabolites for elimination and to prevent drug accumulation The first-pass effect is the extent to which a drug is metabolized by the liver before reaching systemic circulation influences activity of several drugs such drugs have to be given in large oral doses or by another route of administration to bypass or overcome metabolism by the liver

26. Metabolism by the Liver or Excretion by the Kidney Age-related or disease-related changes in liver or kidney function can cause: drug accumulation toxicity Older patients are often prescribed lower doses of medication If patients are on multiple potent prescription drugs, there is a risk of a drug-drug interaction drug accumulation toxic blood levels increases

27. Toxicity Toxicology is the study of toxic effects of drugs or other substances on the body Physicians must weigh therapeutic benefit against the risk of toxicity Some drugs have a narrow therapeutic-toxic index called the “therapeutic window” very little difference exists in the therapeutic versus toxic blood level laboratory drug levels are ordered if the physician suspects toxicity Toxicity of a drug may affect route of administration

28. Oral Routes of Administration Oral refers to two methods of administration: applying topically to the mouth swallowing for absorption along the gastrointestinal (GI) tract into systemic circulation po (from the Latin per os ) is the abbreviation used to indicate oral route of medication administration

29. Oral Dose Forms   Common dose forms for oral administration tablets capsules liquids solutions suspensions syrups elixirs

30. Oral Dose Forms  Sublingual administration is where the dose form is placed under the tongue rapidly absorbed by sublingual mucosa Buccal administration is where the dose form is placed between gums and inner lining of the cheek (buccal pouch) absorbed by buccal mucosa Dose forms for sublingual and buccal administration: tablets – lozenges – gum

31. Oral Dose Forms   Capsules are preferred over tablets for patients with difficulty swallowing Water preferred over beverages to aid in swallowing Some dose forms are designed to be sprinkled on food when swallowing a solid is difficult Liquid doses are swallowed more easily and are suitable for: patients with swallowing difficulties small children

32. Oral Dose Forms The oral route is not appropriate for patients who are unable to swallow. Safety Note

33. Advantages and Disadvantages of the Oral Route Ease and safety of administration Active ingredient is generally contained in powders or granules which dissolve in GI tract Sublingual (and buccal) administration has a rapid onset (less than 5 minutes)

34. Advantages and Disadvantages of the Oral Route Delayed onset dose form must disintegrate before absorption Destruction or dilution of drug by GI fluids food or drink in stomach or intestines Not indicated in patients who have nausea or vomiting are comatose, sedated, or otherwise unable to swallow Unpleasant taste of some liquid dose forms must be masked by flavorings to promote compliance

35. Advantages and Disadvantages of the Oral Route Sublingual (and buccal) administration has a short duration of action less than 30 to 60 minutes not appropriate for routine delivery of medication Buccal route may have medicinal taste local mouth irritation

36. Topical Routes of Administration Topical administration is the application of a drug directly to the surface of the skin Includes administration of drugs to any mucous membrane eye – vagina nose – urethra ears – colon lungs

37. Topical Dose Forms Dose forms for topical administration include: Skin: creams ointments lotions gels transdermal patches disks Eye or ear: solutions suspensions ointments Nose and lungs: sprays and powders

38. Topical Dose Forms Vagina: tablets creams ointments Urethra: inserts suppositories Rectum: creams ointments solutions foams Dose forms for topical administration include:

39. Topical Dose Forms Transdermal administration: delivers drug to bloodstream via absorption through the skin via a patch or disk Skin presents a barrier to ready absorption absorption occurs slowly therapeutic effects last for 24 hours up to 1 week Chemicals in the patch or disc force drug across membranes of the skin into layer where absorption into bloodstream occurs

40. Topical Dose Forms Ocular administration is the application of a drug to the eye Conjunctival administration is the application of a drug to the conjunctival mucosa or lining of the inside of the eyelid Nasal administration is the application of a drug into the passages of the nose Otic administration is the application of a drug to the ear canal

41. Topical Dose Forms Rectal dosage forms: Suppository solid dose form formulated to melt in the rectum at body temperature and release the active drug Creams, ointments, and foams used for local effects Rectal solutions, or enemas used for cleansing the bowel laxative or cathartic action drug administration in colon disease

42. Advantages and Disadvantages of the Topical Route Local therapeutic effects Not well absorbed into the deeper layers of the skin or mucous membrane lower risk of side effects Transdermal route offers steady level of drug in the system sprays for inhalation through the nose may be for local or systemic effects

43. Advantages and Disadvantages of the Topical Route The intrarespiratory route of administration is the application of drug through inhalation into the lungs, typically through the mouth lungs are designed for exchange of gases from tissues into bloodstream usual dose form is an aerosol “environmental friendly” propellants now required to replace chlorofluorocarbons (CFCs)

44. Advantages and Disadvantages of the Topical Route A metered-dose inhaler (MDI) is a common device used to administer a drug in the form of compressed gas through inhalation into the lungs A diskus is a newer dosage form to administer drug to lungs as micronized powder

45. Advantages and Disadvantages of the Topical Route The vaginal route of administration is application of drug via cream or insertion of tablet into the vagina Common dose forms include: emulsion foams sponges inserts suppositories ointments tablets solutions

46. Advantages and Disadvantages of the Topical Route The vaginal route is preferred for: cleansing contraception treatment of infections Major disadvantages: inconvenience “messiness”

47. Advantages and Disadvantages of the Topical Route The urethral route of administration is application of drug by insertion into the urethra Common dose forms include: solutions suppositories Urethral delivery may be used to treat incontinence impotence in men Disadvantages inconvenience localized pain

48. Advantages and Disadvantages of the Topical Route Rectal administration is a preferred method when: An oral drug might be destroyed or diluted by acidic fluids in the stomach An oral drug might be too readily metabolized by the liver and eliminated from the body The patient is unconscious and needs medication Nausea and vomiting or severe acute illness in the GI tract make patient unable to take oral drugs

49. Advantages and Disadvantages of the Topical Route Rectal administration disadvantages: inconvenience erratic and irregular drug absorption

50. Parenteral Routes of Administration Parenteral administration is injection or infusion by means of a needle or catheter inserted into the body Parenteral forms deserve special attention complexity widespread use potential for therapeutic benefit and danger The term parenteral comes from Greek words para, meaning outside enteron, meaning the intestine This route of administration bypasses the alimentary canal

51. Parenteral Dose Forms Parenteral preparations must be sterile free of microorganisms To ensure sterility, parenterals are prepared using aseptic techniques special clothing (gowns, masks, hair net, gloves) laminar flow hoods placed in special rooms

52. Parenteral Dose Forms IV route directly into a vein Prepared in hospitals and home healthcare pharmacies antibiotics chemotherapy nutrition critical care medications

53. Parenteral Dose Forms Intramuscular (IM) injections into a muscle Subcutaneous injections under the skin Intradermal (ID) injections into the skin

54. Parenteral Dose Forms Disposable syringes and needles are used to administer drugs by injection Different sizes are available depending on the type of mediation and injection needed

55. Advantages and Disadvantages of the Parenteral Route The IV route is the fastest method for delivering systemic drugs preferred administration in an emergency situation It can provide fluids, electrolytes, and nutrition patients who cannot take food or have serious problems with the GI tract It provides higher concentration of drug to bloodstream or tissues advantageous in serious bacterial infection

56. Advantages and Disadvantages of the Parenteral Route IV infusion provides a continuous amount of needed medication without fluctuation in blood levels of other routes infusion rate can be adjusted to provide more or less medication as the situation dictates

57. Advantages and Disadvantages of the Parenteral Route Traumatic injury from the insertion of needle Potential for introducing: toxic agents microbes pyrogens Impossible to retrieve if adverse reaction occurs injected directly into the body

58. Advantages and Disadvantages of the Parenteral Route Intramuscular (IM) and subcutaneous routes of administration are convenient ways to deliver medications Compared with the IV route: onset of response of the medication is slower duration of action is much longer Practical for use outside the hospital Used for drugs which are not active orally

59. Advantages and Disadvantages of the Parenteral Route For intramuscular (IM) and subcutaneous routes of administration, the injection site needs to be “prepped” using alcohol wipe Correct syringe, needle, and technique must be used Rotation of injection sites with long-term use prevents scarring and other skin changes can influence drug absorption

60. Advantages and Disadvantages of the Parenteral Route The intradermal (ID) route of administration is used for diagnostic and allergy skin testing patient may experience a severe local reaction if allergic or has prior exposure to a testing antigen

61. Administering Parenteral Medications IV injections and infusions are introduced directly into the bloodstream must be free of air bubbles and particulate matter introduction of air or particles might cause embolism, blockage in a vessel, or severe painful reaction at the injection site

62. Intravenous Injections or Infusions Fast-acting route because the drug goes directly into the bloodstream often used in the emergency department and in critical care areas Commonly used for fluid and electrolyte replacement to provide necessary nutrition to the patient who is critically ill

63. Intravenous Injections or Infusions Intravenous (IV) injections are administered at a 15- to 20-degree angle

64. Intramuscular Injections Care must be taken with deep IM injections to avoid hitting a vein, artery, or nerve In adults, IM injections are given into upper, outer portion of the gluteus maximus large muscle on either side of the buttocks For children and some adults, IM injections are given into the deltoid muscles of the shoulders

65. Intramuscular Injections Typical needle is 22- to 25-gauge ½- to 1-inch needle Intramuscular (IM) injections are administered at a 90-degree angle volume limited to less than 3 mL

66. Intramuscular Injections Used to administer antibiotics vitamins iron vaccines Absorption of drug by IM route is unpredictable not recommended for patients who are unconscious or in a shocklike state

67. Intradermal Injections Given into capillary-rich layer just below epidermis for local anesthesia diagnostic tests immunizations

68. Intradermal Injections Examples of ID injections include skin test for tuberculosis (TB) or fungal infections typical site is the upper forearm, below the area where IV injections are given allergy skin testing small amounts of various allergens are administered to detect allergies usually on the back

69. Subcutaneous Injections Administer medications below the skin into the subcutaneous fat outside of the upper arm top of the thigh lower portion of each side of the abdomen not into grossly adipose, hardened, inflamed, or swollen tissue Often have a longer onset of action and a longer duration of action compared with IM or IV injection

70. Subcutaneous Injections Insulin is given using 28- to 30-gauge short needles in special syringe that measures in units Insulin is administered following a plan for site rotation to avoid or minimize local skin reactions Absorption may vary depending on site of administration activity level of the patient

71. Subcutaneous Injections Medications administered by this route include: epinephrine (or adrenaline) for emergency asthmatic attacks or allergic reactions heparin or low molecular–weight heparins to prevent blood clots sumatriptan or Imitrex for migraines many vaccines

72. Subcutaneous Injections Normally given with the syringe held at a 45-degree angle in lean older patients with less tissue and obese patients with more tissue, the syringe should be held at more of a 90-degree angle Correct length of needle is determined by a skin pinch in the injection area proper length is one half the thickness of the pinch

73. Subcutaneous Injections Given at a 45-degree angle 25- or 26-gauge needle, 3/8 to 5/8 inch length No more then 1.5 mL should be injected into the site to avoid pressure on sensory nerves causing pain and discomfort

74. SUCCESS DOES NOT COME BECAUSE WE WANT IT OR LOVE IT BUT BECAUSE WE MUST WORK AND SACRIFICE FOR IT THANKS FOR LISTENING