PHARMACOLOGY

1. PHARMACOLOGY .

2. Introduction Def1: Pharmacology is the study of pharmacokinetic and pharmacodynamic studies of drugs. Def2: Pharmacology is the study of drugs. Def3: Pharmacology is a scientific discipline that studies about chemical, therapeutic and the side effects of drugs.

3. What is a Drug? • In WHO drug is defined, any substance or product that is used to explore a physiological systems or pathological states for the benefit of the recipient. • Word of drug derived from French word, drogue meaning dry herb which is used for diagnosis, prevention and cure of a disease. • Dose, it is the quantity of the drug. • Dosage, it is the schedule of the dose, frequency and duration of administration of drugs.

4. Drug dosage • Dose is the appropriate amount of a drug needed to produce a certain degree of response in a patient. • Dose can be classified into: • Standard dose e.g contraceptives , chloroquine • Regulated dose e.g anticoagulants, diuretics • Target level dose e.gdigoxin, lithium • Titrated dose e.g anticancer drugs & levodopa

5. Rights of Pharmacology • Right drug • Right dose • Right time • Right route • Right patient

6. Pharmacokinetics • Pharmacokinetic is the study of what actually happens to a drug from the time it is put into the body until the time all of it and it is metabolites have left the body. • Pharmacokinetic is what body do to the drug. • Pharmacokinetic is the study of absorption, distribution, metabolism and excretion (ADME).

7. Absorption • Drug absorption is the processes of incorporating a drug into the body and its various tissues, organs and other biological sites. • If two medications have the same bioavailability, they are said to be bio-equivalent. • Bioavailability is the amount of a drug in a particular dosage form that is absorbed into the circulation. • There are various factors that affecting the rate of drug absorption, these include administration route of a drug, food, and fluids, administered with a drug, the dosage formulation, the status of the absorptive surface, and the acidity of the stomach.

8. Distribution • Once a drug enters the blood stream (circulation), it is distributed throughout the body. • A drug can be freely distributed to extravascular tissue only if it is not bound to a protein. If a drug is bound in to a protein, it is generally too large to pass into tissues. • The transport of a drug that in the body by the blood stream to its site of action is referred to us distribution.

9. Continue • There are three primary proteins that carry that bind to and carry drugs throughout the body and they are: • Albumin (most important) • Alpha 1 acid glycoprotein • Corticosteroid binding globulin • Distribution can be classified into two compartments: • Rapid distribution like heart, liver, kidney and brain. • Slow distribution like muscle, skin and fat

10. continue • A theoretical volume, called volume of distribution, is sometimes used to describe the various areas where drugs may be distributed. • Typically a drug that is highly water soluble will have a small volume of distribution and high blood concentrations. • Fat soluble drugs have a large volume of distribution and low blood concentrations.

11. Metabolism • Metabolism is also referred to as biotransformation because it involves the biologic transformation of a drug into an inactive metabolite, a more soluble compound or a more potent metabolite. • Biotransformation is the next step after absorption and distribution. • The organ most responsible for the biotransformation or metabolism of drugs is the liver. Other tissues and organs that aid in the metabolism of drugs are the kidney, lungs, plasma, and intestinal mucosa.

12. Continue • Biotransformation means chemical alteration of the drug in the body. • The biotransformation capabilities of the liver can vary considerably from patient to patient. • Hepatic biotransformation involves the use of an enormous variety of microsomal enzymes.

13. Assignment • Biotransformation reactions can be classified into: • non-synthetic or phase I reactions: like oxidation, reduction, hydrolysis, cyclization, and decyclization. • Synthetic reactions: like glucuronide conjugation, acetylation, methylation, sulfate conjugation, Glycine conjugation, glutathione conjugation.

14. Excretion • The elimination of drugs from the body is referred to as excretion. • The primary organ that is responsible for excretion is kidney. • Two other organs that also play an important role in the excretion of drugs are the liver and the bowel. • The actual act of excretion is accomplished through glomerular filtration, resorption, and tubular

15. Continue • Excretion is the passage out of systemically absorbed drug. • The excretion of drugs by the intestines is another common route of elimination. This is also referred to as biliary excretion. Drugs that are eliminated by this route are taken up by the liver, released into the bile, and eliminated in the feces.

16. Half life • It is the time it takes for one half of the original amount of a drug in the body to be removed and is a measure of the rate at which drugs are removed from the body. • E.g tetracycline 500mg, it is first half life is 250mg.

17. Half life of some representative drugs • Aspirin 4 hours • Penicillin G 30 minutes • Doxycycline 20 hours • Digoxin 40 hours • Digitoxin 7 days • Phenobarbitone 90 hours

18. Onset, Peak, Duration • The terms onset, peak, and duration are used to describe drug effects. • A drug onset of action is the time it takes for the drug to elicit a therapeutic response. • The time it takes for a drug to reach it is maximum therapeutic response is its peak effect. • The duration of action of a drug is the time that drug concentration is sufficient to elicit a therapeutic response.

19. Pharmacodynamics • The study of the mechanism of drug actions in living tissues is called pharmacodynamics. • Pharmacodynamics is what drug does to the body. • Pharmacodynamics can be classified into: • Therapeutic utility • Mechanism of action • Receptor interactions

20. Principles of drug action • The principles of drug actions are as the following: • Stimulation • Depression • Irritation • Replacement • Cytotoxic actions

21. Stimulation • It refers to selective enhancement of the level of activity of speacilized cells. e.g adrenaline stimulates heart, pilocarpine stimulates salivary glands. However excessive stimulation is often followed by depression of that function, e.g picrotoxin a central nervous system stimulant produces convulsions followed by coma and respiratory depression.

22. Depression • It means selective diminution of activity of specialized cells. E.g barbitutares depress CNS, quinidine depresses heart. Certain drugs stimulate one type of cells but depress the other. E,g acetylcholine stimulates intestinal smooth muscle but depress sinoatrial node in heart, thus most drugs cannot be simply classed as stimulants or depressants.

23. Irritation • This connotes a nonselective often noxious effect and is particularly applied to less speacilized cells. Mild irritation may stimulate associated function. E.g bitters increase salivary and gastric secretion, counterirritants increase blood flow to the site, but strong irritation results in inflammation, necrosis, and morphological damage.

24. Replacement • This refers to the use of natural metabolites, hormones or their congeners in deficiency states. E.g levodopa in parkinsonian, iron in anemia, insulin in diabettes.

25. Cytotoxic action • Selective Cytotoxic action for invading parasites or cancer cells, attenuating them with out significantly affecting the host cells is utilized for cure of infections and neoplasm's. E.g. zidovudine, chloroquine, penicillin.

26. Assignment • Describe the therapeutic index concept including formula and ways of calculation.

27. Combined effects of drugs • When two or more drugs are given simultaneously or in quick succession, they may be either indifferent to each other or exhibit synergism or antagonism. • The interaction may take place at pharmacokinetic level or at pharmacodynamic level.

28. Synergism • When the action of one drug is facilitated or increased by other, they are said to be synergistic. In synergistic pair both the drugs can have action in the same direction or given alone one may be inactive but still enhance the action of the other when given together. • Synergism can be: • Additive • Supraadditive

29. additive • The effect of the two drugs is in the same direction and simply adds up. E.g effect of drugs A+B= effect of drug A + effect of drug B. • Examples are the following: • Aspirin + paracetamol = analgesic/antipyretic • Nitrous oxide + halothane = general anesthesia • Amlodipine + atenalol = antihypertensive • Glibenclamide + Metformin = hypoglycemic • Ephedrine + Theophylline = bronchodilator

30. Supraadditive • The effect of combination is greater than the individual effects of the components. • Effect of drug A + B is greater than effect of drug A + effect of drug B. • Examples are the following: • Acetylcholine plus physostigmine • Levodopa plus carbidopa plus benserazide • Adrenaline plus cocaine plus desipramine • Sulfamethaxazole plus trimethoprim • Enalapril plus hydrochlorothiazide

31. Antagonism • When one drug decreases or abolishes the action of another, they are said to be antagonistic. • Effect of drug A + B is less than effect of drug A + effect of drug B. • Antagonism can be classified into: • Physical antagonism e.g charcoal adsorbs alkaloids • Chemical antagonism e.g heparin intercts penicillin • Physiological antagonism e.g glucagon & insulin • Receptor antagonism e.g agonist & antagonist drugs

32. Pharmacotherapeutics • Pharmacotherapy is a dynamic process that should be occurring continuously throughout a patient’s therapy. • The use of a medication to treat a pathologic condition is called Pharmacotherapeutics.

33. Acute Therapy • Acute therapy involves intensive drug therapy and is typically implemented in the critically ill patient. It is generally needed to sustain life. Examples are the administration of vasopressors to maintain blood pressure and cardiac output after open heart surgery or the use of volume expanders in a patient who is in shock.

34. Maintenance Therapy • Maintenance therapy typically does not eradicate the problems the patient may have but doesn’t prevent progression of the disease. It is used for the treatment of chronic illnesses such as hypertension. • The drug therapy maintains the patient’s blood pressure within certain limits, which prevents certain end organ damage.

35. Supplemental Therapy • Supplemental or replacement therapy supplies the body with a substance needed to maintain normal function. • This substance may be needed either because it cannot be made or because it is deficient in quantity. • Examples are the administration of insulin to diabetic patients or iron to patients with iron deficiency anemia.

36. Palliative Therapy • The goal of palliative therapy is to make the patient as comfortable as possible. It is typically used in the end stages of an illness when all possible therapy has failed. • The use of high dose narcotic analgesics to relieve pain in the final stages of cancer is an example; the use of oxygen in end stage of pulmonary disease is another.

37. Supportive Therapy • Supportive therapy maintains the integrity of the body functions while the patient is recovering. Providing fluids and electrolytes to prevent dehydration in a patient with the flu who is vomiting and has a diarrhea is an example. • Giving fluids, volume expanders or blood products to a patient who has lost blood during surgery is an example.

38. Prophylactic Therapy • Prophylactic therapy is drug therapy provided on the basis of prior practical experience. It is based on scientific knowledge often acquired during years of observation of a disease and it is causes.

39. Pharmacology Terminology • Tolerance • Dependance • Onset • Peak • Duration of action • First pass effect • Efficacy • Agonist and antagonist

40. Continue • Idiosyncrasy • Summation • Synergism • Potentiation

41. Pregnancy categories • Pregnancy categories can be divided into: • A • B • C • D • X

42. Drug Classification • Drugs are classified by: • Chemistry, e.g electrolytes • Mechanism, e.g beta-blockers and benzodiazepines. • Disease, e.g anti-hypertensive and anti-emetics

43. Classification of drugs by legal purposes • Drugs are grouped for legal purposes as follows: • Official drugs: drugs which are included in the pharmacopeias of that particular country are termed official drugs. • Dangerous drugs: this include drugs of addiction. E.g opium and cannabis. • Prescription drugs (POM): drugs which are given only by the prescription of the doctor. • Over the counter (OTC): drugs which are available by public with out prescription.

44. Drug Nomenclature • A drug generally has three categories of names: • Chemical name • Non-proprietary name • Proprietary name

45. Chemical name • It describes the substance chemically,. E.g 1-isopropylamino-3-1-naphthyloxy propan 2-ol. • This is cumbersome and not suitable for use in prescribing.

46. Non-proprietary name • It is the name accepted by a competent scientific body/authority, e.g united states adopted name (USAN) by the council of USAN council. • Similarly, there is the British approved name (BAN) of a drug. The non proprietary names of newer drugs are kept uniform by an agreement to use the recommended international non proprietary name (rINN) in all member countries of W.H.O.

47. Proprietary (Brand) name • It is the name assigned by the manufacturers and is his property or trade mark. • One drug may have multiple proprietary names. • Example: altol, atcardil, atecor, aten, betacard, lonol, tenormin, tenalol for atenalol from different manufactures. • Brand names are designed to be catchy, short, easy, to remember.

48. Adverse Drug Reactions • Side-effects. e.g Atropine: dry mouth • Toxic effects: mostly seen with higher doses. E.g Morphine, respiratory depression. • Drug tolerance: single dose of streptomycin producing vestibular dysfunction. • Idiosyncratic reactions: e.g barbiturates produce CNS stimulation. • Allergic reactions: immunologically based adverse reactions to drugs are called allergic reactions which are not related to pharmacological actions of drugs.

49. Factors modifying the action of drugs • Body weight, Clarks rule: dose: body weight in kg times average adult dose divide by 70. Example A patient whose body weight is 65kg has been taken paracetamol. If the average adult dose of paractemol is 500mg. Calculate the dose of this patient. Result: 464.3 mg

50. Continued • Body surface area (BSA): The individual dose = BSA (m2) / 1.7 times average adult dose. • The BSA (m2)= BW(kg) 0.425 times Height (cm) 0.725 times 0.007184 Result: 677.1 mg