LECTURE 3 -BASIC PHARMACODYNAMIC CONCEPT.pptx

Microbiology Roles in Food Industry and Pharmaceutical

1. PHARMACODYNAMICS )

2. OBJECTIVES To define pharmacodynamics To study basic pharmacodynamics concepts Getting to know several important terms in pharmacodynamics DIPLOMA IN PHARMACY PICOMS

3. PHARMACODYNAMICS Definition : THE MECHANISM OF DRUG ACTIONS & EFFECTS. Drugs after being introduced in the body cause various physiological & biochemical changes inside the body & produce its desired EFFECTS Various mechanism responsible for the action of drugs. Action of drug means the interaction between drug & blood or drug & tissue cells, resulting the modification of existing function It is what the drugs do to the body which includes inter alia their indications, contraindications, side effects and adverse effects DIPLOMA IN PHARMACY PICOMS

4. Various types of Drug Action Stimulation- an increase in activity of special cells. ( Caffeine stimulates cerebral cortex, Strychnine stimulates spinal cord) Depression -A decrease in the normal activity of specialised cells ( Barbiturates depress CNS) Irritation- The injurious effects of drugs on growth, nutrition & morphology of non specialised cells capable of producing inflammation ( Irritant purgative of senna) DIPLOMA IN PHARMACY PICOMS

5. Various types of Drug Action Replacement -The use of glandular secretions, namely hormones obtained from animals in the treatment of deficiency diseases in Human ( Insulin in the treatment of Diabetics and Heparin as anti-coagulant) Physical Action- some drugs function because of physical properties ( kaolin and activated charcoal in Dysentery for its absorption properties, Saline purgatives for their osmotic pressure) Chemical Reactions -Drugs act because of their chemical properties, or by chemical combination with substance present in body( Antacids neutralized gastric acidity) DIPLOMA IN PHARMACY PICOMS

6. PHARMACODYNAMIC PHASE Study of drug concentration and its effects on the body. Drug response can cause a primary or secondary physiological effect or both . The primary effect is desirable and the secondary effect may be desirable or undesirable . diphenhydramine / benadryl ( antihistamine ) 1st effect : treat the symptoms of allergy 2 nd effect : drowsy (CNS deppress ) 2 nd effect – drowsiness when driving ( undesirable ). - mild sedation ( desirable ) DIPLOMA IN PHARMACY PICOMS

7. Mechanism of Action Most of drugs produce their effects by combining with enzymes, cell membranes or specialized functional cells. Drug-Cell interaction alter the function of cell component initiating biochemical & physiological changes in the body. The initial consequence of Drug-Cell Interaction combination with Enzymes, cell membranes or other functional components is called Drug Action. The Biochemical & Physiological changes cause by the Drug are called Drug Effects DIPLOMA IN PHARMACY PICOMS

8. DOSE RESPONSE AND MAXIMAL EFFICACY Dose response is relationship between the minimal vs maximal amount of dose needed to produce desired response . Increase in dose may: Increase therapeutic response Increase risk of toxicity Morphine & propoxyphene hydrochloride ( Darvon ) are prescribed to relieve pain. Maximun efficacy of morphine is greater than darvon , regardless of how much darvon is given . DIPLOMA IN PHARMACY PICOMS

9. Definitions Efficacy Degree to which a drug is able to produce the desired response Potency Amount of drug required to produce 50% of the maximal response Used to compare compounds within classes of drugs DIPLOMA IN PHARMACY PICOMS

10. ONSET, PEAK AND DURATION OF ACTION Onset of action is time it takes to reach the minimum effective concentration (MEC) after drug is administered . Peak action occurs when the drug reaches its highest blood or plasma concentration. Duration of action is the length of time the drug has a pharmacologic effect . Some drugs produce effects in minutes, but others may take hours or days . DIPLOMA IN PHARMACY PICOMS

11. ONSET, PEAK AND DURATION OF ACTION DIPLOMA IN PHARMACY PICOMS

12. Definitions Effective Concentration 50% (ED 50 ) Concentration of the drug which induces a specified clinical effect in 50% of subjects Lethal Dose 50% (LD 50 ) Concentration of the drug which induces death in 50% of subjects DIPLOMA IN PHARMACY PICOMS

13. Definitions Therapeutic Index ( TI ) Measure of the safety of a drug Calculation: LD 50 /ED 50 Margin of Safety Margin between the therapeutic and lethal doses of a drug DIPLOMA IN PHARMACY PICOMS

14. DIPLOMA IN PHARMACY PICOMS LD 50

15. PEAK LEVELS Peak drug level - highest plasma concentration of drug at a specific time. If given orally , the peak time might be 1 to 3 hours after drug administration. If given IV, the peak time might occur in 10 minutes. DIPLOMA IN PHARMACY PICOMS

16. SIDE EFFECTS, ADVERSE REACTIONS, AND TOXIC EFFECTS Side effects are physiologic effects not related to desired drugs effects . Steroids : increased appetite , acne , bruising , muscle weakness delayed wound healing , moon face , blood dyscrasia Adverse reactions are more severe than side effects . It includes anaphylaxis which is a life threatening allergic reaction that happens spontaneously from bee stings or peanuts. Many types of drugs can also cause anaphylaxis or anaphylactic shock . Such drugs include antibiotics , Proton Pump Inhibitors The blood pressure drops suddenly and the trachea constricts , rapid weak pulse, nausea and vomiting . Death follows if left untreated . ( Treated with adrenaline , oxygen , IV antihistamine and corticosone , salbutamol ) Toxic effects , or toxicity of a drug can be identified by monitoring the plasma therapeutic range of the drug . The toxic effects of panadol include liver failure , metabolic acidocis and coma DIPLOMA IN PHARMACY PICOMS

17. PLACEBO EFFECT Is a psychologic benefit from compound that may not have the chemical structure of a drug effect . A treatment that appears real but is designed to have no therapeutic benefits . Sometimes employed in clinical studies of drugs . Placebo tablets are sometimes called sugar pills It is effective in approximately one third of subjects who take a placebo compound !!! The mind playing tricks on you ?? DIPLOMA IN PHARMACY PICOMS

18. Receptor: Definition Receptors : macromolecules with which the drugs interact to produce biological effects. They are binding sites where drug molecules attach themselves i. A specific, functionally important tissue components ( Proteins nucleic acids , enzymes ). ii. Complementary ( Lock & key analogy) in chemical & physical structure to the drug interact with them. It is a binding site of high affinity & high specificity . Affinity of Drug : The ability of Drug to get bound to a Receptor. Efficacy of Drug or Intrinsic Activity : The capacity of a drug( Agonist ) to produce Pharmacological Action after interaction with Receptor A Drug may act on One or More Receptor system. DIPLOMA IN PHARMACY PICOMS

19. RECEPTOR THEORY Most receptors , protein in structure, are found on cell membranes. Drug-binding sites are primarily proteins , glycoproteins , proteolipids and enzymes. Silent Receptor : A drug cell interaction in which a drug binds itself to protein or enzymes without initiating any Drug Action Agonists are drugs that produce a response . Antagonists drugs that block a response . B ound to receptors but not producing pharmacological action. It leads only to receptor blockage Isoproterenol ( Isuprel ) – stimulates beta 1 receptors in the heart ( agonist for the treatment of bradycardia and heart blockage Cimetidine ( Tagamet ) – blocks histamine (H2) receptors on the gastric parietal cells ( antagonist for the treatment of peptic ulcers ). Partial Agonist : The Drugs have affinity equal to or less than that of agonist but with less intrinsic activity DIPLOMA IN PHARMACY PICOMS

20. Drug Actions DIPLOMA IN PHARMACY PICOMS

21. Factors Modifying drug Action FACTORS Modifying Drug Action General mechanism of drug action is not clearly explained or understood Deep study of various factors are yet to be made to decide the proper desired drug effects with the optimum dosage of drugs. DIPLOMA IN PHARMACY PICOMS

22. Factors Modifying drug Action Body Weight Age – babies, children, adults and geriatrics Sex / gender Routes of Administration – oral, injection, IV Time of Administration – morning, nighttime, with food Climate and seasons of the year Genetic Factor or genetic predisposition including race Emotional Factor – happy or sad Presence of other diseases or comorbidities DIPLOMA IN PHARMACY PICOMS

23. FacTors modifying drug action 10. Metabolic disturbances 11. accumulation of drugs or cumulation phenomenon 12. Drug interaction such as with herbal products 13. Additive Effects 14. Synergistic Effects 15. Antagonistic effects of other drugs, foods 16. Drug Tolerance 17. Drug dependence DIPLOMA IN PHARMACY PICOMS

24. 1.Body Weight Average Dose: Total single dose for adult weighing 50kg – 100 kg. May not be effective in excessively obese persons. In malnourished patients, the nutritional factor also affects drug action & metabolisms. DIPLOMA IN PHARMACY PICOMS

25. 2.Age Children are more sensitive to CNS Depressant Drugs but at the same time can tolerate large doses of digitalis, ethanol & belladonna on basis of body weight compared to adults. Dosage for children is calculated based on body weight and age. Infant below 1 year are devoid of enzymes that metabolised drugs.This fact must be considered while calculating the optimum dosage for Infants. In Geriatrics, normal dosage may be excessive due to their inability to metabolize drugs . Their livers are no more young. DIPLOMA IN PHARMACY PICOMS

26. 3.Sex Drugs producing pelvic congestion suc as Strong Purgatives & Drugs having stimulant effects on uterus or fetus should not be given to menstrual or pregnant ladies. Morphine crosses the placental barrier & depresses fetal respiration. Not advisable to give drugs during pregnancy except those which are essential to maintain the pregnancy. Pregnant mothers must take extra precaution Certain Drugs effect differ in the two sexes . Women are more likely to experience adverse drug reaction . Men are more robust , is it true ? DIPLOMA IN PHARMACY PICOMS

27. 4.Routes of Administration The rate & extent of absorption differs with different routes of administration. Dosage of drug should be considered & calculated cautiously. IV Injection dose of drug is smaller that SC Injection & which is smaller than oral dose. Injection is administered if a quick onset of action is required such as in an emergency situation following an accident. DIPLOMA IN PHARMACY PICOMS

28. 5.Time of Administration Medicines usually taken after meals to reduce gastric irritation, but delays drug action as the drug better absorbed on empty stomach. For a desired action, certain drugs are given on empty stomach . They are given before meals. Some examples include sildenafil, ampicillin and catopril Metformin should be taken before bed for maximum result. Metformin prevents gluconeogenesis in the liver by preventing the hormone glucagon from converting stored glycogen in the liver to glucose. Alendronate / Fosamax is a drug for osteoporosis. Must swallow the tablet whole with a full glass of water. Do not chew. Take immediately after getting out of bed before you drink or eat anything. Never take the drug at bedtime DIPLOMA IN PHARMACY PICOMS

29. 6.Climate Alcohol is well tolerated in winter than in summer season. Drinking alcohol gives you a false sensation of warmth. The alcohol makes the blood vessels dilate sending more blood to the skin. Then you are actually losing more heat and eventually you end up with hypothermia which can be fatal. DIPLOMA IN PHARMACY PICOMS

30. 7.Genetic Factor Some people cannot metabolize certain drugs because of the absence of metabolizing enzymes. Thus the drugs produce toxic effect. Absence of enzymes is a hereditary character(genetic factor). Example:. Deficiency of enzyme Glucose-6-phosphate dehydrogenase(G6PD) in some patients-Primaquine will cause hemolysis in such patients. Primaquine is an anti-malarial drug and also to prevent relapse of the disease . People with G6PD deficiency cannot eat several types of foods especially fava beans , beans, legumes. Drugs to be avoided are aspirin, sulfa antibiotic drugs. NSAIDs and antibiotics such as quinolones which include levofloxacin, ciprofloxacin DIPLOMA IN PHARMACY PICOMS

31. 8.Emotional Factor The p ersonality of the Physician produces psychological relief. Hence even inert medication(placebo) have beneficial effects. Placebos are generally prescribed to seemingly psychologically disturbed patients who are not suffering any physiological disorders . Some patients always think that they are always in the state of illness. They are called hypochondriacs . DIPLOMA IN PHARMACY PICOMS

32. 9.Presence of Disease Streptomycin & Kanamycin are mainly excreted by the kidneys . They are toxic on parenteral administration in patients with impaired kidneys. We have to exercise caution with all medications with patients who are having kidney problems . Other antibiotics such as gentamycin is also used with caution in patients with kidney failures Some safe antibiotics for kidney patients are azithromycin, doxycycline clindamycin. Barbiturates & Chlorpromazine produce unusual prolonged effects in cirrhotic patients. Liver cirrhosis is the fibrosis of the liver tissues caused by long term alcohol abuse, drug abuse, hepatitis and fatty liver syndrome. The fibrosis prevents the liver from working properly . A diseased liver will have less ability to metabolise drugs due to its decreased production of liver enzymes such as cytochrome P450 DIPLOMA IN PHARMACY PICOMS

33. 10.Metabolic Disturbances Changes in physiological factor such Electrolyte Balance, Water Balance & Body Temperature modify drug effect. Example: Vasoconstrictor action of Noradrenalin is reduced in presence of metabolic acidosis due to the buildup of acid in the body due to kidney disease or kidney failure. It is a serious condition whereby one may suffer from confusion, vomiting, loss of appetite, headache, fast heartbeat and fatigue. Absorption of iron from GIT is enhanced in cases of iron deficiency anemia. You can further increase your iron absorption by taking iron tablets with vitaminc . DIPLOMA IN PHARMACY PICOMS

34. 11.Cumulation Drug accumulation in the body happens following repeated administrations & the drug is excreted slowly. The build-up can give rise to an increase in the therapeutic and toxic effects. If the drug exceeds its elimination rate it will cumulate in the body. Dosage schedule of the drug must cautiously determined and then adhered to to prevent cumulative effects or side effects. Example: Digitalis, emetine ( Emetine is used as anti- protozoal and to induce vomiting in poisoning incidents) Digitalis is used to treat cardiac arrhythmmia . Cumulation increases blood concentration of the drug & increases its toxicity as a result Sometimes cumulative effect is desired such as in the case of Phenobarbitone in the treatment of Epilepsy. It is taken only once a day, promoting compliance. DIPLOMA IN PHARMACY PICOMS

35. 12.Other Drug(S) Therapy Effect of one Drug modified by the presence of another drug, Example: Acetylcholine inhibits the action of Atropine. Alcohol inhibits the stimulating effect of amphetamine on CNS Nasal decongestants such as oxymetazoline and pseudoephedrine are contraindicated in people with HTN DIPLOMA IN PHARMACY PICOMS

36. 13.Additive Effect It is the total pharmacological of 2 or more drugs administered together is equal the sum of their individual effects Example: Ephedrine & Aminophylline show additive effect in the treatment of bronchial asthma. Thus reduces the development of tolerance. Ephedrine 15 mg tablets can be given concurrently with aminophylline 100mg tablets for the treatment of bronchospasm in asthma, it should be given 1 tds PC Ephedrine is a nasal decongestant and bronchodilator Aminiphylline relaxes and opens air passages in the lungs Both drugs are useful for asthma, wheezing, bronchospasm and enphysema . DIPLOMA IN PHARMACY PICOMS

37. 14.Synergism The phenomenon of facilitation of pharmacological response by use of 2 drugs at the same time. It is a pharmacological co-operation resulting in the total effect greater than the sum of their individual effects. Examples : Mersalyl & Aminophylline therapy as diuretics. Mersalyl is an organo -mercury compound diuretic. It is no more in use Codeine & Aspirin as Analgesics, Reserpine & Hydrochlorothiazide as antihypertensive drugs Some drugs act sequentially & the combination of the drugs have higher therapeutic efficacy than used alone ( Sulphamethoxazol + Trimethoprim, Bactrim is the trade name . It is the well known sulphur drug If synergism results in prolongation of action of one of the drug , it is termed “Time Synergism” ( Procaine & Adrenalin combination increases duration of action on Procaine, a local anesthetic drug. DIPLOMA IN PHARMACY PICOMS

38. 15.Antagonism 4 types of Antagonism: i. Chemical Antagonism: Biological Activity of the drug is abolished or reduced by chemical reaction between 2 drugs such as Acid & Alkali neutralise each other. Another one is a chelating agent known as BAL which is British Anti-Lewisite , it is used as antidote in arsenic, mercuric, and lead poisoning. BAL is Dimercarpol . It is given by subcutaneous injection It is sometimes used to address Wilson Disease where copper accumulate in the brain, liver and other organs . Symptoms include fatigue, lack of appetite, problem with speech, jaundice   ii. Competitive or Reversal Antagonism Agonist & Antagonist compete on the same receptors. To oppose the effect of pharmacological action of agonist. The effect can be overcome by increasing the concentration of agonist at receptor.   DIPLOMA IN PHARMACY PICOMS

39. 15.Antagonism iii. Non Competitive (Irreversible) Antagonism The antagonist inactivates the receptor by some mechanism in such a way that effective complex with agonist is not possible. Even increasing conc. of agonist at receptor site, the receptor is inactive to combine with the agonist. Any type of pharmacological action with agonist not produced. Example : Blockage produced by Alpha Adrenergic Blocker, Phenoxybenzamine can’t be overcome by Alpha Agonist, Noradrenaline. iv. Physiological Antagonism 2 Drugs produced opposite effects by acting through different receptors. Example : Broncho-constriction produced by Histamine released in analphylactic shock can be antagonised by Adrenaline which will reduce the body’s allergic response. Oxygen should be administered plus antihistamine and cortisone by IV . A beta agonist may be added to improve breathing difficulties. DIPLOMA IN PHARMACY PICOMS

40. 16.Drug Tolerance Repeated administration of some drugs, can become ineffective at the usual therapeutic dose after a prolonged use. Most Drugs of abuse fall into this category, you keep wanting more, higher dosage and more frequently Progressive increase in the dose is necessary to get desired effect . You keep wanting for more DIPLOMA IN PHARMACY PICOMS

41. 16.Drug Tolerance 2 Types of Drug Tolerance: True and Pseudo 1. True Tolerance It happens in Oral & Parenteral Administration. Can be Natural or Acquired Tolerance . a) Natural Tolerance: Exists from birth & results in differences between species and races . Species Tolerance -Certain animal species tolerate large amount of particular drugs which is lethal to man. ( Rabbit tolerates large amount of atropine but lethal to human.) Racial Tolerance- Ephedrine when instilled in conjunctival sacs of Caucasians, produce prompt dilation of pupil, but Black Africans show no effect.   DIPLOMA IN PHARMACY PICOMS

42. 16.Drug Tolerance b) Acquired Tolerance Repeated administration of certain drugs produce tendency to tolerate that particular drug. Commonly seen in Barbiturates, opiates & xanthine therapies. 2 Types Tolerance in Acquired Tolerance i. Tissue tolerance Tolerance develops to certain effect of Drug ( Morphine is able to produce tolerance to its euphoriant effect but the pupil of the eyes and GIT do not show signs of tolerance). ii. Cross Tolerance Individual develops tolerance to drug belonging to a particular class, also shows tolerance to other drugs belonging to the same group. Example : Tolerance to vasodilation effect of GTN in an individual shows tolerance to Pentaerythritol trinitrate from the same group. DIPLOMA IN PHARMACY PICOMS

43. 16.Drug Tolerance 2. Pseudo Tolerance Observed only with oral route administration. A small dose of drug repeatedly taken orally , tolerance develops. Due to poor absorption of drug in GIT. The individual becomes highly tolerant to such drug. The drug is losing its effect on him/her Example: Chronic alcoholics, the intestine mucosa thickening affecting absorption of alcohol DIPLOMA IN PHARMACY PICOMS

44. 16.Drug Tolerance  TACHYPHYLAXIS Also known as Acute Tolerance Drugs administered repeatedly at very short intervals of time, pharmacological response decreases. Ephedrine in the treatment of Asthma may produce diminishing response . Tacyhphylaxis also occurs if a drug disappears very slowly from its receptor site combination, resulting continuous receptor blockage. Next dose of drug does not have receptors to react resulting reduce effect of drug. Drug tolerance to narcotics can result in decreased pain relief for the patient DIPLOMA IN PHARMACY PICOMS

45. SUMMARY Definition of Pharmacodynamics Types of Drug Action Pharmacodynamic Phase Dose response and maximal efficacy Onset, peak and duration of action Lethal dose and effective concentration Side effects, adverse effects and toxic effects Receptor definition and receptor theory Factors modifying drug action DIPLOMA IN PHARMACY PICOMS

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