Basic Principles of Pharmacology 1.pptx

Principles of pharmacology 2

1. Basic Principles of Pharmacology Dr. Kabiru Abubakar (B. Pharm, M Sc. PhD)

2. Definitions Pharmacology: the study of the interaction of drugs with living organisms. It also includes history, source, physicochemical properties, dosage forms, methods of administration, absorption, distribution mechanism of action, biotransformation, excretion, clinical uses and adverse effects of drugs. Drugs: chemicals that alter the function of living organisms. Drugs are generally given for the diagnosis, prevention, control or cure of disease.

3. Definitions Pharmacodynamics: the study of the biological and therapeutic effects of drugs ( i.e , “what the drug does to the body”) Pharmacokinetics: study of the absorption, distribution metabolism and excretion (ADME) of drugs (“ i.e what the body does to the drug”) Toxicology: the science of poisons. Many drugs in larger doses may act as poisons. Poisons are substances that cause harmful, dangerous or fatal symptoms in living substances

4. Pharmacodynamics Involves how the drugs act on target cells to alter cellular function

5. Receptor and non-receptor mechanisms Receptors are protein molecules present either on the cell surface or within the cell, e.g. adrenergic receptors, cholinoceptors, insulin receptors, etc. Most drugs act by interacting with a cellular component called a receptor . Some drugs act through simple physical or chemical reactions without interacting with any receptor.

6. Receptor and non-receptor mechanisms Endogenous neurotransmitters, hormones, autacoids and most drugs produce their effects by binding with their specific receptors Aluminum hydroxide and magnesium trisilicate, which are used in the treatment of peptic ulcer disease, act via non-receptor mechanisms by neutralizing the gastric acid (chemical reaction)

7. Receptor and non-receptor mechanisms Many drugs are similar to or have similar chemical groups to the naturally occurring chemical and have the ability to bind onto a receptor where one of two things can happen - either the receptor will respond or it will be blocked. A drug, which is able to fit onto a receptor, is said to have affinity for that receptor. Efficacy is the ability of a drug to produce an effect at a receptor. An agonist has both an affinity and efficacy whereas antagonist has affinity but not efficacy or intrinsic activity.

8. Agonist vs. Antagonist When a drug is able to stimulate a receptor and produce an effect, it is known as an agonist and therefore mimics the endogenous transmitter. When the drug blocks a receptor, it is known as an antagonist and therefore blocks the action of the endogenous transmitter (i.e. it will prevent the natural chemical from acting on the receptor). However, as most drug binding is reversible , there will be competition between the drug and the natural chemical to the receptor.

9. Chemical Bonding The forces that attract the drug to its receptor are termed chemical bonds and they are: Hydrogen Ionic (between charged ions) Covalent Vander Waals Force (weakest) Covalent bond is the strongest bond and the drug-receptor complex is usually irreversible.

10. Drug Receptor Complex When first messengers like neurotransmitters, hormones, autacoids and most other drugs bind with their specific receptors, the drug receptor complex is formed The drug receptor complex causes the synthesis and release of another intracellular molecule termed second messengers e.g. cyclic AMP, calcium, inositol triphosphate (IP3), etc. These second messengers produce the molecular mechanism of drug action

11. Site of Drug Action A drug may act: Extracellularly e.g : osmotic diuretics, plasma expanders On the cell surface e.g.: digitalis, penicillin, catecholamines Intracellularly e.g.: anti-cancer drugs, steroid hormones

12. Dose Response Relationship The amount of drug administered will determine the kind of response you get Minimum dose: the smallest dose that can produce a therapeutic effect Maximum dose: the largest dose that can be safely administered Toxic dose: the amount of drug that can cause a harmful effect Lethal dose: the amount of drug that can cause death

13. Therapeutic Index The ratio of the dose that produces the desired therapeutic effect ( effective dose ) to the dose that produces a toxic effect ( toxic dose ) Safer drugs have wider therapeutic windows (penicillin); drugs that require more frequent monitoring have narrow therapeutic windows (digoxin, warfarin)

14. Pharmacokinetics Deals with the absorption, distribution, metabolism and excretion drugs in the body. “What the body does to the drug”

15. Absorption The process by which a drug enters into the systemic circulation from the site of administration through a biological barrier In the case of intravenous or intra-arterial administration, the drug bypasses rigorous absorption processes and enters into the circulation directly Routes of administration: alimentary tract (enteral) and parenteral

16. Alimentary Tract Buccal cavity: e.g. ondansetron ODT Sublingual: e.g. nitrates Oral: e.g. aspirin, alcohol Rectum: e.g. PCM rectal suppositories, enemas

17. Enteral Routes ADVANTAGES Safe Convenient Economical DISADVANTAGES Slow onset of action Irritant drugs cannot be administered this way Not useful in vomiting and severe diarrhea Gastric acid and digestive enzymes may destroy some drugs

18. Parenteral Routes Intradermal: layers of the skin, e.g. B.C.G. vaccine Subcutaneous: Non-irritant, into subcutaneous tissue, e.g. insulin Intramuscular: Soluble substances, mild irritants, suspensions and colloids can be injected by this route. These injections can be given to deltoid or gluteal muscle Intravenous: into veins Intrathecal: subarachnoid space of spinal cord, e.g. anesthesia Intraarticular: into joints, e.g. hydrocortisone

19. Parenteral Routes ADVANTAGES Fast onset of action Uniform rate of absorption Can be given in critical condition Can be given in large volumes DISADVANTAGES Pain at injection site Drug effect cannot be halted immediately Trained professionals have to administer

20. Topical/Local Route Application of a drug directly to the surface of the skin Doesn’t reach systemic circulation in large quantities Includes administration of drugs to any mucous membrane Eye, nose, ears, vagina Dusting powder, paste, lotion, drops, ointment, suppository for vagina, patches

21. Topical Route ADVANTAGES Useful for the local delivery of agents, especially those which have toxic effects if administered systematically Convenient to use and easy to apply Avoidance of first pass metabolism DISADVANTAGES Not absorbed via skin or mucous membranes Possibility of local skin irritation Contact dermatitis likely due to excipients

22. Inhalation Route Used for gaseous and volatile agents and aerosols Solids and liquids are excluded if particle size is larger than 20 microns Administered as dry powders, and nebulized particles when sprayed as fine droplets get deposited over the mucous membrane producing local effects and may be absorbed for systemic effects Salbutamol inhaler used in bronchial asthma and volatile general anesthetics

23. Inhalation Route ADVANTAGES Fewer systemic side effects Effective for patients with respiratory problems Rapid onset of action DISADVANTAGES Patient may have difficulty administering/measuring dose Some require assembly May cause irritation

24. Bioavailability The rate and amount of drug that reaches the systemic circulation and is available at the site of action after nonvascular administration When the drug is given IV, the bioavailability is 100% The route of administration determines the period between administration and onset of action

25. Bioavailability Drugs given by mouth may be inactive for the following reasons: Enzymatic degradation Poor absorption through gastrointestinal tract e.g. aminoglycosides Inactivation by liver e.g. during first passage through the liver before it reaches systemic circulation

26. First Pass Metabolism Drugs that are absorbed via the GIT are circulated to the liver first Liver acts as a filter Only part of the drug enters systematic circulation

27. Factors affecting absorption Physio-chemical properties of drug Gas > Liquid > Solid Lipid Soluble > Water Soluble (Unionized > Ionized) Nature of the dosage form Small particles > Big particles Pharmacogenetic factors Disease states

28. Factors affecting absorption Physiological factors Administration without, with, or after food Presence of other agents (vit C w/ iron vs. tetracyclines w/ antacids) First pass effect Surface area (vasculature): small intestine > stomach

29. Distribution Penetration of a drug to the sites of action through the walls of blood vessels from the administered site after absorption Drugs distribute through various body fluid compartments such as: (a) plasma (b) interstitial fluid compartment (c) trans-cellular compartment

30. Factors affecting distribution Protein binding Protein bound vs free drug Plasma concentration IV, falls sharply Oral, rises and falls gradually Sublingual, rises sharply and falls gradually Clearance Physiological barriers Blood brain barrier (BBB) Placenta

31. Plasma Concentration Graph

32. Metabolism Drugs are chemical substances, which interact with living organisms and produce some pharmacological effects After, they should be eliminated from the body unchanged or changed to some easily excretable molecule The chemical reactions involved in biotransformation are classified as Phase 1 and Phase 2 reactions

33. Phase 1 Reactions Make the drug polar (water soluble) so it can be excreted via urine Oxidation Reduction Hydrolysis Typically involves the use of cytochrome P450 enzymes

34. Phase 2 Reactions Some drugs may not be excretable after Phase 1 and will need to undergo further metabolism Combines an endogenous substance with the drug ( conjugation ) Glucuronidation Methylation Acetylation Sulfation

35. Excretion The transportation of unaltered or altered form of drug out of the body. Major processes of excretion include renal excretion, hepatobiliary excretion and pulmonary excretion Minor routes of excretion are saliva, sweat, tears, breast milk, vaginal fluid, nails and hair

36. Excretion