PRINCIPLES OF PHARMOCODYNAMICS 2 [Autosaved].pptx

Pharmacology

1. PRINCIPLES OF PHARMOCODYNAMICS PHARM JOSEPH O.T

2. INTRODUCTION Pharmacodynamics is the branch of pharmacology is a branch of pharmacology concerned with the effects of drugs and their mechanism of action. It is the study of the biochemical, physiologic and molecular effects of drugs on the body. It involves the mechanisms of drug action and the relationship between drug concentration and effect. In summary, it is the study of what a drug does to the body and how it does it to the body. It involves receptor binding, drug-receptor interactions.

3. PRINCIPLES OF PHARMACODYNAMICS For a drug to exert an action, it must interact with specific receptors at its target site. Receptors are molecules in a biological system with which drugs interacts to cause changes in the function and physiology of the system. Receptors are involved in chemical signalling between and within cells. They can be located on cell surface membrane or within cytoplasm. A receptor is any structural component of a cell which a drug binds to, in a dose related manner. Receptors are selective in their ligand binding characteristics in order to respond to chemical signal. They are responsible for selectivity of drug action.

4. PRINCIPLES OF PHARMACODYNAMICS Drugs or natural substances attach to their receptors like a lock and key. A molecule that binds or attaches to a receptor is called a ligand. It may be a protein, hormone, drug, toxin, neurotransmitter e.t.c The receptor concept has important practical consequences in drug development and in arriving at therapeutic decisions in clinical practise. The affinity of a receptor in binding to a drug determines the concentration required to form significant number of complexes. The molecular size, shape and electric charge of a drug determines whether and with what affinity it will bind to a particular receptor among vast array of chemically different binding sites available.

5. PRINCIPLES OF PHARMACODYNAMICS Receptors can be activated or inactivated by either endogeneous ( e.g hormones, neurotransmitters) or exogeneous substances ( e.g drugs). These substances can be agonists or antagonists and their interaction with receptors results to either stimulation or inhibition of biological processes. An endogeneous agonist for a particular receptor is a compound naturally produced by the body that binds to and activates a receptor. E.g endogeneous agonist for serotonin receptors is serotonin, for dopamine receptors; dopamine. Some drug actions are not linked to a receptor but are connected directly to cell function such as changing membrane excitability or stability of a nerve or muscle cell.

6. CHARACTERISTICS OF DRUG RECEPTORS Receptors must be selective in their ligand binding characteristics. Hence, responsible for selectivity in drug action. They mediate the actions of both pharmacologic agonists and antagonists. They are specific in their interaction with drugs and other ligands. Drug-receptor binding relationship is closely related to the dose- response relationship. Receptors determine the quantitative relations between dose or drug concentration and pharmacologic effect.

7. CHARACTERISTICS OF RECEPTORS Most receptors are proteins. Regulatory proteins are the best characterized drug receptors which mediates the actions of endogenous chemical signals such as neurotransmitters, autacoids and hormones. Examples of receptors include channel linked receptors like nicotinic acetylcholine receptors and GABA receptors, G coupled protein receptors like muscarinic acetylcholine receptors, beta adrenoceptors, dopamine receptors and serotonin receptors, Kinase linked receptors like insulin receptors . Other classes of proteins that have being clearly identified as drug receptors are enzymes, carrier molecules (transport proteins e.g Na+/K+ Atpase , structural proteins ( e.g tubulin, a receptor for colchicine an anti inflammatory agent), ion channels.

8. ROLES OF DRUG RECEPTORS Receptors largely determine the quantitative relations between dose or concentration of drug and pharmacologic effects. That is, the receptor’s affinity for binding a drug determines the concentration to form a significant number of complexes, and the total number of receptors may limit the maximal effect a drug may produce. Receptors are responsible for selectivity of drug action. The molecular size, shape and electrical charge of a drug determine whether and with what affinity it will bind to a particular receptor among the vast array of chemically different binding sites available in a cell, tissue or patient. Accordingly changes in the chemical structure of a drug can dramatically increase or decrease a new drug’s affinities for different classes of receptors, with resulting alterations in therapeutic and toxic effects. Receptors mediate the actions of both pharmacologic agonists and antagonists: some drugs and natural ligands such as hormones and neurotransmitters regulate the function of receptor macromolecules as agonists, that is, they activate the receptor to signal as a direct result of binding to it.

9. DRUG-RECEPTOR INTERACTION This is characterized by the binding of drug to receptor and the generation of a response in a biological system i.e a binding and an activation. Binding and activation represent two distinct steps in the generation of the receptor-mediated response by an agonist. Binding of a drug molecule may or may not result in activation of the receptor. If a drug binds to the receptor without causing activation and thereby prevents the agonist from binding, it is termed receptor antagonist. The site on the receptor at which a drug binds is called its binding sites. The favorability of a drug-receptor interaction is referred to as the affinity of the drug for its binding site on the receptor.

10. AGONISTS Agonists are drugs capable of binding to receptors and inducing a cellular response. Agonists are facilitators of cellular action (that is have affinity for and activate a receptor). Whenever they are present in the blood stream, agonists induce the cell to respond, resulting in a therapeutic action. Allosteric agonists are agonists that bind to an adjacent site or a different site on a receptor. Types of agonist include:- full agonist, partial agonist, inverse agonists, super agonists, co-agonists, irreversible agonists etc

11. ANTAGONISTS Antagonists are drugs that inhibit or block the responses of agonists. They are sometimes called blockers . Antagonists are of receptor ligands or drugs that do not provoke a biological response upon binding to a receptor, but blocks or dampens agonist-mediated responses. Antagonists mediate their effects by binding to the active site or to allosteric sites on receptors, They may also interact at unique binding sites not normally involved in the biological regulation of the receptor’s activity.

12. DEFINATION OF TERMS AFFINITY : refers to the degree of effectiveness of the interaction between a drug and a receptor. It is a measure of the ability of the drug to bind to its target molecule. POTENCY : refers to a drug’s strength at a concentration or dose. It is the concentration or the amount of drug required to produce a maximum response. Dose response curves are used to compare potencies of different drugs. If a drug has a higher potency, it means that if the medication is taken at the same dose as another similarly acting drug , it will produce a more intense effect. A higher potency also means a smaller dose of this medication will be required to produce the same effect as another drug. EFFICACY : refers to the magnitude of response produced from interaction between a drug and its receptor. In pharmacotherapeutics, it is very important to have a drug with higher efficacy, than one with higher potency.

13. DEFINATION OF TERMS Tolerance  is a decrease in response to a drug that is used repeatedly.  Examples of drugs that result in tolerance include alcohol and opioids. One mechanism responsible for tolerance is accelerated metabolism, for example, by induction of hepatic enzymes metabolizing the drugs, so it becomes effective at eliminating the drug. Other possible mechanism is receptors becoming less sensitive to the drug due to its regular presence. a decrease in binding affinity between a drug and receptor, a decrease in the number of receptors. The mechanisms responsible for drug tolerance are not always known. Generally , tolerance leads to increasing doses of a drug being required to produce the same effect. Resistance  is development of the ability to withstand the previously destructive effect of a drug by microorganisms or tumor cells .

14. FACTORS INFLUENCING PHARMACODYNAMICS OF DRUGS These include: Sex Disease state Age Weight Occupation Diet Presence of other drugs and other substances Route of administration

15. STRUCTURE ACTIVITY RELATIONSHIPS (SARs ) Structure activity relationship (SARs) is the relationship between the chemical structure of a molecule and its biological activity. It is a means by which the effect of a drug or toxic chemical on an animal, plant or the environment can be related to its molecular structure. This type of relationship may be assessed by considering series of molecules and making gradual changes to them, noting the effect upon their biological activity of each change. The analysis of SARs enables the determination of the chemical groups responsible for evoking a target biological effect in the organism. This allows modification of the effect or the potency of a bioactive compound (typically a drug) by changing its chemical structure Medicinal chemists use the techniques of chemical synthesis to insert new chemical groups into the biomedical compound and test the modifications for their biological effects.

16. STRUCTURE ACTIVITY RELATIONSHIP The science of the SAR is in relating the structure to activity, i.e identifying the key aspects of structure, pertaining to the molecular event(s) in the mechanism of action for the chemical or biological actions of interest. Factors contributing to SARs are:- Shape , size, stereochemical arrangement, and distribution of functional groups. Chemical reactivity. Electronic effects. Resonance. Inductive effects.

17. ADHERENCE TO DRUG THERAPY Adherence is the degree to which a patient follows a treatment regimen. It is required that the prescription be obtained promptly and the drug be taken as prescribed in terms of dose, dosing interval, duration of treatment, and any additional special instructions ( eg , taking the drug without food). Reasons for non-adherence include: Frequent dosing interval Psychology : this can be denial of illness, patient’s belief in drug efficacy, reduction or disappearance of symptoms, poor comprehension of the benefits of taking the drug. Drug’s cost Concern about taking drugs ( eg , adverse effects, addiction) Forgetfulness Misunderstanding prescribed instruction. Physical difficulties ( eg , with swallowing tablets or capsules, opening bottles, or obtaining prescriptions)

18. DRUG DEPENDENCE Dependence is a related term often defined as either physiological or psychological need for a substance. Physical dependence refers to an altered physical condition caused by the nervous system adapting to repeated drug use. In this case, when the drug is no longer available the individual expresses physical signs of discomfort known as withdrawal. Psychological dependence is a case in which little or no sign of physical discomfort is observed when a drug is no longer available, however the individual feels a need for a strong, compelling need to continue drug use. Drugs that cause dependency are restricted for use in situations of medical necessity if at all.

19. CONTROLLED DRUGS This includes drugs and substances tightly controlled by the government as a result of its potential for abuse or addiction. The control applies to how the drug/substance is made, handled, used, stored and eventually distributed. Controlled substances include drugs like opioids, stimulants, depressants, hallucinogens and anabolic steroids. Controlled substances with known medical use include: diazepam, morphine, nitrazepam etc are available only by prescription from licensed medical professional. There are special prescription requirements for controlled drugs to restrict their inappropriate distribution.

20. SELF MEDICATION Self medication is referred to the treatment of any illness without consulting a medical doctor. The world Health Organization defines self medication as the use of drugs by individuals in order to treat a particular illness without consultation from a trained and certified medical professional. Self medication can be harmful at times as the medicines prescribed can have long term negative effects in the user. It involves the continual use of old prescriptions, consultation of friends who are not certified medical professionals. Self medication can lead to drug addiction, drug abuse, drug resistance and death.

21. DRUG ADDICTION It is defined as a chronic, relapsing brain disease that is characterized by compulsive drug seeking and use, despite harmful consequences. It is said to be an overwhelming feeling that drives someone to repeat drug taking behaviour , despite serious health and social consequences. It disrupts the normal, healthy functioning of the underlying organ, has serious harmful consequences. It can be prevented and treated, but if left untreated, can last a lifetime. Addiction is not only a problem for the client, but for society as well because of its negative influence on public health, safety, productivity and financial resources. Examples of commonly used illegal drugs include heroin, cocaine, ecstasy, methamphetamine, marijuana, methadone e.t.c

22. DRUG ABUSE It refers to the habitual use of legal/illegal drug. It is also said to be the use of certain substances for the purpose of creating pleasurable effects on the brain. It can lead to addiction or dependence. The theory that addiction results from reward and positive reinforcement may be valid. Simply put, some people take drugs because they like the state of mind the drug produces. It should be noted that prescription drugs rarely cause addiction when used according to accepted medical protocols . The risk of addiction is a function of the drug dose and the length of therapy. Hence, drugs having a potential for abuse are usually prescribed at the lowest effective dose and for the shortest time necessary to correct the medical problem. Examples of drugs easily abused and misused include the following: benzodiazepines, antidepressants, opioid painkillers, stimulants, mood stabilizers etc.

23. DRUG OVERDOSE Drug overdose is taking too much of a substance whether it is prescription, over the counter, legal or illegal. Drug overdose may be accidental or intentional. Drug overdose can lead to serious medical complications including death. The severity of a drug overdose depends on the drug, the amount taken and the physical and medical history of the person who overdosed. Risk factors involved in drug overdose include the following History of drug misuse or addiction History of mental illness Improper drug storage Non compliance or lack of knowledge of the dosage instruction.

24. SYMPTOMS OF DRUG OVERDOSE Symptoms of drug overdose include the following:- Difficulty walking Trouble breathing Nausea and vomiting Agitation Enlarged pupils Hallucinations Aggression Convulsions Tremors Drowsiness Delusions

25. GENERAL TREATMENT OF DRUG OVERDOSE Induction of vomiting to remove the substance/drug/chemical ingested. Pumping of the stomach to remove the ingested drug/ substance/chemical. Clearing the airway or inserting a breathing tube when there is a problem with breathing. Administration of activated charcoal which acts in the digestive tract to absorb the ingested drug/chemical/substance. Administration of intravenous fluid to help speed up the removal of the ingested drug/chemical/substance.

26. GENERAL PRINCIPLES IN THE MANAGEMENT OF POISON A poison is a substance that is harmful to life as it affects one or more vital functions of the body. Poisoning can be acute or chronic. Short term exposure to poisons is labelled as acute poisoning, while a long term exposure is known as chronic poisoning. Management of poisoning is based on the following :- Stabilization and evaluation of the patient which will require first aid like clearing the airways when breathing is affected. Decontamination and elimination of the poison which might require a gastric lavage, the use of laxatives, purgatives, activated charcoal, diuresis, hemodialysis or hemoperfusion. Administration of specific antidotes that counteract the effect of the poison.

27. EXAMPLES OF ANTIDOTE EXAMPLES OF ANTIDOTES TOXIN ANTIDOTE ACETAMINOPHEN N-ACETYLCYSTEINE CYANIDE NITRITES NARCOTICS NALOXONE BENZODIAZEPINES FLUMAZENIL ORGANOPHOSPHATES ATROPINE ISONIAZID PYRIDOXINE METHANOL FOMEPIZOLE

28. DRUG INTERACTION This is defined as the modification of the effect of a drug when administered with another drug or chemical or food. This is defined as an interaction between a drug and another substance that prevents the drug from performing as expected. This definition applies to interactions of drugs with other drugs and drugs with food or other substances. There are basically three types of drug interactions namely: Pharmaceutical interaction Pharmacodynamic interaction Pharmacokinetic interaction

29. DRUG INTERACTION Pharmaceutical interactions occur before the absorption of the drug in to the body as a result of chemical or physical incompatibility of the two drugs. Pharmaceutical interactions is the reason why no drug is added to blood transfusion. Pharmacodynamic drug interactions is the effect of a drug on the strength and the duration of action of another drug. There are four types of Pharmacodynamic drug interactions Synergism Addition Indifference Antagonism

30. DRUG INTERACTION Synergism or synergistic effect occurs when the combined effect of two drugs exceeds the sum of the effects of each drug given alone, For example, both sulphamethoxazole and trimethoprim are antibiotics, but together they produce a greater inhibition of organisms than expected from the sum of their individual effects. Addition or additive effects occurs when the combination of the effects of the two drugs equals the sum of each drug given alone, for example, the combination of benzodiazepines and alcohol as CNS depressants. Indifference effect occurs when the combined effect of two drugs administered together is not greater than that of the more effective drug. Antagonism effects when their interaction of two drugs produces an effect that is less than that of the more effective of the two drugs. For example: The administration of certain antacids with tetracycline. The antacids may chemically interact with the tetracycline and impair its absorption into the bloodstream, thus reducing the effectiveness of the tetracycline.

31. DRUG INTERACTION Antagonism can be classified into the following namely:- Non-competitive antagonism Competitive antagonism(this antagonism is occasionally useful in toxicology practice for example in the treatment of morphine poisoning). Functional antagonism( also called physiological antagonism). Chemical antagonism Pharmacokinetic interaction is the effect of a drug on the fate of another when administered concomitantly. The effect may be a change in the rate of absorption, the binding to either plasma proteins or to active site of the metabolic enzymes or receptor sites or the rate of diffusion. For example, drugs that contain calcium, magnesium, aluminum and iron form non absorbable complexes with tetracycline .

32. EXAMPLES OF DRUG INTERACTION Aspirin and anticoagulants causing an increased anticoagulant effect. Antacids and drugs causing decreased absorption . Guanethidine and tricyclic antidepressants causing a loss of the antihypertensive effect of guanethidine . Alcohol and sedative hypnotics, tranquilizers causing increased central nervous system effects. Oral hypoglycemic agents and salicylates, Sulphonamides , phenylbutazone , chloramphenicol causing increased hypoglycemic effects

33. EXAMPLES OF DRUG INTERACTION IN LABORATORY TESTS Diuretics interact with plasma potassium resulting in a decrease in plasma potassium levels. Aspirin interacts with plasma uric acid resulting in a decrease of plasma uric acid levels. Indomethacin, thiazide, narcotic analgesic and diuretics interact with serum amylase resulting in increased serum amylase levels. Phenothiazines affect a pregnancy test resulting in a false positive. Lithium, nitrofurantoin , zinc salts , fluorides interact with alkaline phosphates resulting in an increase of alkaline phosphates. Ascorbic acid causes urine glucose levels to be false positive.

34. DRUG FOOD INTERACTION Drug food interaction: depending on the drug given, food may impair or enhance its absorption. Eating certain foods at the same time a specific drug is taken may also influence the action of some drugs. When a drug is taken on empty stomach, it is absorbed into the blood stream at a faster rate than when taken with food in the stomach (this happens not in all cases). Some drugs, especially those capable of irritating the stomach, result in nausea, or vomiting and epigastric distress and are best given with foods or meals.

35. DRUG FOOD INTERACTION Drug food interaction: An example is taking monoamine oxidase inhibitors plus a food containing tyramine (found in cheese) causes hypertensive crisis. Drug or food interactions may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances. Some drugs must be taken on empty stomach to achieve an optimal effect., other drugs should be taken with food. When it is necessary to take a drug on empty stomach or with food manufacturers, give these directions. This information must be placed on the label of the dispensed drug