EHS 202 Pharmacology for EMS Week 3 Lecture 1 PDF

EHS 202 Pharmacology for EMS Week 3 Basic Principles of Pharmacology Part 1 – Pharmacodynamics  Objectives this week: 1. Explain the principles of pharmacodynamics. 2. Drug receptor interactions ‘the lock & key’ principle 3. Enzyme systems...

EHS 202 Pharmacology for EMS Week 3 Basic Principles of Pharmacology Part 1 – Pharmacodynamics  Objectives this week: 1. Explain the principles of pharmacodynamics. 2. Drug receptor interactions ‘the lock & key’ principle 3. Enzyme systems 2 Basic Principles of Pharmacology : Throughout this module we will consider the following points: Routes of administration How the drug moves around the body Which sites / tissues and cells can the drug reach What makes each drug work The way the drug works at the target tissue – mechanism of action How is the drug metabolised How does the body process and remove the drub administered 3 Pharmacodynamics Pharmacodynamics – explains how a drug works and interacts with various receptors, other drugs, and enzyme systems within the body (what the drug does to the body). (Guy, 2020). 4 Key Terms Agonist – a drug that produces the desired physiological response following binding with a receptor Partial agonist – a drug which binds to the receptor site and produces a reduced response, reducing the efficacy of other similar agonists Antagonist – a drug which either diminishes or stops the physiological response of the agonist Competitive antagonists – can bind in a temporary or reversible way. If the agonist is increased the antagonist can be over- powered or removed from the receptor site Non-competitive antagonist – a drug which binds irreversibly to a site of action and regardless of the amount of agonist administered the antagonist will remain in the receptor 5 How do drugs work? Step 1 Step 2 Step 3 Physiological Something response Happens A drug is introduced to Contraction the body via one of a Relaxation number of Excretion routes and may or may Activation not even enter Up or Down the regulation bloodstream 6 Pharmacodynamics Drugs adjust or influence the bodies existing functions, via interactions with cells within the body and utilise a variety of methods to achieve this. Paramedics must have an understanding of how a drug or group of drugs work to deliver the most effective care, confidently and operate within the required legal framework. The way a drug functions at the target tissue is called the ‘mechanism of action’ typically through one of the following mechanisms: Drug receptor interactions Drug enzyme interactions Nonspecific drug interactions 7 Mechanisms of Action - Targets ‘a drug will not work unless it is bound’ and these binding sites are generally referred to as ‘drug targets’. The majority of drugs that we deal with (but not all) bind to receptor sites and trigger a stimulus, in some cases they change the chemical properties of cells and tissues. Medications may combine with other chemicals within cells or organ systems to aid in elimination of receptors, to alter the normal metabolic function of cells and tissues. 8  Receptors ‘Receptors are specialized target sites that are present on the surface of cells or within cells. They bind a medication and mediate its pharmacological response’. Receptors Medication and receptor site bind resulting in a biological response The degree of response is proportional to number of drug receptor sites. 10  Most drug targets are protein molecules. The four main kinds of regulatory proteins commonly involved as drug targets are: a) Receptors; b) Ion Channels; c) Enzymes; and d) Carrier molecules (transporters). 11 Receptors – the lock and key principle Receptors have chemical specificity in terms of which molecules they interact with based on a number of factors including shape, size and charge. The ability of molecules to bind to a receptor is similar to that of a lock and key. If the key has the wrong dimensions or properties then it can not engage with the lock. 12 Receptors – the lock and key principle Cells can only respond to a drug when the correct drug fits into its receptor, if the wrong drug attempt to bind it will not activate the receptor. E.g. Cells that are targets for antihistamine drugs are those that have histamine receptors on their surface Drugs that interact with the same receptor to produce a similar physiological response often have similar generic names (propranolol, atenolol & sotalol) 13 Reversible and Irreversible Binding Once the drug has engaged with the receptor site the drug unlocks the target tissue and a response is produced. However, this response can be temporary or permeant. Reversible binding – occurs when the drug or key is able to remove itself from the receptor site or lock. When this happens the effect of the drug stops Irreversible binding – occurs when the drug or key cannot leave the receptor site or lock. In this case the drug will produce a prolonged effect 14 Receptors and Physiological Response A physiological response from a particular receptor cannot be produced where there are no receptors: Adrenaline – binds to beta-adrenoreceptor which is a functionally silent receptor when adrenaline does not bind. Adrenaline – vasoconstrictor & bronchodilator. 15 Drug Enzyme Interactions Enzymes are proteins which assist chemical reactions in the body. Drugs administered interact with theses enzymes & either increase or decrease the chemical reaction. Enzymes work by binding to a substrate. Some drugs administered mimic the naturally occurring substrate which could block the chemical reaction whilst others can accelerate the reaction. 16  Nonspecific Drug Interactions These interactions occur when the drug administered does not require interaction with a receptor or enzyme. Instead, the drug interacts directly with the cell or cell’s membrane. Examples of these include medications which contain electrolytes which are administered to affect fluid concentrations. Some medications administered alter the pH of certain bodily fluids, improving cellular metabolism and can promote excretion of toxic substances. Antibiotics for example are designed to target microorganism cells resulting in cellular death. 17 Drug Dose & Response The dose refers to the amount of medication administered for example milligrams (mg) or grams (g). Dose administered is directly linked to the concentration of the drug at the receptor site and resulting effects. The higher the dose, the higher the concentration the higher the physiological effect. However, there comes a point when despite increasing the dose, the medication no longer produces a response. This is known as does-response relationship or dose-response curve. 18 Dose-response Curve 19  Drug Dose If the two drugs interact with the same receptors……….. why are different physiological responses produced at the same concentration of each drug? The attraction between a medication and its receptors is referred to as its affinity. Some medications may have the same affinity for the same receptor site but it is unlikely they will bind with the same affinity. 20  Drug Affinity Affinity can be considered in pharmacological terms as: ‘The likeliness of a drug to interact and bind with a receptor’. Ability of a medication to bind with a particular receptor site The higher the affinity of a drug, the more likely it is to bind to a receptor and greater time it will spend bound to that receptor. Potent drugs have a high affinity and drug molecules will interact and bind with receptors to produce a biological response even at very low concentrations. 21  Receptor Affinity To stimulate a biological effect requires the occupation of a receptor by a drug (affinity) as they must bind to a receptor in order to produce a physiological response. Increasing concentrations increase effects until: All receptor sites become occupied. Maximum capacity of cell is reached 22 Concentration and Response How do we illicit a greater physiological response with a drug? We stimulate a greater physiological response by increasing the concentration of the drug which in turn increases the number of receptors occupied. Increasing the drug concentration above 80% max response achieves little therapeutic effect but significantly increases Therapeutic window of the risk of adverse drug action reactions. Sub-therapeutic dose that does not produce a measurable biological effect. 23  The strength of a response stimulated by a medication at a receptor site, depends upon the concentration of medication (agonist) at that site. The concentration at this site will depends on the dose administered the its absorption rate, distribution and metabolism. 24  Drug Characteristics Drug efficacy in the ‘lock and key’ analogy refers to the likelihood of the key being turned and the lock activated. The effectiveness of agonist drug depends on how tightly & how long it binds to its receptors. 25  Receptor Activation - Efficacy What does efficacy determine? (response) To stimulate a physiological effect actually requires both the occupation of a receptor (affinity) and the activation of that receptor (efficacy) by an agonist. 26  Drug Efficacy Efficacy can be considered in pharmacological terms as: ‘The ability to activate a receptor once a drug is bound’. Efficacy: ability to initiate or alter cell activity in a therapeutic or desired manner The ability of a drug molecule to activate a receptor is a graded response. The higher the efficacy, the greater Physiological response the physiological response. 27  Receptor Occupancy and Efficacy A full agonist is a drug that can stimulate the maximal physiological response from a biological system if sufficient drug concentration is present. A partial agonist can only produce a sub-maximal response even with 100% occupancy of the receptors. Affinity describes the likelihood of a drug to bind to a receptor. However, efficacy explains why when all of the receptors are occupied some drugs cannot illicit a maximal biological effect. 28  Antagonist Drugs Antagonism can be considered in pharmacological terms as: ‘A drug which reduces the physiological response of another drug’. Frequently the effect of one drug is diminished or completely abolished in the presence of another. 29  Receptor Activation - Efficacy The clinical importance of drug affinity (competition) No Efficacy To stimulate a biological effect actually requires both the occupation of a receptor (affinity) and the activation of that receptor (efficacy) by an agonist. Antagonists have affinity but no efficacy. 30  Antagonist Characteristics Antagonists in the ‘lock and key’ analogy refers to the key being inserted into the lock but not turning the key. There are no endogenous receptor antagonists. Antagonist occupation of a receptor inhibits other drugs from binding but generally does not produce any biological effect in its own right. 31 Competitive Antagonists Competitive antagonists Temporarily bind with cellular receptor sites Efficacy is related to: Its concentration near the receptor sites Its affinity compared with the affinity of the agonist chemicals present 32 Noncompetitive Antagonists Noncompetitive antagonists Permanently bind with receptor sites and prevent activation by agonist chemicals. Effects continue until new receptor sites or cells are created. Cannot be overcome by increased doses of agonist chemicals 33  Desensitisation The effect of drugs predominantly and gradually diminish when given continuously or repeatedly. This can result in increasing doses of a drug required to achieve the same Can you think of an biological effect, which in turn can lead to greater example of this you may desensitisation. come across, when working as a paramedic? 34  Tachyphylaxis An acute onset and sudden decrease in response to a drug following administration – rapid and short term drug tolerance. Where desensitisation describes a reduced drug response following continuous or repeated doses, tachyphylaxis is desensitisation that occurs much more rapidly. 35 Drug Revision For next week’s class please study the following drugs which you will be assessed on: Saline Oxygen Aspirin 36 Questions? 37