EHS 202 Pharmacology for EMS Week 4 Lecture 2 Adverse Drug Reactions PDF

EHS 202Pharmacology for EMS Week 4 Lecture 2: Adverse Drug Reactions At the end of this session, you shall be able to: 1. Describe the different types of adverse drug reactions and understand the current classification system used; 2. Describe the concept of an allergic drug reaction; 3. Identi...

EHS 202Pharmacology for EMS Week 4 Lecture 2: Adverse Drug Reactions At the end of this session, you shall be able to: 1. Describe the different types of adverse drug reactions and understand the current classification system used; 2. Describe the concept of an allergic drug reaction; 3. Identify common risk factors for developing an adverse drug reaction. 4. Define the clinical implications of drug interactions and strategies for limiting adverse drug reactions. 5. Describe the difference between carcinogenic, mutagenic and teratogenic drugs. 2 Any substance that is capable of producing a therapeutic effect is also capable of producing unwanted or adverse effects. 3 Phases of drug discovery 4 Population Pharmacokinetics and Pharmacodynamics Is the study of the variability of the concentration of drugs and their pharmacological effect on individuals when the same or standard dose is administered. A drug dose that is safe and with few side effects in one person can have a significantly different effect in another. 5 Adverse Drug Reactions 6  What is an adverse drug event? An adverse drug event can be defined as: ‘injury resulting from medical intervention related to a drug’. An adverse drug event occurs whilst a person is taking a drug, but it is not necessarily due to the drug (including mistakes in administration – wrong drug, dose, route, situation etc.) 7 Identification of Adverse Drug Reactions (ADR’s) The identification process must include timing, pattern recognition and investigations. Extra articles and clips on ADR in clinical trials: http://www.bbc.com/news/health-22556736 8  Classification of ADR’s ADR’s occur in people of all ages but are twice as common in women and are a major cause of morbidity and mortality particularly in the elderly. A study found that the incidence of ADR’s in hospitalised children was 9.53%. The two main categories of ADR; type A (augmented) and type B (bizarre), together with two subordinate categories related to dose and time; type C (continuous) and type D (delayed). Type D reactions can be further sub-classified with division into time-related reactions type D (delayed) and withdrawal effects type E (end of use). The unexpected failure of a therapy was also recently added as type F (failure). 9  Risk factors for developing ADR’s Age – the elderly and neonates have a higher incidence. Gender – Women have a higher incidence. Concurrent diseases - ? Activated immune system. Genetic factors – may expose genetic enzyme deficiency. History of prior drug reaction – some individuals appear to be more susceptible (asthma, eczema, hay fever). 10  Risk factors continued... Chemical characteristics Route of administration – topical and oral have a lower incidence. Dose – many ADR’s are dose related. Duration and frequency – prolonged and frequent therapy can increase the likelihood of ADR’s. 11  Type A (augmented) ADRs: Common occurrence (approximately 80% of ADRs). Are typically predictable as usually a consequence of the drug's primary pharmacological effect (e.g. bleeding when using the anticoagulant warfarin). Usually mild with high morbidity and low mortality. Able to be reproduced in animal studies. Factors contributing to type A reactions include the dose, variation in drug formulation, pharmacokinetic variation, pharmacodynamic variation and drug interactions. 12 Therapeutic index. A drug must be judged not only by it’s useful properties, but also it’s toxic effects indicated by the therapeutic index. Maximum non-toxic dose Therapeutic index = Minimum effective dose This definition does not take into account variability amongst individuals and the large range between minimum effective dose and maximum non-toxic dose (the effective dose in some individuals may be toxic to others). Some side effects or toxic effects are difficult to predict. 13  Therapeutic index Allowing for individual variation: Therapeutic index = LD50/ED50 Where the LD50 is the dose that is lethal in 50% of the population and the ED50 is the dose that is ‘effective’ in 50% of the population. Although the therapeutic index expresses the general concept of the balance between risk and benefit, it is a flawed measure and does not take into account peculiar reactions or how the drug may be used in clinical practice. Measures from clinical trials in terms of benefit (survival or analgesia) and adverse effects of defined degree are required. 14 Type B (bizarre) ADRs: Uncommon (approximately 20% of ADRs). Unpredictable Not related to a known pharmacological action of the drug. High morbidity and high mortality. Lack of reproducibility in animal studies. Factors contributing to type B reactions include pharmaceutical variation, receptor abnormalities, unmasking of a biological deficiency, abnormalities in drug metabolism and drug allergy. 15  Allergic drug reactions: A drug allergy or hypersensitivity is a ‘type B’ ADR. Some drugs are notorious for producing an allergic reaction (penicillin, streptomycin, radiological contrast media) 16  Allergic drug reactions: Most commonly occur following an antibody response in the patient. Upon first administration the patient becomes sensitized to the drug, following subsequent exposure the patient responds with signs and symptoms including rash, itching and swelling. Drug allergies are often difficult to establish and characterised by; Occurrence in a small number of individuals. A previous exposure to either the same or chemically similar drug. The rapid development of allergic reaction after re- exposure. The production of clinical manifestations of an 17 allergic reaction Allergic Drug Reaction Whilst many reactions are simple or self- limiting, a minority can be severe or life- threatening. Anaphylactic reaction present with airway swelling, difficulty breathing, hypotension and shock. 18 Type C (chronic) ADRs: Uncommon Related to cumulative dose Type C reactions occur as a result of cumulative, long-term use of a drug. These reactions include the development of drug tolerance and physical dependence, tardive dyskinesia with neuroleptic drugs and a rebound effect. Type D (delayed) ADRs: Uncommon (approximately 20% of ADRs). Usually dose-related Occurs or becomes apparent some time after the use of the drug The delayed effects are sometimes acceptable if the benefit outweighs the risk (infertility v cancer). 19 Teratogenic drugs and chemicals. A substance that causes a transient or permanent physical or functional disorder in the foetus without causing toxicity to the mother.’ The susceptibility of the developing foetus to teratogenic drugs and chemicals varies depending on the stage of development of the foetus at the time of exposure and the duration of exposure. 20  Mutagenic and carcinogenic drugs & chemicals Mutagenesis involves the modification of DNA and mutation of cells which can cause cancers. A carcinogen may damage the genome or to the disruption of cellular metabolic processes resulting in abnormal cells/cancers. 21 Medication Interactions Medication interference: undesirable medication interactions Major concern: incompatibility during administration Medication may increase, decrease, or alter the effect of another medication. 22 Limiting Adverse Drug Reactions 23  Risk vs Benefit High Risk Risk Minimal Significant Benefit Benefit Benefit Low Risk The acceptable risk of a drug must be weighed against its potential therapeutic benefit (Penthrane analgesia with renal failure). The high potential for a serious adverse reaction for some drugs are outweighed by the potential benefits (cytotoxic drugs for cancer) 24 Risk vs Benefit High Risk The same drug can have a different risk vs benefit analysis with different variables including: Minimal Significant Benefit Benefit Different dose administered Different patient Different time administered Low Risk Different route of administration 25  When treating a patient with any drug we must consider the pharmacokinetic effect of absorption, distribution, metabolism and excretion. Most ADR’s are dose/concentration related. Therefore many are preventable. 26 The ‘7-rights’ of drug administration Right patient Right drug (form). Right dose. Right route. Right time (frequency). Right documentation 7th right: Right to refuse! 27 Right Drug. Clinicians have a select number of drugs that they become very familiar with – When using unfamiliar drugs/presentations (or tired) take more time and double check. 28  Right Dose (Presentation, familiarisation and Ensure that you are administering the correct drug (read the label labeling). out-loud). Not expired (read out-loud) Correct concentration/presentation (read out-loud). Dilute the drug where appropriate. Standard preparation of the required drug. 29  (Presentation, Familiarisation and Labeling). 30 If in doubt, throw it out. Unless you are 100% confident in knowing the contents of a syringe (or tablet), then don’t administer it!!! 31  Right Dose/Route of Administration Check the clinical guideline to confirm the correct dose and route of administration For example, treatment of a hypoglycemic patient (buccal, intramuscular, intravenous or intraosseous) 32 Right Time/Duration Is this a once only dose? What is the maximum dose? How often should you administer repeat doses? 33  Frequent smaller (conservative) doses Repeated dose administration time can have a significant effect on the circulating concentration. 34 Medication Revision for Next Week – Week 5 In preparation for next weeks medication quiz please review the following medications: Misoprostol Syntometrine Epinephrine 1:1,000 35 References 1. ‘Rang and Dale’s Pharmacology’, 6th Edition. (Rang et al.) 2. ‘Pharmacology for Health Professionals’, 2nd Edition. (Bryant & Knights) 3. ‘Fundamentals of Pharmacology’, 5th Edition. (Bullock et al.) 4. ‘Prescribing medicines in pregnancy’, 4th Edition. (Australian drug evaluation committee & TGA) 5. ‘Adverse drug reactions: definitions, diagnosis and management’. (Edwards & Aronson, 2000) 36