Drug Development & Safety PDF

HSHG 2090 – Basic Principles of Pharmacology Drug Development and Safety Learning Outcomes 5.1 Describe drug development and the processes for evaluating drug safety and efficacy 5.2 Define therapeutic effect 5.3 Define therapeutic index 5.4 Distinguish contraindication and precaution 5...

HSHG 2090 – Basic Principles of Pharmacology Drug Development and Safety Learning Outcomes 5.1 Describe drug development and the processes for evaluating drug safety and efficacy 5.2 Define therapeutic effect 5.3 Define therapeutic index 5.4 Distinguish contraindication and precaution 5.5 Discuss various types of adverse effects and interactions that are caused by drugs Learning Outcomes 5.6 Define and explain the following terms related to adverse effects: 5.6.1 Side effects 5.6.2 Hypersensitivity reactions 5.6.3 Idiosyncratic reactions 5.6.4 Iatrogenic overdose 5.6.5 Drug interactions 5.6.5.1 Pharmaceutical interactions 5.6.5.2 Pharmacodynamic interactions 5.7 Discuss the following factors affecting drug safety and efficacy: 5.7.1 Age 5.7.2 Disease 5.7.3 Pregnancy and lactation Drug Development Extensive, time-consuming, and expensive++ process must be followed before a new drug can be marketed Development and approval process meant to ensure: Safety and efficacy of the drug Pharmacokinetic and pharmacodynamic characteristics Typical New Drug Approval Discovery and characterization Pre-clinical studies Application for clinical studies Clinical studies Application for approval Approval for marketing Surveillance and reporting Typical Approval Process Discovery and characterization Isolate or synthesize new product Determine chemical and pharmaceutical properties Pre-Clinical studies Animal testing Test for acute, subacute, and chronic toxicity, teratogenesis, mutagenesis, and carcinogenesis Typical Approval Process (cont’d) Investigational drug application Report properties of drug and all results of pre-clinical trials to date Describe proposed clinical trials Clinical studies Phase 1: healthy volunteers (safety and pharmacokinetic properties) Phase 2: patients (efficacy, safety, dosage) Phase 3: statistical (safety, efficacy, side effects) Typical Approval Process (cont’d) New drug application Describe properties of drug Results of all experimental & clinical studies Propose labeling, advertising, and clinical indications for use Regulatory approval Marketing of the drug Surveillance Voluntary reports of adverse effects Drug Effects Drugs can cause 2 types of responses: 1. Therapeutic effect – the desired and intended effect 2. Adverse effect – an unintended effect – can be beneficial, neutral, or harmful or unwanted Therapeutic Window Amount of drug in the blood that is therapeutic but not toxic  Therapeutic Index Patient effect Ratio between the median lethal dose (kills 50% of people) and the median effective dose (works in 50% of people) General indication of the margin of safety; the lower the TI the more difficult it is to administer an effective dose safely Drug dose Therapeutic Index Smaller index = more dangerous drug Question Time A drug with a large/wide therapeutic index would be considered relatively safe. a) True b) False 13 Administration and Safety Indication The disease or symptom the drug is approved to treat Medical evidence that a specific treatment would be therapeutic Off label use Use of an approved drug for non-approved situations Warnings and Precautions Serious adverse reaction is possible or anticipated Administration and Safety Contraindication Evidence that it would be harmful or inappropriate to administer a treatment that might otherwise be indicated A situation in which there is increased risk associated with a drug Relative – use if benefit outweighs the risk Absolute – drug could cause life-threat  must not give the drug Adverse Effects Adverse effects (side effects) can be classified by mechanism of action and predictability Different types of adverse effects include: 1. Excessive pharmacological activity 2. Organ toxicity 3. Hypersensitivity 4. Idiosyncratic reactions 5. Iatrogenic overdose Adverse Effects (cont’d) Excessive pharmacologic activity: Adverse effects produced by same mechanism responsible for therapeutic effect Easiest to predict and to prevent or counteract Adverse Effects (cont’d) Organ toxicity: Adverse effects are caused by mechanisms other than the intended therapeutic effect Often unpredictable, as occurrence depends on individual susceptibility, dosage, and numerous other factors Adverse Effects (cont’d) Hypersensitivity reactions: Drug allergies Severity may range from mild skin rash to major organ system failure (i.e. anaphylactic reaction) Idiosyncratic reactions: Unexpected drug reactions caused by a genetically determined susceptibility Unpredictable unless a known genetic abnormality exists Adverse Effects (cont’d) Iatrogenic condition: State of illness or adverse effect caused by medical treatment Usually results from a mistake made in diagnosis or treatment, and can also be the fault of any member of the healthcare team Iatrogenic overdose: Adverse effects caused by excess administration of drugs by a health care professional during medical examination or treatment Question Time A patient has been prescribed ibuprofen for the back pain. After taking it, he complains of GI upset. This is an example of a(n): a) Adverse effect b) Therapeutic Effect c) Contraindication d) Anaphylactic Reaction 21 Drug Interactions Defined as a change in the pharmacologic effect of a drug that results when it is given at the same time as another drug or food Pharmaceutical interactions are caused by a chemical reaction between two drugs before their absorption Usually occurs when two drug solutions are combined prior to administration Drugs must not be mixed or administered concurrently unless they are known to be compatible Pharmacodynamic Interactions Occur when two drugs have additive, synergistic, or antagonistic effects: Additive effect: Total effect is equal to the sum of the individual drug effects Synergistic effect: Effect is > than the sum of the individual effects Antagonistic effect: Action of one drug blocks or decreases the effect of another Drug Safety and Efficacy Important biological variables that can alter the response to drugs in specific patients include: Age Disease Pregnancy Lactation Factors Affecting Drug Responses Age: Neonates and infants have reduced levels of drug metabolizing enzymes, lower renal function, and the blood-brain barrier is not completely developed Elderly adults tend to have higher than normal distribution of fat- soluble drugs, reduced renal function, and may be more prone to hypersensitivity Factors Affecting Drug Responses Disease: Hepatic and renal disease may reduce metabolism and excretion Hepatic blood flow may be reduced by cardiovascular disease, heart failure, etc. Dosage adjustment guidelines available for hepatic or renal disease – reduced dosage, increased time between doses, or both Factors Affecting Drug Responses Pregnancy and Lactation: Drugs taken by a woman during pregnancy can cause adverse effects in the fetus (teratogenic effects) Drugs are categorized according to safety in pregnant women Many drugs are excreted in breast milk, and will therefore pose a risk to a breast-feeding infant if taken by the mother Learning Outcomes 5.8 Sharps Disposal 5.8.1 Describe the appropriate procedures for disposal of sharps and contaminated supplies Sharps Disposal “Sharps”: any contaminated item that can cause injury Anything that has punctured a patient’s skin is contaminated Includes needles, cannulas, broken ampoules, or anything else that can penetrate or lacerate the skin Must be immediately disposed of in approved container Sharps Disposal (cont’d) Communicate with other personnel that sharps is out Dispose of sharps immediately after use Never leave sharps to be disposed by other personnel Remain clear of the person using the sharp Sharps Disposal (cont’d) DO NOT RECAP NEEDLES Limit use of needles with needleless system and safety cannulas and needles Do not overfill sharps containers Sharps Disposal (cont’d) What is the most common route for disease transmission in the healthcare setting? ACCIDENTAL NEEDLESTICK Worksheet Summary Drug development Drug terminology Indications/contraindications Therapeutic index Adverse effects Factors affecting drug safety and efficacy Sharps safety References 1. Indications and Usage Section of Labeling for Human Prescription Drug and Biological Products – Content and Format, US Department of Health and Human Services. July, 2018. Accessed at https://www.fda.gov/files/drugs/published/Indications-and-Usage-Section-of-Labeling-for- Human-Prescription-Drug-and-Biological-Products-%E2%80%94-Content-and-Format- Guidance-for-Industry.pdf 2. Shah, S.F., et al. The epidemiology of needle stick injuries among health care workers in a newly developed country, Safety Science. June, 2006; 44(5):387-394 3. Uetrecht, J, et al. Isiosyncratic Adverse Drug Reactions: Current Concepts. Pharmacological review. 2013; 65(2):772-808 4. Warnings and Precautions, Contraindications, and Boxed Warning Sections of Labeling for Human Prescription Drug and Biological Products – Content and Format. October, 2011. Accessed at https://www.fda.gov/files/drugs/published/Warnings-and-Precautions-- Contraindications--and-Boxed-Warning-Sections-of-Labeling-for-Human-Prescription-Drug-and- Biological-Products-%E2%80%94-Content-and-Format.pdf Any questions?