EMS Pharmacology Week 4: Adverse Drug Reactions

EMS Pharmacology Week 4, Lecture 2: Adverse Drug Reactions

• Adverse drug reactions (ADRs) are injuries resulting from medical intervention related to a drug.
• ADRs may not be directly caused by the drug itself, but rather due to errors in administration (wrong drug, dose, route, situation).
• Learning objectives include describing different types of adverse drug reactions, understanding the classification system, defining allergic reactions, identifying risk factors for adverse drug reactions, defining the clinical implications of drug interactions, and differentiating between carcinogenic, mutagenic, and teratogenic drugs.

Phases of Drug Discovery

• Drug discovery involves several phases, taking years.
• 100 drug projects typically yield 20 compounds.
• Preclinical development (2-5 years) includes target selection, lead optimization, pharmacological profiling, and synthesis scale-up.
• Clinical development (5-7 years) includes trials testing drug efficacy, dosage, toxicity in healthy volunteers and assess reactions in patients.
• Regulatory approval involves the submission of data for review by agencies.
• Post-marketing surveillance monitors potential risks associated with the drug after approval.

Population Pharmacokinetics and Pharmacodynamics

• Population pharmacokinetics studies how drug concentrations and effects vary among individuals.
• The same dose can have widely different effects on different people.

Adverse Drug Reactions

• The process of identifying ADRs must include timing, pattern recognition, and investigations.
• There are additional resources (articles and videos) on ADRs in clinical trials, including a case study concerning a drug trial disaster.

Classification of ADRs

• ADRs occur in people of all ages but are more common in women and the elderly.
• Type A (augmented) ADRs are common, predictable, and typically mild.
• Type B (bizarre) ADRs are less common, unpredictable, and can be severe.
• Other types include Type C (chronic) and Type D (delayed).

Risk Factors for Developing ADRs

• Age (elderly and neonates have higher risk), gender (women have a higher risk), concurrent diseases, genetic factors, and history of prior drug reactions can increase susceptibility to ADRs.
• Chemical characteristics and route of administration, dose, and duration/frequency of therapy are also important.

Type A ADRs

• Account for roughly 80% of ADRs.
• Predominantly predictable and linked to the drug's primary pharmacological action (e.g., anticoagulant bleeding).
• Usually mild, with high morbidity and low mortality.
• Can usually be reproduced in animal studies.
• Contributing factors include drug dose, formulation variability, pharmacokinetic variations, pharmacodynamic variations, and drug interactions.

Therapeutic Index

• The therapeutic index is the ratio of the maximum non-toxic dose to the minimum effective dose.
• It's a measure of a drug's safety margin.
• Variability between individuals can make interpreting the therapeutic index challenging since the same dose can have different effects.
• Additional measures like clinical trial data are needed to evaluate true benefit/risk ratios.

Type B ADRs

• Represent approximately 20% of ADRs.
• Unpredictable
• Not related to the drug's primary pharmacological action.
• Often associated with high morbidity and mortality.
• Usually not reproducible in animal studies.
• Contributing factors can be pharmaceutical variability, receptor abnormalities, unmasking of a biological deficiency, abnormalities in drug metabolism, or drug allergy.

Allergic Drug Reactions

• A drug allergy or hypersensitivity is a type B ADR.
• Common drugs involved are penicillin, streptomycin, and radiologic contrast media.
• Allergic reactions typically follow an antibody response in the patient.
• Reactions are often characterized by a rapid onset, occurrence in a small number of people, a previous exposure to a chemically similar drug, rapid development after re-exposure, and clinical manifestations of an allergic response.
• Severe reactions can be life-threatening and involve anaphylaxis, airway swelling, difficulty breathing, hypotension, and shock.

Type C (Chronic) ADRs

• Uncommon ADRs arising from cumulative, long-term drug use.
• Can include drug tolerance/physical dependence, tardive dyskinesia, or rebound effects.

Type D (Delayed) ADRs

• Uncommon (approximately 20%)
• Appear some time after drug use
• Usually dose-related
• May be acceptable if benefit outweighs the risk (e.g., infertility vs. cancer treatment).

Teratogenic Drugs and Chemicals

• Teratogens cause physical or functional disorders in a fetus (but not to the mother).
• Susceptibility depends on the stage of fetal development and the duration of exposure.

Mutagenic and Carcinogenic Drugs

• Mutagenic drugs modify DNA and cause mutations, potentially leading to cancer.
• Carcinogens damage the genome and disrupt cellular metabolic processes, potentially leading to the formation of abnormal cells, such as cancer cells.

Medication Interactions

• Medication interactions involve an undesirable effect from combined use of medications.
• Incompatibility of medications during administration is a major concern leading to altered effects on other drugs.

Limiting Adverse Drug Reactions

• Risk—benefit assessment is crucial for deciding whether to use a drug, despite potential adverse effects.
• Dose/concentration plays a significant role in determining adverse reactions, and many are therefore preventable.
• The "7 rights" of drug administration include considering the right patient, medication, dose, route of administration, time, and documentation. The 7th right is the right for the patient to refuse.
• Clinicians should meticulously check and verify information on potentially unfamiliar drugs.

Medication Review for Next Week

• The next week's medication quiz requires review of Misoprostol, Syntometrine, and Epinephrine 1:1,000.