Drug-Related Problems & Adverse Reactions PDF

Therapeutic planning and Drug- related Problems Dr/ Asmaa A. Elsayed Clinical Pharmacy Department  Adverse Drug Reactions (ADRs) –response to a drug that is noxious and unintended and that occurs at doses normally used in humans for prophylaxis, diagnosis or therapy...

Therapeutic planning and Drug- related Problems Dr/ Asmaa A. Elsayed Clinical Pharmacy Department  Adverse Drug Reactions (ADRs) –response to a drug that is noxious and unintended and that occurs at doses normally used in humans for prophylaxis, diagnosis or therapy of disease or for the modification of physiologic function –excluding therapeutic failures, overdose, drug abuse, non-compliance and medication errors –In sum, an adverse drug reaction is harm directly caused by the drug at normal doses, during normal use. Relationship Between ADEs and ADRs  Classification − Onset − Severity − Type  Onset of event: Acute within 60 minutes Sub-acute 1 to 24 hours Latent > 2 days  Severity of reaction: Mild bothersome but requires no change in therapy Moderate requires change in therapy, additional treatment, hospitalization Severe disabling or life-threatening  FDA Serious ADR: –Result in death –Life-threatening –Require hospitalization –Prolong hospitalization –Cause disability –Cause congenital anomalies –Require intervention to prevent permanent injury  Type of adverse reactions: Type A (Augmented) –Exaggerated pharmacological response Type B (Bizarre) –Nonpharmacological, often allergic response Type C (Chronic) –Osteoporosis with oral steroids Type D (Delayed) –Teratogenic effects Type E (End of use) –Withdrawal syndrome Type F (Failure of efficacy (no response)) –Resistance to antimicrobials  Type A (augmented, intrinsic, dose- related) predictable reaction Drug intoxication is the occurrence of an undesirable effect of drug due to an exaggerated drug effect Drug toxicity can occur as a result of increased drug dose or decreased drug elimination which leads to increased drug concentration in the blood at its site of action. Can be predicted from the known pharmacology of the drug or a secondary effect of drug e.g: anticholinergics and dry mouth, antibiotics and diarrhoea due to altered GIT bacterial flora  Type A (augmented, intrinsic, dose- related) predictable reaction Dose dependent (related to the amount of drug in the body) Accounting for 75% or more of ADRs High incidence (affects many people). Dose-related reactions (can be reproduced in animals). Can be managed (largely avoidable with care).  Type B (bizarre) (idiosyncratic) (non– dose related) reactions: Not part of normal pharmacology of the drug. Rare and occurs only in some people (low incidence). Unpredictable. Account for most drug fatalities. May not be discovered until drug used in many patients Can not be easily managed. Often allergic but sometimes associated with congenital enzyme deficiencies. e.g., Chloramphenicol and bone marrow suppression which leads to aplastic anemia (late onset :3-6 weeks after use).  Type B reactions Immunological reactions: Pseudo-allergic reactions: (drug allergy or hypersensitivity Mimic allergic reactions but have reaction) no immunological basis (Not due It is an IgE mediated allergic to IgE release but due to direct reaction in sensitized patients mast cell activation) e.g. Asthma and skin rashes with aspirin  Type C (continuous or chronic) (long term) reactions: -Adverse effects are related to the duration of treatment (associated with long-term use) as well as dose (involves dose accumulation) e.g. antimalarials and ocular toxicity -Repeated drug use e.g: anti-hypertensive drugs use daily Type D (delayed) reactions: Dose-independent Take time to develop (appear after stopping the drug) Carcinogenicity (e.g., immunosuppressants) Teratogenicity (e.g., fetal hydantoin syndrome caused by pheytoin) Type E (ending of use) reactions Adaptive changes: e.g. Tolerance and physical dependence (narcotic analgesics) Rebound phenomena: When adaptive changes occur during long-term therapy (type C), sudden withdrawal of drug may result in rebound reactions. e.g. Corticosteroids causing acute adrenal insufficiency  Predisposing factors of ADR: I.Non-drug factors: A.Intrinsic to the patient (age, sex, genetics, tendency to allergy, disease, personality & habits) B.Extrinsic to the patient (the environment) II.Drug factors: Intrinsic to the drug Include simultaneous use of several different drugs and Drug-drug interactions (multiple medications).  ADR Risk Factors Age (children and elderly) Pregnancy and breast feeding Genetic predisposition Multiple medications Concurrent diseases (renal ,liver , cardiac) End-organ dysfunction Inappropriate medication prescribing, use, or monitoring Prior history of ADRs Extent of exposure (dose and duration)  Risk Factors Examples: Age Related Issues ⚫ADRs, including drug interactions, are a common cause of admission to hospitals in the “Elderly” ⚫Reasons for ADRs in the elderly: –Concomitant use of several medications –Disease states leading to drug ADME changes –Decreased drug ADME activity due to age ⚫These conditions are exacerbated by malnutrition and dehydration, common in the elderly  ADR Frequency by Drug Use The more medications in a regimen, the greater likelihood of an ADR  Infants and young children are at high risk of ADRs because their ability to metabolize drugs are not fully developed Newborn cannot metabolize chloramphenicol causing gray baby syndrome (hypotension and cyanosis) a serious and fatal reaction Children are at risk of developping reye syndrome if given aspirin during a viral infection  Risk Factors Examples: Pregnancy ⚫Use of sulfonamides (antibiotic) can lead to jaundice and brain damage in the fetus ⚫Warfarin use for anticoagulation can lead to birth defects, and increased risk of bleeding problems in newborns and mothers ⚫Lithium, for psychitaric disorder, can lead to defects of the heart, lethargy, reduced muscle tone, and underactivity of the thyroid gland. Risk Factors Examples: Breastfeeding ⚫Similar concerns, as for other children with underdeveloped capability to metabolize or excrete drugs ⚫Many drugs can be passed from mother to infant via breast milk –Amantadine (antiviral) –Cyclophosphamide (antineoplastic) –Cocaine (Schedule 2 FDA drug)  Risk Factors Examples: Disease States ⚫Metabolism may be impaired with hepatic disease –Cirrhosis –Hepatic Carcinoma ⚫Elimination may be impaired with Renal Insufficiency –Acute or Chronic Renal Failure –Decreased glomerular filtration rate (GFR) ❖Drug levels may become toxic if too high, so dosing modifications may be indicated Risk Factors Examples: genetic diferences ⚫Glucose 6 phosphate dehydrogenase deficiency (G6PD) renders patients more susceptible to the hemolytic effect of drugs. ⚫This enzyme is responsible for protection of RBCs  Role of pharmacist to Reduce of the risk of ADR: The pharmacist assists in the prevention , detection and monitoring of ADR Reduction of the risk of ADR: Age, hepatic and renal disease may impair clearance of drugs so smaller doses may be needed. Check need for continuing treatment and stop drugs which are no longer necessary. Prescribe as few drugs as possible and give clear instructions If serious ADRs are liable to occur warn the patient Check the patient history of drug allergy We Must Always Ask: Do the potential benefits outweigh the potential risks for this individual? Detecting and reporting ADR BLUE CARD