Chapter 5 Deck 2 Flashcards
one distinuguishing feature for ADRs
Is the relation between administration and tissue exposure times of the reaction.
The world allergy organization classifiesimmunolgogical reactions as
immediate or delayed
symptom presentations that occur within one hour after exposure is classified as a
Immediate reaction
A delayed reaction occurs more than
One hour after reaction
Rapid reaction
Occurred during or immediately after the ministration of the medication
Vancomycin can cause an adverse reaction known as
Red man syndrome, when administered to rapidly
Phenytoin can cause an adverse reaction known as
purple glove syndrome
first dose reactions
occur after the first dose of the medication
an example of the first dose reduction
orthostatic hypotension is a common reaction occurs after the first dose of doxazosin
early reactions
occur early in treatment and generally resolve the continued treatment as the patient develops tolerance.
Is often useful to initiate drugs likely to cause early reactions with
low starting doses and sequentially titrate the dose upward to mitigate the severity and duration of adverse effects
examples of early reactions
gastrointestinal upset after initiation of metformin or selective serotonin reuptake inhibitors
immediate reactions
occur after repeated exposure to medication examples include hyperuricemia from furosemide
late reactions occur
after prolonged exposure to an offending agent. Examples include osteoporosis or thinning of the skin due to prolonged corticosteroid use in hypogonadism after prolonged use of opioids. It may be possible to symptomatically treat plate ADRs, but most predictable and occur after repeated exposures. Thus it is often recommended to remove the offending agent for the reaction is predicted to occur to manage this type of adverse effect.
Delayed reactions
occur at variable points in time after drug exposure and can even occur after discontinuation of a drug. For example, drug-induced tardive dyskinesia may occur after prolonged exposure to antipsychotics, with symptoms persisted for months to years after discontinuation of the precipitating drug.
The FDA defined serious ADRs as those tab and result in death, or life-threatening, resulting hospitalization, are disabling Orkin incapacitating, produce congenital abnormality or birth defect, require an intervention to prevent one of these outcomes.
that result in death, or life-threatening, resulting hospitalization, are disabling Or incapacitating, produce congenital abnormality or birth defect, require an intervention to prevent one of these outcomes.
Any ADR that meets FDA criteria should be reported to
the FDA Medwatch program
mild adverse events can typically be managed by
dose reduction
moderate adverse events often require
discontinuation of the drug and minimal medical intervention
severe ADRs may be
life-threatening and result in hospitalization, disability, birth defects, or even death, and require intensive medical intervention
approximately one third of ADRs result from
medication errors and up to one third from allergic reactions.
top five drug classes responsible for ADRs
insulin, opioid -containing analgesics, anticoagulants, amoxicillin containing medications, antihistamines or cold remedies
top five drug classes indicated in precipitating hospitalizations after admission to the ED include
anticoagulants, insulins, opioid containing analgesics, oral hypoglycemic medications, and antineoplastic agents
in older adult population, more than half of all ADRs require treatment in the ED are due to
drugs influencing blood clotting, predominantly warfarin
Steven Johnson syndrome
(SJS) is a rare, serious disorder of the skin and mucous membranes. It’s usually a reaction to medication that starts with flu-like symptoms, followed by a painful rash that spreads and blisters. Then the top layer of affected skin dies, sheds and begins to heal after several days.
Of the top 10 drugs linked to skin reactions the majority are
Antibiotics, amoxicillin, ampicillin, the date, blood products, cephalosporins, erythromycin, diatribe losing hydrochloride, penicillin G,
Risk factors for ADRs include
Genetic abnormalities, age, sex, polypharmacy, and con commitment medical conditions.
Genetic factors that affect the bodies ability to
Metabolize medications can contribute to pharmacological and idiosyncratic reactions. Although rare, some people have DNA mutations that predispose them to develop ADRs. For example, an individual has an alteration in liver enzyme activity secondary to a gene mutation, the rate at which effective medications are metabolized may be increased or decreased, thus altering the concentration of active, inactive, and potentially toxic drug products in the circulation.
A common mediator for immune responses is variations in the
HLA – B allele. For example, patients who express the HLA – B5701 allele are not at a significantly increased risk of severe T cell mediated hypersensitivity reactions to the HIV medication abcavir. Additionally, Han Chinese, who express HLA – B15024 HLA – B*5801 alleles, are at higher risk of hypersensitivity reactions to carbamazepine and allopurinol, respectively.
Children are at higher risk primarily because
Medication dosages must be tailored to their specific weight or body mass index.
Hospitalizations in individuals over 65 due to ADRs are most commonly a result of
Unintentional overdose. More than half of ADRs and hospitalized patients 70 years of age or older are considered to be preventable. Therefore all prescriptions working with these population should take care to minimize polypharmacy, unless clinically necessary, to reduce the risk of drug to drug interactions, confusion between medications, and drug accumulation with insufficient renal and hepatic function.
It is been estimated that 90% of pediatric ADRs might be prevented by
Prescriber computer order entry and clinical decision support and clinical pharmacist consultation in this high-risk population
Women have more ADRs than men in part due to
Differences in body composition. Furthermore ADRs may be related to pregnancy and lactation.
Induction
Liver enzymes speed up the effects of a drug
Inhibition
Liver enzymes slow down the rate of metabolism and clearance of drugs that flow through the same enzyme pathway.
Carbamazepine does want to oral contraceptives
Make some less effective due to the induction of the medication increasing metabolism and clearance
Amlodipine does what to simvastatin
Inhibits liver enzymes that metabolize it and can result in myopathy and possibly rhabdomyolysis.
Most drug interactions can be identified by
Reviewing patient medication profiles and using computerized drug interaction screening tool such as micro medics, online facts and comparisons, orthodoxy can’t.
The best example of food drug interactions is
Grapefruit reducing the clearance of simvastatin and increasing risk of myopathy, or herbal products such as St. John’s wort reducing clearance of cyclosporine.
Trimethoprim-sulfamethoxazole does what to warfarin
Metabolism is reduced, resulting in an increase in the international normalized ratio and prothrombin time. Ultimately this increases the risk of bleeding and should be avoided if possible,
Medications that are extensively cleared from the body through the kidneys have,
specific dosage adjustments or contraindications for use based on creating clearance or estimated communal or filtration rate
Ranitidine requires a dose reduction to hundred and 50 mg per 24 hours when
Creatine clearances less than 50 mL a minute and Metformin is contraindicated when estimated globular filtration rate is less than 30.
Heart failure decreases
Liver and kidney perfusion and can reduce metabolism and clearance. Similarly thyroid dysfunction can alter drug metabolism
It’s important to remember that most (90%) identify drug interactions will
not have clinical consequences for an individual patient but to represent a warning to monitor the patient for a potential problem.
Smaller number (perhaps 2%) of identified drug interactions will
Have profound clinical consequences, thus identifying and preventing these ADRs are crucial.
Many drug suspected of causing an ADR are
Probably discontinued and should be if the offending drug can be safely stopped, if the event is life-threatening or intolerable, if continuing the medication will worsen the patient’s condition, and if there is a reasonable alternative treatment.
Drugs responsible for an ADR may be continued in
A patient if the drug is medically necessary and there is no acceptable alternative treatment or if the adverse reactions tolerable and reversible. Most adverse reactions related to dose and pharmacological effects or respond favorably to dosage adjustment.
If the ADR resolves after discontinuation of the medication and the adverse event was
Likely caused by the discontinuation medication. The only definitive indicator for casualty is the recurrence of an adverse event after re-challenge, which is three administration of the potential for new drug. As long as no other medication changes are made and no change in the patient’s health status occurs, the reappearance of an ADR after rechallenge confirms casualty. Rechallenge is not a common practice and is generally not appropriate, especially for life-threatening ADRs.
Naranjo ADR probability scale
Developed framework for assessing the probability that an adverse reaction is related to administration of a particular drug. The Naranjo protocol, based on timing partner history and reports, rechallenge, alternative causes, dose dependency, and objective evidence, defines relationship between drug and adverse reaction as definite probable possible or doubtful based on scoring.
FDA post marketing reporting program seek to identify
Problems not identified before approval, as well as many problems that may arise related to drug labeling manufacturing.
The FDA maintains the
Adverse event reporting system, a computerized database of adverse events for approved drugs and biologicals.
Medwatch is the FDA’s
Safety information and adverse event reporting program that provides health care professionals with medical product information on prescription and nonprescription drugs, biologicals, medical devices, and nutritional products,
A separate program used to report adverse events related to vaccinations unlike Medwatch allows voluntary reporting of adverse events by both healthcare professionals and consumers
Vaccine adverse event reporting system
