had the effect wanted, but to a larger degree than expected
immune response to drug. Can occur at any time, even if drug was taken successfully in the past
unexpected abnormal response. Almost always genetically and liver related
adverse effects related to taking two or more drugs
happens second time taken. First time develops antibodies, Second time develops reaction.
Types of drug allergies
antibody response with immune reactivity and release of histamine with resulting signs and symptoms Most likely to happen after an injection instead of oral.
circulating antibodies attach the drug on cell sites and cause cell death. See drop in HCT and WBC, elevated LFT, elevated BUN/Creat. Tends to be delayed and seen over a few days.
immune complexes deposit in blood vessels. Cause rash, fever, lymphadenopathy, swollen joints, impaired renal function, splenomegaly. Occurs 1-3 weeks after exposure.
with reaction of sensitized T lymphocytes and macrophages.
High Alert Medications
medications that associated with errors and have a high risk of adverse effects
what percent of adverse drug affects in the elderly are related to anti-coagulants and insulin?
Narrow theraputic index
not a big difference between effective concentration and toxicity Ex. 10 mg good, 20 mg kill you
Wide theraputic index
Wider range between effective concentration and toxicity Ex. 10 mg good, 500 mg kill you
Critical periods for drug effects on fetus is
first two weeks of rapid cell proliferation and weeks 3-12 during organogenesis
physiologic changes in pregnancy that impact pharmacokinetics include
·delayed gastric emptying and decreased motility
·increased pulmonary ventilation and increased blood flow and surface area
·increased GFR and renal blood flow
·decreased hepatic enzyme activity
·change in body mass and fluid distribution
Majority of drugs pass by ________ with fetal serum levels equal to maternal levels, but may actually be higher
tranfer across the placenta depends on
other drug properties
FDA approved for that use and in that age group
Off label prescribing
drug is being used that the FDA has not approved for that use or use in that age group
what percent of drugs used in children have not been tested in children
separate category due to thin permeable skin, lack of stomach acid, poor temperature regulation, propensity for dehydration, immature liver and kidneys and lungs
receive almost all forms of drugs that are in maternal circulation although usually at lower doses due to maternal biotransformation. High lipid soluble drugs will be more concentrated in breast milk, low serum protein results in more free drug, slower metabolic reactions by liver, delayed drug excretion due to immature kidneys.
most pharmacokinetic patterns (other than hepatic) are similar to those in an adult. Liver enzymes are increased due to larger liver size in proportion to body weight. So drugs that are eliminated by hepatic mechanisms may need more frequent dosing or change in dosing. Liver function advances rapidly with ability to excrete medication mature at about 1 year.
renal system may excrete more rapidly than adults. Due to increased percentages of body water and less fat, water soluble drugs may be administered in larger doses to infants. Thin skin and large surface area in proportion to weight enhances action of topical medications.
Little research on exact therapeutic dosages in pediatrics, often by off label use. Use Body Surface Area (based on weight and height).
Drug induced or Organ specific damage
toxicity with liver or renal injury
altered glucose metabolism
1)Avoid in all elderly 2) Avoid in adults with certain conditions 3)Use this medicine with caution
·increased use of multiple medications (polypharmacy)
·multiple chronic conditions including deficits in hepatic and renal systems that affect pharmacokinetics
·lower body weights may necessitate use of children’s dosages
·reduced gastric acidity and motility alters absorption
·increases in body fat with resulting increase in fat storage of medications
·less total body water so more risk of toxicity in water soluble drugs
·decreased serum albumin results in less protein binding and more free drug
·alteration in blood flow due to CHF impacts functioning of liver and kidneys as well as transport of drug from site of administration
·overall changes may result in higher blood and tissue levels of drug with increased adverse effects and likelihood of toxicity
·altered numbers or sensitivity of receptors may occur