Pharmacology - Individual Variations

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what is the bioavailability variation in absorption?

*Ability of the drug to reach the systemic circulation from its site of administration -When a medication is administered intravenously, its bioavailability is 100 %. -When a medication is administered via other routes (such as orally), its bioavailability generally decreases (due to incomplete absorption and first-pass metabolism) or may vary from patient to patient.

what is geriatric distribution? [review slide 32/37]

*Increased percentage of body fat - Storage depot for lipid-soluble drugs Decreased percentage of lean body mass *Decreased total body water - Distributed in smaller volume; thus concentration is increased and effects are more intense Reduced concentration of serum albumin - May be significantly reduced in the malnourished *Causes decreased protein binding of drugs and increase in levels of free drugs

what is geriatric drug adherence?

Nonadherence is common among the elderly Most cases (75%) of nonadherence are intentional. Reasons include: Expense, side effects, patient's conviction that the drug is unnecessary or the dosage too high patient not following medication education and not taking some drugs purposefully.

what/who are geriatric patients?

Old patients are generally more sensitive to drugs that are younger adults. *Individualization of therapy for the elderly is essential. Symptoms in elderly often nonspecific - Dizziness, cognitive impairment (hard to judge since symptoms could be due to old age)

what is drug therapy during pregnancy?

Placental drug transfer - All drugs can cross placenta. Some can cross more easily than others. Drugs that are lipid soluble cross the placenta easily, whereas drugs that are ionized, highly polar, or protein bound cross with difficulty.

what is the distribution drug therapy in neonates and infants?

Protein-binding capacity is limited early in life. Hence, free concentrations of some drugs may be especially high - metabolism/excretion is much slower/not fully developed. The blood-brain barrier is not fully developed at birth. Hence neonates are especially sensitive to drugs that affect the CNS More concerning in 3-5 months that over a year because metabolism increases then.

what is geriatric absorption?

Rate of absorption may slow, although the extent of absorption is usually unchanged. similar to infants

what is geriatric excretion?

Renal function undergoes progressive decline beginning in elderly adulthood - Reductions in renal blood flow, GFR, active tubular secretion, and number of nephrons *Drug accumulation secondary to reduced renal excretion is the most important cause of adverse drug reactions in the elderly. *most important concern.

what is the diet aspect of individual variation in drug responses?

Starvation reduces protein binding of drugs (by decreasing the level of plasma albumin), which increases levels of free drugs. Good health and nutrition can enable drugs to elicit therapeutic responses.

what is the metabolism drug therapy in neonates and infants?

The drug-metabolizing capacity of neonates is low. Hence, neonates are especially sensitive to drugs that are eliminated primarily by metabolism Renal excretion of drugs is low in neonates. Hence, drugs that are eliminated primarily by the kidney must be given in reduced dose

what is pharmacogenomics? what is an example?

The study of how genes affect individual drug responses - Alterations in the genes that code for drug-metabolizing enzymes can result increased or decreased metabolism Eg: Warfarin-CYP2C9 (Warfarin is metabolized very slowly in some patients because their gene codes)

how many of pediatric patients use drugs? what are the 2 laws? why are the sensitive to drugs?

Two-thirds of drugs or more used in pediatrics have never been tested in pediatrics Two laws- Best Pharmaceuticals for Children Act - 2002 & Pediatric Research Equity Act of 2003 Because of organ system immaturity, very young patients are highly sensitive to drugs

what are ADRs related to organ immaturity/ongoing growth+development? [will be on quiz for sure]

Growth suppression (caused by glucocorticoids) - used to treat asthma - for peds patients, one of the major things to monitor is gross retardation & adults: immune suppression osteoporosis. Discoloration of developing teeth (tetracyclines) - pregnant women should not take these - nor should it be mixed with milk/high calcium foods - the drug can cause the fetal barrier and can cause permanent tooth discoloration -affect those less than 8 years old.

what is geriatric metabolism?

Hepatic metabolism declines with age. Half-life of some drugs may increase, and responses are prolonged. Responses to oral drugs (those that undergo extensive first-pass effect - becomes decreased) may be enhanced.

what is the pregnancy aspect of individual variation in drug responses?

Increased maternal HR, CO and blood volume, which might affect absorption, distribution and effectiveness Drugs may cross placenta Drugs may cross into breast milk

what is the absorption drug therapy in neonates and infants?

Increased sensitivity in infants due to: Immature state of pharmacokinetic Absorption of IM drugs in infants is more rapid than in adults - slower in neonates because blood flow is much poorly developed.

what is the kidney/liver pathophysiology of individual variation in drug responses?

Kidney disease: Reduced excretion and increased toxicity Liver disease: Reduced metabolism and increased toxicity

how do you minimize and respond to teratogenesis?

Minimizing - Avoid unnecessary drug use (for example, alcohol). 50% of pregnancies are unintended - risks for teratogenesis apply to these pregnancies, too. Responding exposure - Identifying details of exposure & Ultrasound scans

what are the pharmacokinetics of children 1+ years?

Most pharmacokinetic parameters similar to those in adults Drug sensitivity more like that for adults than for children less than 1 year old One important difference: Metabolize drugs faster than adults (1-12 years) - Markedly faster until 2 years of age, then a gradual decline & Sharp decline at puberty

what are the categories of pregnancy?

A: controlled studies in pregnancy (<1 %) - ex. acetaminophen. B: animal studies show no risk; Inadequate human data. C: animal studies show risk, inadequate human data. D: human data show possible risk, benefit may outweigh risk (have seizures so you have to take the medicine cause its safer than having a seizure when pregnant) X: animal or human data positive for risk. Use unwarranted.

what is the tolerance aspect of individual variation in drug responses?

Decreased responsiveness to a drug as a result of repeated drug administration - Require higher doses due to receptor changes (hypersensitivity/desensitization) metabolism can be the reason for tolerance - MOA: morphrine: (pharmacodynamic tolerance) and barbiturates (metabolism increases over time, require higher dose)

what are teratogenesis? what are examples of teratogenesis?

About 3% of all babies are born with gross structural malformations - don't always blame the drugs. Less than 1% of birth defects are caused by drugs Teratogen-induced malformations results exposure early in pregnancy (Week 3-Week 8) If drug exposure is not from week 3 to week 8, the drug-induced malformation is minimal - Functional impairments (eg mental retardation) result from exposure to teratogens later in pregnancy - ie., drug induced down syndrome (exposure in 2/3rd trimester because its a mental abnormality) Live-virus vaccines are contraindicated for pregnancy due to possible teratogenic effects (killed viruses are more effective anyway) ex. gross malformation (cleft palate, clubfoot, hydrocephalus) & neurobehavioral/metabolic anomalies.

what is the race aspect of individual variation in drug responses?

African American respond to cardiovascular drugs less effective Asian much smaller dose

what are the age, body weight and composition of individual variation in drug responses?

Age: Infants and elderly patients especially sensitive to drugs - Infants = those under 1 yr old, organ immaturity &Elderly patients = organ degeneration (due to increased severity of illness, multiple pathologies, treatment with multiple drugs) Body weight and composition: BSA (body surface area) versus weight Dosage adjustments made often base on BSA, rather than simply on body weight (puts fat into consideration)

what is the gender aspect of individual variation in drug responses?

Alcohol is metabolized more slowly by women than by men. Certain opioid analgesics are much more effective in women than in men (due to hormones such as estrogen) Quinidine causes greater QT-interval prolongation in women than in men (never give 2 prolonging drugs together).

what is breast feeding in relation to drugs?

Although most drugs can be detected in breast milk, concentrations are usually too low to harm the nursing infant. If drugs are not be avoided during breast-feeding, common sense dictates choosing drugs known to be safe and avoiding drugs known to be dangerous. Dosing immediately after breast-feeding to minimize drug concentrations in milk at the next feeding.

what is the placebo effect?

Any response a patient has to a placebo is based solely on his or her psychologic reaction to the idea of taking a medication and not to any direct physiologic or biochemical action of the placebo itself.

what is geriatric drug management?

Current medications should be reviewed before prescribing new medications - "start low, go slow!" *Prescribe the smallest effective number of medications for the shortest effective time in the smallest effective number of doses

what is the summary of pediatric considerations?

Decrease oral absorption (Decreased gastric acid production and slower gastric emptying time)/Thinner skin (increased topical absorption) Decreased plasma protein concentration distribution Increased Free protein-bound drug availability Increased extracellular fluid in neonate Decreased Elimination/metabolism (neonate/infant) BSA/weight based dosing important! Neonates to adolescence = higher % of body water (younger) and body fat (older individuals) which affect the distribution of drugs.

what is the summary of geriatric considerations?

Decreased oral absorption (decreased GI function) Decreased plasma protein concentration Decreased Muscle mass, body fat Decreased Liver/renal function Multiple drugs Multiple diseases Cognitive function decreased

how are pediatric patients categorized?

premature: <36 wks gestational full term: 36-40 neonates: first 4 postnatal wks infants; 5-52 postnatal children: 1-12 years adolescents: 12-16 years


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