Prescribing for Adults, Children, & Pregnant Women - PDF

Prescribing Cautions For Women, Pregnant Women, Breastfeeding Women, Infants, Children and the Elderly Limitations of Drug Therapy in Children 75% of FDA approved medications lack indications in children Pediatric practitioners actually prescibe “of...

Prescribing Cautions For Women, Pregnant Women, Breastfeeding Women, Infants, Children and the Elderly Limitations of Drug Therapy in Children 75% of FDA approved medications lack indications in children Pediatric practitioners actually prescibe “off label” FDA indications for dosing regimens are lacking Safety is based on post marketing reports of adverse events Despite interest in pediatric drug therapy research, conducting clinical trials poses unique challenges Consider: Recent reports of suicide with SSRI Treatment/ over treatment of ADHD Treatment of GERD Basis for Safe and Effective Pediatric Drug Therapy pediatricpatients are not little adults! long-term effects need to be considered Pharmacological Pediatric Age Groups Preterm (gestational age Parkinsonism ->Sinemet – Dihydropyridine -> edema ->furosemide – NSAID ->H2 blocker ->delirium ->haldol – HCTZ ->gout->NSAID ->2nd antihypertensive – Sudafed ->urinary retention ->alpha blocker – Antipsychotic ->akithesia ->more meds  Drugs and Cognitive Impairment Common cause of potentially reversible cognitive impairment Demented patients are particularly prone to delirium from drugs Anticholinergic drugs are common offenders (TCAs, benadryl and other antihistamines, many others) Other offenders cimetidine, steroids, NSAIDs Contributing Lifestyle Factors for ADRs Alcohol and recreational drugs – The combination of comorbid conditions, physiological changes with age, and concomitant medications is often potentiated with alcohol and drug usage. Caffeine and nicotine use – Caffeine and nicotine are among some of the most commonly used products that have the potential to interact with certain drugs, thereby altering efficacy and therapeutic drug levels.  Drugs and Falls Biggest risk drugs are long acting benzodiazepines and other sedative-hypnotics Both SSRIs and TCAs associated with increased risk of falling Mild increase in fall risk from diuretics, anti- arrythmics, and digoxin Evidence based practice??? Be careful…… – Most guidelines are based on a single disease focus, but most elderly patients have comorbidities. – This makes the risks of drug-to-drug interactions more likely. A new medication added to an older adult's regimen may cause an adverse event that is then misinterpreted as a new medical problem. – This starts a vicious circle of testing, more medication, more drug/drug reactions, and more adverse events. 4 medications/classes caused most of the problem: warfarin (33%), insulin (14%), oral antiplateletes (13%), oral antihypoglycemics (11%). always reconcile what the patient is actually taking before prescribing something new. Reviewing patients' medications by having them bring them all to an office visit in a "brown bag" annually may uncover problems. Beers Criteria Potentially inappropiate Medications for the Elderly  Rules for Geriatric Prescribing Review current drug therapy Get complete drug histories – Medications patient is taking or has taken – Assess compliance potential – OTC’s and Herbals – Allergies / hypersensitivities Start Low and GO SLOW – Allow patient to fully adjust to dose and assess prior to increasing dose  Discontinue unnecessary therapy Use the fewest number of drugs possible Double check dosing for renal and liver insufficiency Vigilantly look for toxicity – CNS changes are often a primary marker – May have atypical presentation of ADR’s Consider adverse drug events for any new symptom If the patient presents with a new problem, FIRST THINK “ What adjustments have we recently made for this patient.”  High Risk Situations Patient seeing multiple providers Patient on multiple drugs Patient lives alone and/or has cognitive impairment Discharge from hospital or any change in venue  Consider nonpharmacologic approaches Use non-pharmacologic options whenever possible Discuss options with seniors prior to initiation of TX – Patient’s concerns – Treatment options – Consequences of non-treatment – Bring the patient “on board”  Substitute with safer alternatives — – Tylenol vs ibuprofen?  Prescribe beneficial therapy Rules Continued Use functional outcomes as a measure of drug efficacy Regularly review all medications Continually assess patient satisfaction and compliance Use samples cautiously Adherence Issues with Pharmacotherapy Complexity of medication regime Belief medication is not needed at prescribed dose Interference with lifestyle Cost factors Side effects Physical and mental changes Self-medication/use of OTC drugs  Summary The elderly take more medications than any other age group Pharmacokinetics and pharmacodynamics are altered Adverse drug reactions are common Risks go up with the number of drugs used Nonprescription and herbal therapies are common With care and common sense, we can probably do a better job Summary Three quotes summarize best practice: – “Any symptom in an elderly patient should be considered a drug side effect until proved otherwise” (Leslie Fine, RPh). – Medications in older adults should “start low and go slow” but to be complete should include “but get there.” – “A medication only works if the patient takes it” (C. Evert Koop). Prescribing for Women  Women historically have not be included in clinical trials around drugs. But they are different Women Absorption – Women have longer gastric emptying times – May need to extend interval between eating and taking meds on an empty stomach – Secrete less gastric acid Distribution Altered by body composition – women have more fat Greater volumes of drug distribution Lipophilic meds like BNZ have longer duration of action Metabolism and excretion Renal clearance slower than in men Liver enzyme system and cytochrome P-450 affect and are affected by drugs women take, like Ocs and HRT Women metabolize ETOH more slowly than men and their livers are more susceptible to damage  Pharmacodynamics – Greater sensitivity to beta blockers, SSRIs, antipsychotics  50-75% more likely to have ADR More prone to torsade de pointes Factors that influence medication administration Women receive more prescriptive drugs then men Are more apt to take meds Depression and connective tissue disorders more common Common diseases may present differently in women Pregnancy and Breastfeeding Pregnancy-Induced Maternal Physiologic Changes/Absorption Gastrointestinal absorption – Decreases in GI tract – Reduction in gastric acid secretions and increase in gastric mucus secretion equals an increase in gastric pH and decrease in absorption of medications that need an acidic pH. – Nausea and vomiting common during pregnancy Pregnancy-Induced Maternal Physiologic Changes/Absorption Lung absorption – Increased cardiac and tidal volumes (50%) result in hyperventilation and increased pulmonary blood flow. – This aids transfer of medications through the alveoli into the maternal bloodstream. Transdermal absorption – Increase in peripheral vasodilation, increase in blood flow to skin, and increase in total body water enhances absorption. Pregnancy-Induced Maternal Physiologic Changes/Distribution Maternal blood volume increases significantly during pregnancy (30% to 50%) and is distributed to organs serving the growing fetus. Total body water increases 8 L causing the volume of distribution of medications to dilute drug concentration.  Drug distribution is affected by an increase in maternal fat deposits, which acts as a reservoir for drugs that favor a fat-soluble environment. Plasma albumin decreases, causing decreased albumin binding and increased free drug concentration. Pregnancy-Induced Maternal Physiologic Changes/Elimination With the increase in renal blood flow by 50% and increased glomerular filtration rate, drugs excreted primarily by the kidney show increased elimination. Factors Affecting the Ability of a Drug to Cross the Placenta Lipid-soluble drugs can cross the placenta more freely than water-soluble drugs because the outer layers of most cell membranes are made up of lipids. Factors Affecting the Ability of a Drug to Cross the Placenta (cont.) Themolecular weight of the drug can determine the ease of placental transfer. The lower the molecular weight or the smaller the drug molecule, the more readily the drug crosses the placenta. Factors Affecting the Ability of a Drug to Cross the Placenta Only drugs that are not bound to a protein (e.g., albumin) can cross the placenta. During pregnancy, the concentration of albumin decreases, and therefore fewer proteins are present, allowing for more unbound or “free” drug to cross the placental membrane. Epidemiology ~35% of women take some medications during pregnancy, npot including OTCs WHO study showed that non-white, unmarried, less educated women less likely to use medications Over 1,000 drugs per year are evaluated for teratogenic potential Resources for Information Dataon drugs in pregnancy and lactation are almost always POST marketing – Constantly being updated-need for immediate access to drug updates Pregnancy categories A – Adequate studies in pregnant women have failed to show a risk to the fetus in the first trimester and there is no evidence of risk in later trimesters B – Animal studies have failed to show a risk to the fetus but there are no adequate studies in pregnancy women; or animal studies have shown an adverse effect but human studies have not shown a risk to the fetus in the first trimester and there is no evidence of risk in later trimesters c  C – Animal studies have shown an adverse effect on the fetus but there are no adequate studies in humans, but the benefits may outweigh the risks; or there are no animal studies and no adequate human studies D – Positive evidence of human fetal risk but the benefits may outweigh the risks X – Animal or human studies have shown fetal abnormalities or toxicity, and the risk outweighs the benefits FDA Categories Category X: Studies, adequate well-controlled or observational, in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. – The use of the drug is contraindicated in women who are or may become pregnant. X-Rated Drugs Accutane Estrogen Propecia Vaccines: MMR, Varicella – CDC Advisory Committee on immunization Practices Vaccinate all pregnant women with INACTIVATED influenza vaccine in the fall or throughout influenza season The safest pregnancy-related pharmacy is as little pharmacy as possible However, women with a history of psychiatric, seizure-related, or hematologic illnesses frequently require medication throughout pregnancy. In such patients, care must to be taken to select the safest drug from the necessary class of medication. Misri and Kendrick noted that prescribing drugs for women during the antenatal and postnatal period is a balancing act and that no risk-free alternatives exist Lessons from the Past Thalidomide first appeared in Germany on 1st October 1957 – marketed as a sedative with few side effects – Considered safe, used for morning sickness – Drug testing procedures were less rigorous – limited testing failed to reveal teratrogenic side effects Pre-marketing tests conducted on rodents which metabolize the drug in a different way to humans – Subsequent tests on rabbits and monkeys produced similar SEs as in humans. – Late 1950’s: post marketing reports – Pharcomelia: babies born with flipper-like limbs AKA: 'Thalidomide Babies’  Some drugs safety varies by trimester – Bactrim contains a folic acid inhibitor and is a category C in the third trimester Harmful in 1st trimester ACE inhibitors/ARBs lung and kidney hypoplasia, hypocalvaria Androgens virilisation of female fetus Antiepileptics cardiac, facial and limb defects, neural tube defects Cytotoxic drugs multiple defects and spontaneous abortion Lithium cardiovascular defects Methotrexate skeletal defects Oestrogens feminisation of male fetus Retinoids ear, cardiovascular, skeletal defects Warfarin nasal hypoplasia, chondrodysplasia,  pregnancy outcome data regarding drug exposure is lacking, especially for newer drugs and those that are rarely used in women of childbearing age. This is in part due to the ethical constraints of enrolling pregnant women into clinical trials.  assess or reassess the need for medication in any woman planning a pregnancy,or who becomes pregnant consider whether it is appropriate to try nondrug measures review medical history balance risks of medication against benefit of treatment on mother and fetus  consider safety of medication (stage of pregnancy, route of administration, dose) use the lowest effective dose for the shortest possible time monitor efficacy of medication throughout exposure The Male Partner… Research is increasingly addressing the role of paternal exposure to medications before conception or during his partner’s pregnancy Certain exposures may alter the size, shape, performance, and production of sperm – suggests that drug exposure in the male may put the fetus at risk Animal studies have shown that paternal teratogenic exposure may lead to pregnancy loss or failure of the embryo to develop – unlike teratogenic agents affecting pregnant woman, teratogenic agents affecting the father do not seem to directly interfere with normal fetal development – Animal studies showing that paternal teratogenic exposure may lead to pregnancy loss or embryonic failure. For example: Colchicine Pregnancy category - D Trimester of risk - Unknown Associated defects and complications - potential chromosome aberrations Studies: Colchicine has been shown to cause birth defects in animals. The drug can lower sperm counts and cause sperm defects, resulting in birth defects.  Finasteride Category X Finasteride is present in semen and therefore may pose a risk to the fetus. Male patients should be instructed to wear a condom during intercourse with women of childbearing potential or discontinue finasteride. The drug should be discontinued in patients wishing to conceive a child. -Women who are or may become pregnant should not handle crushed or broken finasteride tablets when they are pregnant or may potentially be pregnant because of the possibility of absorption of finasteride and the subsequent potential risk to a male fetus. Breastfeeding The mammary gland can be viewed as an elimination organ – the properties of the medication determine how much of the medication will be in the breast milk Breast milk slightly more acidic than plasma Drugs with high molecular weight transfer less easily into the milk Medications Contraindicated or Cautioned in Breast-Feeding Anticonvulsants Antidepressants Chemotherapeutic agents Radioactive isotopes Recreational drugs Factors Affecting Distribution of a Drug into Breast Milk Blood blow to the breast Plasma pH (7.45) and milk pH (7.08) Mammary tissue composition Breast milk composition Physicochemical properties of the drug Extend of drug protein binding in plasma and breast milk Rate of breast milk production  Use the same caution as prescribing for a pregnant woman – Review the safety of the drug during lactation – If it is relatively safe, discuss the risks with the mother – Drug should be taken just after nursing or before the infants sleep – Measure drug concentrations in infants serum if toxicity is likely – Monitor the infant for signs of actions or toxicity Lactation Treatment Goals – Utilize appropriate resources to determine teratogenic risk and excretion in breast milk – Assess the risk: benefit ratio of pharmacotherapy – Utilize drug regimen that is safe, effective and minimizes risk to fetus or infant – Minimize drug exposure to neonate/infant during lactation Selecting a Drug for a Pregnant or Nursing Mother – Timing of exposure in fetal development – If exposure occurs in first 14 days after conception when the cells can assume another cell’s function (totipotential), the fetus may not be damaged Most sensitive period: time from implantation to the end of organogenesis (days 18- 60) – Damage to developing organs – heart is most sensitive during the 3rd and 4th weeks of gestation, external genitalia are most sensitive during the 8th and 9th weeks – brain and skeleton are sensitive from the beginning of the 3rd week to the end of pregnancy and into the neonatal period. Options Avoid long acting/medications with long half lives Temporarily withhold breast feeding – Can safely resume after 1-2 half lives (50%-75% elimination) For drugs with high toxicity, must delay 4-5 half lives A few meds are absolutely contraindicated… Antineoplastic Iodinecontaining radioactive meds Accutane