Dosing Considerations for Vulnerable Populations

1. Dosing Considerations for Vulnerable Populations

2. Vulnerable Populations • Are groups of patients with a high riskforadverse drug effects • Require careful dosing and/or medication selection

3. At-Risk Groups Include • Men and women of reproductive age • Pregnant or breastfeeding women • Children and infants • Elderly patients • People with renal or hepatic disease • Obese or underweight patients

4. Reproductive Age • In women: Drugs can affect fertility or damage ova • In men: Drugs can alter sperm quality and quantity

5. Pregnancy Safety CategoriesA, B, C, D, X • A: Studies have not shown a risk to the fetus • B: Studies have not shown a risk to an animal fetus; however, there are no well-controlled studies in humans • C: Animal studies show an adverse effect and there are no adequate studies in pregnant women or noanimal studies have been conducted and there are no adequate studies in pregnant women • Many drugs fall in category C

6. Pregnancy Safety Categories (cont’d) • D: Studies in pregnant women have shown a risk to the fetus; benefits may outweigh potential risks • X: Studies in animals and pregnant women have shown evidence of fetal abnormalities; the drug is contraindicated in women who are or may become pregnant

7. Drug Properties Impacting Drug Transfer to Fetus • Dosage • Drug chemistry • Lipid solubility • Protein binding

8. Pregnant Women First trimester • A woman is least likely to know she is pregnant • Exposure of fetus to drugs is most harmful during the first trimester • Teratogenic drugs may lead to fetal malformation or miscarriage

9. Pregnant Women (cont’d) Third trimester • Drugs may not be safely metabolized and excreted by the fetus After delivery • Infants no longer have the placenta to help with drug excretion, and drugs given before delivery may cause toxicity

10. Pregnant Women (cont’d) • For pregnant women who require medication, both mother and fetusmust be considered • Weigh risks and benefits Rule of thumb: LOWEST EFFECTIVE DOSE for the SHORTEST PERIOD OF TIME

11. Lactation • Many drugs are known or thought to be excreted in breast milk • Dose in breast milk will be low,but still may cause adverse effects in the infant • Some drugs interfere with milk supply • American Academy of Pediatrics (AAP) lists drugs usually compatible with breastfeeding: http://pediatrics.aappublications.org

12. Lactation (cont’d) • AAP encourages breastfeeding if drug is unlikely to cause harm • In poorer nations, bottle feeding may not be an alternative • Research medication at LactMed: http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT

13. Pediatric Classifications • Premature Infant: <38 week gestation • Neonate/newborn: Younger than 1 month • Infant: 1 month up to 1 year • Child: 1 year up to 12 years

14. Pediatrics: Neonates and Preemies Difficulty in dosing is secondary to • Immature function of body systems • Rapid weight changes • Progressive maturation of hepatic and renal function

15. Pediatric Dosing • Doses for children are not automatically less than those for adults • Higher metabolic rate inchildrencauses drugs to be processed more quickly • Higher doses are needed to maintain therapeutic blood levels

16. Pediatric Dosing (cont’d) Medication doses are based on body weight or body surface area (BSA) • Body weight doses expressed as mg/kg • BSA doses expressed asmg/m2

17. Geriatrics • Physiological changes of people 65 and older affect the action of many drugs • Beers criteria: Drug classes found to increase the risk of adverse effects in older adults. See Davis’ Drug Guide under Medication Safety Tools • Age-related changes affect pharmacokinetics • Absorption: Gastric pH less acidic, gastric emptying slowed, peristalsis slowed, reduction of blood flow in the GI tract

18. Geriatrics (cont’d) • Distribution: Decrease in lean body mass, increase in fat content, reduction in total body water content, protein-binding sites are reduced caused by aging liver • Metabolism: Aging liver, decrease in liver blood flow causes a decrease in liver metabolism • Excretion: Decreased renal filtration rate due to reduction in blood flow, decrease in amount of nephrons • Aging changes lead to greater incidence of toxicity • Prescribe lowest possible dose at initiation of drug(s)

19. Geriatrics (cont’d) Monitor for • Signs and symptoms of toxicity and side effects • Drug interactions • Usage and complications of OTCs and herbal drugs • Effectiveness

20. Patients With Renal Disease • Kidneys are the major organ of drug elimination • Failure to account for decreased renal function is apreventablesource of adverse drug reactions • Assess • Creatinine clearance • BUN and creatinine • Medication blood levels

21. Patients With Liver Disease • The liver is the major organ of metabolism • The liver changes drugs from fat soluble to water soluble so that kidneys can excrete them • Liver damage leads to higher levels of active drug and more toxicity

22. Patients With Liver Disease (cont’d) Monitor • Liver enzymes • Albumin, total protein Assess patient for • Enlarged liver • Ascites, jaundice

23. Patients With Extremes of Body Size Obese patients • Drug dosing often based on body weight • Some drugs do not penetrate fatty tissues • To prevent toxicity when giving drugs that do not penetrate fatty tissue (e.g.,digoxin), determine dose by ideal body weight or estimated lean body mass

24. Patients With Extremes of Body Size (cont’d) Underweight patients likely to be • Chronic alcoholics • Patients with AIDS • Patients terminally ill with cancer and other debilitating illnesses • Patients with amputations No standard formula for calculating dose in underweight patients; watch for toxicity