Obesity, DMII, Smoking, Illicit Drug use, Unhealthy Diet, and Alcohol abuse

Pregnancy induced hypertension --> Preeclampsia Ectopic Pregnancy Gestational Diabetes Infections Anemia Psychiatric Conditions Fetal health problems

Fetus most vulnerable during the first 12 weeks. There are a range of possible effects that may include infant withdrawal from substances, low birth weight, premature birth, miscarriage and stillbirth

-Total body weight increases by 7-9 liters: 40% to mom; 60% to amniotic fluid, placenta, and fetus. -Colloidal osmotic pressure drops -Considerable amount of Na+ retained -Circulating levels of renin increase until term -> without an expected rise in BP

-Increased absorption of nutrients -Delay in gastric emptying and motility -Decreased gastric acid secretion in 1st trimester—later the pH increases -Prolonged drug absorption and lower peak drug concentrations -Lower serum albumin levels

-Heart enlarges and undergoes hypertrophy -HR and CO increase -Distribution of blood flow change -BP does not rise

-GFR increases increasing elimination of substances -Ability of kidney to concentrate and dilute urine unchanged -Creatinine clearance to 120-220 cc/minute

-Hyperemia of nasopharynx -Higher O2 demands -Stimulant effect of progesterone -> Hyperventilation -Increase in CO2 gradient between mother and fetus = fetus can off load its CO2

-Prolonged gastric transit time -Change in gastric pH -Decreased gastric tone and mobility -Increased absorption through skin, lungs & mucous membrane

-Increased HR, CO, & blood volume -Increased total body water = greater Vd -> increased effect on polar drugs -Increased Vd on polar and fat-soluble drugs -Ratio of albumin to water decreases— decreasing protein binding capacity -T ½ prolonged unless increase in metabolism or elimination drug clearance

-Metabolism promoted by progesterone -Hepatic metabolism increased -During labor hepatic met decreases -Elimination—GFR ↑ [drugs excreted rapidly]

Drugs that are lipid-soluble will pass with ease through the membrane, whereas more polar drugs will be impeded.

Drug in the nonionized form can readily cross the placenta. The ionized form will establish an equilibrium across the placenta.

Drugs up to a molecular weight of 5000 D can cross readily. Drugs, which have low molecular weight, high lipid solubility and a non-ionizable component, however, can easily cross the placenta.

The unbound drug is free to cross the placenta. Drug that becomes bound to fetal proteins would prolong fetal exposure potentially causing ADEs.

-Maternal BP -maternal position -Is there fetal cord compression?

Category A

Category B

Category C

Category D

Category X

Acetaminophen

PCN or a Cephalosporin

Methyldopa, Labetalol, and Nifedipine

Calcium antacids and H2 antagonists

Vit B6, meclizine, Benadryl, Dramamine, diphenhydramine, metoclopramide

Psyllium and polycarbophil, magnesium hydroxide or magnesium citrate, bisacodyl and lactulose

Loperamide

Budesonide, fluticasone, and mometasone nasal sprays

Insulin is the gold standard, but can also use metformin and glyburide

Albuterol and levalbuterol

Lamotrigine and levetiracetam

Citalopram, sertraline, escitalopram, and fluoxetine

-Lipid soluble most readily concentrate -Ionized, polar, or protein bound to a lesser degree -LMW more easily than HMW pass

-Maternal pharmacokinetics -Infant suckling behavior -Amount of milk consumed per feeding -Frequency of breast-feeding -Infant pharmacokinetics

-Avoid sustained release or long acting drugs -Schedule drug so least amount possible gets into milk -Take drug immediately after breastfeeding -Choose a drug that produces lowest levels of drug in milk -Watch for signs of drug reaction in infant

-Amphetamines -Cocaine, heroin, and marijuana -Anticancer drugs -Nicotine -Lithium -Methotrexate -Ergotamine

-Allergic Rhinitis – Beclomethasone; Fluticasone -HTN – HCTZ; Metoprolol -MDD – Zoloft; Paxil -DM – Insulin; Glyburide; Glipizide -Epilepsy – Dilantin; Tegretol -Pain – Ibuprofen; Tylenol; Codeine -Asthma – Cromolyn; Singular -Contraception – Barrier or progestin only

Amoxycillin, Azithromycin, Cefaclor, Cefuroxime, Cephalexin, Cefalexin, Erythromycin, Flucloxacillin, Penicillin V, Trimethoprim

-Premature infant = birth takes place before the 37th week of pregnancy. -Full term = 39 weeks -Neonate = birth to one month -Infant = one month – 2 years -Child = 2 – 12 years -Adolescent = 12-18 years

-Nenonates, infants, and young children -> Increased gastric pH, little muscle tissue, immature peripheral circulation -Neonates and infants -> increased gastric emptying time -Infants and children -> Increased gastric intestinal motility -Neonates -> Decreased bile acid

Reduced albumin concentration and protein binding

Blood brain barrier does not mature until 2 years, and more permeable to drugs

Immature hepatic enzyme capacities and activity placing them at risk of hypoglycemia, hyperbilirubinemia, cholestasis, bleeding, and impaired drug metabolism.

Babies are not as adaptable as adults to temperature change. A baby's body surface is about three times greater than an adult's. Babies can lose heat rapidly, as much as four times more quickly than adults.

The infant has a (basic metabolic rate) BMR/kg more than twice that of the normal adult.

-Increased HR, CO, & blood volume -Increased total body water = greater Vd -Increased effect on polar drugs -Distribution of fat-soluble drugs -Ratio of albumin to water decreases— altering protein binding capacity -T ½ prolonged unless increase in metabolism or elimination drug clearance

Renal function in preterm infants is physiologically still reduced due to ongoing nephrogenesis. Tubular reabsorption remains relatively immature at birth, especially in preterm infants. Ineffective renal concentration before 12-18 months.

The rate at which most drugs are absorbed is slower in neonates and young infants than in older children

-A reduction in the quantity of total plasma proteins (including albumin) in the neonate and young infant increases the free fraction of drug, thereby increasing the availability of the active compound. Increases in the free fraction of a drug may also increase drug distribution in the tissues and can produce adverse effects. -The volumes of extracellular and intracellular water are also greater in neonates, infants, and children than in adults. Thus, hydrophilic drugs will have larger volumes of distribution in newborns and infants on a per kilogram of body weight basis than adults. Similarly, infants have a higher proportion of body fat than adults, which may cause them to have a larger volume of distribution for lipophilic drugs.

-Lack or ↓ activity of liver enzymes—metabolism of drugs is low until age 1 year -T 1/2 prolonged in younger children -T 1/2 in older child can be shorter due to ↑ in metabolic rate—higher doses may be needed to off set ↑ in rate -Temp regulatory mechanism unstable & fluctuates -Faster resting respiratory rate

A reduction in the quantity of total plasma proteins (including albumin) in the neonate and young infant increases the free fraction of drug, thereby increasing the availability of the active compound. Increases in the free fraction of a drug may also increase drug distribution in the tissues and can produce adverse effects.

-Infants have a higher proportion of body fat than adults, which may cause them to have a larger volume of distribution for lipophilic drugs -Highly lipophylic drug (e.g., propofol) will have a smaller volume of distribution in neonates, potentially resulting in higher drug concentrations

The ratio of surface area to body weight is much higher in the full-term neonate than in an adult. Thus, the newborn will be exposed to a relatively greater amount (approximately 2.7 times) of drug topically than an older infant or adult -> leading to potential ADEs

-The ratio of total body water to body weight is greater in the newborn than in older children and adults -Hydrophilic drugs will have larger volumes of distribution in newborns and infants than adults.

-In the pediatric population, gold standard clinical trials are often not available, so practitioners must rely on either less definitive information, such as expert opinion for the age group that they are treating or use evidence from a different population to guide practice. -But NPs cannot prescribe off label

-ASA -Chloramphenicol -Oral Glucocorticoids (prednisone) -Fluoroquinolones (Ciprofloxacin) -Tetracyclines

Tylenol, ASA, and ibuprofen

Reduction in total body water and lean body mass, resulting in a relative increase in body fat

-Higher systolic arterial pressure, increased impedance to left ventricular ejection, and subsequent left ventricular hypertrophy and interstitial fibrosis -Left ventricle becomes stiffer and takes longer to relax and fill in diastole -Reduction in the intrinsic heart rate and increased sinoatrial node conduction time -> elderly subjects rely on an increase in stroke volume to compensate -Aerobic capacity is reduced

-Aging is associated with reduction in chest wall compliance and increased air trapping -Respiratory muscle strength decreases with age -Respiratory system reserve is limited with age, and diminished ventilatory response to hypoxia and hypercapnia makes it more vulnerable to ventilatory failure during high demand states (ie, heart failure, pneumonia, etc)

-Stomach and Duodenum: Decreased hydrochloric acid and pepsin -Small Intestine: Reduced absorption of several substances (e.g. sugar, calcium, iron) while digestion and motility remain relatively unchanged -Pancreas: Some (amylase) remain constant whereas others (lipase, trypsin) decrease dramatically. Secretin-stimulated pancreatic juice and bicarbonate concentrations remain unchanged -Liver: Advancing age is associated with a progressive reduction in liver volume and liver blood flow

-Renal mass decreases with age -> leading to reduced blood flow in the afferent arterioles -Both renal plasma flow and glomerular filtration rate decline with age -The ability to concentrate the urine during water deprivation is reduced -Creatinine is not a reliable indicator of glomerular filtration rate in the elderly subject

Changes in body composition, hepatic and renal function are responsible for an increase in the volume of distribution of lipid soluble drugs, reduced clearance of lipid soluble and water-soluble drugs, respectively. All these changes lead to a prolongation of plasma elimination half-life leading to ADEs

-Amount absorbed [bioavailability] is not changed, but absorption may be slowed -Peak serum concentrations may be lower and delayed -Exceptions—drugs with extensive first-pass effect—bioavailability may increase, and serum concentrations may be higher because less drug is extracted by the liver, which is smaller with reduced blood flow -Divalent cations [Ca++, Mg+, Fe+] can affect absorption of many fluoroquinolones -Enteral feedings interfere with absorption of some drugs [e.g., phenytoin, levothyroxine] -Increased gastric pH may increase or decrease absorption of some drugs -Drugs that affect GI motility can affect absorption

-Body water → lower Vd for hydrophilic drugs [e.g. Ethanol, lithium] -Lean body mass → lower Vd for drugs that bind to muscle [e.g. Digoxin] -Fat stores → higher Vd for lipophilic drugs [e.g. Diazepam, trazodone] -Plasma protein [albumin] → higher percentage of drug that is unbound [active]

-The liver is the most common site of drug metabolism -Metabolic clearance of a drug by the liver may be reduced because aging decreases liver blood flow, size and mass -Drug clearance is reduced for drugs subject to phase I pathways or reactions -Phase II reactions are preferred in older adults

-Induced by rifampin, phenytoin, and carbamazepine -Inhibited by macrolide antibiotics, nefazodone, itraconazole, ketoconazole, and grapefruit juice

Is involved in metabolism of many psychotropic drugs, and can be inhibited by many agents

Oxazepam is metabolized faster in older men than in older women; nefazodone concentrations are 50% higher in older women than in younger women

-Reduced kidney size, blood flow, and functioning nephrons -Reduced renal tubular secretion -Result—decreased kidney function , reduced elimination → drug accumulation and toxicity

Lean body mass → lower creatinine production and glomerular filtration rate (GFR) Result: In older people, serum creatinine stays in normal range, masking change in creatinine clearance (CrCl)

Time-consuming • Requires 24° urine collection • 8° collection may be accurate but not widely accepted Estimate • Usually done with the Cockroft-Gault equation

-Common examples are oversedation, confusion, hallucinations, falls, and bleeding -Benzodiazepines have reduced clearance of the drug and resultant higher plasma levels -Older patients may experience longer pain relief with morphine

Meperidine, ciprofloxacin, warfarin, carbamazepine, brompheniramine, beta-blockers

-Absorption can be increased or reduced -Use of drugs with similar or opposite effects can result in exaggerated or diminished effects -Drug metabolism may be inhibited or induced

-Neuropsychologic—primarily delirium -Arterial hypotension -Acute kidney failure

The use of multiple drugs that may or may not be medically necessary.

The use of several benzodiazepines or several antipsychotics at the same time

Benztropine to manage side effects from haloperidol

-Is this medication necessary? -What are the therapeutic end points? -Do the benefits outweigh the risks? -Is it used to treat effects of another drug? -Could 1 drug be used to treat 2 conditions? -Could it interact with diseases, other drugs? -Does patient know what it’s for, how to take it, and what ADEs to look for?

-Strengthen the Relationship/Partnership With Patients. ... -Help Patients Understand How and Why to Take Each Prescribed Medication. ... -Simplify the Medication Regimen. ... -Understand the Importance of Cost. ... -Use Tools to Build Patients' Self-Efficacy and Support Adherence.

-Medication reviews and counseling to identify barriers, simplify regimens, and provide education -Telephone call reminders -Reminder charts and calendars have been shown to be less effective -Interactive technology to supervise, remind, and monitor drug adherence -Involve a caregiver -Utilize a medication tray

Plasma protein binding

The absorption of topically applied drugs is enhanced in children as compared to adults

Prolonged transit through the gut

Saw Palmetto, Goldenseal, Dong Quai, Ephedra, Yohimbe, Black Cohosh, Roman Chamomile, St. John’s Wortaw Palmetto, Goldenseal, Dong Quai, Ephedra, Yohimbe, Black Cohosh, Roman Chamomile, St. John’s Wort

Red Raspberry Leaf, Peppermint Leaf, Ginger root, Slippery Elm Bark, Psyllium, Garlic, Capsicum

Delay until after first trimester

-Drug elimination ↓ until 1st year of life -GFR 30-40% of adult rate -↓ drug excretion = longer t 1/2 -Perfusion of kidneys often low -Antibiotics & analgesics excreted slowly -↓ ability to concentrate urine

Ideal body weight for age and height

Use their Body Surface Area (BSA)

IV

Reduces metabolism of warfarin

Increases clearance of theophylline

Underestimates