Lifespan Considerations Flashcards
Fluid balance during pregnancy
Total body weight increases by 7-9 liters
40% to mum
60% total amniotic fluid, placenta and fetus
Colloidal osmotic pressure drops
Considerable amount of Na+ retained
Circulating levels of renin ↑ until term–Without and expected rise in BP
Pregnancy: GI system
Increased absorption of nutrients
Gastric motility is decreased
Delay in gastric emptying, prolonged drug absorption and lower peak drug concentrations
Decreased gastric acid secretion in 1st trimester—later the pH increases
Reduced gastric tone
Lower serum albumin levels
Pregnancy: cardiovascular
Heart enlarges by about 12% Myocardium undergoes hypertrophy Capacity of the heart for blood increases 10% HR increases 15-20 bpm Cardiac output increases Distribution of blood flow changes BP does not rise
Pregnancy: renal
GFR increases 40-50% at conception
Reaches 150% of normal
Greater elimination of amino acids, glucose, protein, water soluble vitamins, certain drugs and more
Ability of kidney to concentrate and dilute urine unchanged
Creatinine clearance to 120-220 cc/minute
Pregnancy: respiratory
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
Pharmacokinetic Changes
of Pregnancy—Absorption
Prolonged gastric transit time
Change in gastric pH
Decreased gastric tone and mobility
Increased absorption through skin, lungs & mucous membrane
Pharmacokinetic Changes
of Pregnancy—Distribution
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
Pharmacokinetic Changes of
Pregnancy—Metabolism & Elimination
Metabolism promoted by progesterone
Hepatic metabolism increased
During labor hepatic met decreases
Elimination—GFR ↑ [drugs excreted rapidly]
Factors that Affect Placental Transfer of
Medications
Are they lipid soluble? What is the ionized state? What is the molecular weight? Are the drugs protein bound? Maternal BP, maternal position, is there fetal cord compression?
Use of Drugs During
Pregnancy—FDA Classes
***How Teratogenic a Drug Is Category A Category B Category C Category D Category X
Category A
Controlled studies failed to demonstrate risk to fetus—1st or later trimesters Safe for use in pregnancy Fetal harm appears remote Examples—levothyroxine, folic acid
Category B
Animal studies not demonstrated a fetal =risk—but no adequate or well controlled studies in pregnant women
Animal studies showed adverse effects other than decreased fertility but not confirmed in humans
Examples—acetaminophen, amoxicillin, metformin, NPH insulin, Insulin aspart, cimetidine 16
Category C
Animal studies revealed teratogenic, embryocidal or other AE on fetus
No adequate or well controlled studies in pregnant women
“Risk vs Benefit”
Examples—albuterol, ciprofloxin, furosemide,
propranolol, labetalol, pseudoephedrine,
trazadone
Category D
Positive evidence of human fetal risk through well controlled or observational studies in pregnant women
Benefits may justify risks
Examples—ETOH, phenytoin, warfarin, reserpine,
propylthiouracil, Levophed, thiazides, lithium, tetracycline
Category X
Well controlled or observational studies in animals or pregnant women have demonstrated fetal abnormalities
Use of Product Contraindicated
Fetal risk outweighs benefits
Examples—estrogen, progestins, misoprostol, warfarin, statins, Accutane, ACE’s, Thalidomide, Cocaine, Anticancer drugs
Herbals During Pregnancy
Herbs unsafe or likely unsafe—Saw Palmetto, Goldenseal, Dong Quai, Ephedra, Yohimbe, Black Cohosh, Roman Chamomile, St. John’s Wort
Herbs “likely safe or Possibly Safe”—Red Raspberry Leaf, Peppermint Leaf, Ginger root, Slippery Elm Bark, Psyllium, Garlic, Capsicum
General Drug Rules in the
Pregnant Patient
Few drugs a possible Only if clear need Delay until after first trimester Smallest dose for shortest time Monitor mother & fetus Avoid combination medications
Drugs that Can Be Used during pregnancy
Headache –Acetaminophen
Urinary tract infection—PCN or a
Cephalosporin
Hypertension—Methyldopa, Labetalol, Nifedipine
Gastric problems—Calcium antacids, H2 antagonists, ??PPIs—data has changed about PPIs [may not be safe]
Nausea—B6, meclizine, diphenhydramine, metoclopramide
Lactation Considerations
Drug excretion in breast milk—factors which influence an infant’s exposure to drugs in breast milk
All drugs to some degree enter breast milk
-Lipid soluble most readily concentrate [milk fat 3-5% of
total milk volume
-Ionized, polar, or protein bound to a lesser degree
-LMW more easily than HMW pass
Drugs Contraindicated…
While Breastfeeding
Amphetamines Cocaine, heroin, and marijuana Anticancer drugs Nicotine Lithium Methotrexate Ergotamine
Factors Which Can Affect
Infant Drug Exposure
Maternal pharmacokinetics Infant suckling behavior Amount of milk consumed per feeding Frequency of breast-feeding Infant pharmacokinetics
Minimize Infant Exposure!!!
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
Commonly Prescribed
During Breastfeeding
HTN: HCTZ; metoprolol
MDD: zoloft; paxil
DM: insulin, glyburide, glipizide
Epileipsy: dilantin, tegretol
Pain: ibuprofen, tylenol, codeine
Asthma: cromoly, singular
Contraception, barrier or progestin only
Considering the Physical
Factors… Absorption in pediatrics
Neonates/Infants/Young Children: increased gastric pH, little muscle tissue, immature peripheral circulation
Neonates/Infants: increased gastric empyting
Infants/Children: increased gastric intestinal motility
Neonates: decreased bile acid
Considering the Physical
Factors…
Absorption: Route of Administration,PO – pH dependent diffusion, gastric emptying; motility; IM, SQ, IV; Topical
TBW greater in infants & small child (70-80%)
Less body fat (5-12%)
Protein binding is ↓
Serum albumin lower
Immature blood brain barrier
Lower BP affects blood flow to tissues
Metabolism in pediatrics
Immature liver
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
Elimination in pediatrics
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
When considering drug use—the following age groups should be used:
Neonates—birth to one month
Infants—1 month to 2 years
Children—2 years to 12 years
Adolescents—12 years to 18 years
Check with weight of the pediatric patient
Confirm whether the weight is appropriate for the age
If there is any difference in the weight relative to the age—find out about underlying disease states—
cerebral palsy [under weight as a baby]
Check if there is a need to calculate the dose based on BSA
Weight of the baby should be rechecked at each visit before prescribing
Developmental Differences
and Changes
Larger body surface area
Increased total body water in neonates & infants
Metabolic rate 2 times higher than adult
25 % infants weight is muscle mass
Peripheral circulation less developed
Heart rate more rapid
Increased gastric pH
Immature hepatic enzyme capacities and activity
Reduced albumin concentration and protein binding
Unstable glucose concentrations
Unable to concentrate bilirubin
Ineffective renal concentration before 12-18 months
Blood brain barrier not mature until 2 years
Immature immune system
Smaller body size—height and weight
Body Surface Area (BSA), nomogram’s
Greater body fluid than adults
Body fat
Formulas used to calculate dose for pediatric patients
Clark’s formula—Dose = weight in pounds
[divided by 150] X Average adult dose
Fried’s formula—Dose = Age in months
[divided by 150] X Average adult dose
Young’s formula—Dose = Age in years
[divided by age + 12] X Average adult dose
What to consider when prescribing for pediatrics
While mentioning the dose in the prescription, always put a zero in front of the decimal points e.g. 0.5g (better
to write 500mg) and hence never omit a zero before the decimal point
Do not prescribe liquids in mL unless indicated in your drug reference
If prescribing in mL, specify the concentration
Always rewrite a prescription when
dose or timing altered
When calculating the dosage for an overweight child you should not base it on their actual weight but on____
their ideal weight related to age and height
What else can you use for calculating weight?
body surface area is more accurate the body weight
Body surface area may be calculated from height and weight by means of a nomogram or using Body surface area (BSA) calculator
√Ht in cm X Wt. in kilogram [divided by 3600]
Route of Drug Administration
and Timing…
- Choose suitable route of administration before prescribing a drug for a pediatric
- Wherever possible, painful intramuscular (IM) injections should be avoided in children
- take into consideration school timing
What route of medication is preferred for neonates
parenteral IV
Adverse reactions unique to pediatrics
ASA Chloramphenicol Oral Glucocorticoids (prednisone) Fluoroquinolones (Ciprofloxacin) Tetracyclines
Why is geriatric pharmacotherapy challenging
- More drugs are available each year
- FDA and off-label indications are expanding
- Formularies change frequently
- Scientific advances in the understanding of drug-drug interactions
- Drugs change from prescription to OTC
- “Nutraceuticals” (herbal preparations, nutritional supplements) are booming
Age-Associated Changes in
Pharmacokinetics
- Absorption
- Distribution
- Metabolism
- Elimination
Aging and Absorption
- 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
Factors that Affect Drug Absorption
- 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
Effects of Aging on Volume of Distribution (Vd)
- Age-associated changes in body composition can alter drug distribution—distribution refers to the locations in the body a drug penetrates and the time required for the drug to reach these levels; expressed as the volume of distribution [Vd]
- 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]
Metabolism changes in aging
- Aging decreases liver blood flow, size and mass
* Drug clearance is reduced for drugs subject to phase I pathways or reactions
Which metabolic pathways is preferred for geriatrics and why
Phase II
Phase II pathways convert drugs to inactive
metabolites that do not accumulate—with few exceptions, drugs metabolized by phase II pathways are preferred for older patients
CYP450 changes in aging
• In vivo age- and gender-related reductions in drug clearance have been found for CYP3A4 substrates
CYP3A4 is:
➢ Induced by rifampin, phenytoin, and carbamazepine
➢ Inhibited by macrolide antibiotics, nefazodone, itraconazole, ketoconazole, and grapefruit juice
Other factors that affect drug metabolism
- age and gender
- hepatic congestion from heart failure-reduces metabolism of warfarin
- smoking-increase clearance of theophylline
Elimination and aging
- Half-life—time for serum concentration of drug to decline by 50%
- Clearance—volume of serum from which the drug is removed per unit of time [L/hour or mL/minute]
Kidney function in aging
- Reduced elimination → drug accumulation and toxicity
- Aging and common geriatric disorders can impair kidney function
kidney size decreases
renal blood flow decreases
number of functioning nephrons decreases
renal tubular secretion decreases
What does a decrease in lean body mass lead to as you age
lower creatinine production and lower GFR
**the serum creatinine stays in normal range, masking change in creatinine clearance
2 ways to determine creatinine clearance
- 24 hour urine collection
- estimated with the Cockroft-Gault
(weight in kg) (140 – age) / (72) (stable serum creatinine in mg/dL) x (0.85 if female)
Commonly overprescribed and inappropriately used drugs
Androgens/testosterone • Anti-infective agents • Anticholinergic agents • Urinary & GI antispasmodics • Antipsychotics • Benzodiazepines • Non-benzodiazepine hypnotics • Digoxin as 1st line for AF or CHF • Dipyridamole • H2 receptor antagonists • Insulin, sliding scale • NSAIDs • Proton-pump inhibitors • Sedating antihistamines • Skeletal muscle relaxants • Tricyclic antidepressants
Commonly under-prescribed drugs
- ACE inhibitors for patients with diabetes and proteinuria
- Angiotensin-receptor blockers
- Anticoagulants
- Antihypertensives and diuretics for uncontrolled hypertension
- β-blockers for patients after MI or with heart failure
- Bronchodilators
- Proton-pump inhibitors or misoprostol for GI protection from NSAIDs
- Statins
- Vitamin D and calcium for patients with or at risk of osteoporosis
Risk factors for ADEs in the aging
- 6 or more concurrent chronic conditions
- 12 or more doses of drugs/day
- 9 or more medications
- Prior adverse drug event
- Low body weight or low BMI
- Age 85 or older
- Estimated CrCl < 50 mL/min
ADE prescribing cascade
Drug 1» Adverse drug effect—
misinterpreted as a new medical condition»_space; Drug 2» Adverse drug effect—
misinterpreted as a new medical condition
What are the most common drug drug interactions
CV and psychotropic drugs
Key facts about drug drug interactions
• Absorption can be increased or decreased
• Use of drugs with similar or opposite effects can result in exaggerated or diminished effects
• Drug metabolism may be inhibited or
induced• Absorption can be or
Most common adverse effects of drug drug interactions
- Neuropsychologic—primarily delirium
- Arterial hypotension
- Acute kidney failure
ADE: ACE inhibitor + potassium-sparing
diuretic
Hyperkalemia
ADE: Anticholinergic + anticholinergic
Cognitive decline
ADE: Calcium channel blockers +
erythromycin or clarithromycin
Hypotension and shock
ADE: Concurrent use of ≥3 CNS active
drugs
Falls and fractures
ADE: Digoxin + erythromycin,
clarithromycin, or azithromycin
Digoxin toxicity
ADE: Lithium + loop diuretics or ACE
inhibitor
Lithium toxicity
ADE: Peripheral alpha1 blockers + loop
diuretics
Urinary incontinence in women
ADE: Phenytoin + SMX/TMP
Phenytoin toxicity
ADE: Sulfonylureas + SMX/TMP,
ciprofloxacin, levofloxacin,
erythromycin, clarithromycin,
azithromycin, and cephalexin
Hypoglycemia
TADE: amoxifen + paroxetine (other
CYP2D6 inhibitors)
Prevention of converting tamoxifen to its active
moiety, resulting in increased breast cancer related deaths
ADE: Theophylline + ciprofloxacin
Theophylline toxicity
ADE: Trimethoprim (alone or as
SMX/TMP) + ACE inhibitor or ARB or
spironolactone
Hyperkalemia
ADE: Warfarin + SMX/TMP, ciprofloxacin,
levofloxacin, gatifloxacin,
fluconazole, amoxicillin,
cephalexin, and amiodarone
Bleeding
ADE: Warfarin + NSAIDs
GI bleeding
COMMON DRUG-DISEASE INTERACTIONS
• Obesity alters Vd of lipophilic drugs
• Ascites alters Vd of hydrophilic drugs
• Dementia may sensitivity, induce paradoxical
reactions to drugs with CNS or anticholinergic activity
• Renal or hepatic impairment may impair detoxification
and excretion of drugs
BEFORE PRESCRIBING
A NEW DRUG, CONSIDER…
• 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?
Predictors of non-adherence
➢Asymptomatic disease
➢Inadequate follow-up
➢Patient’s lack of insight of value of treatment
➢ Missed appointments/transportation difficulties
➢Poor provider-patient relationship
Interventions to improve drug compliance
➢ 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 (limited availability, has not undergone extensive scientific analysis)
➢ Involve a caregiver
➢ Utilize a medication tray
Goals of Beers Criteria
▪ Improve care by ↓ exposure to PIMS
▪ Educational tool
▪ Quality measure
▪ Research too
Prescribing measures vs quality measures is balanced
