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Lifespan Considerations Flashcards

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1
Q

Fluid balance during pregnancy

A

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

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2
Q

Pregnancy: GI system

A

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

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3
Q

Pregnancy: cardiovascular

A 
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
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4
Q

Pregnancy: renal

A

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

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5
Q

Pregnancy: respiratory

A 
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
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6
Q

Pharmacokinetic Changes

of Pregnancy—Absorption

A

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

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7
Q

Pharmacokinetic Changes

of Pregnancy—Distribution

A 
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
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8
Q

Pharmacokinetic Changes of

Pregnancy—Metabolism & Elimination

A

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

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9
Q

Factors that Affect Placental Transfer of

Medications

A 
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?
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10
Q

Use of Drugs During

Pregnancy—FDA Classes

A 
***How Teratogenic a Drug Is
Category A
Category B
Category C
Category D
Category X
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11
Q

Category A

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
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12
Q

Category B

A

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

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13
Q

Category C

A

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

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14
Q

Category D

A

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

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15
Q

Category X

A

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

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16
Q

Herbals During Pregnancy

A

 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

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17
Q

General Drug Rules in the

Pregnant Patient

A 
Few drugs a possible
Only if clear need 
Delay until after first trimester 
Smallest dose for shortest time
Monitor mother & fetus
Avoid combination medications
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18
Q

Drugs that Can Be Used during pregnancy

A

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

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19
Q

Lactation Considerations

A

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

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20
Q

Drugs Contraindicated…

While Breastfeeding

A 
Amphetamines
Cocaine, heroin, and marijuana 
Anticancer drugs 
Nicotine
Lithium 
Methotrexate 
Ergotamine
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21
Q

Factors Which Can Affect

Infant Drug Exposure

A 
Maternal pharmacokinetics
Infant suckling behavior 
Amount of milk consumed per feeding
Frequency of breast-feeding 
Infant pharmacokinetics
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22
Q

Minimize Infant Exposure!!!

A

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

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23
Q

Commonly Prescribed

During Breastfeeding

A

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

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24
Q

Considering the Physical

Factors… Absorption in pediatrics

A

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

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25
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
26
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
27
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
28
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
29
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
30
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
31
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
32
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
33
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]
34
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
35
What route of medication is preferred for neonates
parenteral IV
36
Adverse reactions unique to pediatrics
```  ASA  Chloramphenicol  Oral Glucocorticoids (prednisone)  Fluoroquinolones (Ciprofloxacin)  Tetracyclines ```
37
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
38
Age-Associated Changes in | Pharmacokinetics
* Absorption * Distribution * Metabolism * Elimination
39
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
40
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
41
``` 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]
42
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
43
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
44
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
45
Other factors that affect drug metabolism
- age and gender - hepatic congestion from heart failure-reduces metabolism of warfarin - smoking-increase clearance of theophylline
46
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]
47
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
48
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
49
2 ways to determine creatinine clearance
1. 24 hour urine collection 2. estimated with the Cockroft-Gault (weight in kg) (140 – age) / (72) (stable serum creatinine in mg/dL) x (0.85 if female)
50
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 ```
51
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
52
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
53
ADE prescribing cascade
Drug 1>> Adverse drug effect— misinterpreted as a new medical condition >> Drug 2>> Adverse drug effect— misinterpreted as a new medical condition
54
What are the most common drug drug interactions
CV and psychotropic drugs
55
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 
56
Most common adverse effects of drug drug interactions
* Neuropsychologic—primarily delirium * Arterial hypotension * Acute kidney failure
57
ADE: ACE inhibitor + potassium-sparing | diuretic
Hyperkalemia
58
ADE: Anticholinergic + anticholinergic
Cognitive decline
59
ADE: Calcium channel blockers + | erythromycin or clarithromycin
Hypotension and shock
60
ADE: Concurrent use of ≥3 CNS active | drugs
Falls and fractures
61
ADE: Digoxin + erythromycin, | clarithromycin, or azithromycin
Digoxin toxicity
62
ADE: Lithium + loop diuretics or ACE | inhibitor
Lithium toxicity
63
ADE: Peripheral alpha1 blockers + loop | diuretics
Urinary incontinence in women
64
ADE: Phenytoin + SMX/TMP
Phenytoin toxicity
65
ADE: Sulfonylureas + SMX/TMP, ciprofloxacin, levofloxacin, erythromycin, clarithromycin, azithromycin, and cephalexin
Hypoglycemia
66
TADE: amoxifen + paroxetine (other | CYP2D6 inhibitors)
Prevention of converting tamoxifen to its active | moiety, resulting in increased breast cancer related deaths
67
ADE: Theophylline + ciprofloxacin
Theophylline toxicity
68
ADE: Trimethoprim (alone or as SMX/TMP) + ACE inhibitor or ARB or spironolactone
Hyperkalemia
69
ADE: Warfarin + SMX/TMP, ciprofloxacin, levofloxacin, gatifloxacin, fluconazole, amoxicillin, cephalexin, and amiodarone
Bleeding
70
ADE: Warfarin + NSAIDs
GI bleeding
71
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
72
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?
73
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
74
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
75
Goals of Beers Criteria
▪ Improve care by ↓ exposure to PIMS ▪ Educational tool ▪ Quality measure ▪ Research too Prescribing measures vs quality measures is balanced

Advanced Pharmacology (18 decks)

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