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Advanced Pharmacology > Lifespan Considerations > Flashcards

Lifespan Considerations Flashcards

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
Q

Considering the Physical

Factors…

A

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

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26
Q

Metabolism in pediatrics

A

 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

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27
Q

Elimination in pediatrics

A

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

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28
Q

When considering drug use—the following age groups should be used:

A

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

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29
Q

Developmental Differences

and Changes

A

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

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30
Q

Formulas used to calculate dose for pediatric patients

A

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

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31
Q

What to consider when prescribing for pediatrics

A

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
Q

When calculating the dosage for an overweight child you should not base it on their actual weight but on____

A

their ideal weight related to age and height

33
Q

What else can you use for calculating weight?

A

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
Q

Route of Drug Administration

and Timing…

A
  • 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
Q

What route of medication is preferred for neonates

A

parenteral IV

36
Q

Adverse reactions unique to pediatrics

A 
 ASA
 Chloramphenicol
 Oral Glucocorticoids (prednisone)
 Fluoroquinolones (Ciprofloxacin)
 Tetracyclines
37
Q

Why is geriatric pharmacotherapy challenging

A
  • 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
Q

Age-Associated Changes in

Pharmacokinetics

A
  • Absorption
  • Distribution
  • Metabolism
  • Elimination
39
Q

Aging and Absorption

A
  • 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
Q

Factors that Affect Drug Absorption

A
  • 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
Q 
Effects of Aging on Volume
of Distribution (Vd)
A
  • 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
Q

Metabolism changes in aging

A
  • Aging decreases liver blood flow, size and mass

* Drug clearance is reduced for drugs subject to phase I pathways or reactions

43
Q

Which metabolic pathways is preferred for geriatrics and why

A

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
Q

CYP450 changes in aging

A

• 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
Q

Other factors that affect drug metabolism

A
  • age and gender
  • hepatic congestion from heart failure-reduces metabolism of warfarin
  • smoking-increase clearance of theophylline
46
Q

Elimination and aging

A
  • 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
Q

Kidney function in aging

A
  • 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
Q

What does a decrease in lean body mass lead to as you age

A

lower creatinine production and lower GFR

**the serum creatinine stays in normal range, masking change in creatinine clearance

49
Q

2 ways to determine creatinine clearance

A
  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
Q

Commonly overprescribed and inappropriately used drugs

A 
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
Q

Commonly under-prescribed drugs

A
  • 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
Q

Risk factors for ADEs in the aging

A
  • 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
Q

ADE prescribing cascade

A

Drug 1» Adverse drug effect—
misinterpreted as a new medical condition&raquo_space; Drug 2» Adverse drug effect—
misinterpreted as a new medical condition

54
Q

What are the most common drug drug interactions

A

CV and psychotropic drugs

55
Q

Key facts about drug drug interactions

A

• 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
Q

Most common adverse effects of drug drug interactions

A
  • Neuropsychologic—primarily delirium
  • Arterial hypotension
  • Acute kidney failure
57
Q

ADE: ACE inhibitor + potassium-sparing

diuretic

A

Hyperkalemia

58
Q

ADE: Anticholinergic + anticholinergic

A

Cognitive decline

59
Q

ADE: Calcium channel blockers +

erythromycin or clarithromycin

A

Hypotension and shock

60
Q

ADE: Concurrent use of ≥3 CNS active

drugs

A

Falls and fractures

61
Q

ADE: Digoxin + erythromycin,

clarithromycin, or azithromycin

A

Digoxin toxicity

62
Q

ADE: Lithium + loop diuretics or ACE

inhibitor

A

Lithium toxicity

63
Q

ADE: Peripheral alpha1 blockers + loop

diuretics

A

Urinary incontinence in women

64
Q

ADE: Phenytoin + SMX/TMP

A

Phenytoin toxicity

65
Q

ADE: Sulfonylureas + SMX/TMP,
ciprofloxacin, levofloxacin,
erythromycin, clarithromycin,
azithromycin, and cephalexin

A

Hypoglycemia

66
Q

TADE: amoxifen + paroxetine (other

CYP2D6 inhibitors)

A

Prevention of converting tamoxifen to its active

moiety, resulting in increased breast cancer related deaths

67
Q

ADE: Theophylline + ciprofloxacin

A

Theophylline toxicity

68
Q

ADE: Trimethoprim (alone or as
SMX/TMP) + ACE inhibitor or ARB or
spironolactone

A

Hyperkalemia

69
Q

ADE: Warfarin + SMX/TMP, ciprofloxacin,
levofloxacin, gatifloxacin,
fluconazole, amoxicillin,
cephalexin, and amiodarone

A

Bleeding

70
Q

ADE: Warfarin + NSAIDs

A

GI bleeding

71
Q

COMMON DRUG-DISEASE INTERACTIONS

A

• 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
Q

BEFORE PRESCRIBING

A NEW DRUG, CONSIDER…

A

• 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
Q

Predictors of non-adherence

A

➢Asymptomatic disease
➢Inadequate follow-up
➢Patient’s lack of insight of value of treatment
➢ Missed appointments/transportation difficulties
➢Poor provider-patient relationship

74
Q

Interventions to improve drug compliance

A

➢ 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
Q

Goals of Beers Criteria

A

▪ 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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