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Pathophysiology > 4.1 Individual Variation in Pharmacology Across Lifespan > Flashcards

4.1 Individual Variation in Pharmacology Across Lifespan Flashcards

1
Q

Individual Variation

A
  • Patients respond to drugs differently than other patients

- Bodyweight/composition, diet, pathophysiology, tolerance, placebo effect, gender, race, genetics, age.

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2
Q

Body Weight and Composition (Excess Weight)

A
  • Causes more body mass for the drug to saturate
  • Effects how quickly a drug is metabolized/eliminated
    Obese
  • Higher fat and lower lean tissue and water effects distribution of drugs in tissues.
  • Binding of drugs to Albumin is not effected
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3
Q

Body Weight and Composition (Nutrient Deficiency)

A
  • Effects both pharmacokinetics and pharmacodynamics

UNDERNUTRITION/MALNUTRITION - Great potential for altering drug metabolism.
- Effects absorption, plasma protein binding, distribution, bio-transformation/metabolism, and excretion

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4
Q

Diet

A
  • Starvation reduces protein binding of drugs and increases levels of free drugs
  • Certain foods block or enhance absorption of medication
  • Grapefruit - Statis (high cholesterol medication)
  • Calcium rich food - Certain Antibiotics
  • Alcohol - Prescription Stimulants
  • Aged/Pickled/Cured/Fermented Food - Monoamine Oxidase Inhibitors (MAOIs)
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5
Q

Diet Habits

A

Infants - Milk/Formula is primary food intake. This decreases acidity in stomach and alters pH which effects drug absorption. (considered when giving oral meds)

School-Aged and Adolescents - Assess for use of Caffeine, Alcohol, Tobacco, Street Drugs.

  • Question Children/Parents about use of Herbal Therpaies
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6
Q

Environment

A

Economic - Insurance and other resource availability

Safety of Medication - Proper places to store and administer medication

Can drugs be stored away from children’s reach and are parents/guardians responsible for adherence

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7
Q

Pathophysiology

A

Alterations in physiological processes can cause or result from disease/injury

  • Kidney disease results in reduced excretion and increased toxicity
  • Liver disease resulting in reduced metabolism of drug and increased toxicity
  • Acid-Base balances and pH alter absorption, distribution, metabolism, and excretion.
  • Altered electrolytes rarely have a significant impact on drug response
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8
Q

Tolerance

A
  • Decreased response to drug from repeated administrations
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9
Q

Pharmacodynamic Tolerance

A

Results from long term administration of drugs such as morphine/heroin

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10
Q

Metabolic Tolerance

A

Accelerated drug metabolism. (Ethanol induces activity of liver enzymes that metabolize ethanol, resulting in rapid elimination and lower alcohol levels

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11
Q

Tachyphylaxis

A

Acute, sudden decrease in response to drug after administration. (Rapid and short-term onset of drug tolerance)
- It can occur after a single initial dose or series of small doses
(Possible to restore original response from higher dose)

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12
Q

Placebo Effect

A

Individuals experience response from a drug with no therapeutic value solely on the idea of taking a medication.
- Primary use is in control groups for clinical trials

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13
Q

Variation in Absorption

A

Bioavailability - How much drug reaches the systemic circulation from site of administration

Occurs primarily with oral preparations and not parental administration.

  • Changes in gastric pH, diarrhea, constipation, food in stomach also effect variation in absorption
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14
Q

Pharmacogenomics

A
  • Genes affect drug response (New Study)
  • Goals of studying is to develop medications effective and safe for a persons specific genetic makeup
    Genetic Differences Include
  • Altered drug metabolism
  • Altered drug targets; genetics alter structure of drug receptors
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15
Q

Gender

A
  • Alcohol is metabolized slower in women than men
  • Certain opioids are more effective in women than men
  • Quinidine (antidysrhythmic drug) causes greater QT interval prolongation on electrocardiogram in women than men
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16
Q

Race/Ethnicity

A
  • Variations in pharmacokinetics and pharmacodynamics
  • Tied to genetic/psychosocial/environmental factors
    Black respond better than white to diuretics and calcium channel blockers.
    Whites response better than blacks to angiotensin converting enzyme (ACE) inhibitors and B Blockers.
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17
Q

Adherence

A
  • Lack of adherence (failure to take medicine as prescribed)
  • Issues include manual dexterity, visual acuity, intellectual capacity, psychological state, attitude towards drug, ability to pay for medication
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18
Q

Drug Interaction/Age

A
  • Interactions effect Individual Variation
    Age
  • Infants/Elderly are especially sensitive to drugs
    Infants - Due to organ immaturity
    Elderly - Organ degeneration
    Aging also effects severity of illness, pathologies, treatment with multiple drugs
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19
Q

Pharmacology in Pediatrics

A
  • They undergo physiological changes throughout development that influence both pharmacodynamics and pharmacokinetics
  • Absorption/Distribution/Metabolism/Excretion are all altered in pediatric patients compared to adults
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20
Q

Pharmacodynamics in PEDS

A

Pharmacodynamics target cells and alter cellular reactions and functions

  • Pharmacodynamic variables in ped patients vary because of differences in target cells and fluctuating number of protein receptors on cells.
  • Different body composition, immature systems, and genetics also vary pharmacology in peds
  • Total body water, fat stores, and protein levels change throughout childhood which influences effectiveness of drugs on children
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21
Q

Pharmacokinetics in PEDS

A

Infants - Drug effects are unusually intense and prolonged. Elevated drug levels increase intensity and delayed elimination leads to prolonged response

Liver - Maturity completed in 1 year. Lower doses required
Kidney - Excretion reduced, given lower doses via this route
GI Tract - Gastric emptying reaches adult values by 6-8 months. Delayed emptying in GI tract causes drug absorption in stomach and delayed absorption in small intestines.

22
Q

GI TRACT PEDS (cont)

A

Gastric acidity - Reach adult values at 2 years.
Usually more acidic than adults causing increase in absorption of drugs.

IM absorption is delayed in first days of life due to circulation. Early infancy, IM absorption greater than adults. Percutaneous drugs significantly greater in infants than older children and adults

23
Q

Distribution in Infants

A
  • Infants have greater body water and lower fat
  • Water soluble drugs dilute to a greater degree (lower serum levels)
  • Low levels of albumin so drugs compete for receptor sites (Results in more free drugs and intensified effect)
  • BBB isn’t fully developed so drugs can reach CNS easier
24
Q

Pharmacokinetics (Age 1+)

A
  • Most parameters are similar to those of adults
    Age 1-2
  • Metabolize drugs significantly faster than adults. Requires increase in dosage and reduction in dosing intervals.
    After Age 2
  • Pharmacokinetics reach adult levels
25
Q

Adverse Effects in Children

A

Glucocorticoids - Growth Suppression
Tetracyclines - Discoloration of developing teeth
Sulfonamides - Kernicterus (Brain damage)
Chloramphenicol - Gray Baby Syndrome
Phenothiazines - Sudden Infant Death Syndrome
Aspirin - Reye’s Syndrome (lethal) Swelling of liver and brain

26
Q

Pediatric Dosing

A
  • Doses are almost always weight based
  • Doses are all approximate
  • Subsequent doses based on clinical outcome and plasma drug levels
    (Always consider children’s cooperation, ability to communicate, and adherence to drug requirements)
27
Q

Birth - 12 Months

A
  • Like to suck medication off nipple; can also administer to buccal pouch with oral syringe
  • Rectal Suppository (hold cheeks together for short time)
  • IM - preferred site Vastus Lateralis (upper outer thigh) or Rectus Femoris (anterior mid thigh)
  • IV - Peripheral Scalp Veins
    DOSAGE MUST BE PRECISE
28
Q

13 Months - 3 Years

A
  • Can swallow liquids. Older toddlers can chew oral drugs. (Have parents nearby)
  • IM - Vastus Lateralis, Rectus Femoris
  • IV - Scalp Veins up to 18 months. (If hair must be clipped save it for parents)
29
Q

3-5 Years

A
  • Often uncooperative. Reassure drug will make them feel better
  • Oral - Best are chewable or liquid
    IM - Use EMLA (anesthetic). Vastus Lateralis, Rectus Femoris, Ventrogluteal sites, dorsal gluteal as last resort only if child has been walking for a year.
    IV - Peripheral sites.
30
Q

6-12 Years

A
  • Cooperative
    Oral - Chewable/liquid. Can swallow pills. Embarrassed of Rectal. (Offer privacy)
    IM - Ventrogluteal recommended. Vastus lateralis and Rectus Femoris can also be used. Deltoid in 0.5mL or less for vaccines
  • Peripheral IV sites
31
Q

13-16 Years

A
  • Cooperative (Insure Privacy)

- IM and IV same as adult. Use smallest gauge (3/8”)

32
Q

Maximizing Therapeutic Effects

A
  • Select appropriate drug administration sites, equipment, and techniques.
  • Give in smallest amounts in order to ensure full dose is delivered
  • If drug is spat out estimate amount and report to prescriber
33
Q

Minimizing Adverse Effects

A

Reduce psychological stress and anxiety
Infants - Reduce parental anxiety and infants will respond. (Do not ask parents to restrain infant)
Praise toddlers for receiving a drug. Do not tell them they are bad

34
Q

Prevention of Medication Errors

A
  • Know child’s weight
  • Use reliable information sources
  • Double check dose
  • Only give oral liquids with oral syringe
  • Involve Family
  • Communicate Drug Plan Clearly
  • Document Accuracy
35
Q

Pediatric Patient and Family Education

A
  • Generic and Trade name of Drug
  • Rationale for drug therapy
  • Description of intended therapeutic effect
  • Dose and route of administration
  • Schedule and duration of administration
  • Potential adverse effects
  • Special drug precautions or restrictions
36
Q

Drug Therapy during Pregnancy

A
  • 1/3 trimester renal blood flow doubles and excretion is accelerated. (accelerated excretion of drugs so dosage must be increased.
  • Hepatic metabolism of some drugs increase.
  • Tone and motility of bowels decreased resulting in prolonged transit and increased absorption
37
Q

Placental Drug Transfer

A
  • All drugs can cross placenta

- Lipid soluble drugs cross more easily, ionized or protein bound drugs cross with difficulty

38
Q

Unique Drug Effects During Pregnancy

A
  • Heparin can cause osteoporosis
  • Prostaglandins stimulate uterine contractions
  • Pain relievers can depress respiration in neonate
  • Aspirin use near term can suppress labor contractions and increase risk of serious bleeding
39
Q

Teratogenesis (creating a monster)

A
  • Drugs that cause malformation in an embryo
  • Proof of teratogenesis does not mean it will happen every time and no proof of it happening does not mean it will not happen
  • Difficult to identify
40
Q

Proof of Teratogenesis Criteria

A
  • Drug must cause characteristic set of malformation
  • Must act during a specific window of gestational vulnerability
  • Incidence of malformation should increase with increased dosage and time of exposure
41
Q

Teratogenesis Stages of Development

A

Occurs in 3 stages
Conception - Week 2
Embryotic Period - 3-8 weeks
(Gross malformations produced by teratogens)
Fetal Period - week 9 - term
(Functions disrupted with teratogen exposure)

42
Q

Teratogenesis (cont)

A
  • Minimize risk by avoiding unnecessary drug use (alcohol, cocaine)
  • Response includes assessing what drug was taken, when pregnancy began. Ultrasounds can be utilized to identify potential malformations.
43
Q

FDA Pregnancy Risk Categories

A

A,B,C,D,X has been ruled out

PLLR (Pregnancy and Lactation Labeling Rule) is the new way

44
Q

Drug Therapy during Breast Feeding

A
  • Dose immediately after nursing to minimize concentration at the next feeding.
  • Avoid drugs that have long half lives
  • ## Choose drugs least likely to be excluded in milk
45
Q

Pharmacology and Older Adults

A

15.2% of US Population are 65+
1/3 Take 5 or more medications
50% take 1 or more medications that are not medically necessary

46
Q

Pharmacology of Older Adults

A
  • Increased sensitivity to drugs
  • Wider individual variation in response to drugs
  • More adverse drug reactions
  • More drug-drug interactions
  • Related to degenerating organs which leads to altered pharmacokinetics, multiple and severe illness, multiple drug therapy, and poor adherence.
47
Q

Hepatic Metabolism

A
  • Decreased hepatic blood flow
  • decreased liver mass
  • decreased activation of certain hepatic enzymes.
  • These cause increased half-life and prolonged response
48
Q

Excretion in Older Adults

A
  • Decreased glomerular filtration, decreased renal blood flow, decreased nephrons.
  • Drug accumulation due to decreased renal excretion is the most important cause of adverse drug effects in elderly.
  • Important to evaluate renal function before starting drug therapy. (Creatinine Clearance Test)
  • Better than serum creatinine because elderly have decreased lean muscle mass.
49
Q

Alterations in Pharmacodynamics of Elderly

A
  • Some drugs are more effective in elderly others may be less effective
  • May be due to increase or decrease in number of receptors or increased/decreased affinity to receptors
50
Q

Adverse Drug Reactions (Elderly)

A
  • 7x more common in elderly than adults
  • Accounts for 16% hospital admissions and 50% medication related deaths in elderly.
  • Difficult to identify because they are usually non-specific (dizziness or cognitive impairment)
    (Reduced by gathering drug history, initiate drug therapy in low doses, monitor clinical response, avoid drugs on AGS Beers criteria list)
51
Q

Nonadherence in older patients

A

40% of older adults fail to take drugs as prescribed

75% of nonadherence is intentional where patient doesn’t believe a drug is needed in prescribed dose

52
Q

Core Patient Variables in Older Adults

A

Health Status - Assess mental status for presence of disease. Assess functional ability, environment, and polypharmacy

Lifestyle, diet habits - Level of activity, dietary patterns, ability to swallow, use of alternative medication, preferred schedule of medication at home

Cultural and inherited traits and beliefs of drug therapy

Pathophysiology (18 decks)

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