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Advanced Pediatric Pharmacology Exam 1 > Principles of Pharmacotherapy (Week 1) > Flashcards

Principles of Pharmacotherapy (Week 1) Flashcards

1
Q

Pharmacokinetics

A

Study of the absorption, distribution, metabolism, and excretion of drugs (ADME)

*How the body affects the drug

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2
Q

Pharmacodynamics

A

The study of the relationship of the action of a drug in the body over a period of time

*How the drug affects the body

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3
Q

Half Life (3)

A
  1. Time required for serum concentration to decrease by 50% after absorption/distribution
  2. Approximately 5 half-lives to reach steady-state
  3. Dose frequencies are based on half life
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4
Q

Steady State

A

When drug concentration is consistent after each dose
-5 half lives to reach steady state values

*Give a dose, then wait a certain amount of time, then re-dose and it accumulates over time to eventually reach state state with multiple dosing

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5
Q

Efficacy Max

A

Maximum response of the system to the drug

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6
Q

EC50

A

Concentration of drug that produces 1/2 of the maximum response
*Dose at which 50% of individuals exhibit an effect

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7
Q

Potency

A

Comparative measure referring to the different doses of 2 drugs needed to produce the same effect

Example: Famotidine 1mg/kg produces same effect as Rantidine 5mg/kg

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8
Q

AUC

A

Area Under Curve –> the duration of effects of a drug; may be much larger in certain drugs but you won’t see as large of a maximum

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9
Q

Tmax, MEC, MTV

A

Tmax: time it takes to get to maximum concentration

MEC: Minimum effective concentration (below this it won’t be effective)

MTC: Maximum toxic concentration (above this will be toxic)

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10
Q

Absorption

A

Movement of a drug into the stream
*IV DOES NOT HAVE ABSORPTION! goes straight to bloodstream

Routes:
Oral
Rectal
Intramuscular
Percutaneous
Transdermal
Intraosseous
Peritoneal
Inhalation
Intraocular
Intrathecal
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11
Q

Factors affecting absorption w/ age comparisons (4)

A
  1. Gastric pH
    - Premature infants have higher pH
  2. Gastric emptying time
    - Children have increased gastric emptying, so less is absorbed
    - Neonates have decreased gastric emptying, so more is absorbed
  3. Bile acid and bilirubin excretion
  4. Pancreatic enzymes
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12
Q

How does gastric pH affect absorption

A

It affects drug dissolution and changes will either increase or decrease drugs depending on their chemical structure
-Premature neonates have much higher gastric pH so acid labile drugs are going to have increased absorption

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13
Q

First Pass Effect

A

Drug concentration can be significantly reduced before getting into the circulation because it goes through the liver first

  • Only occurs with oral administration
  • Can bypass first pass effect by giving sublingual or buccal mucosa
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14
Q

Absorption differences in infants (5)

A
  1. Gastric pH
    - Increased in infants (prolonged absorption of acid labile drugs)
    - Higher stomach pH increases absorption in premature infants
  2. Prolonged gastric emptying
  3. Reduced bile acids and pancreatic enzymes
    - Decreased pancreatic enzyme and biliary activity decreases absorption of lipid soluble drugs
  4. Reduced bilirubin excretion
  5. Immature or altered permeability of intestinal mucosa
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15
Q

What age does absorption normalize?

A

2

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16
Q

Rectal Absorption (4)

A
  1. Absorption is typically erratic and incomplete
  2. Reduced bioavailabiluty
  3. Rectal absorption is decreased
  4. Rectal administration isn’t 100% effective
    * Would need increased dose for rectal admin
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17
Q

Percutaneous Absorption in Children (4)

A
  1. Thinner striatum
  2. Higher water content in dermis
  3. Greater body surface area to body weight ratio

THIS MEANS ABSORPTION IS INCREASED IN NEWBORNS (pharmacokinetics) – greatly increased in newborns

  1. Patches on children (up to age 5) will have greater absorption **
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18
Q

Drug distribution

A

Movement of drug from one compartment to another within the body

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19
Q

One compartment vs. Two compartment model

A

One compartment: Drug is immediately distributed through the body (take a pill and it will go to entire body evenly)

Two compartment: Drug is first distributed to central compartment (ex: lungs, heart, kidney) then is distributed throughout the body
-Goes to systemic circulation and then rest of the body

20
Q

Factors Affecting Drug Distribution (7)

A
  1. Concentration gradient
  2. Blood flow
  3. Lipophilicity/hydrophilicity
  4. Molecular weight (ex: if drug is very big it may not go through BBB)
  5. Protein binding –> only unbound drugs will be able to exert pharmacologic activity
    * Some drugs are highly protein bound and only the unbound drug will be available to go to site of action and exert effects
  6. Permeability of capillary beds
  7. Blood brain barriers
21
Q

Protein Binding (5)

A
  1. Only unbound drugs exert pharmacologic effects
    - ONLY FREE DRUGS CAN HAVE ACTIVITY
  2. If two drugs are competing for protein binding, you may see toxic effects
  3. If a drug binds to the same site as bilirubin binds and a baby has high bilirubin, then you’re at risk for kinecteris or encephalopathy
  4. Neonates see more free drugs
  5. If a patient is sick and has low serum albumin, you need to do a calculation to adjust dose for it
22
Q

Drugs with high protein binding (30)

A
  1. Phenytoin – would require serum albumin dose adjustment

2. Ceftriaxone – binds to same site as bilirubin so never give to neonates under 30 days

23
Q

Distribution Differences in Children: Plasma Protein Binding (3)

A
  1. Decreased in younger infants – increased free drug (increased availability)
  2. Fetal albumin: decreased binding affinity with acidic drugs
  3. Competitive binding: bilirubin, free fatty acids and drug competed for albumin binding sites
    - Highly protein bound drugs displace bilirubin from protein binding sites (kernicterus)
24
Q

Plasma Protein Comparisons to Adults (3)

A
  1. Total protein: decreased in neonate/infant
  2. Plasma albumin: decreased or equal in neonate/infant
  3. Unconjugated bilirubin: increased or equal in neonate/infant

All are equal in children

25
Q

Blood Brain Barrier (3)

A

Most drugs do not easily pass through BBB

  1. Drugs with low lipid solubility can’t cross BBB
  2. Drugs with high lipid solubility can cross BBB
  3. Inflammation can increase concentrations into the brain because junctions are separated (helpful when treating sepsis)
26
Q

Drug metabolism

A

Transformation of a drug into the active formulation to allow the pharmacologic effects
-Transforms drug from inactive to active state

Not all drugs undergo this but an example of one that does is Plavix

27
Q

Phase I Metabolism (3)

A
  1. CYP enzymes (mixed function oxidase enzyme system)
  2. Increases hydrophilicity of drugs to facilitate elimination of drugs by the kidney
  3. This is decreased in neonates
28
Q

Phase II Metabolism (3)

A
  1. Conjugation reactions
  2. Enzymes which catalyze the formation of conjugates with the oxidized drug or parent compound; metabolism influences the drug action
    * Can end up with an active metabolism
  3. Has variable effects in neonates; some drugs have increased metabolism and some have decreased
29
Q

Metabolism Alterations in Children (3)

A

HEPATIC CLEARANCE

  1. Somewhat delayed and then increased in first 3 months of life
  2. Exceeds adult clearance during preschool years
  3. Declines to adult levels in adolescent years
30
Q

Substrate (2)

A
  1. A drug can be a substrate of an enzyme (gets acted upon by an enzyme) so if you are also taking an inducer or inhibitor, the drug will be affected
  2. The substrate undergoes metabolism and may affect the enzyme that it goes through
31
Q

Inducer

A

Stimulates synthesis of enzyme capacity

-Increases expression of an enzyme and therefore metabolism will increase

32
Q

Inhibitor

A

Prevents enzyme from synthesizing drug (inhibits enzyme activity); may need to increase dose of drug

33
Q

CYP450

A

enzyme that metabolizes

  • Heme containing membrane proteins located on smooth reticulum of liver, kidneys, skin, GI, lungs
  • Responsible for transformation of drugs via oxidation
34
Q

Excretion

A

Removal of active and inactive drugs via renal or biliary excretion (can be active or passive)

35
Q

Renal Excretion

A

Main route that drugs exit the body

Rate is dependent on property and concentration of the drug (pharmacological properties) in the body and rate of urine elimination and kidney function

36
Q

Estimating Renal Function: Schhwartz Equation

A

CrCl = K x L/SCr

CrCl: Creatinine Clearance
K: Constant
L: Length (height) in cm
SCr: Serum creatinine (mg/dL)

*May not be accurate for infants

37
Q

Biliary Excretion

A

Drugs in the liver may be secreted along with bile into the duodenum
*May also be reabsorbed

38
Q

Excretion Alterations in Children

A
  1. Decreased GFR and tubular secretion at birth (especially during first week of life)
  2. Reaches relative adult function at 6 months of age
39
Q

Adverse Effects Associated with PK changes in pediatrics

A

Increased risk of toxicity

  • impedes linear growth
  • acute dystonic rxn
  • respiratory depression
  • paradoxical hyperactivity
  • cognitive impairments
  • kernicterus
40
Q

Therapeutic Drug Monitoring (TDM)

A

Ensures we are treating patients effectively while limiting adverse effects or toxicity

*Target concentrations are dependent on peak vs. trough and unbound vs. bound drug concentrations

41
Q

TDM Indications (7)

A
  1. Any drug with a therapeutic range
  2. Inadequate response of the medication
  3. Suspected toxicities (i.e. serious or persistent ADE)

Other indicators to monitor

  1. Higher than standard dose required
  2. Suspected noncompliance
  3. New preparations or change in medications
  4. Change in clinical status
42
Q

Peak concentration

A

highest concentration that a medication reaches in the bloodstream

43
Q

Trough concentration

A

lowest concentration that a drug reaches in the blood stream

44
Q

FDA Pregnancy Categories (A-X)

A

A: No risk to fetus during pregnancy

B: Animal studies failed to show risk to fetus

C: Animal studies showed an adverse effect on fetus

D: Positive evidence of human fetal risk

X: No!

D and X are contraindicated in pregnancy

45
Q

Pediatric Dosing

A
  1. Based off on weight (kg) or body surface (BSA)
    - Always write meter dosing on exam: mg/kg
  2. Once child reaches >40kg then standard dosing can be utilized
  3. Can also be based off of gestational age

Advanced Pediatric Pharmacology Exam 1 (8 decks)

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