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Intro to Pharmacology > Targeted Pharmacology > Flashcards

Targeted Pharmacology Flashcards

1
Q

Historically what has been the protective barrier for the fetus?

A

uterus

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2
Q

What drug was prescribed in the 1960s that left children with developmental abnormalities?

A

Thalidomide

Prescribed for pregnant females for anxiety or morning sicknesss

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3
Q

What drug produced gray baby syndrome?

A

choramphenical

drug is cleared thrlough liver and kidneys

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4
Q

What would sulfonamide cause?

A

kernicterus-build of bilirubin

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5
Q

What is increased in pregnant women?

7

A

Blood flow to the skin

pH
Nausea and Vomiting

Blood volume (causes drug concentration in serum to decrease)
Water content of skin
Fat tissue
Renal blood flow/GFR/faster elimination

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6
Q

What is decreased in pregnant women?

4

A

Gastric motility
Gastric Acid secretions (causes increased pH which makes it easier for drugs of a more basic nature to get absorbed and harder for drugs of a more acidic nature to get absorbed)

Albumin concentration
Drug concentration in the serum

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7
Q

Why is nausea and vomiting a risk factor for pregnant women?

A

they are likely to not absorb an adequate amount of nutrients

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8
Q

How much does the blood volume increase?

A

30-50%

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9
Q

Why is the serum concentration reduced in pregnant women?

A

its diluted. An example is phenytoin. you have the same amounts of drug but in more volume

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10
Q

Why does increase in adipose composition affect drug activity?

A

reduced serum drug concentrations of hydrophobic drugs

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11
Q

What does reduced albumin concentration cause?

A

Since there is not as many proteins to bind to there is increased levels of drugs in the blood (increased serum levels)

More free phenytoin to be excreted and working on the body

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12
Q

How do progesterone levels relate to CYP enzyme activity?

A

Induce or inhibit the CYP enzyme. So if CYP enzymes are induced then there will be less drug in the blood. If they are inhibited there will be less drug in the blood.
(totally dependant on the person, and specifically their progesterone levels)

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13
Q

How is elimination affected during pregnancy?

A

Increased renal blood flow
increased GFR
Increased urination

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14
Q

What are the factors that affect medicaiton distribution across the placenta?

A
  1. Lipophilic, hydrophobic, non-ionized
  2. Molecular size
  3. Osmotic gradient
  4. Protein binding affinity
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15
Q

Describe issues with fetal drug exposure and the liver?

A

Fetal hepatic metabolism develops slowly- mother can clear it quickly but the child won’t be able to

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16
Q

When are the critical periods of development in the fetus and how does this relate to drug exposure?

A

critical period is usually during first trimeter

Some meds are considered safer during certain trimesters

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17
Q

What drugs do we want to consider for labor in the final trimester?

A

bleeding during labor

Anticoagulants and antiplatelets

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18
Q

Risk Category A what kind of risk?

A
  • Remote possibility of fetal harm

- No risk of fetal harm demonstrated in controlled trials

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19
Q

Risk Category B what kind of risk?

A
  • Animal studies have no demonstrated fetal harm,
  • human studies have not been conducted

OR

  • Animal studies have demonstrated potential fetal harm,
  • but controlled human trials have been done without evidence of harm
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20
Q

Risk Category C what kind of risk?

A
  • Animal studies have demonstrated potential fetal harm,
  • but there are no controlled trials to confirm the event in humans

OR

No animal or human studies are available

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21
Q

Risk Category D what kind of risk?

A

Evidence of fetal risk has been demonstrated in humans, but use may be justified in some cases based on benefit:risk (benefit risk ratio)

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22
Q

Category X: Teratogens

4

A

NEVER USE:

  • Significant fetal harm shown in studies with animals or humans
  • Significant functional or structural fetal harm
  • Contraindicated in women of childbearing age & throughout pregnancy
  • Risk of use clearly outweighs any potential benefit
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23
Q

When treating pregnant women how do we treat them first?

3

A
  • Non-pharmacologic strategies- use first
  • Minimal effective dose for least amount of time
  • If alternative medications are available use the agent with the best safety profil first
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24
Q

Regarding pregnancy pharmacokinetics, which of the follow is true?

Pregnant patients have:

  1. Increased gastric motility
  2. Decreased water content of skin
  3. Decreased blood flow
  4. Increased blood volume
A

Increased blood volume by 30-50%

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25
Q

Benefits for mother during lactation (why you should breast feed!)
3

A
  • Post-partum depression
  • hypertension
  • epilepsy
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26
Q

What does the rate and extent of passive diffusion depend on?
5

A

Physical properties of the drug:

  1. lipophilic, hydrophobic and nonionized
  2. Degree of ionization
    - the pH of breast milk is around 7-7.2 (serum of 7.4)
    - drug with high pKa = ion trapping
  3. molecular size
  4. Osmotic gradient
  5. protein binding affinity
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27
Q

Maternal factors that you should consider while breastfeeding and whether a drug should be takem or not?
4

A

Blood flow to the breast
Mammary tissue composition
Milk composition
Rate of milk production

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28
Q

How much of the drug does the infant get from the maternal dose?

A

1-2%

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29
Q

All drugs will ingested by the mother will be present in the breast milk to some extent. Why is this rarely an issue?
2

A
  1. Amount of exposure is rarely significant enough to produce clinical doses in a healthy infant
  2. Drugs present in breast milk may not be orally bioavailable
30
Q

What medications could cause adverse effects in the fetus, specifically dowsiness or sedation?
4

A

Analgesics,
anti-histamines,
anti-depressants,
anti-epileptics

31
Q

What medications could cause adverse effects in the fetus, specifically diarrhea?

A

antibiotics

32
Q

What medications could cause adverse effects in the fetus, specifically withdrawl symptoms?
3

A

Some anti-depressants,
nicotine,
drugs of abuse

33
Q

Ways to mimize exposure to the infant?

A
  1. Avoid unnecessary medications
  2. Coordinate medication and feeding schedules
  3. Use minimal effective dose for shortest possible duration
  4. Select drugs with established data & favorable PK profiles
34
Q

Strategies for Coordinate medication and feeding schedules?

2

A
  1. Pump and dump strategy? - pump out the first round and toss it. give the baby the second round
  2. Formula supplementation
35
Q

What kind of drugs would have a favoralbe PK profile?

A
  1. Drugs with established safety in pediatrics may be OK
  2. High molecular weight(> 500 daltons) with short half-lives
  3. High degree of protein binding
36
Q

What kind of drugs inhibit prolactin therefore inhibiting lactation?
2

A

oral contraceptives
levadopa -parkinsons
ropinirole

37
Q

Why would you monitor a newborn or premi more closely?

A

metabolism and execretion issues

38
Q

Which of the following affect(s) the extent of drug that is able to get into breast milk?

  1. Molecular size of the drug
  2. Protein binding affinity of the drug
  3. Degree of ionization of the drug
  4. All of the above
A

All of the above

39
Q

What cannot we not assume about pediatric pharmacology?

A

CANNOT be simplified into the “small adult” principle

40
Q

Is the pediatric population included in most clinical trials?

A

no

41
Q

Differences in bioavailbility of a drug in regards to oral absorption in pediatrics compared to adults?
4

A

Highly variable, dependent on age and development:

  1. Gut pH
  2. Gastric emptying time
  3. Intestinal motility
  4. Biliary and pancreatic function = digestive enzymes
42
Q

Name the fastest aborptions rate mediums in order of fastest to slowest?

A

Liquid formations are generally faster:

  1. Solution
  2. Suspension
  3. Capsule
  4. Tablet
43
Q

Why do we have to be mindful fo alcohol and sugar content in the liquid preps we give children?

A

smaller child is the less alcohol (and sugar) you want because their livers cant handle it

44
Q

How would we describe the bioavailability in percutaneous absorption in premis and neonates compared to adults?
5

A

increased skin permability in prematures and neonates:

  1. Higher degree of hydration
  2. thin skin
  3. increased topical absorption

Normalizes in infancy

45
Q

How would we describe the bioavailability in rectal absorption in peds compared to adults?
5

A
  1. First pass effect is avoided just like in adults (absorbed in hemorrhoidal veins)
  2. Rectal absorption: More erratic absorption than adults because of:
    - Frequent bowel movements
    - lack of anal sphincter muscle development
    - decreased blood flow
46
Q

Describe total body water composition in premature neonates up to adults
4

A

Premature neonates :85%
Term newborns: 75-80%
Infants

47
Q

Describe protein binding issues in infants

A
  1. Protein levels are reduced though infancy
  2. Because there is less drug to bind to then drug displacement reactions occur and the displaced drug will increase in the blood stream (serum).
48
Q

Describe the differences in drug metabolism in peds than adults
2

A

Children’s enzymes and metabolic pathways are immature.

  1. They have slower metabolic processes which lead to a longer duration of action (drug effect lasts longer)
  2. Adults have compensation pathways, children may not have them developed yet
49
Q

Explain ped issues with compensation pathways

A

Compensation pathways- tylenol- two different ways we can metabolize tylenol but children might not have developed both of these pathways yet
Ex. APAP: glucuronidation vs. sulfation

50
Q

Describe elimination differences in peds comapred to adults?

A
  1. Slower metabolism → slower elimination
  2. Hepatic and renal systems are not fully developed yet (Active drug may accumulate to a greater degree in neonates and infants due to immature hepatic enzymes )
  3. Reduced glomerular filtration rate
51
Q

What drugs should be monitored because they have narrow therapeutic indices?
3

A

theophylline, gentamicin, vancomycin

52
Q

What is Clark’s body area rule?

A

BSA (m2) x adult dose/

1.73 m2

53
Q

What is Clark’s body weight rule?

A

Weight (lb) x adult dose/

150 lb

54
Q

A 5 mo female presents with 5 day history of severe ear pain, constant irritability, and persistent fever 99-101° F.
NKDA, wt = 15.7 lbs, ht = 24.8 in
Amoxicillin is recommended for acute otitis media dx
Pediatric Dosage Handbook: 80-90 mg/kg/day dosed q12h

What does needs to be prescribed?

Using this answer, What volume will be dispensed?

  1. 125 mg/5 mL (80 mL, 100 mL, 150 mL)
  2. 200 mg/5 mL (50 mL, 75 mL, 100 mL)
  3. 250 mg/5 mL (80 mL, 100 mL, 150 mL)
  4. 400 mg/5 mL (50 mL, 75 mL, 100 mL)
A

Convert weight to kg (2.2 lbs = 1kg):
15.7lbs ÷2.2 =7.14 kg
Calculate daily dosage:
80-90 mg/kg/day *7.14 = 571.2mg – 642.6mg/day
Determine dose and interval:
Daily dose/2 doses per day = 285.6 mg - 321.3 mg/dose

B

55
Q

Regarding pediatric pharmacology, which of the follow is true?

  1. Neonates have decreased skin permeability
  2. Pediatric pateitns have incomplete or erratic rectal absorption
  3. Decreased total body water content (compared to adults)
  4. Increased glomerular filtration rate
A

2

or b

56
Q

How does absorption change in the geratric population?

2

A

Increased gastric pH

Delayed gastric emptying

57
Q

How does distribution change in the geriatric populaiton?

3

A

Decreased lean muscle mass
Increased body fat composition
Decreased drug-protein binding

58
Q

How does metabolism change in the geriatric population?

A

Decreased liver size
Decreased hepatic blood flow and efficiency
Decreased first pass effect
Extended half-life of an active drug

59
Q

How does elimination change in the geriatriic population?

3

A
  1. Reduced renal function
  2. Decreased rate of active drug and metabolite elimination
  3. Longer half-lives and increased drug concentrations of renally eliminated medications
60
Q

What makes the geriatric population more sesitive to side effects?

A
  1. Homeostatic mechanisms are more difficult to maintain with aging organ systems
    Ex: orthostatic hypotension
  2. Higher sensitivity to drug-receptor interactions; Increased receptor responsiveness
  3. CNS effects especially more pronounced
    -Opiates, benzodiazepines- more significant hangover effect
    -Anticholinergics (non-selective anti-histamines, TCAs)
    -Antispasmodics (“muscle relaxants”)
61
Q

What factors increase polypharmacy?

A 
Several different medical conditions
Multiple different prescription
OTC agents  
=
more complex drug regimens
62
Q

What does polpharmacy result from?

7

A
  1. Multiple co-morbidities and chronic conditions
  2. Multiple providers or specialists
  3. Patients may fill at multiple pharmacies
  4. Increased drug interactions and/or side effects
  5. Old, expired, or discontinued prescriptions
  6. Misinformation or misunderstanding
  7. Self-diagnosing or prescribing OTC and herbal products
63
Q

What does polypharmacy result in?

5

A
  1. Increased drug interactions and/or side effects
  2. Potentially unnecessary drug therapy
  3. Complicated regimens
  4. Increased cost (medication and readmission rates)
  5. Reduced compliance
64
Q

What questions should you ask to reduce polypharmacy?

6

A
  1. Does every disease state have a treatment plan?
  2. Does every medication have a purpose?
  3. Are there any duplicate or redundant therapies?
  4. Are med combination products commercially available?
  5. Is there a single medication that can treat multiple conditions?
  6. Is each medication appropriately dosed for elderly patients?
65
Q

Strategies to avoid polypharmacy?

4

A
  1. Start with lowest effective dose, titrate slowly
  2. Evaluate potential med-related causes for new symptoms
    - Temporal relationship
    - Rule out potential side effects and drug interactions
  3. Minimize emergence of new side effects with close therapeutic monitoring if indicated
  4. Use non-drug therapy when appropriate
66
Q 
Fill in the following regarding geriatric pharmacology:
\_\_\_\_\_\_\_\_\_\_ gastric pH
\_\_\_\_\_\_\_\_\_\_ receptor responsiveness
\_\_\_\_\_\_\_\_\_\_ body fat composition
\_\_\_\_\_\_\_\_\_\_  first pass effect
A

increase
increase
increase
decrease

67
Q

Types of adverse drug events?

5

A
  1. Course of the use of a drug product in professional practice
  2. Drug overdose whether accidental or intentional
  3. Drug abuse
  4. Drug withdrawal
  5. Failure of expected pharmacological action
68
Q

What should we take into account when giving drugs regarding allergies?

A

No way of predicting the inital reaction so we need to take a complete patient history to give us possible indicators

69
Q

If a mother has anaphylactic to penecilin how would we use it with the child?

A

then you would air on the side of caution and not prescribe it to the child
(even though they are probably not affected)

70
Q

Things we want to remember about side effects?

3

A
  1. Predictable
    - found in drug references, clinical studies
  2. May be caused via same or different mechanism as therapeutic use of drug
  3. Can be the primary determinant in choice of drug therapy in some instances
    (i. e., can the patient tolerate side effect, or which side effect will be more beneficial/less harmful?)
71
Q

What is the definition of an adverse drug reaction?

A

Unintended noxious response to a drug when used at normal doses for usual purposes

72
Q

What are the characteristics of an adverse drug reaction?

A
  1. Cannot be predicted
  2. Often rare occurrences not seen in early clinical trials (discovered in “post-marketing surveillance”)
  3. Suggests direct causal relationship between drug therapy and the unintended effect

Intro to Pharmacology (6 decks)

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