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Pharm > Gen/multisys > Flashcards

Gen/multisys Flashcards

1
Q

INR range on warfarin

A

2 - 3

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2
Q

CyP450 inducers

A

Dec efficacy of warfarin by inc elimination

» CRAP GPS MaN «
Carbamazepine 
Rifampin
Alcohol, chronic
Phenytoin

Griseofulvin
Phenobarbital
St. John’s wort

Modafinil
Nevirapine

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3
Q

CyP450 inhibitors

A

Inc warfarin effect

» ABCG «

Amiodarone
Azole antifungal
antiBiotics (metronidazole. Macrolides)
Cimetidine
Grapefruit juice
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4
Q

CyP450 subtypes

CYP1A2:

CYP2E1:

CYP2C9:

CYP2D6:

CYPEA4:

A

CYP1A2: Acetaminophen

CYP2E1: Ethanol

CYP2C9: Warfarin

CYP2D6: Cardiac drugs

CYPEA4: #MC

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5
Q

MAB elimination

A
  1. Against cell surface Ag undergo internalization (receptor mediated encpdocytosis) : bind to target, removed from circulation
  2. NS : taken up by RES macrophages (Fc receptor) + vasc endoth cella (pinocytosis)

Catabolized into AA within lysosomes

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6
Q

Inhibition of which efflux pump improves drug delivery to brain?

A

P-glycoprotein

efflux pump on brain capillary endoth cells, part of BBB

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7
Q

Sustained release preparations of drugs

A
  1. Reduced SE d/t dampening of peak levels
  2. Longer duration of therapeutic effect due to prolonged absorption of the drug
  3. Improved patient compliance due to less frequent administration
  • useful for drugs with short half-lives (ie, allowing prolonged effect without need for multiple doses) or narrow therapeutic windows (ie, maintaining effective drug levels while minimizing absorption peaks).
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8
Q

Enterohepatic cycling of drugs

A

Drugs excreted into bile undergo enterohepatic cycling which inc drug’s effect longer than its t1/2

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9
Q

Compared to adults, which of the following neonatal factors is the most likely cause of the difference in drug effectiveness?

A
  1. ↑ Proportion of body water (↑ Distribution of water-soluble drugs may necessitate higher mg/kg dose)
  2. Blood-brain barrier immaturity (↑ CNS toxicity)
  3. ↓ CYP enzyme activity + ↓ Hepatic glucuronidation (↑ Sensitivity to hepatically metabolized drugs)
  4. ↓ Renal blood flow & GFR
  5. ↑ TBW : ↑ Vd : ↓ plasma concentration
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10
Q

Changes in log dose-response curve

  1. Full agonist + Rev comp antag
  2. Full ag + Noncomp antag
A
  1. Full agonist + Rev comp antag :
    - parallel shift to right, inc in ED50
    - no change in Emax
  2. Full ag + Noncomp antag:
    - shift down d/t dec Emax
    - no change in ED50

» Competitive = change ED50 = shift right;
Noncompetitive = change Emax = shift down. «

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11
Q

Drug conc mg/L =

A

Drug conc mg/L = drug dose (mg) / Vd (L)

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12
Q

Vd (L)

A

Vd (L) = amount of drug given (mg) / plasma concentration of drug (mg/L)

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14
Q

Zero vs First order kinetics

A

Zero-order:
Same AMOUNT of drug metabolized per unit time independent of serum levels/ dose

First-order:
Same FRACTION/ PROPORTION of drug metabolized

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15
Q

TBW

A

TBW ~ 41L

  • ECF ~ 14L or 1/3 TBW
    • Plasma ~ 3L
    • Interstitial fluid ~ 10L
  • ICF ~ 25L or 2/3 TBW
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16
Q

Vd based on properties of drugs

A 
Low Vd(3-5L): 
since remains in plasma/ bloodstream
- plasma protein bound
- highly charged (hydrophilic)
- large molecular weight
❗️renal elimination
High Vd (14-16L)
- small molecular wt, but
-highly charged (hydrophilic)
Drug in plasma + interstitial fluid ❗️most affected by body weight!

Highest Vd (41L)
- small molecular weight
- uncharted (hydrophobic or lipophillic) since can cross cell memb n reach into intracellular compartment n bound to tissues
- highest conc in skeletal muscle, bone, adipose tissue
❗️ hepatic elimination into bile + urine

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17
Q

Bioavailability

A

Bioavailability is the fraction of an administered drug that reaches the systemic circulation unchanged.

  • decreases with oral administration due to incomplete absorption and first-pass metabolism compared to parenteral administration.
18
Q

Why’s dosing based on body weight required?

A

To improve safety, efficacy,
For meds w narrow therapeutic index eg. Heparin, Aminoglycosides, Anesthetics

🌟 dosing based on adjusted/ lean body wt in obese pts which includes only a portion (~40%) excess adipose mass. Usually for hydrophilic drugs that do not distribute in adipose tissue.

19
Q

What is drug clearance based on?

A

Lean body weight (wt of nonadipose tissue: muscle, liver, kidney)

20
Q

Lean body mass req for?

A
  1. Vd

2. Drug clearance

21
Q

Loading dose req for?

A

Lipophilic drugs eg. Phenytoin

- sequestered w/in adipose, : loading dose req to saturate fat stores to achieve adequate serum levels

22
Q

How is drug toxicity of a drug reduced?

A

Frequent small dosing : lower peak, lower avg drug conc

❗️Drug toxicity = peak/ avg plasma drug levels

23
Q

Serum trough conc of a drug

A

Lowest conc level before next dose

24
Q

Drug clearance

A

Cl = amt of plasma cleared of the drug / time (mL/min)

25
Q

Therapeutic window

A

range of drug dosages that have an appropriate clinical effect.
From the lowest dose at which the drug is effective to the highest dose without significant toxic effects.

❗️narrow TI drugs : frequent dose age to prevent peak/ toxicity of drug

26
Q

Tachyphylaxis

A

rapidly diminishing response to successive doses of a drug, rendering it less effective.
The effect is common with drugs acting on the nervous system.

27
Q

CyP450 subtypes

A

Subtypes

1A2: Acetaminophen 
2E1: ethanol
2C9: Warfarin
2D6: (2d echo) heart
3A4: most common
28
Q

Drug metabolism of lipophilic drugs

A

Lipophilic - rapidly cross barriers to distribute in organs w inc blood flow (brain, liver, kidney, lungs) — redistribution to organs w low blood flow (skeletal muscle, bone, fat) : highest Vd for lipophilic drugs

29
Q

MAB clearance

A
  1. Receptor mediated endocytosis
  2. Macrophages
  • catabolized into AA in lysosomes
30
Q

Advantages of sustained-release prep/ delayed abs

A
  1. Slow peak = dec SE/tox
  2. Longer duration d/t prolonged absorption
  3. Improved pt compliance d/t less frequent dosage
31
Q

Targeted drug delivery to tumor sites

A
  1. Minimize toxicity
  2. Inc drug response

Drug in lysosomes coated w anti-EGFR Abx : drug easily taken up by tumor cells

32
Q

Beers criteria?

A

Reduces inappropriate rx in elderly

» ABCD NOPe «

α-blockers
BDZ
antiCholinergics
antiDepressants

NSAIDs
Opioids
PPIs

33
Q

Drug interaction types

Additive:

Permissive:

Synergistic:

Potentiation:

Antagonistic:

Tachyphylaxis:

A

Additive: 2+2=4. Aspirin+Acetaminophen

Permissive: drug A req for full effect of drug B. Cortisol+ catecholamine

Synergistic: 2+2>4. Clopidogrel + Aspirin

Potentiation: drug B w no effect inc action of drug A, 2+0>2. Carbidopa+ Levodopa

Antagonistic:2+2<4. Ethanol+Methanol

Tachyphylaxis: dec response to a drug after repeated adm. Nitrates, Niacin, Phenylephrine, LSD, MDMA.

34
Q

t1/2 formula

A

t1/2 = Vd x 0.7 / CL

35
Q

Maintenance dose formula

A

MD = Cpss x CL / B (F)

  • dec in hepatic/ renal dys(f)
36
Q

Loading dose formula

A

LD = Vd x Cpss / B (F)

Unchanged in hepatic/ renal dys(f)

37
Q

Which inhibitors inc Km ?

A

» Kompetitive inhibitors

  • no change in Vmax
  • bind to active site
  • reversible, effects can be overcome by inc concentration
38
Q

Which inhibitors dec Vmax?

A

Non-competitive inhibitors

  • bind to allosteric sites
  • irreversible

Pharm (11 decks)

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