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Pharm 2024 > PPT 3 > Flashcards

PPT 3 Flashcards

Unit 1

1
Q

Define permeation

A

getting drug to where it needs to be

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2
Q

What are the different ways a ligand can accomplish permeation?

A

Aqueous diffusion, lipid diffusion, special carriers, endocytosis/exocytosis

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3
Q

What are the pores on the cell membrane that allow water/water soluble drug into cell?

A

Aquaporins

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4
Q

Describe aqueous diffusion

A

Diffusion by concentration gradient, aquaporins allow water-soluble drugs through cell membrane

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5
Q

What ligands can’t cross the membrane via aqueous diffusion?

A
  • Highly charged
  • Bound to large proteins (carriers - albumin)
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6
Q

Describe lipid diffusion

A

Lipid soluble ligands (steroid hormones, cholesterol); diffuse across a concentration gradient

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7
Q

What makes a drug permeable?

A
  • Ability to move between lipid and aqueous phases is important for good drug
  • Go from charged → uncharged (to cross barrier)→ charged (depends on pH and pKa of drug)
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8
Q

Describe how special carriers work to move ligands across the cell membrane

A

Molecules bind to drug and move across barriers; active transport and facilitated diffusion

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9
Q

What type of permeation keeps exogenous substances out of body that shouldn’t be there?

A

Special carriers

Ex. Liver screens special carriers to filter

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10
Q

Describe the roles of endocytosis and exocytosis in permeation

A

Endocytosis - membrane engulfment
- Receptor mediated endocytosis (clathrin coated pit)
- Needed for big drugs to get across membranes
Exocytosis - merging of vesicle with membrane

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11
Q

What is rational dosing?

A

Goal – to achieve desired beneficial effect with minimal adverse effects

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12
Q

What are the main two components of standard drug dosing?

A

Volume of distribution and clearance

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13
Q

What is volume of distribution?

A

Apparent volume in blood
- How much did we give them vs how much stayed in blood (how much stayed in blood vs how much went to other areas)

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14
Q

What is clearance?

A

Ability of body to eliminate drug in relation to drug concentration in body

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15
Q

What is the difference between elimination and clearance?

A

Elimination changes based on clearance (doesn’t change)

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16
Q

What is the equation for Vd?

A

Vd = dose/initial concentration
Dose = Vd x target concentration

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17
Q

How much whole blood is in 1 kg?

A

0.08 L/kg
5.6 L for 70 kg person

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18
Q

What is meant by a high Vd?

A

The higher the Vd, the less amount of drug is in the blood; drug distributed in other areas

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19
Q

What is the equation for clearance?

A

CL = Rate of elimination/C
Rate of elimination = CL x C

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20
Q

First-order elimination

A

Rate of elimination varies with concentration - clearance constant

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21
Q

Zero-order elimination

A

Rate of elimination is constant, clearance varies with concentration

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22
Q

Describe what occurs in zero-order elimination

A

Occurs when the body’s ability to eliminate a drug has reached its maximum capability (i.e., all transporters are being used). As the dose and drug concentration increase, the amount of drug eliminated per hour does not increase, and the fraction of drug removed declines.

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23
Q

What order of elimination do most drugs follow?

A

First-order

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24
Q

Capacity-Limited Elimination

A

Psuedo zero-order elimination; occurs when any drug given at high enough concentrations

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25
Q

Flow Dependent Elimination

A

Depends on blood flow through the organ
Some drugs are highly sensitive to first pass metabolism - high extraction drugs

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26
Q

Flow Dependent Elimination equation

A

Organ clearance = blood flow × extraction ratio

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27
Q

Half-life

A

Time required to change drug in body to ½ of concentration

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28
Q

Half-life can be affected by ______

A

disease states

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29
Q

Define accumulation

A

-Drug accumulates until dosing stops

30
Q

How does accumulation relate to half life?

A

If dosing interval is shorter than four half-lives, accumulation is detectable

31
Q

How many half-lives are usually required for drug to achieve full effects?

A

4

32
Q

What drugs follow capacity-limited elimination?

A

Ethanol, phenytoin, aspirin

33
Q

What are other terms for capacity-limited elimination?

A

Non-linear, saturable, michaelis-menten

34
Q

Why is the rate of elimination constant in capacity-limited elimination?

A

Saturated ability for body to eliminate drug

35
Q

Plasma volume constant equation

A

0.04 L/kg

36
Q

A high volume distribution means

A

a low concentration of the drug in the blood

37
Q

Which 2 factors determine flow-dependent elimination organ clearance?

A

1) If drug is a “high extraction drug” - sensitive to first pass metabolism
2) Blood flow through the organ

38
Q

What is a “high extraction drug”

A

A high amount of the drug is extracted prior to reaching systemic circulation (i.e. morphine, large amount extracted in liver)

39
Q

What organ if unhealthy would affect how much drug reaches systemic circulation?

A

Liver

40
Q

How is clearance calculated?

A

Organ clearance (CI) = blood flow (Q) × extraction ratio (E)

41
Q

What is the extraction ratio and how is it calculated calculated?

A

Extraction ratio is what percentage of the drug actually came out on the other side
E = (Cin - Cout)/Cin

42
Q

How is the extraction ratio determined?

A

> 0.7 = high (normal)
0.3-0.7 = intermediate
< 0.3 = low

43
Q

What is half-life? What does it help us determine?

A

Time it takes for body to get rid of 1/2 of current concentration of drug
When should we dose and how often

44
Q

What is the half life equation?

A

T1/2 = (0.7 x Vd)/CL

45
Q

How many half-lives does it take for a steady-state drug to reach the target concentration in the plasma?

A

4 half-lives

46
Q

How many half-lives does it take for drug to completely eliminate from the body after stopping drug administration

A

after 4x half-lives

47
Q

If we don’t want to wait to get to target concentration, we would give a _______ and then start steady state dosing

A

Bolus

48
Q

True half-life will be _______ than calculated

A

Greater

49
Q

If dosing interval is shorter than four half-lives, __________ is detectable

A

accumulation

50
Q

When taking an oral dose, you would wait ________ until taking next dose

A

4 half-lives; want drug to be eliminated before another dose
Accumulation can lead to reaching toxic levels quicker

51
Q

___________ is how much drug reaches systemic circulation

A

Bioavailability (F)

52
Q

100% bioavailability

A

IV

53
Q

What factors effect bioavailability?

A
  • Physical properties of the drug (hydrophylicity, pKa, solubility, etc.)
  • Formulation/route
  • GI – diet, gastric emptying, transporters, health of GI tract
  • Interactions with other drugs
  • Overall health/disease state
  • Circadian rhythms
54
Q

_________ is biotransformation that may occur prior to reaching systemic circulation

A

Portal circulation
- High absorption (gut) does not always indicate high bioavailability (due to biotransformation in liver)
- Drugs can become more or less active

55
Q

Which routes can bypass the first route (liver) effect?

A

IV, IM, SC, inhalation, oral (sublingual), transdermal, rectal suppositories (only 50%)

56
Q

The lungs have the same _______ as in the liver

A

enzymes, different quantity

57
Q

What are the 3 different time courses of drug effect?

A

Immediate - GPCR, ions - usually not linear response, but sigmoidal
Delayed - effect on transcription/translation, growth
Cumulative - especially if you dose before the 4 half-lives are done

58
Q

The _______ is the concentration that will produce desired effect

A

Target concentration, calculated before you give the drug by manufacturer

59
Q

How can a drug dose change based on the target concentration?

A

Target concentration depends on desired effect
- Ex: Digoxin
- 2 ng/mL – controls atrial fibrillation
- 1 ng/mL – manage heart failure

60
Q

Maintain steady state of drug by giving just enough to replace eliminated drug

A

Maintenance dosing

61
Q

What is the most important factor of maintenance dosing?

A

Clearance

62
Q

In maintenance dosing, we want the dosing rate to =

A

Rate of elimination(ss)
Dosing rate(ss) = CL x Target Concentration

63
Q

Maintenance dose for bioavailability less than 100%:

A

Dosing rate(oral) = Dosing rate (calc.)/F(oral)

64
Q

Maintenance dose for intermittent doses

A

Maintenance dose = dosing rate x dosing interval

65
Q

_______ is needed to reach steady state quickly

A

Loading dose

66
Q

Loading dose equation

A

LD = Vd x TC

67
Q

__________ is critical for potentially toxic drugs – need time for distribution into compartments

A

Rate of administration; slow administration is key

68
Q

“Peak and Trough” Test

A
  • Peak – 5-10 minutes after IV drug administration
  • Trough – 30 minutes prior to next dose of drug
  • Random – Any time
69
Q

When is ideal body weight used (IBW) instead of weight?

A

Drugs that do not penetrate fat - can’t use actual weight
- obese

70
Q

_________ gives us idea of patient’s kidney function

A

Estimated Creatinine Clearance (ml/min)

Pharm 2024 (28 decks)

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