Lecture 7 Flashcards

Drug Distribution and Bioavailability

1
Q

Distribution depends on… (4)

A
  1. Blood flow to and through tissue
  2. Drug solubility
  3. Drug ionization
  4. Binding to plasma proteins of tissues

Distribution is required for drug to reach its target, must get to target and USUALLY into cells

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2
Q

Where can drugs distribute? (6)

A
  1. Total water - small water-soluble molecules ex: ethanol
  2. Extracellular water - larger water-soluble molecules ex: gentamycin
  3. Plasma restricted - strongly plasma protein-bound molecules and very large molecules ex: heparin
  4. Fat - highly lipid soluble molecules ex: DDT
  5. Bone - certain ions ex: lead, fluoride, tetracycline
  6. Muscle, etc.
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3
Q

Distribution in Pharmacology

A

Vd = Volume of Distribution

Vd = Amount of drug in body / C

C = concentration of drug in blood, plasma, or water

Vd can be greater than actual volume in body

Tissue can be storage depot for drugs

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4
Q

Protein Binding + Distribution

A
  • Plasma protein binding is related to metabolism, excretion, and drug effect
  • Drug deposits in tissue “free up” plasma protein binding sites
  • Binding is in equilibrium based on relative binding constants (affinities)
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5
Q

Capillary Permeability

A
  • One cell thick
  • Absorption properties apply (diffusion, etc.)
  • Gaps between endothelial cells differ in specialized tissue (large in excretory tissue, small/tight in barriers)
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6
Q

Specialized Barriers

A
  1. Blood-Brain Barrier
  2. Placenta

Exclude certain drugs

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7
Q

Blood-Brain Barrier

A

AKA BBB

  • Tight junctions of endothelium
  • Astrocytes form additional barrier around capillaries
  • Decrease in permeability to water-soluble or ionized molecules
  • Lipid-soluble substances diffuse easily
  • More permeable when disrupted by infection or injury
  • Also has drug efflux transporters
  • Not fully formed until about 6 months of age
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8
Q

Placenta

A
  • Connects fetus with maternal uterine wall and has sinuses to take maternal blood to baby
  • Lipid-soluble materials move easily
  • Water-soluble materials move more slowly
  • Large molecules are less likely to pass barrier
  • Fastest equilibrium possible between mother and fetus is 40 minutes
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9
Q

Limited entry to body compartments can occur by…

A
  1. Physical barriers (tight junctions)

2. Transporter barriers - high concentrations of efflux transporters or low concentrations of influx transporters

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10
Q

Half-life

A
  • Denoted by t1/2
  • Time it takes for half a drug concentrations to be eliminated
  • Simplest case is a single compartment
  • Drug residence depends on Vd and CL (CL = clearance)
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11
Q

Delayed Effections

A
  • Drug effect doesn’t usually parallel drug concentrations
  • Can occur due to distribution to site of action
  • Drug action can be indirect or require a cellular response for an affect to manifest
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12
Q

Therapeutic Window Definition

A

The range of dosage of a drug or of its concentration that provides safe effective therapy.

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13
Q

Distribution Definition

A

The dispersion or dissemination of substances throughout the fluids and tissues of the body.

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14
Q

Volume of Distribution Definition

A

The apparent volume in which a drug is

distributed (Vd).

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15
Q

Pregnancy Class A

A

Adequate, well-controlled studies in pregnant women have not shown an increased risk of fetal abnormalities.

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16
Q

Pregnancy Class B

A

Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate and well-controlled studies in pregnant women. Or animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus.

17
Q

Pregnancy Class C

A

Animal studies have shown an adverse effect and there are no adequate and well-controlled studies in pregnant women. Or no animal studies have been conducted and there are no adequate and well controlled studies in pregnant women.

18
Q

Pregnancy Class D

A

Studies, adequate well-controlled or observational, in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy may outweigh the potential risk.

19
Q

Pregnancy Class E

A

Studies, adequate well-controlled or observational, in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. The use of the product is contraindicated in women who are or may become pregnant.