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Pharmacology > Absorption > Flashcards

Absorption Flashcards

1
Q

What type of structures are animal cell membranes?

A

phospholipid bilayers

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2
Q

What is lipophilicity?

A

lipid solubility of drug; most important characteristic allowing it to diffuse across cell mbs

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3
Q

What factor other than lipophilicity is important in allowing a drug to diffuse across cell mb?

A

molecular size

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4
Q

How do chemicals cross cell mbs?

A
  1. passive transport (simple diffusion)
  2. filtration (bulk flow)
  3. facilitated diffusion
  4. active transport
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5
Q

What is passive transport (simple diffusion)?

A

chem follows concentration gradient across cell mb; termed transcellular diffusion

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6
Q

What is filtration (bulk flow)?

A

passive transport through cell junctions due to pressure gradient; termed paracellular transport

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7
Q

what is facilitated diffusion?

A

also passive transport following concentration gradient, but requires transporter to assist movement across mb

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8
Q

what is active transport?

A

movement against concentration gradient, requires ATP

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9
Q

What is most common way that drugs cross cell mbs?

A

passive transport

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10
Q

What on either side of the mb determines direction of diffusion?

A

concentration gradient

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11
Q

In order for drug mc to passively diffuse across cell mb, it must be…?

A

lipophilic (lipid soluble)

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12
Q

Pharmaceuticals can be categorized into 2 types of chemicals, influencing their absorption:

A
  1. lipophilic organic chemicals
  2. weak organic acids & bases
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13
Q

What are lipid organic chemicals?

A

about 25% of drugs are organic molecules w/ varying degrees of lipid solubility

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14
Q

what are weak organic acids & bases?

A

about 75% of drugs are weak acids & bases; such chems exist in both ionized & nonionized forms in soln, & relative proportion of ionized vs nonionized form depends on pKa of drug & pH of solution; ONLY NONIONIZED FORM OF DRUG CAN PASSIVELY DIFFUSE ACROSS CELL MBS

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15
Q

What can the Henderson-Hasselbach eqn be used to determine?

A

ratio of nonionized vs ionized form of drug

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16
Q

What is the Henderson-Hasselbach eqn?

A

Log ([protonated]/[nonprotonated]) = pKa - pH

17
Q

Remind me what pKa is:

A

number that measures strength of an acid or tendency of mc to keep a proton.
calculated as negative base-10 log of acid dissociation constant (Ka).
lower pKa value indicates a stronger acid, meaning acid dissociates more completely in water.

18
Q

protonated form of an acid is?

A

nonionized (HA)

19
Q

Protonated form of a base is?

A

ionized (BH+)

20
Q

weak acids (HA) donate … to form …

A

proton (H+), anions (A-)

21
Q

weak bases (B) accept … to form …

A

a proton, cations (HB+)

22
Q

what form of drug can readily penetrate cell mbs?

A

nonionized

23
Q

pKa of weak acid or base is …

A

… pH @ which there are equal amts of protonated form & nonprotonated form

24
Q

What is nonionized in what?

A

like is nonionized in like!
(weak base is more nonionized in basic soln & weak acid is more non-ionized in acidic soln)

25
Q

would benzoic acid (pKa =4, acid) be ionized @ neutral pH?

A

yes

26
Q

would aniline (pKa =5, base) be ionized @ neutral pH?

A

no

27
Q

What is clinical significance of a drug that is a weak base being 10 times more ionized in breast milk (more acidic) than plasma?

A

More ionized means more protonated. Clinical significance is concept of “ion trapping”. as nonionized form diffuses into breast milk, more acidic pH causes more of drug to be ionized, & thus “trapped”.
treating mammary gland infection (mastitis) w/ an antimicrobial drug that is a weak base will result in increased drug concentration @ site of infection & increase efficacy.

28
Q

What is filtration (bulk flow) of a drug?

A
  • drug moves w/ H2O through gap jxns btwn cells due to pressure gradient (ex: blood press)
29
Q

how big are the gaps btwn most cells?

A

4 nm

30
Q

how big are the gaps btwn most blood vessel endothelial cells?

A

2 nm

31
Q

how big are the gaps in glomerulus?

A

70 nm

32
Q

How big are gaps in CNS?

A

0 nm

33
Q

what is the most important characteristic about a drug in order for it to move via filtration (bulk flow)?

A

size of drug mc

34
Q

What is the importance of facilitated diffusion of a drug?

A
  • important for nutrients & electrolytes; certain drugs can compete for these systems
  • mjr families are the organic anion transporters (OATs) & organic cation transporters (OCTs)
  • important for excretion too
35
Q

How is active transport related to drugs?

A
  • important for excretion: brain, liver, & kidney all have active transport systems
  • all are “ATP-binding cassette” (ABC) prots; major families are multi-drug resistance prots (MDRs & MRPs) & breast cancer resistance prot (BCRP)
  • names originated from high expression in certain cancer cells, severely limiting chemotherapeutic treatments
  • referred to as “lipophilic vacuum cleaners”

Pharmacology (14 decks)

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