Module 3 Flashcards

1
Q

Drugs _________ into compartments in the body where they may be _______, _________, ________ or exert their ___________ effect.

A
distribute
stored
metabolized
excreted
pharmacological
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2
Q

The extracellular fluid that surrounds cells. Low molecular weight, water soluble drugs distribute here.

A

Interstitial space

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3
Q

Includes the fluid in the interstitial space, intracellular fluid and the plasma

A

Total body water

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4
Q

The acellular component of blood.

A

plasma

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5
Q

Lipid soluble drugs tend to distribute here. The body’s fat stores.

A

Adipose tissue

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6
Q

Drug distribution is determined by three factors, what are they?

A

Blood flow to tissues
Ability of drug to move out of capillaries
Ability of drug to move into cells

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7
Q

The more drug that distributes out of the blood, the ______ the concentration of drug in the blood.

A

lower

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8
Q

What are well perfused organs/tissues (i.e. name them)?

A

Liver, kidney, brain

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9
Q

What are poorly perfused tissues/organs?

A

Fat, (muscle), bone, skin

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10
Q

Describe blood flow in newborns

A

Neonates have limited blood flow

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11
Q

Describe how heart failure or shock affects blood flow.

A

Decreased CO or BP reduces blood flow and can limit distribution

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12
Q

Describe blood flow in solid tumours.

A

The outer portion of solid tumours are well perfused; the innner region is not - hard to attain high drug concentrations within the tumour

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13
Q

Describe blood flow in abscesses.

A

They have no blood supply and are thus hard to treat with antibiotics. Often drained before drug therapy.

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14
Q

Drugs move out of capillaries through ________ except in the _______.

A

fenestrations

brain

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15
Q

What are the different ways in which drugs can pass the cell membrane?

A

Lipophilic - pass membrane
Transporter - hydrophilc drug
- efflux - pumps out
- uptake - pumps in

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16
Q

Most widely studied efflux transporter.

A

P-glycoprotein

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17
Q

P-glycoprotein is an _______ transporter, meaning it requires ______ in order to transport drugs _________ a concentration gradient.

A

active
ATP
against

18
Q

How does P-gp function in the liver?

A

Pumps drugs into the bile to facilitate excretion

19
Q

How does P-gp function in the SI?

A

Pumps drugs into the lumen, preventing drug absorption into the blood

20
Q

How does P-gp function in the kidney?

A

Pumps drugs into the lumen to facilitate excretion.

21
Q

How does P-gp function in the brain?

A

Pumps drugs into the blood, limiting exposure to the brain

22
Q
For each of the following organs, describe which side (lumenal or towards the blood) that p-gp is located.
Liver
SI
Kidney
Brain
A

Liver - transcellular (bile canalicular membrane) - pumps into bile duct
SI - lumenal (apical membrane)
Kidney - lumenal (apical side)
Brain - blood

23
Q

Where is P-gp expressed in the liver?

Intestine?

A

hepatocytes

enterocytes

24
Q

Where is P-gp found in the kidney?

A

PCT

25
Q

What are the two major plasma proteins that bind drugs in the plasma?

A

Albumin

Alpha 1 acid glycoprotein

26
Q

Albumin has high affinity for what types of drugs?

A

lipophilic and anionic (weakly acidic)

27
Q

Alpha 1 acidic glycoprotein has high affinity for what types of drugs?

A

cationic (weakly basic) and very hydrophilic drugs

28
Q

Plasma protein binding is ________.

A

reversible

29
Q

What are pathologies that decrease plasma albumin concentration

A

Malnutrition, trauma, aging, liver and kidney disease

30
Q

How does decreased plasma albumin concentration affect drug concentration?

A

Will increase free drug concentration, which may lead to toxicity

31
Q

What factors/pathologies affect alpha 1 acidic glycoprotein levels?

A

Hepatic inflammation, aging, trauma cause increased alpha 1 acidic glycoprotein

32
Q

How does increased alpha 1 acidic glycoprotein affect drug concentration?

A

causes decreased free drug concentration

33
Q

apparent volume into which a drug distributes

A

Volume of distribution

34
Q

What is the equation for Vd?

A

Vd = D/C
D - dose
C - concentration in the blood

35
Q

What are the characteristics of drugs with a small Vd?
Where do they distribute into?
What volume per kg, and what percentage of body weight is their Vd?

A

High affinity for plasma proteins
Large MW

Distribute into the plasma

0.0057L/kg or 5.7% of body weight

36
Q

What are the characteristics of drugs with an intermediate Vd?

Where do they distribute?

What volume per kg, and what percentage of body weight is their Vd?

A

Low MW
Very hydrophilic
Intermediate affinity for plasma proteins

Distribute into the ECF

0.2L/kg
20% of body weight

37
Q

What are the characteristics of drugs with a large Vd?

Where do they distribute?

What volume per kg, and what percentage of body weight is their Vd?

A

Low MW
Lipophilic
Minimal protein binding

Distribute into the body compartments

> 0.2L/kg

38
Q

When the Vd of a displaced drug is small, where does it distribute?

A

Stays in the plasma - so free drug concentration increases

39
Q

When the Vd of a displaced drug is large, where does it distribute?

A

Distributes into the tissues.

This decreases plasma drug concentration, but increases the apparent Vd.

40
Q

Describe how age affects distribution (Vd) of certain drugs (do not describe the effects on plasma proteins).

A

There is typically more fat as part of body mass as we age - thus drugs distributing into fat will have a larger Vd.

There is typically less muscle mass as we age and thus drugs distributing into muscle will have a lower Vd.

41
Q

Describe how total body water changes with age? Consider obese individuals as well.

A

Decreases from infancy to elderly. (obese people are lower than healthy adults)

42
Q

Describe how muscle mass changes with age, include obese people in your answer.

A

Highest in healthy adults, decreases to obese individuals, elderly than infants.