PHARM - Pharmacokinetics - Drug Metabolism and Excretion - Week 1 Flashcards

1
Q

Describe distribution equilibrium.

A

Most drugs administered via IV distribute rapidly, and reach a distribution equilibrium, behaving as if in a single compartment.

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2
Q

How does drug elimination rate relate to the amount of drug in the body?

A

Most drugs are eliminated at a rate proportional to the concentration in plasma.

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3
Q

Name two ways drugs are eliminated by the body, and where it typically occurs.

A

Excretion - by the kidney
Metabolism - by the liver

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4
Q

Describe renal excretion briefly in three simple steps.

A

Glomerular filtration - fluid/drug enters the collecting tubule through Bowmans capsule

Tubular secretion - fluid/drug enters the collecting tubule through the peritubular capillary (after the efferent arteriole)

Tubular reabsorption - fluid/drug re-enters the peritubular capillary

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5
Q

Breifly describe glomerular filtration.

A

The drug is taken out of the blood through the leaky fenestrated glomerulus.

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6
Q

What is glomerular filtration limited by? Does glomerular filtration affect drugs bound to plasma proteins?

A

It is limited by the glomerular filtration rate. Glomerular filtration doesnt affect plasma protein-bound drugs (i.e. theyre not filtered at this stage).

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7
Q

Briefly define tubular secretion. Does it affect plasma protein-bound drugs?

A

Takes drugs out of the blood, and uses active carriers for drugs. It can remove plasma protein-bound drugs as well.

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8
Q

Describe competitive inhibition for tubular secretion, and briefly give an example.

A

Certain drugs can mask the appearance of other drugs. It does so by competitively inhibiting tubular secretion of that masked drug.
For example, probenecid reduces excretion of acidic drugs.

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9
Q

Breifly describe tubular reabsorption, and how this occurs. What is this dependent on?

A

It puts drugs back into the blood. It is the passive movement across cell membranes of the tubule and peritubular capillary.
It is pH dependent.

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10
Q

What is lipid solubility affected by that affects drug diffusion?

A

pH

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11
Q

Consider the following ionisation of the acidic drug A below:
A-H A- + H+
On the left it is uncharged, and on the right, it is charged.
Describe the lipid solubility state for each, and how this will affect passage through a lipid membrane.

A

In its uncharged state, the drug is more lipid soluble, and thus would have better passage through a plasma membrane.
In its charged state, it is less lipid soluble, and thus has poorer passage through a plasma membrane.

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12
Q

Consider the following ionisation of the basic drug A below:
BH+ B + H+
On the left it is charged, and on the right, it is uncharged.
Describe the lipid solubility state for each, and how this will affect passage through a lipid membrane.

A

In its uncharged state, the drug is more lipid soluble, and thus would have better passage through a plasma membrane.
In its charged state, it is less lipid soluble, and thus has poorer passage through a plasma membrane.

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13
Q

Consider an overdose of aspirin, an acidic drug. How can urine pH be manipulated to alter its lipid solublity and thus, reabsorption/excretion?

A

Administer NaHCO3. This will makes the urine basic, and therefore increases the amount of ionised aspirin.
This will reduce reabsorption and increases excretion.

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14
Q

Describe biotransformation.
What does it involve, where does it occur, and what typically happens as a result?

A

It involves a chemical change to a drug, typically via enzyme-catalysed reactions.
It occurs in most tissue, most mainly in the liver.
It increases water solubility to facilitate excretion.

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15
Q

Describe phase I metabolism.

A

The creation of a functional group on a drug, such as:
-OH, -NH2, -SH, -COOH

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16
Q

Name the superfamily of enzymes responsible for many phase I metabolic reactions. Describe how drug-drug interactions can occur as a result of enzymes such as this.

A

Cytochrome p450
Its action can be inhibited or enhanced by drugs, and thus can lead to drug-drug interactions.

17
Q

Describe phase II metabolism.

A

The conjugation of a water soluble molecule onto a functional group of a drug.

18
Q

Describe the interaction between phase I metabolism, phase II metabolism, and excretion on a drug.

A

A drug may be directly excreted.
It may be converted to a phase I metabolite by phase I metabolism, and then excreted.
It may be converted to a phase II metabolite by phase II metabolism, and then excreted.
It may be converted sequentially into a phase I, then phase II metabolite, before being excreted.

19
Q

What is the rate of drug elimination (by both renal excretion and drug metabolism) dependent on?

A

The concentration of drug in the blood.

20
Q

Define first order kinetics.

A

Most drugs are eliminated at a rate proportional to the concentration in the plasma.

21
Q

Describe what a [drug in blood] vs time curve would look like following rapid IV administration.

A

A very rapid rise in concentration, followed by an exponential decay.

22
Q

How can the peak of a [drug in blood] vs time curve be determined? Describe using the formula.

A

Done using Vd:
X = Vd * C

23
Q

Describe what a [drug in blood] vs time curve would look like following short-term IV administration (an infusion).

A

A drug infused at a constant rate will have a concentration increase in a logarithmic fashion, followed by an exponential decay at the point where the infusion is stopped.

24
Q

What is the most common route of administration and why?

A

Oral due to convenience

25
Q

Where must oral drugs be absorbed?

A

In the GI tract, predominantly in the small intestines.

26
Q

How does drug absorption take place in the GI tract?

A

Primarily via lipid absorption.

27
Q

Following oral administration, where does the drug first end up?
What happens if the drug is extensively metabolised or rendered inactive?

A

Enters the hepatic portal vein, and taken directly to the liver.
If extensively metabolised or rendered inactive, the amount of drug in the systemic circulation will be reduced.

28
Q

What kind of [drug in blood] vs time curve would oral administration result in?

A

Rapid rise to a peak, followed by a steady decline.

29
Q

Compare the peaks for oral administration vs IV.

A

Peak for oral administration is not as high as IV

30
Q

Define bioavailability.

A

Proportion of active drug which enters systemic circulation.

31
Q

What is the bioavailability of a drug when administered by IV? What about other routes?

A

IV is 100%
Other routes may be less than 100%

32
Q

What two factors is bioavailability of a drug affected by?

A

How much drug is absorbed, and how much drug undergoes first pass hepatic metabolism