Pharmokinetics I

Question 1

What is pharmokinetics?

Answer 1

It is the time course of a drug

Question 2

What is ADME?

Answer 2

Absorption
Distribution
Metabolism
Elimination

Question 3

What is the minimum effective concentration?

Answer 3

Min threshold required for therapeutic effect

Question 4

What is the maximum tolerated concentration?

Answer 4

Max point were the adverse effects begin to outweigh the benefits

Question 5

What is the equation for the bioavailability (F)?

Answer 5

F = AUC (oral) / AUC (IV)

Question 6

What are the uses of the AUC?

Answer 6

• Compare clearance (CL) between individuals

- Determine the bioavailability (F)

Question 7

What types of drugs are absorbed the fastest?

Answer 7

Non-polar

Question 8

What is the problem with 2 drugs that use the same active transport carrier?

Answer 8

The process is saturable and so they will compete with each other and limit their absorption.

Question 9

What are the advantages of oral administration?

Answer 9

Many forms of the drug can be used (solution, tablets, etc)

Question 10

Wha tis the first-pass effect?

Answer 10

Some drugs become metabolized when they pass thorough the liver which makes only a fraction of the absorbed drug making it to the systemic circulation

Question 11

What is the problem with drugs and the enterohepatic circulation?

Answer 11

Drugs may be secreted into the bile and reabsorbed via the intestine. This can delay delivery to the systemic circulation and may reduce bioavailability.

Question 12

What is the salt factor?

Answer 12

The fraction of total drug that will be delivered as active drug to the systemic circulation is called the “salt factor” (S).

Question 13

What are the advantages and disadvantages of sublingual and buccal administration?

Answer 13

• Advantages:
– by-passes portal circulation and therefore avoids first pass metabolism.
– higher pH may be beneficial for absorption of more basic drugs.

• Disadvantages:
– taste and/or discomfort

Question 14

What are the advantages and disadvantages of rectal administration?

Answer 14

• Advantages:
– ~50-60% of absorbed drug by-passes portal circulation and therefore avoids first pass metabolism.
– useful in cases of nausea and vomiting.

• Disadvantages:
– discomfort, inconvenience, etc.

Question 15

What are the advantages and disadvantages of inhalation?

Answer 15

• Absorption is via passive diffusion and is facilitated by a large surface area.

Question 16

What are the advantages and disadvantages of transdermal administration?

Answer 16

• Potential benefits:
– controlled release of the drug into the patient— enables a steady blood-level profile
– user-friendly, convenient, painless, multi-day dosing—improved patient compliance
– bypassing the gastrointestinal (GI) tract obviates GI irritation that occurs with some drugs and avoids partial first-pass inactivation by the liver

• Limitations/risks:
– skin barrier limits the number of drugs that can be delivered by passive diffusion from an adhesive patch
– potential discomfort, irritation

Question 17

What are the advantages of intravenous administration?

Answer 17

• Advantages:
– greater degree of reliability and precision of administered dose
– fewer problems with absorption • not affected by food in the stomach • no “first-pass effect”

• Disadvantages:
– sight of the needle
– pain
– tissue damage and irritation – drugs must be in solution
– limited volume

Question 18

What are the advantages and disadvantages of subcutaneous administration?

Answer 18

– Advantages
• slow, even absorption
• may be used as a depot
• rate of absorption may be modified by altering blood flow

– Disadvantages
• not effective when peripheral circulation is impaired (e.g. in shock)
• limited volume

Question 19

What are the advantages and disadvantages of intramuscular administration?

Answer 19

– Advantages
• more rapid absorption than subcutaneous
• rate of absorption may be modified by altering blood flow

– Disadvantages
• potential for infection and nerve damage • risk of inadvertent i.v. administration

Question 20

What is the bolus effect?

Answer 20

Rapid injection can lead to locally exceeding the MTC which can have adverse effects

Question 21

What is the volume of distribution (Vd)?

Answer 21

Measure of how even distribution is and it is the theoretical volume of fluid where the drug would have been diluted with

Question 22

What do large Vd values indicate?

Answer 22

Indicates distribution to tissues and organs

Question 23

The antibiotic tobramycin is given to a patient with gram-negative bacteremia. The patient weight is 60 kg and the patient receives a loading dose of 1.5 mg/kg (90 mg total). If the initial plasma concentration of tobramycin is 6 mg/liter after intravenous dosing, what is the apparent volume of distribution (Vd) for this drug?

A) 10 liters 
B) 15 liters 
C) 20 liters 
D) 30 liters 
E) 60 liters

Answer 23

B.

90 mg/ (6mg/L)

= 15 L

Question 24

Theophylline is given to a patient with bronchial asthma in the emergency room. The target plasma level is 10 􏰅µg/ml and the patient weighs 50 kg. The average volume ofdistributionfor theophyllineis0.5 liters/kg. Which of the following is the correct loading dose?

A) 100 mg 
B) 250 mg 
C) 500 mg 
D) 1000 mg 
E) 2500 mg

Answer 24

B.

10 􏰅µg/ml = 0.00001 kg/L

0. 5 L/kg = dose/0.00001 kg/L
1. 00005 = dose/50kg
2. 00025 kg = dose

dose = 250 mg

Question 25

What tissues can act as drug reservoirs?

Answer 25

Muscle and Fat as well as plasma proteins like albumin