Pharmokinetics I Flashcards
What is pharmokinetics?
It is the time course of a drug
What is ADME?
Absorption
Distribution
Metabolism
Elimination
What is the minimum effective concentration?
Min threshold required for therapeutic effect
What is the maximum tolerated concentration?
Max point were the adverse effects begin to outweigh the benefits
What is the equation for the bioavailability (F)?
F = AUC (oral) / AUC (IV)
What are the uses of the AUC?
- Compare clearance (CL) between individuals
- Determine the bioavailability (F)
What types of drugs are absorbed the fastest?
Non-polar
What is the problem with 2 drugs that use the same active transport carrier?
The process is saturable and so they will compete with each other and limit their absorption.
What are the advantages of oral administration?
Many forms of the drug can be used (solution, tablets, etc)
Wha tis the first-pass effect?
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
What is the problem with drugs and the enterohepatic circulation?
Drugs may be secreted into the bile and reabsorbed via the intestine. This can delay delivery to the systemic circulation and may reduce bioavailability.
What is the salt factor?
The fraction of total drug that will be delivered as active drug to the systemic circulation is called the “salt factor” (S).
What are the advantages and disadvantages of sublingual and buccal administration?
• 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
What are the advantages and disadvantages of rectal administration?
• 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.
What are the advantages and disadvantages of inhalation?
• Absorption is via passive diffusion and is facilitated by a large surface area.
What are the advantages and disadvantages of transdermal administration?
• 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
What are the advantages of intravenous administration?
• 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
What are the advantages and disadvantages of subcutaneous administration?
– 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
What are the advantages and disadvantages of intramuscular administration?
– 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
What is the bolus effect?
Rapid injection can lead to locally exceeding the MTC which can have adverse effects
What is the volume of distribution (Vd)?
Measure of how even distribution is and it is the theoretical volume of fluid where the drug would have been diluted with
What do large Vd values indicate?
Indicates distribution to tissues and organs
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
B.
90 mg/ (6mg/L)
= 15 L
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
B.
10 µg/ml = 0.00001 kg/L
- 5 L/kg = dose/0.00001 kg/L
- 00005 = dose/50kg
- 00025 kg = dose
dose = 250 mg
What tissues can act as drug reservoirs?
Muscle and Fat as well as plasma proteins like albumin
