Block 1 Pharmacokinetics/dynamics Flashcards
Pharmacokinetics
What the body does to the drug (absorption & distribution)
Pharmacodynamics
What the drug does to the body (metabolism/excretion i.e elimination)
An 18-year-old female patient is brought to the emergency department due to drug overdose. Which of the following routes of administration is the most desirable for administering the antidote for the drug overdose?
A. Intramuscular
B. Intravenous
C. Oral
D. Subcutaneous
E. Transdermal
B. Intravenous
With regards to a graph what is the equation for bioavailability
F (bioavail) =
AUC (Drug conc oral)/ AUC (drug conc IV) x 100%
what area in the graph represents the concentration of a drug in systemic circulation?
The total amount of drug in the systemic circulation is defined by the area under the concentration-time curve (AUC).
Time from administration to the time we see the drug in the blood
Lag time
The max concentration of drug that we can get with a certain dose
Cmax
The time that a drug hits Cmax
Tmax
The time from drug administration to when the level of the drug in the blood reaches its minimal effective concentration (smallest dosage that still produces an effect)
Onset of activity
The time that the plasma concentration of the drug stays higher than the MEC
Duration of action
The time of administration to Cmax
Time to peak
Describe the first pass effect
Happens with oral drugs because they get somewhat metabolized before passing through the GI wall & entering systemic circulation
Less bioavailability & therapeutic effect
Drugs that are administered IV are
A. Slowly absorbed
B. Subject to first-pass metabolism
C. 100% bioavailable
D. Rapidly excreted by the kidneys
E. Rapidly metabolized by the liver
C. 100% bioavailable
In a research study,To assess bioavailability of a drug, investigators administered
drug intravenously to a volunteer and measured the plasma concentration
over the time. The investigators subsequently administered the same dose of the
drug orally to the same person and similarly measured the plasma concentration of the drug over time.
Which of the following is the best determinant of oral bioavailability of the drug in this person?
A.Slope of the IV curve divided by the slope of the oral curve
B.Area under the oral curve
C.Maximal concentration at the peak of the oral curve
D.Rate of elimination for the IV curve divided by rate of elimination for the oral curve
E. Area under the oral curve divided by area under the IV curve
E. Area under the oral curve divided by area under the IV curve
How does portal hypertension effect drug bioavailability?
It increases the bioavailability of oral drugs because blood flow will be diverted away from the liver meaning it can’t metabolize the drug
What factors increase distribution of a drug? (delivery to tissues)
Small
Lipophilic
High affinity for tissue proteins
ex. Chloroquine
What factors decrease distribution of a drug? (delivery to tissues)
Large
High molecular weight
Charged
High affinity for plasma proteins (albumin)
High binding affinity for albumin means what for volume of distribution
Low volume distribution & high concentration of the drug within circulation
Small lipophilic drugs with a tendency to bind to tissue proteins have a ______ Vd
High Vd to all tissues including fat
Large, charged drugs with a tendency to bind to plasma proteins have a ______ Vd
Low Vd, typically target intravascular compartments as it loves to bind to albumin
Small hydrophilic drugs tend to have a ______ Vd
medium Vd these are best for targeting the ECF compartment
Distribution into the water compartments in the body:
Total
ECM
Blood volume
Plasma
Total = 36-40L
ECF = 12-14L
Blood volume = 5L
Plasma = 3L
If a drug has a high molecular weight or is extensively protein bound
too large to pass through the slit junctions of the capillaries & is trapped within the plasma (vascular) compartment. As a result, it has a low Vd
ex. Plasma vol 3L i.e heparin
How to conditions like Liver disease, nephrotic syndrome, or general hypoalbuminemia effect Vd?
They increase Vd because the drug can’t bind to Plasma proteins well
KR2250 is an investigational cholesterol-lowering agent. KR2250 has a high molecular weight and is extensively bound to albumin. KR2250 will have a(n) _______________ apparent volume of distribution (Vd).
A. High
B. Low
C. Extremely high
D. Normal
B. Low
A new aminoglycoside antibiotic is developed that is believed to be effective against Pseudomonas. The volume of distribution of the drug is measured in a group of volunteers and is determined to be 4.5 L. This new drug is most likely to have which of the following properties?
A. It has low molecular weight
B. It is lipophilic
C. It does not bind to albumin
D. It is highly charged
E. It has high oral bioavailability
D. It is highly charged
Hoffman’s elimination
- When a compound/drug is spontaneously degraded/inactivated in the plasma & tissue
Drug admin types:
Oral =
Sublingual =
Rectal =
Topical =
Parenteral =
Oral has the 1st pass effect (less bioavailable)
Drug admin types:
Sublingual =
- Sublingual has faster absorption (nitroglycerin)
- Bypass 1st effect
Drug admin types:
Rectal =
Rectal (ex diazepam for kids with status epilepticus)
- Avoids 1st pass effect
- Avoids vomiting
- Good for conscious patients
- Poor absorption
What is the formula for Vd?
Vd =
Amount of drug in the body
/
plasma drug concentration
OR
Vd = Q/C0
What’s the equation for loading dose?
Loading dose = (Vd) × (desired steady-state plasma concentration)/F
estimates the volume of blood from which the drug is cleared per unit of time. What is the equation?
When a drug is spontaneously inactivated by methylation this is a good example of ________ & it’s ideal for patients with renal & hepatic insuff (Atracurium)
Hoffman’s elimination
Which drugs are most capable of crossing the BBB or placenta?
Small molecular weight &/or very lipophilic drugs.
Phase 1
Safety & Max dose
Safety & Max dose
What’s the phase of drug trial?
Phase 1
Key word: Max dose
* Look for the max tolerable dose
* Other treatments have failed
* Normal organ function
* Test drugs on a small sample
phase 1
Describe phase 1 of drug trial
Key word: Max dose
* Look for the max tolerable dose
* Other treatments have failed
* Normal organ function
* Test drugs on a small sample
Describe Phase 0
No therapeutic effect
Key words: FDA approval
* Done on large studies
Phase 3
Describe phase 3 of drug trials
Key words: FDA approval
* Done on large studies
Describe phase 4 of drug trials
Key words: S-W-I-M (Safety-Work-Improvement- Market)
* Long term effects and safety concerns
Key words: S-W-I-M (Safety-Work-Improvement- Market)
* Long term effects and safety concerns
Which drug trial phase id this describing?
Phase 4
Describe phase 2 trials
evaluate drug efficacy among a small group of patients with the disease of interest
evaluate drug efficacy among a small group of patients with the disease of interest
Describes which phase of drug trial?
phase 2
