S1L3: Pharmacokinetics and Drug Distribution Flashcards
FACTORS AFFECTING DISTRIBUTION
- The more the tissue is permeable to that drug and the more the drug is in its form can permeate the tissue, ideally in a lipid form, then the faster/larger the distribution of that drug
- Higher blood flow, the greater distribution to organ
A. Tissue Permeability
B. Plasma Protein Binding
C. Binding to Subcellular Components
D. Blood Flow
- A.
- D.
FACTORS AFFECTING DISTRIBUTION
- Binding to subcellular components decreases drug distribution
- The higher the drug is bound to a plasma protein (ex: albumin), it is not in its free form, thereforem the distribution is smaller
A. Tissue Permeability
B. Plasma Protein Binding
C. Binding to Subcellular Components
D. Blood Flow
- C
- B
Which of the following is true?
BRAIN’s Mass: 1.4 kg
BRAIN’s Blood Flow: 750 ml/min
BRAIN’s Cardiac Output: 13.9%
MUSCLE’s Mass: 34.4 kg
MUSCLE’s Blood Flow: 840 ml/min
MUSCLE’s Cardiac output: 15.6%
A. The brain has higher blood flow than the muscle
B. The muscle has higher blood flow than the brain
C. They have equal amount of blood flow
A. The brain has higher blood flow than the muscle in relation to their mass
What measures the apparent space in the body available to contain the drug?
Volume of Distribution
Not the real space in the body but if we were to distribute the drug across the body, this gives an overview of how much volume should the body have for it to contain the drug.
How do you compute for the Volume of Distribution?
VD = Amount of drug administered/Concentration of drug in plasma
Compute for this individual’s Volume of Distribution
60 kg male
Blood volume of 5.5 L
Extracellular fluid of 12.0 L
Intracellular fluid of 24.5 L
Total body water of 42 L
AMOUNT OF DRUG ADMINISTERED: 500ug
BLOOD PLASMA LEVEL OF 0.78 ng/ml
VD = 500 ug/0.78 ng/mL = 645 L
VOLUME OF DISTRIBUTION
- High tissue concentration
- Low plasma concentration
- Shorter duration of action
- Excretion of drugs is slower
A. Large volume of distribution
B. Small volume of distribution
- A
- A
- B
- A
Modified T/F
Low tissue concentration means less in organs. High plasma conctration means more in plasma
TT
Identifiy the following
1.VD of 100 L
2. VD of 500 L
3. VD of 600 L
A. Low tissue concentration = less in organs
B. Low plasma concentration
- A (Small Volume of Dsitrib)
- B (Large Volume of Distrib)
- B (Large Volume of Distrib)
Modified T/F
VD allows mathematical analysis/prediction of the effectiveness of drug doses and duration of recovery. VD allows comparison between drugs and aids in determining toxic doses only for specific disease entitites.
TF
VD aids in determining THERAPUETIC DOSES OR TOXIC DOSES for specific disease entities
What is the significance of volume of distribution in patients with diseases? How can we apply this when handling patients with kidney/liver problems?
If your patient has liver/kidney failure, for example, we do not give the same dose to the patient as compared to a patient with a healthy liver/kidney.
T/F
Drugs does not get stored in the adipose tissue which is why it is not significant in the drug distribution
False. Drugs get stored here and by the time that the
plasma levels go down, the drug can now go into the
plasma because of the difference in the concentration gradient (high concentration in fat, low
concentration in plasma)
Adipose tissue has the highest depository site
What are the possible drug storage sites discussed?
- Adipose tissue
- Bone
- Muscle
- Others (Gallbladder, bile)
The patient reported to you that the drug’s effects span for a few days. You saw that the drug is N-acetyldesipramine and is known to have high concentrations and stores itself in the adipose tissue.
What concept explains this? And what is the name of this effect?
Hangover Effect: Happens when the drugs from fat is deposited to the plasma. Once the plasma concentration decreases, the drugs stored in the fat will be released to the plasma
How can you explain why the sedatives’ effects span for 2 to 3 days?
This is also related to hangover effect wherein the seadatives goes high in plasma and some is stored in the fat -> Plasma is metabolized d/t change in concentration gradient -> When the concentration gradient is released, the stored drug in the fat is released back to the plasma
T/F: Tetracycline is an antibiotic that is used to treat infection which stores itself in the adipose tissue
False. It is stored in the bone. It deposits itself in the teeth of children. Thus, leading to teeth staining in pediatric pts.
T/F: A pharmacologically active drug is liphophobic, ionized or partialliy ionized at physiologic pH, and oftenly strongly bound to plasma proteins
False. A pharmacologically active drug is lipophilic, unionized or partially ionized at physiologic pH, and often strongly bound to plasma proteins.
Volume of Distribution:
If we give a patient 300 ug of Digoxin with a blood plasma concentration level of 0.50 ng/mL, what is the patient’s volume of distribution? Is it small or large?
VD = 600 L; Large
What is the critical value when it comes to drugs binding to plasma proteins?
90% and above
When it is 90% bound, it becomes difficult for
the drug to be released and be free in the
plasma to exert its pharmacologic effect
A scientist made a drug that has 80% - 85% binding to plasma proteins. Is it a pharmacologically active drug?
Yes
■ 85% and below is still a strong binding, then it
is easily released by the plasma protein
● Majority of drugs are within 80-85% and
are still pharmacologically active drugs
How can we tell if the drug can be renally excreted?
If it is hydrophilic/water soluble, ionized/polar, and unbound
Modified T/F: In biotransformation or metabolism of drugs, enzymatic alteration of a drug leads to the
formation of metabolites. It also occurs at some point between absorption of the drug into the circulation and its renal elimination.
Both are True
T/F: There are drugs that achieve their active form after metabolism
True
T/F: There are drugs that become toxic after metabolism
True
It is stated in the patient’s chart that they have kidney failure and you read in the drug insert (parang pamphlet) of the prescribed medication that its metabolites are toxic. What will you do in this situation?
Discontinue the medication. We have to make sure that the kidney is functioning well so that the metabolites (of the said drug) are urinated since they might accumulate and become toxic
T/F: The moment you take the drug, biotransformation
already happens up to its elimination
True. Example of this is the first-pass effect.
What is a parent compound/drug?
Parent compound/drug: majority of the drug goes into an inactive form
PHASES OF METABOLISM:
1. Converts the parent drug to a more polar metabolite by introducing or unmasking a functional group
2. Synthetic reactions to form a highly polar conjugate
A. Phase 1
B. Phase 2
- A
- B
What are the four (4) cellular mechanisms of phase 1 of metabolism?
- Oxidation
- Reduction
- Oxidation reduction
- Hydrolysis
What is the cellular mechanism of phase 2 of metabolism?
Conjugation
T/F: All drugs that went to phase 1 has to go to phase 2
True.
The general rule is that when a drug goes into phase 1, it has to go to phase 2 (since you need the conjugation reaction to happen)However, some drugs can go directly to phase 2.
RATE OF METABOLISM
- Metabolism of a constant amount of drug per unit time
- Constant fraction of available drug is metabolized in a given period
A. First Order Kinetics
B. Zero Order Kinetics
- B
- A
FIRST ORDER KINETICS
If a drug is metabolized by 50% (fraction) every 6
hours (given period)
● If I give you 1000mg at 6am, how much drug is there at 12 noon? 6 pm? 12 am?
12 noon: 500 mg
6 pm: 250 mg
12 am: 125 mg
FIRST ORDER KINETICS
If a drug is metabolized by 60% (fraction) every 8
hours (given period)
● If I give you 1200mg at 6 am, how much drug is there at 2pm? 10 pm?
2 pm: 720 mg
10 pm: 432 mg
ZERO ODER KINETICS
If a drug is metabolized 500mg (amount) every 6 hours (time)
If I give you 1000mg at 6am, how much drug is there after 6 hours?
12 nn → 500mg
6 pm → 0mg
ZERO ODER KINETICS
If a drug is metabolized 400mg (amount) every 6 hours (time)
If I give you 1200mg at 6am, how much drug is there after 6 hours?
12 noon: 800 mg
6 pm: 400 mg
12 am: 0 mg