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
Modified T/F
All drugs have the same kinetics. At some instrances, drugs at high doses it follow the first order kinetics; at low doses, it follows the zero order kinetics
FT
● Drugs will have their own kinetics
What are the five (5) organs for metabolism?
- Liver
- Lungs
- Kidneys
- GI epithelium
- Skin
What is the main organ for metabolism?
Liver
T/F: Kidneys have small amount of metabolism
True
ENZYMES ABILITIES
- Ability of drugs to stimulate the activity of enzymes
- Ability of drugs to inhibit the activity of enzymes
A. Enzyme Induction
B. Enzyme Inhibition
- A
- B
You have 2 drugs (A & B) and Drug A is an enzyme inducer for the enzymes that metabolizes Drug B
What will happen if you give both of these drugs to the patient?
There would be less drug B because drug A will stimulate the enzymes to metabolize drug B.
You have 2 drugs (A & B) and Drug B is an enzyme inhibitor for the enzymes that metabolizes Drug A
What will happen if you give both of these drugs to the patient?
Drug A will be increased since drug B will induce its enzyme inhibition effects
Giving multiple drugs to the same patient (looking at drug interactions)
Polypharmacy
DRUG EXCRETION:
1. Main organ for excretion
2. Minor way to excrete the drug
3. Weird taste in mouth when started drug intake (e.g. salty, metallic)
4. Some drugs are excreted here so we need to be extra careful with mothers
5. May smell it
6. When you take the drugs, your feces may smell/have different colors (iron - black)/etc. because of the drug
7. When we exhale, you can smell the drug
A. Kidney
B. Lungs
C. Gastrointesitnal tract (GIT)
D. Sweat
E. Saliva
F. Breast milk
G. Bile
- A
- G
- E
- F
- D
- C
- B
DRUG ELIMINATION RATES
Total elimination rate of a drug is the sum of all the individual organs added together
Clearance
T/F: Each organ has a clearance rate
True
What is the formula for clearance?
( Concentration inside - concentration outside)/concentration inside
T/F: Not all organs need to eliminate the drug
False
All organs need to eliminate the drug, therefore all organs should have a parameter for clearance
Given the following circumstances:
Concentration inside the liver: 6 g/100ml or 6%
Concentration outside the liver: 2 g/100ml or 2%
What is the clearance rate of the said organ?
0.67
(not sure me sa units since hindi siya namention sa class)
Given the following circumstances:
Concentration inside the kidney: 10 g/100ml or 10%
Concentration outside the liver: 8 g/100ml or 8%
What is the clearance rate of the said organ?
0.2
(not sure me sa units since hindi siya namention sa class)
Time necessary for the plasma concentration of a drug to decrease 50% during elimination phase
Half-life (t1/2)
Give three (3) importance of knowing a drug’s half life
- The time that you are supposed to give the next dose already
- To achieve a steady state
- Dictates the schedule (how often)
and the dose
DOSING SCHEDULE AND PLASMA CONCENTRATION:
T/F: Equilibrium/Steady State/ Plateau level is the dose administered that is equal to the amount of eliminated
True. This is where it is within therapeutic range. Doctors should maintain the dose in the plasma that can elicit a cure/treatment in prescribing medications.
DOSING SCHEDULE AND PLASMA CONCENTRATION
Why is continuous infusion is better than IV bolus?
Continuous infusion - drug is continuously being infused. When you start with the infusion, you are achieving a good therapeutic range. It maintains a steady state once infusion starts.
On the other hand, we need to keep on giving IV boluses to keep on achieving plasma levels. Steady state will be only achieved after 4 half lives.
T/F: There would be toxic effects below the steady state of a drug
False
Below - no good therapeutic effect
Above - toxic effects
What are the four (4) different drug receptors?
- Ligand Gated Ion Channels
- G-protein coupled receptors
- Enzyme-linked receptors
- Intracellular receptors
DRUG RECEPTORS
1. Cholinergic nicotinic receptors
2. Steroid receptors
3. Alpha and beta adreno receptors
4. Insulin receptors
A. Ligand Gated Ion Channels
B. G-Protein Coupled Receptors
C. Enzyme-linked Receptors
D. Intracellular Receptors
- A
- D
- B
- C
What is the drug receptor mechanism behind sedatives? Use the following hints/terms to answer the question
- ligand gated ion channels
- neuron for wakefulness (reticular activating system)
- binding to chloride ions
If you allow a sedative drug to bind to the chloride ions → enter the ligand dated ion channels → the neuron will not allow wakefulness → sleep
DRUG RECEPTOR INTERACTION
Enumerate the four (4) concepts under this
- Size and Surface of the Drug
- Receptor Bonding
- Affinity
- Status of the Receptor
Drug-Receptor Interaction: Size and Surface of the Drug
What law states that increasing the concentration of a drug causes an increase in binding to receptors?
Law of Mass action
T/F: High dose will cause a faster receptor bindin. Thus, increasing effect
True
Drug-Receptor Interaction: Receptor Bonding
Enumerate the four (4) types of bonding
- Covalent
- Ionic
- Hydrogen Bond
- Van der Walls
Drug-Receptor Interaction: Receptor Bonding
1. Sharing of pair of electrons
2. Strongest bond
3. Weakest bond between atoms
4. Electrostatic attraction between opposite charges
A. Hydrogen Bond
B. Ionic
C. Van der Walls
D. Covalent
- D
- D
- C
- B
What is the measure of attraction between drug and receptor?
Affinity
Modified T/F: Low affinitiy means low attraction. High or Avid affinity means high attraction
TT
DRUG RECEPTOR INTERACTION: STATUS OF THE RECEPTOR
Once the drug binds to the receptor, either goes into ___ state or ___ state
activated state or inactivated state
Enumerate the three (3) functional aspects of drug-receptor interaction
● Drug selectivity
● Dose response (Higher dose = Greater response)
● Drug classification
DRUG CLASSIFICATION
1. Binds to a receptor and produces an
action (classic)
2. Binds to a receptor and produces a
lesser effect than a (real) agonist yet
prevents an agonist from binding
3. Used for drugs that are already given
but you still want to increase the
effect
4. Binds to a receptor but does not
produce an action
5. A drug that will take an effect
A. Agonist
B. Antagonist or blocker
C. Partial agonist
- A
- C
- C
- B
- A
ANTAGONIST OR BLOCKER DRUG CLASSIFICATION
Blocks the other drugs available to take an effect
Blocker
ANTAGONIST OR BLOCKER DRUG CLASSIFICATION
binds to the receptor and can displace if the dose is higher than the other drug
Competitive Antagonist
ANTAGONIST OR BLOCKER DRUG CLASSIFICATION
Even if you give a lot of other drugs, you cannot displace it; we just have to wait for the drug to be metabolized/excreted or reversed
Non-competitive Antagonist
DETERMINE WHAT KIND OF DRUG CLASSFICATION
Drug A binds to a receptor and produces its therapeutic effects to the patient’s muscles
Agonist
DRUG CLASSFICATION
Drug A is a blocker. If this was given along with drug B and both of them have the same receptors, what would happen?
Drug A would block drug B’s effects
DRUG CLASSFICATION
Drug X and Drug Y were given to the patient at the same time. Given that these two share similar receptors and Drug X is a competitive antagoist, what would happen if Drug X has a higher dosage?
Drug X will bind to the receptor and will displace Drug Y
DRUG CLASSFICATION
T/F: A non-competitive antagonist can prevent the action of an agonist without any effect on the binding of the agonist to the receptor
True
Source: Deranged Physiology
DRUG CLASSFICATION
T/F: A drug antagonist binds but does not fit well → still has little effect
False. A drug antagonist binds but does not fit well → no effect → blocks the other drugs from binding
RECEPTOR REGULATION
T/F: Receptor Down Regulation is decreasing concentration of receptors
True
RECEPTOR REGULATION
T/F: Decrease in the concentration of receptors → producing more effect
False. This involves the concept of tolerance.
Decrease in the concentration of receptors →
producing less effect
T/F: Production of lesser effect d/t the decrease in the concentration of receptors happens in chronic intake of the drug.
True
T/F: When you have been taking the drug for a while, you will notice that there is no more effect and that there is longer duration to develop.
True
What concept talks about the shorter duration of the drug’s effects to develop?
Tachyphylaxis
What concept talks about increasing concentration of receptors and receptor supersensitivity?
Receptor Up Regulation
RECEPTOR REGULATION
The patient has been taking a drug for a long time now and reported to the doctor that there is already no effect. What concept can explain this?
A. Tolerance
B. Tachyphylaxis
C. Receptor Up Regulation
Tolerance. In this case, we need a higher dose to produce the same effect. This is commonly seen in orally administered drugs.
RECEPTOR REGULATION
You noticed that the drug suddenly does not work anymore after administering it for 2 or 3 doses through IV route. What concept can explain this?
A. Tolerance
B. Tachyphylaxis
C. Receptor Up Regulation
Tachyphylaxis. This is usually seen in acute cases and mostly in hospital set-up
RECEPTOR REGULATION
The patient states that they feel drowsy after the doctor prescribed them their medication. However, upon consulting the doctor, they were told that they were given their usual dose. What concept can explain this?
A. Tolerance
B. Tachyphylaxis
C. Receptor Up Regulation
Receptor Up Regulation. This is due to the hypersensitivity of the patient’s receptors.
How come people respond differently or have varied reactions to the same drug? Enumerate the three (3) factors that influence such variations in drug response and metabolism
- Genetics
- Comorbidities
- Diet
T/F Regarding Variations in Drug Response and Metabolism
- Genetics play a major role
- True
T/F Regarding Variations in Drug Response and Metabolism
2. It is not important to ask if the patient has a family history of allergies
- False. This is also realted to the concept genetics.
T/F Regarding Variations in Drug Response and Metabolism
3. All drugs are needed to be taken with meals to avoid gastric irrtiation
- False. There are drugs that are needed to be taken before a meal. E.g. anti TB drugs need to be taken before breakfast to maintain the bioavailability. Moreover, there are also drugs that are needed to be taken with meals to avoid gastric irritation
T/F Regarding Variations in Drug Response and Metabolism
4. Comorbidities, such as Htn and DM, can change the kinetics and dynamics of a drug
- True
T/F: A drug prescription of three times a day and every 8 hrs are the same.
False.
They are different because TID may have a larger therapeutic window so you are more flexible with the dosing. Some drugs also require strictly counting the hours (esp. for antibiotics).
The scheduling also affects the pharmacokinetics and dynamics of a drug.
