S1L3: Pharmacokinetics and Drug Distribution

Question 1

FACTORS AFFECTING DISTRIBUTION

1. 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
2. Higher blood flow, the greater distribution to organ

A. Tissue Permeability
B. Plasma Protein Binding
C. Binding to Subcellular Components
D. Blood Flow

Answer 1

1. A.
2. D.

Question 2

FACTORS AFFECTING DISTRIBUTION

3. Binding to subcellular components decreases drug distribution
4. 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

Answer 2

3. C
4. B

Question 3

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

Answer 3

A. The brain has higher blood flow than the muscle in relation to their mass

Question 4

What measures the apparent space in the body available to contain the drug?

Answer 4

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.

Question 5

How do you compute for the Volume of Distribution?

Answer 5

VD = Amount of drug administered/Concentration of drug in plasma

Question 6

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

Answer 6

VD = 500 ug/0.78 ng/mL = 645 L

Question 7

VOLUME OF DISTRIBUTION

1. High tissue concentration
2. Low plasma concentration
3. Shorter duration of action
4. Excretion of drugs is slower

A. Large volume of distribution
B. Small volume of distribution

Answer 7

1. A
2. A
3. B
4. A

Question 8

Modified T/F

Low tissue concentration means less in organs. High plasma conctration means more in plasma

Answer 8

TT

Question 9

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

Answer 9

1. A (Small Volume of Dsitrib)
2. B (Large Volume of Distrib)
3. B (Large Volume of Distrib)

Question 10

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.

Answer 10

TF

VD aids in determining THERAPUETIC DOSES OR TOXIC DOSES for specific disease entities

Question 11

What is the significance of volume of distribution in patients with diseases? How can we apply this when handling patients with kidney/liver problems?

Answer 11

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.

Question 12

T/F

Drugs does not get stored in the adipose tissue which is why it is not significant in the drug distribution

Answer 12

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

Question 13

What are the possible drug storage sites discussed?

Answer 13

1. Adipose tissue
2. Bone
3. Muscle
4. Others (Gallbladder, bile)

Question 14

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?

Answer 14

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

Question 15

How can you explain why the sedatives’ effects span for 2 to 3 days?

Answer 15

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

Question 16

T/F: Tetracycline is an antibiotic that is used to treat infection which stores itself in the adipose tissue

Answer 16

False. It is stored in the bone. It deposits itself in the teeth of children. Thus, leading to teeth staining in pediatric pts.

Question 17

T/F: A pharmacologically active drug is liphophobic, ionized or partialliy ionized at physiologic pH, and oftenly strongly bound to plasma proteins

Answer 17

False. A pharmacologically active drug is lipophilic, unionized or partially ionized at physiologic pH, and often strongly bound to plasma proteins.

Question 18

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?

Answer 18

VD = 600 L; Large

Question 19

What is the critical value when it comes to drugs binding to plasma proteins?

Answer 19

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

Question 20

A scientist made a drug that has 80% - 85% binding to plasma proteins. Is it a pharmacologically active drug?

Answer 20

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

Question 21

How can we tell if the drug can be renally excreted?

Answer 21

If it is hydrophilic/water soluble, ionized/polar, and unbound

Question 22

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.

Answer 22

Both are True

Question 23

T/F: There are drugs that achieve their active form after metabolism

Answer 23

True

Question 24

T/F: There are drugs that become toxic after metabolism

Answer 24

True

Question 25

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?

Answer 25

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

Question 26

T/F: The moment you take the drug, biotransformation already happens up to its elimination

Answer 26

True. Example of this is the first-pass effect.

Question 27

What is a parent compound/drug?

Answer 27

Parent compound/drug: majority of the drug goes into an inactive form

Question 28

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

Answer 28

1. A 2. B

Question 29

What are the four (4) cellular mechanisms of phase 1 of metabolism?

Answer 29

1. Oxidation 2. Reduction 3. Oxidation reduction 4. Hydrolysis

Question 30

What is the cellular mechanism of phase 2 of metabolism?

Answer 30

Conjugation

Question 31

T/F: All drugs that went to phase 1 has to go to phase 2

Answer 31

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.

Question 32

RATE OF METABOLISM 1. Metabolism of a constant amount of drug per unit time 2. Constant fraction of available drug is metabolized in a given period A. First Order Kinetics B. Zero Order Kinetics

Answer 32

1. B 2. A

Question 33

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?

Answer 33

12 noon: 500 mg 6 pm: 250 mg 12 am: 125 mg

Question 34

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?

Answer 34

2 pm: 720 mg 10 pm: 432 mg

Question 35

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?

Answer 35

12 nn → 500mg 6 pm → 0mg

Question 36

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?

Answer 36

12 noon: 800 mg 6 pm: 400 mg 12 am: 0 mg

Question 37

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

Answer 37

FT ● Drugs will have their own kinetics

Question 38

What are the five (5) organs for metabolism?

Answer 38

1. Liver 2. Lungs 3. Kidneys 4. GI epithelium 5. Skin

Question 39

What is the main organ for metabolism?

Answer 39

Liver

Question 40

T/F: Kidneys have small amount of metabolism

Answer 40

True

Question 41

ENZYMES ABILITIES 1. Ability of drugs to stimulate the activity of enzymes 2. Ability of drugs to inhibit the activity of enzymes A. Enzyme Induction B. Enzyme Inhibition

Answer 41

1. A 2. B

Question 42

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?

Answer 42

There would be less drug B because drug A will stimulate the enzymes to metabolize drug B.

Question 43

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?

Answer 43

Drug A will be increased since drug B will induce its enzyme inhibition effects

Question 44

Giving multiple drugs to the same patient (looking at drug interactions)

Answer 44

Polypharmacy

Question 45

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

Answer 45

1. A 2. G 3. E 4. F 5. D 6. C 7. B

Question 46

DRUG ELIMINATION RATES Total elimination rate of a drug is the sum of all the individual organs added together

Answer 46

Clearance

Question 47

T/F: Each organ has a clearance rate

Answer 47

True

Question 48

What is the formula for clearance?

Answer 48

( Concentration inside - concentration outside)/concentration inside

Question 49

T/F: Not all organs need to eliminate the drug

Answer 49

False All organs need to eliminate the drug, therefore all organs should have a parameter for clearance

Question 50

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?

Answer 50

0.67 (not sure me sa units since hindi siya namention sa class)

Question 51

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?

Answer 51

0.2 (not sure me sa units since hindi siya namention sa class)

Question 52

Time necessary for the plasma concentration of a drug to decrease 50% during elimination phase

Answer 52

Half-life (t1/2)

Question 53

Give three (3) importance of knowing a drug's half life

Answer 53

1. The time that you are supposed to give the next dose already 2. To achieve a steady state 3. Dictates the schedule (how often) and the dose

Question 54

DOSING SCHEDULE AND PLASMA CONCENTRATION: T/F: Equilibrium/Steady State/ Plateau level is the dose administered that is equal to the amount of eliminated

Answer 54

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.

Question 55

DOSING SCHEDULE AND PLASMA CONCENTRATION Why is continuous infusion is better than IV bolus?

Answer 55

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.

Question 56

T/F: There would be toxic effects below the steady state of a drug

Answer 56

False Below - no good therapeutic effect Above - toxic effects

Question 57

What are the four (4) different drug receptors?

Answer 57

1. Ligand Gated Ion Channels 2. G-protein coupled receptors 3. Enzyme-linked receptors 4. Intracellular receptors

Question 58

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

Answer 58

1. A 2. D 3. B 4. C

Question 59

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

Answer 59

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

Question 60

DRUG RECEPTOR INTERACTION Enumerate the four (4) concepts under this

Answer 60

- Size and Surface of the Drug - Receptor Bonding - Affinity - Status of the Receptor

Question 61

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?

Answer 61

Law of Mass action

Question 62

T/F: High dose will cause a faster receptor bindin. Thus, increasing effect

Answer 62

True

Question 63

Drug-Receptor Interaction: Receptor Bonding Enumerate the four (4) types of bonding

Answer 63

- Covalent - Ionic - Hydrogen Bond - Van der Walls

Question 64

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

Answer 64

1. D 2. D 3. C 4. B

Question 65

What is the measure of attraction between drug and receptor?

Answer 65

Affinity

Question 66

Modified T/F: Low affinitiy means low attraction. High or Avid affinity means high attraction

Answer 66

TT

Question 67

DRUG RECEPTOR INTERACTION: STATUS OF THE RECEPTOR Once the drug binds to the receptor, either goes into ___ state or ___ state

Answer 67

activated state or inactivated state

Question 68

Enumerate the three (3) functional aspects of drug-receptor interaction

Answer 68

● Drug selectivity ● Dose response (Higher dose = Greater response) ● Drug classification

Question 69

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

Answer 69

1. A 2. C 3. C 4. B 5. A

Question 70

ANTAGONIST OR BLOCKER DRUG CLASSIFICATION Blocks the other drugs available to take an effect

Answer 70

Blocker

Question 71

ANTAGONIST OR BLOCKER DRUG CLASSIFICATION binds to the receptor and can displace if the dose is higher than the other drug

Answer 71

Competitive Antagonist

Question 72

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

Answer 72

Non-competitive Antagonist

Question 73

DETERMINE WHAT KIND OF DRUG CLASSFICATION Drug A binds to a receptor and produces its therapeutic effects to the patient's muscles

Answer 73

Agonist

Question 74

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?

Answer 74

Drug A would block drug B's effects

Question 75

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?

Answer 75

Drug X will bind to the receptor and will displace Drug Y

Question 76

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

Answer 76

True Source: Deranged Physiology

Question 77

DRUG CLASSFICATION T/F: A drug antagonist binds but does not fit well → still has little effect

Answer 77

False. A drug antagonist binds but does not fit well → no effect → blocks the other drugs from binding

Question 78

RECEPTOR REGULATION T/F: Receptor Down Regulation is decreasing concentration of receptors

Answer 78

True

Question 79

RECEPTOR REGULATION T/F: Decrease in the concentration of receptors → producing more effect

Answer 79

False. This involves the concept of tolerance. Decrease in the concentration of receptors → producing less effect

Question 80

T/F: Production of lesser effect d/t the decrease in the concentration of receptors happens in chronic intake of the drug.

Answer 80

True

Question 81

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.

Answer 81

True

Question 82

What concept talks about the shorter duration of the drug's effects to develop?

Answer 82

Tachyphylaxis

Question 83

What concept talks about increasing concentration of receptors and receptor supersensitivity?

Answer 83

Receptor Up Regulation

Question 84

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

Answer 84

Tolerance. In this case, we need a higher dose to produce the same effect. This is commonly seen in orally administered drugs.

Question 85

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

Answer 85

Tachyphylaxis. This is usually seen in acute cases and mostly in hospital set-up

Question 86

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

Answer 86

Receptor Up Regulation. This is due to the hypersensitivity of the patient's receptors.

Question 87

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

Answer 87

1. Genetics 2. Comorbidities 3. Diet

Question 88

T/F Regarding Variations in Drug Response and Metabolism 1. Genetics play a major role

Answer 88

1. True

Question 89

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

Answer 89

2. False. This is also realted to the concept genetics.

Question 90

T/F Regarding Variations in Drug Response and Metabolism 3. All drugs are needed to be taken with meals to avoid gastric irrtiation

Answer 90

3. 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

Question 91

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

Answer 91

4. True

Question 92

T/F: A drug prescription of three times a day and every 8 hrs are the same.

Answer 92

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.