Pharmacokinetics and Pharmacodynamics

Question 1

Define pharmacokinetics.

Answer 1

Pharmacokinetics explains the effect of the body on a drug. Determines things such as the half-life, onset and duration of effects and dosing.

Question 2

What four processes are included in pharmacokinetics?

Answer 2

1. Absorption
2. Distribution
3. Metabolism
4. Excretion

Question 3

Define pharmacodynamics.

Answer 3

The effect that the drug has on a specific individual.

Question 4

What three principles are included in pharmacodynamics?

Answer 4

1. MOA
2. Sensitivity
3. Responsiveness

Question 5

What term describes a specific persons reaction to a drug which may be different than another persons reaction to the same drug

Answer 5

Responsiveness.

Question 6

Half-life vs. Half-time

Answer 6

Half life is the duration of effect. So half-life of effect which encompasses all possible active metabolites of the parent compound that may prolong the duration of the parent drug. Time necessary to eliminate 50% of the drug from the BODY.
Half-time- is the how long the parent drug stays in the system. Time necessary for the plasma concentration of drug to decline 50% during the elimination phase. Independent of the dose of the drug administered.

Question 7

The term used to quantify the amounts of a drug that reach the general system circulation after absorption?

Answer 7

Bioavailibility.

Question 8

Explain clearance

Answer 8

plasma clearance (Cl) is the volume of plasma that is entirely cleared of the drug per unit of time.
So the units are volume/time.
cl=keVd
Ke is the rate and takes into account the summation of all routes of elimination for a particular drug.
Vd- volume of distribution (whether the drug stays in the plasma, follows total body water or concentrates in the body tissues).

Question 9

Explain the basics of compartmental model of the body.

Answer 9

Divides the body into compartments that represent THEORETICAL spaces with calculated volumes.

Question 10

Describe the basic principle of the two-compartment model.

Answer 10

The body is made up of two compartments. One central and one peripheral.

Question 11

Describe the central component of the two-compartment model of the body (composed of, receives what % of CO, rate of uptake)

Answer 11

Central component contains the highly perfused tissues (kidney, liver, lungs, heart and brain)
Receives 75% of the CO
Rapid uptake of drug (IV drugs are first introduced into the central compartment, distribute to the second compartment, and then return to the central compartment for clearance)

Question 12

Describe the peripheral compartment of the two-compartment model of the body.

Answer 12

Large calculated volume.
Extensive uptake of drug.
Fat, muscle, hair, bones, nails.

Question 13

The rate of transfer between compartments decreases or increases with aging? And is dependent on what organs function?

Answer 13

1. Decreases.

Cardiac function.

Question 14

Mathematically describe the volume of distribution of a drug.

Answer 14

Dose of the IV drug/Plasma Concentration before elimination

Question 15

What three physiochemical characteristics of a drug influence the volume of distribution? Do they increase or decrease distribution?

Answer 15

1. Lipid Solubility increase
2. Binding to Plasma Proteins decrease
3. Molecular Size decrease

Question 16

What happens if dosing intervals are less than the elimination half time?

Answer 16

Drug accumulation.

Question 17

In two half times how much of the drug has been eliminated?

Answer 17

75%

Question 18

In three half times how much of the drug has been eliminated?

Answer 18

87.5

Question 19

In 4 half times how much of the drug has been eliminated?

Answer 19

93.8

Question 20

In 5 half times how much of the drug has been eliminated?

Answer 20

96.9

Question 21

In 6 half lives how much of the drug has been eliminated?

Answer 21

98.4

Question 22

Following systemic absorption of a drug which tissues receive a large amount of the total dose?

Answer 22

The highly perfused ones.

Heart, brain, kidney, liver.

Question 23

As the ________ decreases below that in the highly perfused tissues drug leaves the highly perfused tissues.

Answer 23

Plasma concentration.

Question 24

When drug leaves the highly perfused tissues because of a decrease in plasma concentration where does it go? And what is this called?

Answer 24

less well perfused sites (muscles and fat)

Redistribution

Question 25

Tissues that accumulate drug preferentially act as a what? to do what? which results in what?

Answer 25

A reservoir. Maintain plasma concentration Prolong effect

Question 26

Large or repeated doses _______ inactive tissue ______ redistribution. They also prolong the ________ but by how?

Answer 26

saturate negating duration of action effects on metabolism rather than distribution

Question 27

What are the driving forces for diffusional distribution (3)?

Answer 27

Solubility Concentration Gradient Rate of Blood Flow.

Question 28

Systemic absorption depends on what?

Answer 28

Solubility.

Question 29

Name two advantages to oral administration and three disadvantages.

Answer 29

1. most convenient 2. most economic 1. Emesis 2. Destruction by enzymes or acidic gastric fluid. 3. Irregular absorption with food or other drugs.

Question 30

When drugs are absorbed from the GI system and enter the portal venous blood to travel to the liver before entering the circulation for delivery to the tissue receptors this is called? What is the result?

Answer 30

The first pass effect. The drug is extensively extracted and metabolized prior to entering the systemic circulation.

Question 31

Sublingual/transmucosal: what type of onset? First pass effect yes or no?

Answer 31

Rapid onset and bypasses the liver which prevents the first pass effect.

Question 32

Transdermal provides ________ therapeutic _______ of a drug.

Answer 32

Sustained. Plasma Concentration.

Question 33

Where does absorption occur in a transdermal application?

Answer 33

Along sweat ducts and hair follicles.

Question 34

Sweat glands and hair follicles serve as what in a transdermal application?

Answer 34

Diffusion shunts

Question 35

What is the rate limiting step in a transdermal application?

Answer 35

Stratum corneum of the epidermis.

Question 36

What is the stratum corneum?

Answer 36

Outermost layer of the skin.

Question 37

What factors reflect the skins permeability for drugs?

Answer 37

Thickness and blood flow.

Question 38

Which area has more blood flow front or back?

Answer 38

Front.

Question 39

What can happen if the site for a transdermal application if the same site is continuously used?

Answer 39

Contact Dermatitis.

Question 40

What makes the distal rectum different than the proximal rectum for drug delivery?

Answer 40

Distal rectum bypasses the portal system Proximal rectum is transported to the portal system via superior hemorrhoidal veins meaning it undergoes the first pass effect.

Question 41

The response to rectal administration of drugs is predictable or unpredictable. Why?

Answer 41

Unpredictable. Because of the differences in absorption of the distal and proximal rectum.

Question 42

With IV administration you are able to achieve _________ precisely and rapidly?

Answer 42

Therapeutic plasma levels.

Question 43

The lung acts as a reservoir to which kind of drugs? Give two examples.

Answer 43

basic lipophilic drugs | lidocaine, fentanyl and demerol

Question 44

What type of drugs does the BBB prevent from crossing into the brain circulation?

Answer 44

Ionized, water soluble drugs

Question 45

Give three instances in which the blood brain barrier can be overcome?

Answer 45

1. Large doses of a drug. 2. In head injuries 3. Hypoxemia

Question 46

Which type of drugs cross the BBB rapidly?

Answer 46

Lipophillic

Question 47

In regards to acid/base, most drugs are either what? What two forms do we find them in?

Answer 47

1. Weak acids or weak bases | 2. ionized or non-ionized form

Question 48

Non-ionized drugs are usually ______ soluble. Meaning what?

Answer 48

lipid soluble. | Meaning that they can diffuse across lipid cell membranes.

Question 49

Is the non-ionized fraction of a drug pharmacologically active or inactive? Meaning what?

Answer 49

Active. It undergoes reabsorption across the renal tubules, is absorbed from the GI tract and is metabolized by the liver.

Question 50

The ionized fraction of the drug is poorly ______ soluble. Meaning what?

Answer 50

lipid. | That it can not penetrate lipid cell membranes and are excreted by the kidneys unchanged.

Question 51

The degree of ionization depends on what two factors?

Answer 51

The dissociation constant pk of a drug and the pH of the surrounding fluid.

Question 52

Lower pH = more or less unprotonated acid and base?

Answer 52

more unprotonated acid | less unprotonated base

Question 53

Higher pH = more or less unprotonated acid and base.

Answer 53

more unprotonated base | less unprotonated acid.

Question 54

What is the significance of giving a weak acid to a person with a pH lower than the pka of the drug.

Answer 54

There will be more unprotonated (non-ionized) drug meaning more drug that can have an effect.

Question 55

What is the term that describes the situation in which a drug can penetrate the placenta and because of the acidic environment and weak basic properties it becomes more ionized and stays there?

Answer 55

Ion-trapping

Question 56

Describe when ion trapping occurs.

Answer 56

Any time that there is a concentration difference of total drug that develops on two separate sides of a membrane that separates fluids with different pHs.

Question 57

Name the two most common proteins to which drug molecules bind.

Answer 57

albumin | alpha 1 acid glycoproteins.

Question 58

The binding of a drug to plasma protein is commonly fairly _____ and the drug molecules detach ______.

Answer 58

Weak | Readily

Question 59

Which portion of a drug that binds to plasma proteins is easily and readily available to cross the cell membranes?

Answer 59

The free or unbound fraction.

Question 60

What kind of an effect can the protein bound portion of a drug have on the overall effect?

Answer 60

Lengthen the DOA. | The drug may be less potent but may have a longer effect.

Question 61

Is the volume of distribution proportional or inversely proportional to protein binding?

Answer 61

Inversely proportional.

Question 62

What types of changes in the patient could lead to a huge effect on highly protein bound drugs?

Answer 62

``` An alteration in plasma proteins. Liver disease (reduced albumin) ```

Question 63

Name 4 highly protein bound drugs.

Answer 63

1. Warfarin 2. propranolol 3. phenytoin 4. Diazepam

Question 64

The volume of plasma cleared of a drug by metabolism and excretion is?

Answer 64

Clearance

Question 65

Almost all drugs administered in the therapeutic dose ranges are cleared at a first order rate. What does this mean?

Answer 65

At a rate proportional to the amount of drug present in the plasma.

Question 66

Few drugs ______ the metabolic or excretory _______ of the body to clear drugs by first order kinetics (even at therapeutic doses) and are then cleared by zero order kinetics. What does this mean.

Answer 66

exceed capacity A constant amount of drug is cleared per unit of time. You run out of enzymes basically.

Question 67

What is hepatic clearance?

Answer 67

The ratio of hepatic blood flow to hepatic extraction.

Question 68

What is the term for when the hepatic extraction ratio of a drug is high (greater than 0.7)

Answer 68

Perfusion-dependent elimination. The clearance of a drug will depend on hepatic blood flow.

Question 69

What does hepatic extraction depend on? Is it the same in everyone?

Answer 69

Enzymatic ability. It's not the same in everyone, big part is genetics.

Question 70

If the hepatic extraction ratio is low (less than 0.3) what is it called? What two factors would increase this type of clearance? What factor would not increase this type of clearance?

Answer 70

Capacity dependent elimination. A decrease in protein binding or an increase in enzyme activity will increase hepatic clearance. Changes in hepatic blood flow will have minimal changes in its clearance.

Question 71

Which organ is the most important site for elimination of unchanged drugs or their metabolites?

Answer 71

Kidney.

Question 72

When it comes to the efficiency of excretion which is more and which one is less efficiently excreted by the kidney? Water soluble compounds or lipid soluble.

Answer 72

More-water soluble | Less-lipid soluble

Question 73

Which type of drugs are reabsorbed such that little or no unchanged drug is excreted in the urine?

Answer 73

Highly lipid soluble.

Question 74

Are water soluble drugs ionized or non-ionized?

Answer 74

Ionized.

Question 75

How are highly lipid soluble drugs excreted?

Answer 75

They have to be metabolized into water soluble metabolites.

Question 76

The process by which pharmacologically active, lipid soluble drugs are converted into water soluble and often inactive drugs is called?

Answer 76

Biotransformation.

Question 77

Increased ___________ reduces the volume of distribution for a drug and enhances it's renal excretion.

Answer 77

water solubility

Question 78

Why is metabolism not always synonymous with inactivation or detoxification?

Answer 78

Because some metabolites of certain drugs are active.

Question 79

Name a drug that has an active metabolite?

Answer 79

Morphine Ketamine Versed

Question 80

Describe first order kinetics in regards to metabolism.

Answer 80

It is the most common form of metabolism. When a constant fraction of an available drug is metabolized in a given time period.

Question 81

Describe zero-order kinetics in regards to metabolism.

Answer 81

Plasma concentration of the drug exceeds the capacity of the metabolizing enzymes. Metabolism of a constant amount of a drug per unit of time.

Question 82

Name the four pathways of metabolism.

Answer 82

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

Question 83

Drugs that undergo phase 1 metabolism are involved in what type of reactions.

Answer 83

Oxidation, reduction and hydrolysis.

Question 84

Drugs that undergo phase 2 metabolism are usually involved in what type of reactions?

Answer 84

1. Conjugation where the parent or a metabolite drug reacts with an endogenous substrate to form water-soluble conjugates.

Question 85

Name 5 sites where metabolism of drugs occurs.

Answer 85

1. Plasma 2. Kidneys 3. Lungs 4. GI tract 5. Liver

Question 86

Which is the biggest site for metabolism? And what is responsible?

Answer 86

The liver. | Hepatic microsomal enzymes are responsible.

Question 87

Where are hepatic microsomal enzymes located?

Answer 87

Smooth ER

Question 88

What is the Cytochrome P-450? Where is this group?

Answer 88

A large number of different protein enzymes involved in oxidation, reduction and conjugation of a large number of drugs. IN THE LIVER.

Question 89

What is enzymatic induction?

Answer 89

When drugs and chemicals stimulate the activity of enzymes required for metabolism.

Question 90

How do nonmicrosomal enzymes metabolize drugs?

Answer 90

Mostly by conjugation and hydrolysis.

Question 91

Where are non-microsomal enzymes present?

Answer 91

Liver, plasma, GI tract.

Question 92

Non-microsomal enzymes are required for the hydrolysis of drugs containing what?

Answer 92

Ester bonds.

Question 93

Name two specific drugs that are metabolized by nonmicrosomal enzymes.

Answer 93

Succhs and esmolol

Question 94

Do we see enzymatic induction in nonmicrosomal enzymes?

Answer 94

No

Question 95

What determines nonmicrosomal enzymes?

Answer 95

Genetics.

Question 96

The most common mechanism by which drugs exert pharmacologic effects is through interaction with?

Answer 96

specific macromolecules in the lipid bi-layer of cell membranes called RECEPTORS!

Question 97

Response to specific stimuli could possibly do what to the concentration of receptors?

Answer 97

up regulate or down regulate

Question 98

Describe the state of receptor activation theory.

Answer 98

The non-activated receptors are converted to active by the drug.

Question 99

Describe the receptor occupancy theory.

Answer 99

The more receptors occupied by a drug the more effect.

Question 100

The affinity of a drug for a specific macromolecular component of the cell and its intrinsic activity are intimately related to?

Answer 100

The drugs chemical structure.

Question 101

Minor changes in the chemical structure of a drug could result in?

Answer 101

Major changes in it's pharmacological properties.

Question 102

What can be produced by sp3 hybridized carbon atoms?

Answer 102

Enantemerism

Question 103

When free rotation about the chiral carbon is not possible, how many stable forms of the molecule can exist?

Answer 103

Two.

Question 104

Does interaction with a biological receptor differ between two enantomers?

Answer 104

Yes, greatly even to the point of no binding. Some isomers may cause side effects or entirely different effects than it's mirror image.

Question 105

If each chiral carbon can exist as two molecules in nature a molecule with two chiral carbon centers has how many isomers?

Answer 105

4.

Question 106

People in whom an unusually low dose of drug produces its expected pharmacologic effect are termed?

Answer 106

Hyper-reactive

Question 107

Explain the principle behind an additive effect. Is it predictable?

Answer 107

The second drug acting with the first will produce an effect equal to the sum of both. Yes, it is predictable

Question 108

Explain the principle behind a synergetic effect.

Answer 108

Two drugs interact to produce an effect greater than their sum.

Question 109

Name a pair of drugs that when given together have a synergetic effect.

Answer 109

Versed and Fentanyl.