Basics of Pharmacokinetics/dynamics

Question 1

The biochemistry of drugs can affect how they are absorbed and utilized by the body. An example is how polarized light will either rotate ___ (levo-rotatory) or _____ (dextro-dextrorotatory) around a carbon atom. This can be shown in molecular diagrams using L- and D- for the respective sides

Answer 1

1. left, 2. right

Question 2

Examples of left and right isomers include ______ or a form of glucose derived from honey and and sweet fruits as well as naturally found in plant and animal tissue. This form of glucose has its name because it rotates to the _____

Answer 2

1. Dextrose, 2. right

Question 3

To identify organic compounds, one must first identify the ____ ___ which will have ____ different groups attached to it.

Answer 3

1. chiral carbon, 2. four

Question 4

In comparing drugs with similar names, i.e. Calcium Chloride and Calcium Gluconate, it is important to remember that the _____ of the molecules can vary

Answer 4

Concentration

Question 5

The ____ of a drug is defined as its ability to cause a certain clinical outcome, i.e. pain relief, lowering BP, etc

Answer 5

Efficacy

Question 6

The ___ and ____ are the dose and concentration respectively of a drug required to produce __ % of the drug’s maximal effect.

Answer 6

1. ED50, 2. EC50, 3. 50

Question 7

When evaluating toxic levels of doses, the ____ is the median value at which __% of the population show toxicity, and the ____ shows the median value where __% of the population will die.

Answer 7

1. TD50, 2. 50, 3. LD50, 4. 50

Question 8

The ____ can be defined as either the ____ required to achieve 50% of a drug’s maximal effect or the ____ at which 50% of the population shows a desired effect.

Answer 8

1. ED50, 2. dose, 3. dose

Question 9

The _____ _____ or margin of safety compares the ____/____ with the ____ to determine the distance of a therapeutic dose from a potentially lethal dose

Answer 9

1. Therapeutic Index, 2. TD50/LD50, 3. ED50

Question 10

The goal when dosing any medication is to find the _____ ______ which is defined as the right balance between efficacy and safety.

Answer 10

Therapeutic Window

Question 11

Drugs are normally cleared by first order kinetics where a fraction of the drug is eliminated based on units of ____ and is determined by the elimination constant ____

Answer 11

1. time, 2. kel

Question 12

There are certain situations where drug elimination rate is constant, which may occur when elimination processes are _____ of degrading enzymes, this is known as ____ _____ ______, this process is not affected by drug concentration.

Answer 12

1. saturated, 2. zero order kinetics

Question 13

The __-___ of a drug is the amount of time needed for the concentration of the drug in plasma to drop by ___% when the drug is stopped.

Answer 13

1. half-life, 2. 50%

Question 14

A _____ ____ _____ is considered a therapeutic effect that is continuous that normally takes about _-_ half lives

Answer 14

1. steady state level, 2. 4-5

Question 15

What makes a molecule ionized or not is determined by a drugs ___ and the pH of the surrounding environment, the ___ is the pH at which the drug is 50% dissociated

Answer 15

1. pKa, 2. pKa

Question 16

Rule of thumb when comparing acids and bases with drug dissociation is that acids are mostly ______, or dissociated, polar and hydrophilic, in ___ pH environments and _____ in __ pH (undissociated, nonpolar, lipophilic)

With bases, these are ______ at low pH (hydrophilic) and _____ at a high pH (lipophilic)

Answer 16

1. ionized, 2. high, 3. neutral, 4. low
2. ionized, 2. neutral

Question 17

CYP450 is one of the common enzymes in the ___ that facilitate chemical reactions in the body with drugs, the 450 comes from the the ______ where it absorbs light. These enzymes also are capable of ___-______ reactions (Phase 1)

Answer 17

1. liver, 2. wavelength, 3. non-synthetic

Question 18

a drug that is transformed by a specific CYP enzyme is called a ____ of the enzyme

Answer 18

1. substrate

Question 19

Some drugs can _____ the amount of biotransformation enzymes in the liver and therefore, other drugs that use this pathway as well will be degraded at a ____ rate and its serum level will be _____

Answer 19

1. induce (increase amount of), 2. faster, 3. lower

Question 20

Phase II reactions or _____ biotransformation creates a brand new organic compound, examples of this include conjugation reactions which involve enzymes adding ____ compounds and the hepatic enyzmes that do this are called ___

Answer 20

1. synthetic, 2. organic, 3. UGT

Question 21

When evaluating drugs as potential teratogens, most experts consider the first 8 weeks the ______ stage and is the time when developmental effects from drugs are most likely.

Answer 21

embryonic

Question 22

_____ are defined as drugs which only contain harmful effects, compared to _____ which are poisons of biologic origin only (plants, animals)

Answer 22

1. Poisons, 2. Toxins

Question 23

For drugs to interact with the correct receptor, the molecule must have the right ____, ___ ____, ____ and ____ _____ as well as being able to be transported to the needed area and be able to be eliminated from the body.

Answer 23

1. size, 2. electrical charge, 3. shape, atomic composition

Question 24

Most organic drugs are either weak ____ or ____

Answer 24

1. acids, 2. bases

Question 25

Drug size is important to determine if the drug can move to other areas of the body, for example a ___ weight can normally move into other areas and a ___ weight may require direct administration to the site. This range for most drugs is 100 to 1000 MW

Answer 25

1. low, 2. heavier

Question 26

Drugs interact with receptors by three major \_\_\_\_, they are: \_\_\_\_\_ bonds are the strongest and normally are irreversible \_\_\_\_\_ bonds are more common in drug receptor interactions and accomodate a variety of strong and weak bonds \_\_\_\_\_\_ bonds are important for lipophilic drug activity and are preferred in the case of interacting with specific drug receptors

Answer 26

1. bonds, 2. covalent, 3. electrostatic, 4. hydrophobic

Question 27

The concept of a drug shape is based on _____ (stereoisomerism) which allows drugs to have pairs of ______ that allows for precise sizing for the drug and respective receptor. It should be noted that drugs with multiples of these will have varying effects depending on which one is used by the body.

Answer 27

1. chirality, 2. isomers

Question 28

When the drug activates its effect, the final changes to the drug involve the ____ mechanism which is activated by the drug-receptor complex.

Answer 28

1. effector

Question 29

Some drugs may bind to the same site but not competitively which are known as acting ______ and may enhance or inhibit the actions of other _____ but may not be overcome by increased doses of other drugs

Answer 29

1. allosterically, 2. agonists

Question 30

Due to thermodynamics, even if _____ receptors are not binding drugs, they are still able to produce similar, but less powerful, effects as if they were binded which is known as _____ or ____ activity

Answer 30

1. constitutive, 2. basal

Question 31

In some cases, drugs may prefer to bind to nonfunctional forms of receptors and will therefore ____ constitutive/basal activity and are termed _____ \_\_\_\_\_\_

Answer 31

1. reduce, 2. inverse agonists

Question 32

Some drugs will bind to non-regulatory molecules, which will cause ___ change biologically, but in the case of albumin will have a ___ \_\_\_\_\_\_ site which may allow the drug to be distributed to other areas of the body or determines the amount of ____ \_\_\_\_\_ in circulation

Answer 32

1. no, 2. inert binding, 3. free drug

Question 33

Sometimes if a drug cannot be absorbed due to lipid solubility, a ____ can be given where the inactive form of the drug is ingested and then activated by biological processes

Answer 33

1. prodrug

Question 34

In addition to carriers that bring certain molecules into cells, there also existss ___ \_\_\_\_\_-\_\_\_ ___ (MRP) which function by expelling drugs or their metabolites from cells to be eliminated.

Answer 34

multidrug resistance-associated protein

Question 35

\_\_\_ allows for reuptake of Norepinephrine as a transporter protein

Answer 35

NET

Question 36

\_\_\_\_ allows for serotonin reuptake as a transporter protein

Answer 36

SERT

Question 37

\_\_\_\_ allows transport of dopamine and norepinephrine into adrenergic vesicles in nerve endings

Answer 37

VMAT

Question 38

\_\_\_\_ transports xenobiotics out of cells

Answer 38

MDR1

Question 39

\_\_\_\_\_ secretes leukotrienes

Answer 39

MRP1

Question 40

the pKa is defined as the pH where the concentrations of the ____ and ____ forms of a molecule are \_\_\_\_

Answer 40

1. ionized, 2. nonionized, 3. equal

Question 41

Understanding the pKa in the case of drug elimination is important in the case of renal excretion where if a drug is _____ soluble then that drug will be \_\_\_\_\_. Note that this concept applies to body fluids as well

Answer 41

1. lipid, 2. reabsorbed

Question 42

Many drugs that are weak bases contain _____ which is a configuration of a combination of carbon and hydrogens where the carbon determiens the level of the \_\_\_\_. It is important to remember that _____ amines cannot reversibly bind to a proton but anything below it can.

Answer 42

1. amines, 2. amine, 3. quaternary

Question 43

In clinical drug trials, certain quantitative levels are desired including the \_\_-\_\_\_ dose which is the maximum dose where a specific toxic effect is not seen as well as a _____ \_\_\_\_ dose and a ____ \_\_\_\_ dose where the former is the smallest dose possible to cause death and the latter is the dose that caused death in 50% of the trials

Answer 43

1. no-effect, 2. minimum lethal, 3. median lethal

Question 44

\_\_\_ is noted at the concentration of a drug that achieves 50% of maximal effect.

Answer 44

EC50

Question 45

The spare receptor theory determines the amount of drug concentration possible to achieve maximal responses by not the amount of _____ but rather serves as a determinant of how much of a drug is needed when it activates the \_\_\_\_\_\_

Answer 45

1. receptors, 2. effector

Question 46

Antagonist drugs can be classified as either _____ or \_\_\_-\_\_\_\_\_\_ where _____ actively binds to receptor sites against agonist activity and \_\_\_\_\_-\_\_\_\_\_\_ does not selectively bind to sites, however their binding is often irreversible and cannot be undone by increased agonist concentrations.

Answer 46

1. competitive, 2. non-competitive, 3. competitive, 4. non-competitive

Question 47

When giving different agonist drugs, it is important that partial and full agonist drugs will _____ for sites despite having the same effect. This is due to the fact that partial agonists cannot cause a _____ response even at ____ concentrations

Answer 47

1. compete, 2. maximal, 3. higher

Question 48

\_\_\_\_\_ are a form of lipid soluble agents that activate ____ transcription when binding to receptors. It is important to recognize that these hormones often have a ____ period where the effects of the drug may not be immediate as well as the effects lasting despite _____ agonist concentration

Answer 48

1. steroids, 2. gene, 3. lag, 4. zero

Question 49

\_\_\_\_-\_\_\_\_\_\_ occurs when cells intentionally take in receptors and degrade them for the purpose of limiting the strength of signals caused by various drugs, e.g. endogenous growth factors are limited to prevent cancer.

Answer 49

down-regulation

Question 50

A feature of G proteins when binding with ligands involves having multiple ____ with each one targeting specific _____ and ______ . An example of this would be norepinephrine activating different g proteins simultaneously during fight or flight responses to cause multiple effects at once.

Answer 50

1. subfamilies, 2. receptors, 3. effectors

Question 51

Phosphorylation involves two principles, the first is _____ which works by attaching phosphoryl to a kinase group (serine, tyrosine) and improve the initial signal. The second is ___ \_\_\_\_ where second messengers are able to alter changes in the cell based on the presence or lack of different kinases

Answer 51

1. amplification, 2. flexible regulation

Question 52

Two important principles of pharmacokinetics when considering medication dosing include \_\_\_\_\_, or the space available in the body for the drug, and _____ or the ability of the body to remove the drug.

Answer 52

1. volume of distribution, 2. clearance

Question 53

Drugs that exhibit capacity limited elimination will have _____ dependent clearance rather than remain constant. Important drugs that are eliminated by this method include \_\_\_\_\_, ______ and \_\_\_\_\_

Answer 53

1. concentration, 2. aspirin, 3. ethanol, 4. phenytoin

Question 54

A rule of thumb when dosing a continuous drug is that it will take ____ half life cycles before the drug reaches its full effect

Answer 54

1. 4

Question 55

When thinking of a drug's half life effects, it is important to remember that this mainly occurs when the concentration of the drug is low in relation to ___ or the concentration associated with \_\_\_% of the maximum effect.

Answer 55

1. C50, 2. 50%

Question 56

From a pharmacokinetic standpoint, three variables account for drug concentration measurements: ___ and ___ of \_\_\_, ______ and ____ (including derived variable and half life)

Answer 56

1. rate and extent of input, 2. clearance, 3. volume of distribution

Question 57

From a pharmacodynamic standpoint, drug concentration measurements can be linked to ____ \_\_\_ and ____ of the tissue to the drug.

Answer 57

1. maximal effect (E Max) , 2. sensitivity (C50)

Question 58

CYP2D6 is a common enzyme that affects metabolism of up to 1/4 of all clinical drugs, the various alleles can be grouped as either \_\_\_\_\_\_, ______ \_\_\_\_\_ or ____ \_\_\_\_\_\_. Examples of drugs affected by this enzyme are beta blockers, anti-depressants and opiod analgesics

Answer 58

1. nonfunctional (3,4,5,6), 2. decreased function (10,17,41), 3. fully functional (1, 2)

Question 59

CYP2C19 enzymes are known for metabolizing ____ drugs including PPI, anti-epileptics and anti-platelet drugs

Answer 59

1. acidic

Question 60

UGT1A1 is important in the conjugation of ______ \_\_\_ onto small lipophilic molecules, examples include \_\_\_\_\_\_

Answer 60

1. glucuronic acid, 2. bilirubin

Question 61

With drugs that may affect a fetus, it is important to recall that the placenta like most biological membranes is _____ soluble, but in cases where concentration gradients are high, ____ compounds may also cross over.

Answer 61

1. lipid, 2. polar

Question 62

While Phase 1 and 2 reactions may not occur in the same order, it can be defined that Phase 1 reactions will occur during the ______ and beginning of ______ phases while Phase 2 will occur during the ______ to _______ phases

Answer 62

1. absorption, 2. metabolism, 3. metabolism, 4. elimination

Question 63

At the microsomal level, drug oxidation requires four components: \_\_\_\_, ____ \_\_\_\_\_, ____ and molecular \_\_\_\_

Answer 63

1. CYP450, 2. P450 reductase, 3. NADPH (Nicotinamide adenine dinucleotide phosphate), 4. oxygen

Question 64

In the liver the following P450 enzymes are considered to be of most importance: \_\_\_\_, \_\_\_\_, \_\_\_\_, \_\_\_\_\_, \_\_\_\_\_, \_\_\_\_\_, \_\_\_\_\_

Answer 64

1. CYP1A2, 2. CYP2A6, 3. CYP2B6, 4. CYP2C9, 5. CYP2D6, 6. CYP2E1, 7. CYP3A4

Question 65

Often in phase 2 reactions, drugs will utilize at least _ pathways for metabolization

Answer 65

2