Kaplan Pharmacology - Section 1 - General Principles

Front 1

A pH - pKa that results in a negative number means that [...] ?

Back 1

It means that there is an acidic environment.

Front 2

What impact does a high pKa have on the ionized state of an acid in a solution?

Back 2

The larger the value of pKa, the smaller the extent of dissociation at any given pH.

Front 3

Draw a curve with % nonionized form of a drug as a function of environment of the drug. Label the state of each acid/base in their particular environments.

Back 3

Front 4

Draw the henderson-hasselbach equation.

Back 4

pH = pKa

Front 5

To increased renal clearance of a weak base drug you would ___________ the pH of the urine.

Back 5

Decrease.

Front 6

To increase renal clearance of a weak acid drug you would ___________ the pH of the urine.

Back 6

Increase.

Front 7

To absorb a weak acid drug you should keep it in what environment?

Back 7

Acidic

Front 8

To absorb a weak base drug you should keep it in what environment?

Back 8

Basic

Front 9

What is the pH of the stomach?

Back 9

1-2

Front 10

What is the pH of the small intestine?

Back 10

6

Front 11

What is the pH of the blood?

Back 11

7.4

Front 12

What is the pH of the urine?

Back 12

4.5 - 8

Front 13

Place a weak acid/weak base drug on a pH scale. Mark the different forms the drugs will appear as based on pH.

Back 13

Front 14

Where is a cephalosporin drug (with a hypothetical pKa of 5) more effectively absorbed (based on pH), in the stomach or small intestine?

Back 14

Stomach

Front 15

In what form is a drug renally cleared?

Back 15

Only free, unbound drug is filtered.

Front 16

What form of drugs are filtered in the kidney, non-ionized or ionized?

Back 16

Both.

Front 17

What form of a drug can undergo secretion and reabsorption in the kidney?

Back 17

Non-ionized form can be actively secreted and active or passive reabsorption.

Front 18

Mention 5 drugs or classes of drugs that are weak acids.

Back 18

(1) Aspirin
(2) Penicillins
(3) Cephalosporins
(4) Loop diuretics
(5) Thiazide diuretics

Front 19

Mention 4 drugs or classes of drugs that are weak bases.

Back 19

(1) Morphine
(2) Local anesthetics
(3) Amphetamines
(4) PCP

Front 20

When would you want to acidify and when would you want to alkalinize the urine to increase renal elimination of a drug?

Back 20

Acidification of urine --> Increased ionization of weak bases --> Increased renal elimination

Alkalinization of urine --> Increased ionization of weak acids --> Increased renal elimination

Front 21

PCP is also known as ____________ (slang)?

Back 21

"Angel dust"

Front 22

PCP is an analogue of ______________.

Back 22

ketamine

Front 23

What happens after ingestion of PCP?

Back 23

Dissociative anesthesia (insensitivity to pain without loss of consciousness) and analgesia.

Front 24

How do you acidify the urine?

Back 24

(1) NH4Cl
(2) Vitamin C
(3) Cranberry juice

Front 25

How could you alkalinize the urine?

Back 25

(1) NaHCO3
(2) Acetazolamide (historically)
- (I) Carbonic anhydrase --> No reclamation of HCO3-

Front 26

A man with end-stage liver disease becomes increasingly confused after eating a high protein meal. How could you ameliorate this situation?

Back 26

Lactulose, which is converted into lactic acid by gut bacteria. This low pH keeps ammonia ionized and not as readily absorbed (NH3 --> NH4+).

Front 27

What are the basic forms of drug transport?

Back 27

(1) Passive diffusion
(2) Facilitated diffusion
(3) Active transport

Front 28

What basic mode of drug transport do drugs most often utilize?

Back 28

Passive diffusion

Front 29

Describe the energy requirement, requirement of carriers and saturability with each basic mode of drug transport.

Back 29

Passive diffusion - No energy required, No carrier needed, Not saturable

Facilitated diffusion - No energy required, Carrier needed and hence it is saturable.

Active transport - Energy required, Carriers needed and hence it is saturable.

Front 30

Give an example of active transport of drugs.

Back 30

Tubular (proximal) secretion of penicillins and diuretics.

Front 31

What does pharmacokinetics and pharmacodynamics mean?

Back 31

Pharmacokinetics: What the body does to the drug.
Pharmacodynamics: What the drug does to the body (mechanisms of action)

Front 32

What does permeation mean?

Back 32

The ability of a drug to move within the body

Front 33

What is permeability dependent on?

Back 33

(1) Solubility
(2) Concentration gradient
(3) Surface area & vascularity (less so)

Front 34

Most drugs are [...]

Back 34

Weak acids or weak bases

Front 35

What is pKa?

Back 35

The pH at which weak bases and weak acids are present as 50% non-ionized and 50% ionized.

Front 36

In a nutshell, ionized drugs are ________ while non-ionized drugs are _______.

Back 36

water soluble; lipid soluble

Front 37

What is absorbed faster, IM or subcutaneous injection of a drug?

Back 37

IM = more vascular

Front 38

Draw a flow chart that encompass the term "Pharmacokinetics".

Back 38

Front 39

What is the bioavailability of IV drugs?

Back 39

100%

Front 40

What is the fastest route of absorption:

A. IV
B. Inhalation
C. IM
D. SubQT
E. Peroral

Back 40

B. Inhalation

(IV does not involve absorption)

Front 41

What does bioavailability mean?

Back 41

How much of the administered drug dose gets into the blood

Front 42

Draw a graph depicting the plasma drug concentration as a function of time when a drug is administered extravasculary.

Back 42

Front 43

Describe the marked area.

Back 43

It's the lag period, it's the time from first administration until the time when molecules first appear in the blood. The flat line represents the drug in your alimentary tract before any molecules are present in your blood.

Front 44

Describe the line.

Back 44

It's the Cmax of peak level of the drug.

Front 45

Describe the line.

Back 45

The line represents the plasma drug concentration (where it intersects with the graph) where you are first seeing a pharmacological effect of the drug. It's called the minimum effective concentration.

Front 46

Describe the blue line.

Back 46

The blue line is the onset of activity. It includes the lag time (when it ascends).

Front 47

Describe the blue line-

Back 47

Duration of action. Notice how the graph is above MEC between the two points.

Front 48

Describe the orange line.

Back 48

Decreased elimination of a drug. Could be a man with renal disease for example.

Front 49

What does the area under this curve represent?

Back 49

Bioavailability

Front 50

How is bioavailability defined?

Back 50

f = fraction of the dose that is available in the blood

Front 51

How can we depict that the bioavailability of a drug is close to 100%?

Back 51

When the area in the shaded part of the curves are equal.

Front 52

What is one thing that greatly affects the bioavailability of a drug (f)?

Back 52

First pass effect

Front 53

What is the first pass effect?

Back 53

The rapid metabolism of a drug that may happen after it is absorbed into the portal circulation and reaches the liver. It may decrease the bioavailability of a drug.

Front 54

Why is IV lidocaine preferred over oral?

Back 54

Extensive hepatic first pass metabolism

Front 55

What does the pharmacokinetic term "distribution" include?

Back 55

Processes of distribution of a drug from systemic circulation into organs and tissues.

Front 56

Many drugs bind to what in the circulation?

Back 56

Plasma proteins. They remain in an equilibrium:

Drug + Protein (active, free) <--> Drug-Protein Complex (inactive, bound)

Front 57

Competition between drugs for plasma protein-binding sites may increase the _____________ , possibly enhancing the __________________.

Back 57

"free fraction"; effects of the drug displaced

Front 58

Sulfonamides are given to a neonate. The neonate develops kernicterus. What has happened?

Back 58

Sulfonamides are bound to albumin, displacing bilirubin.

Front 59

Warfarin is about ____% protein bound.

Back 59

98%

Front 60

What is the mechanism of action of sulfonamides?

Back 60

Front 61

A man with a slowly progressing pneumonia is known to have a nocardia infection in the lungs. He is given sulfonamides. After a short time he starts to bleed from his gingiva and has easy bruising. What other drug was he taking at the time?

Back 61

Warfarin

Front 62

What drugs can penetrate the BBB? Give examples.

Back 62

Lipid soluble drugs of very low molecular weight.

Examples: Lithium (small), Ethanol (polar but small)

Front 63

If a drug crosses the BBB, it will cross the __________.

Back 63

placenta

Front 64

What property would a drug have to have to be considered safe in pregnancy?

Back 64

(1) Water-solubility
(2) Large drug
(3) Protein-bound (highly)

Front 65

What would you choose in pregnancy, PTU or methimazole?

Back 65

PTU (PTU = P = P for Pregnancy)

Front 66

What anti-convulsant drug could you give to a pregnant woman with seizures?

Back 66

Phenobarbital (Phenobarbital = P = P for Pregnancy)

Front 67

What does volume of distribution mean?

Back 67

It's a pharmacokinetic parameter that correlates the dose of a drug with the plasma concentration:

Vd = Dose/C^o where C^o = [plasma] at zero time

Front 68

What happens to the Vd when a drug is highly plasma protein bound?

Back 68

High plasma protein binding keeps more of the drug in the blood (increased Co)

Front 69

What happens to the Vd when a high percentage of a drug is sequestered in tissues?

Back 69

Front 70

Digoxin is highly sequestered in tissues. Which drugs could displace it and enhance digoxin toxicity?

Back 70

Verapamil and quinidine.

Front 71

When considering total body water, intracellular fluid makes up how much?

Back 71

2/3

Front 72

When considering total body water, extracellular fluid makes up how much?

Back 72

1/3

Front 73

For an ideal 70kg body weight man, what normal values for the following:

(1) Plasma volume
(2) Blood volume
(3) Extracellular fluid
(4) TBW

Back 73

"60-40-20 rule":

60% TBW
40% ICF
20% ECF

70 kg x 0.6 = 42 L
70 kg x 0.2 = 14 L
Blood volume is 5 L.
Plasma is 3 L.

Front 74

Plasma is what fraction of extracellular fluid?

Back 74

1/4

Front 75

Interstitial fluid is what fraction of extracellular fluid?

Back 75

3/4

Front 76

What is a simple question that the Vd is really asking?

Back 76

"Where is the drug?" If most is in the plasma, then the Vd is low, if most is outside the plasma then Vd is high.

Front 77

A drug has a volume of distribution that equals 4000 L. Where is the drug most likely in the body?

Back 77

Co has to be low so it is outside the plasma being sequestered in the tissue.

Front 78

What units might Vd be presented in?

Back 78

L or L/kg

("Remember to multiply by the body weight if you see Vd with L/kg to get to liter")

Front 79

What does "Redistribution" mean?

Back 79

It means that, in addition to a drug crossing the BBB, lipid-soluble drugs can redistribute into fat tissues prior to elimination.

Front 80

What is thiopental used for?

Back 80

Induce anesthesia

Front 81

Thiopental reaches the brain in less than a minute and has a rapid recovery. Why does it have a half-life of nine hours?

Back 81

Due to redistribution

Front 82

What does biotransformation mean?

Back 82

Drug metabolism

Front 83

True or false: The role of biotransformation is to always inactivate drugs by making them water-soluble and more readily excreted.

Back 83

False.

Front 84

Give an example where a drug undergoes biotransformation in the liver and produces active metabolites.

Back 84

Benzodiazepines.

Front 85

What does phase I of biotransformation include?

Back 85

Modification of a drug molecule via oxidation, reduction or hydrolysis (nonmicrosomal metabolism) and CYT P450 (microsomal metabolism).

Front 86

Cytochrome P450 isozymes contain ____ families and about ____ different enzymes.

Back 86

13; 100

Front 87

P450 have an absolute requirement for what?

Back 87

Oxygen and NADPH

Front 88

What family of CYP450 enzymes are considered the most important family and metabolizes about 60% of all known drugs today?

Back 88

CYP450 3A4 family

Front 89

What does it mean that a drug or molecule can induce P450 enzymes? Use an example.

Back 89

Aromatic hydrocarbons in smoke can induce (increase production) the family of enzymes called 1A2. This means that drugs that share this enzyme pathway of biotransformation are going to be metabolized more rapidly if you are concurrently smoking.

Front 90

A long term smoker has a higher than normal 1A2 family of CYP450 enzymes in his liver. What other drugs would be metabolized more quickly due to his smoking habit?

Back 90

(1) Theophylline
(2) Acetaminophen

they are metabolized by 1A2

Front 91

A smoker has been on dosage-adjusted theophylline for some time. She is convinced to stop smoking. What dosage adjustment is required to be made now?

Back 91

Lower theophylline dosage

Front 92

What does it mean that a drug or molecule can inhibit P450 enzymes? Use an example.

Back 92

Quinolones or macrolides can inhibit 1A2 family of CYP450 enzymes. This means that drugs that share this biotransformative pathway can possibly reach toxic levels in an individual.

Front 93

What family of CYP450 enzymes would be induced in a patient with chronic bronchitis?

Back 93

CYP450 1A2

Front 94

What are the classes of useful antimicrobial drugs?

Back 94

(1) Penicillins
(2) Cephalosporins
(3) Tetracyclines
(4) Aminoglycosides
(5) Macrolides
(6) Fluoroquinolones

Front 95

Mechanism of action of macrolides?

Back 95

They bind irrversibly to a site on the 50S subunit of the bacterial ribosome, thus inhibiting the translocation step of protein synthesis.

Front 96

Macrolides are considered to be ___________ (bacteriocidal/bacteriostatic).

Back 96

bacteriostatic, however at higher doses are considered bacteriocidal.

Front 97

This drug is eff ective against many of the same
organisms as penicillin G. What drug is it?

Back 97

Erythromycin (macrolide). Can be used in patients who are allergic to penicillins.

Front 98

List some macrolides.

Back 98

(1) Erythromycin
(2) Clarithromycin
(3) Azithromycin
(4) Telithromycin

Front 99

A woman with chronic bronchitis is taking theophylline. You prescribe her macrolide antibiotics for her pneumonia. What should you be thinking about?

Back 99

Macrolides are inhibitors of 1A2 which theophylline is metabolized by. They may increase theophylline plasma levels.

Front 100

What macrolide should you have in mind as an inhibitor of P450 isozymes (1) and what has almost no P450 inhibitory effect (2)?

Back 100

(1) Erythromycin
(2) Azithromycin

Front 101

Give an example of a drug that is inhibited in its metabolism by grapefruit juice.

Back 101

Statin drugs.

Front 102

A man experiences muscle pain and a change in the color of his urine after having started statin drugs and a new healthy diet. What might be going on?

Back 102

Grapefruit juice --> Inhibits statin metabolism --> Toxic levels of statin drugs --> Rhabdomyolysis

Front 103

Hydrolysis involves what enzymes?

Back 103

Esterases and amidases (addition of H2O to break bonds)

Front 104

Genetic polymorphisms exist with these hydrolases. What significance does this have?

Back 104

Pseudocholinesterases.

Genetic polymorphism exists with pseudocholinesterase, causing a deficiency of this enzyme, potentially increasing succinylcholine levels (muscle relaxants).

Front 105

What endogenous molecules are metabolized by monoamine oxidases?

Back 105

(1) Dopamine
(2) NE
(3) Serotonin

Front 106

What exogenous molecule(s) are metabolized by monoamine oxidases?

Back 106

(1) Tyramine

Front 107

Tyramine is found in what foods?

Back 107

Beer, red wine, cheese, fish

Front 108

What category of enzyme metabolizes aldehydes to acids in ethanol metabolism?

Back 108

Dehydrogenases

Front 109

Active components in grapefruit juice include furanocoumarins capable of inhibiting the metabolism of many drugs. Mention 4.

Back 109

(1) Alprazolam
(2) Midazolam
(3) Atorvastatin
(4) Cyclosporine

Front 110

Equation for maintenance dose?

Back 110

Front 111

Equation for infusion rate?

Back 111