Pharm Exam 1 Comprehensive Review

Front 1

Equation for Fick's Law of diffusion

Back 1

FLUX (molecules/unit time) = ([high]-[low]) x (Area x Permeability Coefficient /Thickness of diffusion path)

Front 2

Define bioavailability..

Equation?

Back 2

the extent of absorption of a drug following administration by routes other than IV administration.

AUC oral/AUC injection

Front 3

What is the apparent volume of distribution? Equation?

Back 3

theoratical volume into which a drug distributes after IV administration

Vd = total amt of drug in the body (D) (mg) / conc. In plasma (Cp) (mg/l)

Front 4

What does a large Vd indicate?

Back 4

large amt of drug in the extraplasmic space, which means:

1. limited drug access to excretory organs
2. may indicate sequestration into some organ or comparment

Front 5

What is Kd? equation?

Back 5

Elimination rate constant

Kd = clearance / Vd

Front 6

What is the total body water volume for a 70kg man.
Intracellular volume?
Extracellular volume? interstitial? plasma?

Back 6

42L

28L

14L (10L, 4L)

Front 7

Describe the first-order kinetics

Back 7

1. Rate of drug elimination is directly proportional to the [free drug]
2. Constant percentage of drug is removed per unit time
3. Most clinical situations
4. T1/2 not dependent upon dose; independent of plasma [drug]

Front 8

Describe the zero-order kinetics

Back 8

1. Rate of drug elimination is constant over time
2. Large doses or drug-drug interactions
3. Drugs which undergo metabolism as their primary elimination pathway
4. E.g. alcohol; rate is usually 1 beer/1 hr (T1/2 = 30 min)

Front 9

Clearance equation?

Back 9

Cl = rate of elimination / plasma [drug]

Front 10

half-life equation for first-order kinetics?

Back 10

T1/2 = 0.693 * Vd / Cl or 0.693/Kd

Front 11

Loading dose equation?

dosing rate equation?

what is steady state?

Back 11

Loading dose = Vd * Css (steady state concentration)

Dosing rate = Cl * Css (steady state concentration)

steady state - amt going in = amt going out

Front 12

Define polyphamarcy.

Back 12

the unnecessary, excessive use of prescription and OTC medications.

Front 13

List 6 criteria for polypharmacy.

Back 13

1. Prescription of medications that have no apparent indication.

2. Use of medications with the same PK action (duplicate medications to treat same disease).*

3. Concurrent use of interacting medications

4. Use of inappropriate dosage

5. Use of drug therapy to treat ADR’s (adverse drug rxns)

6. Improvement after discontinuation of medications

Front 14

What 3 qualifications must be met for generic drugs to be approved?

Back 14

Same Tmax, Cmax, AUC (area under the curve) in the plasma [drug] vs time graph.

Front 15

List and describe 4 different types of drug release.

Back 15

1. Extended release - allows a reduction in dosing frequency compared to conventional dosage form.

2. Delayed release - designed to release drug at a time other than promptly after administration.

3. Repeat action - usually contains two single doses, one for immediate release, and the second for delayed release.

4. Targeted release - concentrating the drug in a body region, a tissue or a site

Front 16

What 2 processes can destroy drugs?

Back 16

Oxidation and hydrolysis

Front 17

Definition of Pharmacodynamics?

Back 17

study of biochemical and physiological effect on drugs on living systems

Front 18

Definition of Pharmacokinetics?

What are the 4 main components?

Back 18

ADME

Drug Absorption
Drug Distribution within body
Drug Metabolism
Drug Excretion

Front 19

Agonists?

Antagonists?

Back 19

Agonists - interact with receptors to produced a response

Antagonists - interact with receptors to prevent action of an endogenous or exogenous agonist

Front 20

Define the following terms:

autocrine
paracrine
endocrine
juxtacrine
intracrine

Back 20

autocrine – self

paracrine – near

endocrine – systemic

juxtacrine – adjacent; membrane-bound ligand

intracrine – pre-receptor; enzyme mediated conversion

Front 21

5 factors that influence drug-receptor matching are??

Back 21

1. shape of drug (stereochemistry; chirality)
2. size of drug
3. sum of electorstatic and hydrophobic forces
4. nature of D-R interactions
5. type of chemical bonds

Front 22

What are 5 types of chemical bonds?

Which 2 are associated with "goodness of fit?"

Back 22

1. Covalent bond
2. hydrogen bond
3. Van Der Waal Forces
4. ionic bonds
5. hydrophobic bonds

Hydrogen bonds and Van Der Waal forces are associated with goodness of fit

Front 23

Efficacy (or Max efficacy)?

Potency?

Back 23

Efficacy , Max efficacy – the greatest biological effect an agonist can produce

Potency – [drug] required to achieve a certain biological response

Front 24

What are 3 theories related to receptor-effector coupling?

Describe each.

Back 24

1. Occupational theory of Drug action - Formation of RD is directly 1:1 proportionate to biological/pharmacological Effect; explains agonists, antagonists, and competitive antagonists.

2.Modified occupational theory of drug action - Formation of RD is not directly 1:1 proportionate to biological/pharmacological Effect.; explains spare receptors and partial agonists

3.Allosteric theory of drug action - Receptor conformation (Ri = inactive; Ra = active) determines level of effect. Drugs can bind to either the Ri or Ra conformation, thereby promoting action or inaction; explains inverse agonists

Front 25

What does the modified occupational theory of drug action explain that the (plain) occupational theory of drug can't?

How about allosteric theory of drug action?

Back 25

Modified occupational theory of drug action - explains the concepts of partial agonists and spare receptors

alloesteric theory of drug action explains inverse agonists

Front 26

Spare receptors?

Back 26

unused receptors when at maximum biological effect

Front 27

What are 4 main type of antagonism? Explain each.

Back 27

1. Pharmacological - works through binding to the drug target

2. Chemical - chemically interact within the body to produce antagonism

3. Physiological - produce opposite effects through different receptors

4. Dispositional - alteration in the ADME (pharmacokinetics) resulting in the less drug reaching the target organ and reduced pharmacological effect

Front 28

Name 3 different types of phamacological antagonists.

How does each change the %maximal effect vs. log [drug] graph?

Back 28

1. competitive - shifts to the right but same Max effect

2. noncompetitive - shifts down the Max effect

3. irreversible - shifts down the max effect

Front 29

Define the following:

Partial agonist
Inverse agonist
Potentiation
Additive agonism
Synergistic agonism

Back 29

Partial agonist - Produce lower max responses than full agonists

Inverse agonist - binds to Ri and produces the opposite effect of the agonist

Potentiation - makes the receptor more responsive to the agonists

Additive agonism - when 2 drugs yield a biological response that equals the sum of the individual drug responses for each drug

Synergistic agonism - 2 drugs cause a biological effect greater than the anticipated sum of their pharmacologic effects

Front 30

what are 3 mechanisms of desensitization?

Explain!

Back 30

1. Metabolic - increased metabolism due to induction of liver enzymes that more rapidly decrease drug levels

2. cellular adaptive - less receptors

3. homeostatic - environmental cues are associated with drug administration --> bodily rxn in the opposite direction of the drug effect

Front 31

Tachphylaxis?

Back 31

Rapid loss of responsivity following a single administration of drug

Front 32

What is the main difference b/t the graded dose response curves and the Quantal dose-effect curve

Back 32

Graded dose response curve - effect of a single organ or an individual

Quantal dose-effect curve - effect of a drug on a population

Front 33

Define the following terms:

ED50
TD50
TI
Certain safety margin

Back 33

ED50 – effective dose for 50% of population

TD50 – toxicity dose for 50% population

Therapeutic index (TI) = LD50/ED50

Certain safety margin = LD1/ED99

Front 34

What is the general difference b/t phase 1 and phase 2 reactions of biotransformation?

Back 34

Phase 1 - Do not require energy

Phase 2 - Require high energy intermediates

Front 35

What is the general function of phase I and II reactions?

Back 35

Phase I - to make drugs more polar by adding polar groups or exposing polar groups.

Phase II - to modify insufficient polar compounds to more hydrophilic compounds

Front 36

What are 4 broad types of Phase I reaction?

Back 36

1. microsomal oxidation - uses microsomal cytochrome P450 system, which mediates oxidative reactions

2. nonmicrosomal oxidation - does not use microsomal cytochrome P450 system

3. Reductions

4. Hydrolysis

Front 37

Name 6 different microsomal oxidation reactions.

Back 37

1. alphatic or aromatic hydroxylation

2. N-, O-, and S-dealkylation

3. Sulfoxidation

4. N-oxidation or hydroxylation

5. Oxidative deamination

6. Desulfuration

Front 38

Name 3 phase I reactions that do not involve cytochrome P450 system.

Back 38

1. Reduction (nitroreduction and azoredcution)

2. Hydrolysis

3. non-microsomal oxidation

Front 39

Name the reaction with the following description:

addition of -OH

Phase I or II?

Back 39

hydroxylation

phase I

Front 40

Name the reaction with the following description:

removal of methyl group from N, O, or S

Phase I or II?

Back 40

N, O, S- dealkylation

Phase I

Front 41

Name the reaction with the following description:

adding a carboxyl group ( =O) to S.

Phase I or II?

Back 41

Sulfoxidation

Phase I

Front 42

Name the reaction with the following description:

addition of -O to N

Phase I or II?

Back 42

N-oxidation or hydroxylation

phase I

Front 43

Name the reaction with the following description:

replace -NH2 to =O

Phase I or II?

Back 43

Oxidative deamination

Phase I

Front 44

Name the reaction with the following description:

replace =S with =O

Phase I or II?

Back 44

desulfuration

Phase I

Front 45

What are 2 types of reduction? Describe

Back 45

Nitroreduction - NO2 --> NH2

Azoreduction - breaking the N=N and add -H to each N.

Front 46

Name the reaction with the following description:

addition of water across peptide, amide, or ester bond

Phase I or II?

Back 46

Hydrolysis

non-microsomal phase I

Front 47

Name 5 Phase II reactions.

Back 47

1. Glucuronide conjugation
2. sulfate conjugation
3. N-acetylation
4. O- and N- methylation
5. Glutathione conjugation

Front 48

what are the substrates for Phase II reactions? (2)

Back 48

1. Metabolites of phase I rxns
2. Cpds that already contain –OH, -NH2, and COOH

Front 49

Which phase II reaction utilizes UDP-GT?

What is the clinical importance of this reaction?

Back 49

Glucuronide conjugation

Clinically important in neonates - bilirubin and biliverdim (products of Heme catabolism) need to be conjugated with glucuronide but neonates lack UDP-GT (glucuronyl transferase) --> accumulation of bilirubin --> jaundice

Front 50

Which phase II reaction utilizes sulfotransferases?

Back 50

Sulfate conjugation

Front 51

Which phase II reaction is important in detoxifying acetaminophen?

Back 51

Glutathione conjugation

Front 52

Which phase II reaction is involved in conversion of norepinephrine to epinephrine?

Back 52

N-methylation

Front 53

Name 7 P450 inducers. (optional)

Mnemonic?

Back 53

Quinidine
Barbiturates
Phenytoin
Rifampin
Griseofulvin
Carbamazepine
St. John's wort

"Queen Barb takes Phen-phen and Refuses Greasy CarbS"

Front 54

Name 6 P450 inhibitors (optional)

Mnemonic?

Back 54

Isoniazid
Sulfonamides
Cimetidine
Ketoconazole
Erythromycin
Graphfruit juice

"Inhibitors Stop Cyber-Kids from Eating Grapefruit."

Front 55

What is drug idiosyncrasy?

Back 55

a genetically determined abnormal reactivity to a drug