Pharmacology Exam 1 - Part 1

Front 1

Atropine

source

Back 1

atropa belladonna (deadly nightshade)

Front 2

Paclitaxel

source

Back 2

Western yew

Front 3

Heparin

source

Back 3

animal (bovine lung or porcine intestinal mucosa)

Front 4

Penicillin G

source

Back 4

Penicillium mold

Front 5

Erythromycin

source

Back 5

streptomyces erythrens mold

Front 6

Amoxacillin and mezlocillin are derived from what?

Back 6

Penicillin G

Front 7

Clarithromycin is derived from what?

Back 7

Erythromycin

Front 8

4 examples of semisynthetic drugs

Back 8

amoxicillin
mezlocillin
clarithromycin
atropine methylbromide

Front 9

Semisynthetic drug

definition

Back 9

Natural compounds that are chemically modified to produce new compounds

Front 10

3 examples of monoclonal antibodies used phamaceutically

Back 10

abciximab
infliximab
traztuzumab

Front 11

Controlled Substances Act of 1970

Back 11

drugs considered to have a risk of abuse (i.e.risk of physical and/or psychological dependence) be placed in one of 5 categories depending on their perceived risk.

Front 12

Schedule 1 drugs

Back 12

no accepted medical use in US (heroin, LSD) - illegal to use or possess

Front 13

Schedule 2 drugs

Back 13

high abuse potential (morphine, cocaine, amphetamines) - only written prescriptions limited to 34 day supply & no refills

Front 14

Schedule 3 drugs

Back 14

less abuse potential (codeine plus acetaminophen, hydrocodone plus acetaminophen) - less restrictive prescription requirements

Front 15

Schedule 4 drugs

Back 15

(diazepam) - least restrictive distribution

Front 16

Schedule 5 drugs

Back 16

(codeine-containing cough syrups, pseudoephedrine) - OTC purchase though states may add restrictions (ex. Michigan requires stocking behind the pharmacist counter)

Front 17

3 names for each pharmaceutical

Back 17

chemical
nonproprietary/generic
proprietary or trade name

Front 18

-olol

Back 18

beta-adrenergic antagonist

Front 19

-caine

Back 19

local anesthetic

Front 20

-dipine

Back 20

Ca2+ channel antagonist of the dihydropyridine type

Front 21

-tidine

Back 21

H2 receptor antagonist

Front 22

-prazole

Back 22

proton pump inhibitor (PPI)

Front 23

-zosin

Back 23

alpha-1 receptor antagonist

Front 24

-pril

Back 24

angiotensin converting enzyme inhibitor (ACE inhibitor)

Front 25

By convention, a trade name is written in _______ and a generic name in ______ letters

Back 25

By convention, a trade name is written in all upper case letters and a generic name in lower case letters

Front 26

SYMMETREL

Back 26

amantadine

(Ca2+ channel inhibitor)

Front 27

ABILIFY

Back 27

aripiprazole

(PPI)

Front 28

COGENTIN

Back 28

benztropine

(Anti-Parkinsonian - antagonizes AChR and histamine Rs)

Front 29

PARLODEL

Back 29

bromocriptine

(Anti-Parkinsonian - DA agonist)

Front 30

THORAZINE

Back 30

chlorpromazine

Front 31

CLOZARIL

Back 31

clozapine

Front 32

HALDOL

Back 32

haloperidol

Front 33

DOPAR

Back 33

levoDOPA

Front 34

ZYPREXA

Back 34

olansepine

(anti-psychotic; mania/bipolar)

Front 35

MIRAPEX

Back 35

pramipexole

Anti-Parkinsonian

Front 36

SEROQUEL

Back 36

quetiapine

Anti-psychotic; Mania/bipolar
Black box warning

Front 37

RISPERDAL

Back 37

risperidone

Anti-psychotic

Front 38

REQUIP

Back 38

ropinirole

Anti-Parkinsonian - DA agonist

Front 39

ELDEPRYL

Back 39

selegiline

Anti-Parkinsonian - selectively inhibits MAO type B, increasing striatum levels of DA

Front 40

MELLARIL

Back 40

thioridazine

Anti-psychotics

Front 41

forward pharmacology

Back 41

compounds are discovered and assayed for biologic activity

process directed on the cell or physiology

try to determine the mechanism of the compound's action

Front 42

reverse pharmacology

Back 42

start with known target

try to isolate effective molecule

refine and test product in vivo

Front 43

Biochemical Classes of Drug Targets of Current Therapies

Back 43

45% Receptors
28% Enzymes
7% Unknown
5% Ion channels
2% DNA

Front 44

average duration of preclinical testing and discovery

Back 44

6.5 years (significant monetary investment)

Front 45

Phase I Clinical Trials

Back 45

test new drug on healthy volunteers over 1 year

exceptions: AIDS, CA drugs

goals: level of safety, appropriate dosage

Front 46

Phase II Clinical Trials

Back 46

200 patient volunteers with the target condition.

goals: drug efficacy, side effects

Front 47

Phase III Clinical Trials

Back 47

1000-3000 volunteers
3-4 years duration

verify effectiveness
monitor side effects with "long term" use

Front 48

NDA

Back 48

New Drug Application

given to drug company by FDA
application process takes 1-2 years

Front 49

Post Marketing Studies

Back 49

on-going regulatory requirements
- annual reports
- immediate notification to the FDA of safety issues discovered in patients

Front 50

Phase IV studies

Back 50

Post marketing study

continued exploration of additional formulations, safety data, and characteriziation of efficacy

Front 51

Why are Phase IV studies critically important?

Back 51

Many serious drug reactions are rare and may escape detection in Phase 3 trials.

Clinical trial volunteers generally do not reflect actual user population

Front 52

Category A (wrt pregnancy)

Back 52

controlled studies: no risk in pregnant women

Front 53

Category B (wrt pregnancy)

Back 53

no risk in animal studies, but no human studies

Front 54

Category C (wrt pregnancy)

Back 54

adverse fetal effects in animals; use only if benefit outweighs risk

Front 55

Category D (wrt pregnancy)

Back 55

demonstrated human fetal risk; may use despite risk

Front 56

Category X

Back 56

risk outweighs any possible benefit

Front 57

Pediatric Rule of 1998

Back 57

Pharmacological studies must be done on children unless there is a good reason not to do so.

Front 58

Read through highlighted portions of G&G text in Drug Development Processes and Names Doc.

Back 58

Read through highlighted portions of G&G text in Drug Development Processes and Names Doc.

Front 59

drug metabolism

Back 59

the chemical conversion of one compound to another compound

Front 60

biotransformation

Back 60

metabolic alteration

aka: drug metabolism

Front 61

xenobiotic transformation

Back 61

anything that comes into the body from outside the body and has an action inside the body

Front 62

active drug

Back 62

a drug that can change biological function

Front 63

metabolite

Back 63

a product of drug metabolism

Front 64

3 outcomes of biotransformation

Back 64

activation

maintenance of activity

inactivation

Front 65

activation as a result for biotransformation

Back 65

a xenobiotic may need to be metabolized in order to become an active drug

the administered chemical is called a prodrug

Front 66

3 examples of prodrugs and their active forms

Back 66

L-DOPA --> dopamine

codeine --> morphine

prednisone --> prednisolone

Front 67

maintenance of activitydefinition

Back 67

A xenobiotic may be transformed chemically but still maintain a majority of its normal pharmacological function

Front 68

example of drug that undergoes maintenance of activity in vivo

Back 68

diazepam is converted to oxazepam in vivo, (both compounds have pharmacological function)

Front 69

Inactivation

Back 69

process most commonly associated with biotransformation

chemical alteration to biologically inactive form

Front 70

Biotransformation almost always converts more ____-soluble drugs into more ____-soluble metabolites.

Back 70

Biotransformation almost always converts LIPID-soluble drugs into more WATER-soluble metabolites.

Front 71

predominant organ of drug metabolism

Back 71

liver (ER of hepatocytes)

Front 72

exception of biotransformation trend from lipid to water soluble

Back 72

acetylation of sulfonamides

Front 73

Which form of the drug is exreted in the kidney, water- or lipid- soluble?

Back 73

water-soluble

Front 74

What happens to drugs in the smooth ER of hepatocytes?

Back 74

high-polarity molecules are filtered, but not reabsorbed

Front 75

Role of gallbladder in drug excretion

Back 75

more lipid-soluble form of drug is exreted in bile and then in feces

Front 76

Goal of drug metabolism

Back 76

to facilitate the movement of a xenobiotic agent out of the body

Front 77

Phase I metabolism

Back 77

adding or revealing nucleophilic/electrophilic groups on drug

Front 78

Phase II metabolism

Back 78

making more hydrophilic a drug that has already undergone phase I metabolism

Front 79

Types of chemical reactions involved in phase I metabolism

Back 79

Oxidation
Reduction
Hydrolysis

Front 80

phase II metabolism

Back 80

conjugation

Front 81

5 enzyme (groups) that convert lipophilic drugs into electro-/nucleophilic compounds

Back 81

CYP450
MAO
COX
reductases
hydrolases

Front 82

which phase of metabolism is called functionalization? why?

Back 82

Phase I

makes more water-soluble

Front 83

enzymes predominantly involved in metabolism

Back 83

cytochrome 450 mixed function oxidases (microsomal)

Front 84

amphetamine

inactive metabolite
inactivating process

Back 84

aphetamine --> phenylacetone through deamination

Front 85

phenobarbitol

inactive metabolite
inactivating process

Back 85

hydroxyphenobarbitol through hydroxylation

Front 86

range of MW that cytochrome P450 can handle

Back 86

150 g/mol to 12,000 g/mol

Front 87

most common moeity conjugated to drugs in phase II metabolism

Back 87

glucuronate

Front 88

5 endogenous donors of conjugation

Back 88

glucuronate
sulfate
methyl
acetate
glutathione
glycine

Front 89

where do glucurodination reactions take place?

Back 89

liver
kidney
stomach
intestine

Front 90

where do sulfonation reactions take place?

Back 90

highest in liver
expressed in most tissues

Front 91

UGTs

Back 91

enzymes used in glucurodination

Front 92

SULTS

Back 92

enzymes used in sulfonation reactions

Front 93

To what extent do we need to memorize individual enzymes for biotranfer reactions?

Back 93

??

Front 94

7 factors that influence how a drug is metabolized

Back 94

age
diet
disease
genetic variation
genes
sex hormones
drug interactions

Front 95

3 classical inducers of cyt P450

Back 95

phenytoin
barbituates
chronic alcohol

Front 96

4 cyt P450 inhibitors

Back 96

cimetidine
isoniazid
valproic acid
disulfiram

Front 97

major excretion pathways

Back 97

hepatic
renal
pulmonary

Front 98

Major route of drug excretion

Back 98

urine

Front 99

2 ways drugs act on urine formation to influence the excretion rate of a second drug

Back 99

diuretics - increase (volume) rate of urine formation or may influence acidity

drugs that influence perfusion of kidney and thus renal filtrate and urine formation

Front 100

Renal excretion =

Back 100

Excretion =

Filtration - Reabsorption + Secrtion

Front 101

For 70 kg man, blood flow into afferent arteriole =

Back 101

650 mL/min

Front 102

Average glomerular filtration rate (GFR)

Back 102

GFR = 125 mL/min

Front 103

Most of the fluid that is filtered in the kidneys is subsequently _____

Back 103

reabsorbed

Front 104

Which drug will be filtered in the kidney, free or protein-bound?

Back 104

Free

Front 105

Flow out of collecting duct (to bladder) 1 mL/min ___ than flow into afferent arteriole

Back 105

LESS

Front 106

Amount of drug filtered per unit time is proportional to concentration of ...

Back 106

FREE drug in plasma

Front 107

Why are lipid-soluble drugs much more slowly excreted than polar drugs?

Back 107

Lipid-soluble drugs can penetrate tubular membrane, but are reabsorbed via diffusion

Front 108

Why are polar drugs rapidly excreted

Back 108

filtered, but not reabsorbed

Front 109

pH of urine

Back 109

pH 5-8

Front 110

ion trapping

Back 110

for weak acids and bases, increases in the ionized form in the kidney will enhance excretion

Front 111

increasing urine pH by i.v. NaHCO3 administration -->

Back 111

increased weak acid excretion

Front 112

increasing urine pH by i.v. NH4Cl administration -->

Back 112

increased weak base excretion

Front 113

Generally, for drugs, increase excretion with ____ & decrease excretion with ____

Back 113

increase excretion - NH4Cl

decrease excretion - NaHCO3

Front 114

active reabsorption

Back 114

from renal tubules into blood

e.g.: Na+, Cl-, glucose, amino acids, some drugs

Front 115

active secretion

Back 115

blood plasma into tubules

e.g.: K+

Front 116

where are active transporters located in the glomerular apparatus?

Back 116

proximal tubules

Front 117

When can secretion of a bound drug occur?

Back 117

If affinity of a drug for the active transporter is greater than that for a plasma protein

Front 118

T/F: some drugs are completely secreted into renal tubules during a single passage through the kidney

Back 118

True

Front 119

Renal Clearance definition

Back 119

Renal clearance - volume of plasma that is completely cleared of a substance by the kidney per unit time

Front 120

Units for renal clearance

Back 120

mL/min

Front 121

Renal clearance =

Back 121

C = (U*V)/(Cp*T)

U = drug urine conc.
V = urine volume
Cp = av. plasma conc. of drug (mg/mL)
T = urine collection time (min)

Front 122

Inulin

Back 122

filtered; not absorbed, nor secreted

ergo, clearance rate for inulin = GFR

Front 123

4 types of biliary excretion

Back 123

2 types for organic acids
1 type for organic bases
1 for neutral compounds

Front 124

Biliary excretion is sensitive to what? Why?

Back 124

metabolic state of hepatocytes

b/c transport requires energy

Front 125

locations demarcating enterohepatic cycle

Back 125

liver --> common bile duct --> sup. mesenteric v.

liver also --> systemic circulation
small intestine also --> feces

Front 126

Summary of enterohepatic cycling

Back 126

Large quantities of bile acids discharged into duodenum

80-90% of drug reabsorbed, transported thru the portal blood back to the liver to be available
again for secretion

Front 127

Example of how enterohepatic cycle can be a drug reservoir (e.g.: morphine)

Back 127

morphine metabolized (activated) to morphine-glucoronide in liver

secreted into bile

morphine-glucoronide can’t be reabsorbed by passive diffusion

hydrolyzed back into morphine in intestine by bacterial enzymes and then reabsorbed

Front 128

Pulmonary excretion

Back 128

gases and volatile chemicals
b/c lrg SA, thin alv walls & high blood flow, lungs v. effective in eliminating volatile chemicals

termination fo action of volatile anesthetics depends on this route