Pharmacology Final

Front 1

Define Pharmacokinetics.

Back 1

What body does to drug.
Ex: Adsorption, distribution, biotransformation, excretion, time of course of action

Front 2

Define Pharmacodynamics.

Back 2

What drug does to body.
Ex: Affects, mechanism of action, loaction of action

Front 3

Toxicology is the ________ effect of chemical compounds of drugs used therapeutically.

Back 3

Toxicology is the _adverse_ effect of chemical compounds of drugs used therapeutically.

Front 4

T/F
Every drug is toxic at high enough concentrations, even water.

Back 4

True

Front 5

What is any chemical substance that effects living processes in a manner thats positive or negative?

Back 5

Drug- broad definition
Working def: any chemical substance used in the diagnosis and treatment of disease.

Front 6

In 1883, Dr. Wiley was responsible for preventing what of agricultural products?

Back 6

Adulteration and misbranding

Front 7

The poison squad was put together in what year?

Back 7

1902

Front 8

What was the purpose of the poison squad that Dr Wiley put together?

Back 8

To eat foods treated with measured amounts of chemical preservatives to measure safety.

Front 9

When was the Wiley Act passed? (aka federal pure food and drug act)

Back 9

1906

Front 10

What year was the FDA established?

Back 10

1930

Front 11

What was the Federal Pure Food and Drug Act (aka Wiley Act) prohibiting? What did it require?

Back 11

Misbranding or adulterated foods, drinks or drugs and no false claim on labels
Requires registration and listing of ADDICTING substances

Front 12

What act was passed in 1912 prohibting fradulent therapeutic claims?

Back 12

Sherley Amendment

Front 13

What accident led to the passing of the FDC Act in 1938?

Back 13

The Sulfanilamide disaster,
Diethylene glycol elixer (antifreeze)
107 deaths

Front 14

The Federal Food, Drug, and Cosmetic Act of 1938 required what 3 things?

Back 14

1. Safety testing
2. Accurate and complete labels
3. Factory inspection

Front 15

Act and Date:
Required "Caution: Federal law prohibits dispensing without a prescription" on all labels

Back 15

Durham- Humphrey Amendment of 1951

Front 16

In 1951, what 4 types of drugs were listed under the D-H Amendment requiring a prescription?

Back 16

1. Injections
2. Hypnotics, narcotics, habit forming drugs
3. Drugs that are toxic, side effects or not safe unless administered by a licensed practitioner
4. Investigational use

Front 17

T/F:
The 1951 D-H Amendment created OTC drugs that could be safely used without medical supervision.

Back 17

True

Front 18

Act and year:
Required testing for both safety and effectiveness for new drugs and testing for those approved between _____ and ______.

Back 18

1962 Kefauver- Harris Amendment

Required testing for both safety and effectiveness for new drugs and testing for those approved between _1938_ and _1962_.

Front 19

What act (and year) is responsible for the lack of requirements for safety and effectiveness testing of dietary supplements?

Back 19

Dietary Supplement Health and Education Act of 1994

Front 20

In 1998 the FDA passed this rule to require manufacturers of new and existent biological products to assess safety and efficacy in children.

Back 20

Pediatric Rule

Front 21

T/F:
Drugs are specifically designed to treat the disease they are used for.

Back 21

False, most accidental
Ex: beta blockers for hypertension, minoxidil for hair loss

Front 22

The __________ is how a drug works to produce their therapeutic actions and side effects.

Back 22

The _mechanism of action_ is how a drug works to produce their therapeutic actions and side effects.

Front 23

T/F:
Most drugs are used to treat symptoms

Back 23

True

Front 24

How many years is a patent life in the US?

Back 24

20

Front 25

Roughly how many years does it take for new drug approval?

Back 25

10-15 years

Front 26

What phase of the IND is clincial testing?

Back 26

Phase 4

Front 27

CAST, in 1986-1992, recognized PVC's as risk factors for sudden and nonsudden ________.

Back 27

CAST (Cardiac Arrhythmia Suppression Test), in 1986-1992, recognized PVC's as risk factors for sudden and nonsudden _cardiac death_.

Front 28

Rezulin was marketed in 1997 for ____________ but was removed by the US in 2000 due to cases of ____and _____ failure

Back 28

Rezulin (resensitized body to insulin) was marketed in 1997 for _diabetes_ but was removed by the US in 2000 due to cases of _liver_ and_heart_ failure

Front 29

This drug improved target cell response to insulin without increasing insulin secretion but was given a black box warning in 2007 on CHF.

Back 29

Avandia

Front 30

Vioxx and Naproxen, the Vigor trial, compared GI safety but increased _________ was found.

Back 30

Vioxx and Naproxen, the Vigor trial, compared GI safety but increased _heart risk_ was found.

Front 31

T/F:
Fenfluramine, Dexfenfluramine, and Phentermine were individually approved by the FDA for weight loss.

Back 31

True

Front 32

T/F:
Fenfluramine in combination with Phentermine was approved by the FDA and exceeded 18 million prescriptions in 1996.

Back 32

False, combo not approved

Front 33

Reports of ___________ damage and pulmonary __________ caused dexfenfluramine and fensluramine to be withdrawn from the market.

Back 33

Reports of _valvular_ damage and pulmonary _hypertension_ caused dexfenfluramine and fensluramine to be withdrawn from the market.

Front 34

T/F:
Adverse effects are usually just an extension of the therapeutic actions and occur by same mechanism

Back 34

False

Front 35

T/F:
NDA are submitted to the FDA prior to clinical testing

Back 35

False, IND's not NDA's

Front 36

Which COX2 inhibitors (2) have been removed from the market?

Back 36

Vioxx and Bextra

Front 37

T/F:
In the CAST study the drug caused a three fold increase in number of cardiac deaths versus placebo

Back 37

True

Front 38

T/F:
The CAST measured the ability of encanide and flecanide to reduce premature ventricular contraction vs placebo

Back 38

True

Front 39

What Act and year established the Bureau of Chemistry?

Back 39

1906 Food and Drug Act

Front 40

What is any chemical substance used in the diagnosis and treatment of disease?

Back 40

Drug

Front 41

T/F:
The 1912 Sherley Amendment required the correct listing of all ingredients on the label.

Back 41

False

Front 42

T/F:
Vitamins meet our working definition of a drug

Back 42

False

Front 43

T/F:
An IND app is submitted prior to any screening or toxicity testing

Back 43

False

Front 44

What is the main overall outcome of biotransformations of a drug?

Back 44

The drugs water solubility is increased

Front 45

T/F:
The process of biotransformation can alters a drugs pharmacological activity

Back 45

True

Front 46

What are the 3 biotransformation processes listed in the notes?

Back 46

1. Active drug--> inactive metabolite
2. Active drug--> active metabolite
3. Inactive drug--> active metabolite

Front 47

The rate and extent of biotransformation will affect the ______________ of action of the drug

Back 47

The rate and extent of biotransformation will affect the _duration_ of action of the drug

Front 48

T/F:
Altering a drugs toxicity in concert with a drugs pharmacological activity is the drugs predictable metabolite

Back 48

True

Front 49

Where is the major site of biotransformation in the body?

Back 49

The Liver

Front 50

What site is important for oral administration?

Back 50

the intestine

Front 51

T/F:
Many internal factors can be changed to influence the metabolites produced

Back 51

False, cant change

Front 52

What are 3 internal factors mentioned in the lecture?

Back 52

Genetic makeup
Age
Gender

Front 53

What were a few external factors mentioned in the lecture?

Back 53

Nutritional status, co-admin of drugs, use of alcohol, tea, certain fruits and veggies, disease states

Front 54

T/F:
NDA's are submitted to the FDA after phase 3 clincial trials

Back 54

True

Front 55

T/F:
Seven of the drugs approved by the FDA in 2008 were considered new drug classes because their mechanism was novel

Back 55

True

Front 56

T/F:
Phase 1 clincial testing is to determine the safety and efficacy of a drug in a small number of paid volunteers

Back 56

False, just safety

Front 57

T/F:
The COX2 inhibitors interfere with the balance in actions in the blood vessels between PGI2 and TXA2

Back 57

True

Front 58

T/F:
Glutathione conjugates can undergo entero-hepatic cycling.

Back 58

False

Front 59

T/F:
Newborn babies cannot readily glucuronidate acetaminophen.

Back 59

True

Front 60

T/F:
Approximately 8% of people in the US population cannot readily metabolize substrates for CYP2D6

Back 60

True

Front 61

T/F:
Gilbert’s syndrome is a syndrome in which bilirubin is glucuronidated slowly.

Back 61

True

Front 62

T/F:
Women who take oral contraceptives containing ethynylestradiol should be careful about taking omeprazole for heartburn, because the omeprazole induces a form of cytochrome P450 that metabolizes the ethynylestradiol, and not enough ethynylestradiol will be absorbed to effectively suppress ovulation.

Back 62

False

Front 63

T/F:
A person who has a viral disease may have a lower ability to metabolize drugs than when he or she is healthy

Back 63

True

Front 64

T/F:
A person who does not eat enough protein for good nutrition is likely to have less glutathione in their cells than a well-nourished person

Back 64

True

Front 65

T/F:
Drug-drug interactions can occur when two drugs are biotransformed by the same enzyme.

Back 65

True

Front 66

T/F:
Newborn babies can readily metabolize sulfate acetaminophen.

Back 66

True

Front 67

T/F:
Someone who binge-drinks alcohol will transiently have lower NADPH in their liver and this could result in slower biotransformation of drugs that are normally metabolized by cytochrome P450

Back 67

True

Front 68

T/F:
About 50% of people in the US population have an inactive form of CYP2D6

Back 68

False

Front 69

A person who takes amphetamine every day (an indirect dopamine agonist) may initially experience euphoria, weight loss and increased attention but after a few weeks of daily drug use, these effects wear off. Which of the following changes in dopamine neurotransmission could be the reason?

A.Tyrosine hydroxylase activity is down-regulated.
B.Monoamine oxidase activity is up-regulated.
C.D2 presynaptic autoreceptors are up-regulated.
D.Dopamine stores are being moved into long-term pools.
E.Both A and C are true.
F.All of the above are true
G. None of the above are true

Back 69

F.All of the above are true

Front 70

Propranolol is a very commonly used drug to treat hypertension and angina because it acts as a beta-adrenergic receptor blocker, thereby decreasing how hard the heart is stimulated to work by the autonomic nervous system. However, a clinical disadvantage to its use is that multiple increasing steps in its drug dose must be given over time to maintain the initial effect of the drug. Which of the following changes in norepinephrine neurotransmission could be the reason?
A.Beta1-postsynaptic receptors ability to couple with Gs is decreased.
B.Adenylate cyclase activity becomes less sensitive to stimulation by Gs.
C.Phosphodiesterase activity is increased in the postsynaptic cell.
D.COMT activity is increased.
E.Both A and C are true.
F.All of the above are true
G. None of the above are true

Back 70

G. None of the above are true

Front 71

T/F:
If the potency of Drug A is greater than the potency of Drug B then the EC50 for Drug A will be greater than the EC50 for Drug B.

Back 71

False

Front 72

T/F:
If the potency of Drug A is greater than the potency of Drug B then Drug A will be more clinically useful than Drug B.

Back 72

False

Front 73

T/F:
FDA approval is limited to 24 drugs/year.

Back 73

False

Front 74

Which of the following drugs inhibit cytochrome P450?
A.acetaminophen
B.ketoconazole
C.acetylsalicyclic acid
D.cimetidine
E. isoniazid

Back 74

B.ketoconazole
D.cimetidine.
E. isoniazid

Front 75

Which natural product in the following list is associated with the grapefruit juice effect on drug bioavailability?
A.epicatechin gallate
B.rutin
C.quercetin
D.6’,7’-dihydroxybergamottin
E.Chrysin

Back 75

D.6’,7’-dihydroxybergamottin

Front 76

Which of the following is/are true?
A.The average time for FDA approval is 10-15 years.
B.A new drug receives FDA approval every three months.
C.Use of prescription drugs for weight loss is always a rational use of drugs.
D.The FDA may limit the time a new drug may be under investigation.
E.All of the above are correct.
F.None of the above are correct.

Back 76

A.The average time for FDA approval is 10-15 years.

Front 77

Which of the following is/are true?
A.Most drugs used today are synthetic.
B.Minoxidil use for hair loss is an example of rational drug design.
C.The Cardiac Arrhythmia Suppression Trial measured ability of Flecanide and Encanide to prevent death due to myocardial infarction.
D.Rezulin, an oral anti hyperglycemic, was removed from the market for causing significant renal toxicity.
E.All of the above are correct.
F.None of the above are correct

Back 77

A.Most drugs used today are synthetic

Front 78

Which of the following would require a prescription for use?
A.Drugs deemed to be habit forming
B.Cough syrup containing codeine
C.Drugs given by injection
D.New drugs undergoing clinical trials
E.All of the above are correct F.None of the above are correct

Back 78

E.All of the above are correct

Front 79

Which of the following is/are true?
A.Pharmacodynamics deals with information about drug distribution inthe body
B.Toxicology only deals with chemicals we defined as drugs
C.Pharmacokinetic properties are not important in the therapeutic actions of drugs
D.Pharmacogenomics deals with the role genetics plays in how we respond to drugs
E.All of the above are correct
F.None of the above are correct

Back 79

D.Pharmacogenomics deals with the role genetics plays in how we respond to drugs

Front 80

In which of the following cases would the use of the agent mentioned be regulated by the FDA?
A.Use of morphine to treat an injured dog
B.Use of Vitamin C to help prevent a cold
C.Use of Saw Palmetto (a natural product) in benign prostatic hyperplasia
D.Use of St. Johns Wort (a natural product) for mild depression
E.All of the above are correct
F.None of the above are correct

Back 80

A.Use of morphine to treat an injured dog

Front 81

The Kefauver-Harris amendment
A.Required safety testing of drugs approved after 1938
B.Defined over the counter medication
C.Allowed for compassionate use of drugs without prescriptions
D.Was repealed by the 1994 Dietary Supplement Health and Education Act
E.All of the above are correct
F.None of the above are correct

Back 81

F.None of the above are correct

Front 82

T/F:
Cigarettes smokers who also drink ethanol chronically will have the same complement of CYP450 in their liver as people who do not smoke or drink

Back 82

False

Front 83

T/F:
Elderly people tend to metabolize drugs more slowly than younger adults

Back 83

True

Front 84

T/F:
The water solubility of a drug usually decresses following biotransformation of the drug

Back 84

False

Front 85

Glucuronide conjugates excreted in the bile may be hydrolyzed in the intestine and the parent compound reabsorbed

Back 85

True

Front 86

What receptor subtypes does Gq bind to? (3)

Back 86

Alpha-1 adrenergic
M-1 muscarinic
5HT-2

Front 87

What effects does Gq mediate? (3)

Back 87

INCREASES:
Phospholipase- C activity
Ca release from intracellular stores
DAG- stimulated PKC

Front 88

What receptor subtypes does Gs bind to? (3)

Back 88

Beta- adrenergic receptors
D1 dopamine receptors
D5 dopamine receptors

Front 89

What effects does Gs mediate? (3)

Back 89

INCREASE:
Adenylate Cyclase activity
cAMP- stimulated PKA
ACTIVATE:
Ca channels in cell membrane

Front 90

When bound to, these receptors directly open a cation channel. (5)

Back 90

AMPA receptors
5HT-3 receptors
Nicotinic receptors
Kainate receptors
NMDA receptors

Front 91

What receptor subtypes does Gi and Go probably bind to? (6)

Back 91

GABA- B receptors
Kappa opiod receptors
Alpha-2 adrenergic receptors
D2 dopamine receptors
Mu Opiod receptors
Delta opiod receptors

Front 92

What receptor subtypes does Gi bind to? (1)

Back 92

5HT-1 R

Front 93

What effects does Gi mediate? (3)

Back 93

Decrease Adenylate cyclase
Increase phospholipase A activity
Activate K channels in cell membrane

Front 94

When bound to, which receptor directly opens an ANION channel?

Back 94

GABA- A receptors

Front 95

Does Go inhibit or stimulate Ca channels in the cell membrane?

Back 95

Inhibit

Front 96

Binge drinking affects which cofactors or substrates of drug biotransformation?

Back 96

NADPH

Front 97

What natural product is a very potent inhibitor of CYP3A4 and the p-glycoprotein transporter?
A. epicatechin gallate
B. rutin
C. quercetin
D. 6',7'-dihydroxybergamottin
E. chrysin

Back 97

D. 6',7'-dihydroxybergamottin

Front 98

Which of the following are true about presypnatic receptors?
A. Impulse- regulating autoreceptors increase action potentials
B. Heterologous presypnatic receptors can increase neurotransmitter release
C. Homologous presynaptic receptors usually increase
D. Presynaptic receprots are usually the sam esubtype as post synaptic receptors
E. All of the Above

Back 98

B. Heterologous presypnatic receptors can increase neurotransmitter release

Front 99

Which of the following properties or conditions determine the degree of receptor occupancy by a particular drug?
A. Receptor number and saturability
B. Drug concentration and affinity
C. Ionic concentration
D. The alpha factor and intrinsic activity
E. All of the above

Back 99

B. Drug concentration and affinity

Front 100

The molecular structure of a drug, the affinity of thr drug for the enzyme, the amount of drug metabolizing enzyme present, the availability of co-factors, and the presence of other xenobiotics which compete, are all factors affecting the ________, ________ and ________ of biotransformations of any given drug in the liver.

Back 100

The molecular structure of a drug, the affinity of thr drug for the enzyme, the amount of drug metabolizing enzyme present, the availability of co-factors, and the presence of other xenobiotics which compete, are all factors affecting the _pathway_, _extent_ and _rate_ of biotransformations of any given drug in the liver.

Front 101

T/F:
The genetic variation leads to changes in protein structure, altering the affinity of the drug for the enzyme, this is termed enzyme polymorphism.

Back 101

True

Front 102

Which CYP enzyme hydroxylates a number of drugs containing N and an aliphatic ring or chain, including drugs such as propanolol, dectromethorphan, and was discovered during the studies of debrisoquine (a hypotensive drug)?

Back 102

CYP2D6

Front 103

Which CYP enzyme metabolizes omeprazole and diazepam?

Back 103

CYP2C19

Front 104

T/F:
CYP2C19 was 1st shown in mephenytoin and is poorly metabolized more commonly in Japanese and Chinese than in Caucasians

Back 104

True

Front 105

What wasthe 1st drug metabolizing enzyme polymorphism to be identified through isoniazid observations?

Back 105

N-acetyltransferase (NAT-2)

Front 106

T/F:
Many foods and drugs constituents induce the synthesis of one or more members of the CYP450 family, so that more of these enzymes are expressed in the liver.

Back 106

True

Front 107

What is the most abundant form of CYP450 in the human liver?

Back 107

CYP3A

Front 108

Concentrations of the co-substrate _____ are lowered by starvation but can be increased by taking antioxidants found in certain foods

Back 108

Concentrations of the co-substrate _GSH_ are lowered by starvation but can be increased by taking antioxidants found in certain foods

Front 109

If there has been a super sensitivity (antagonist, too little) at the site of action:
Neurotransmitter
Synthesis_______
Storage________
Release________
Reuptake_______
Metabolism________
Postsynaptic neuron receptors:
Bmax_____
Kd________
Affinity_______
2nd messengers:
Generation_____________
Interaction________
Metabolism_________
Autoreceptors:
Bmax_______
Kd_________
Affinity_______

Back 109

Neurotransmitter:
Synthesis_INCREASES_
Storage_Short term_
Release_INCREASES_
Reuptake_DECREASES_
Metabolism_DECREASES_
Postsynaptic neuron receptors:
Bmax_INCREASES_
Kd_DECREASES_
Affinity_INCREASES_
2nd messengers:
Generation_INCREASES_
Interaction_INCREASES_
Metabolism_DECREASES_
Autoreceptors:
Bmax_DECREASES_
Kd_INCREASES_
Affinity_DECREASES_

Front 110

If there has been a subsensitivity (agonist, too much) at the site of action:
Neurotransmitter
Synthesis_______
Storage________
Release________
Reuptake_______
Metabolism________
Postsynaptic neuron receptors:
Bmax_____
Kd________
Affinity_______
2nd messengers:
Generation_____________
Interaction________
Metabolism_________
Autoreceptors:
Bmax_______
Kd_________
Affinity_______

Back 110

Neurotransmitter:
Synthesis_DECREASES_
Storage_Long term_
Release_DECREASES_
Reuptake_INCREASES_
Metabolism_INCREASES_
Postsynaptic neuron receptors:
Bmax_DECREASES_
Kd_INCREASES_
Affinity_DECREASES_
2nd messengers:
Generation_DECREASES_
Interaction_DECREASES_
Metabolism_INCREASES_
Autoreceptors:
Bmax_INCREASES_
Kd_DECREASES_
Affinity_INCREASES_

Front 111

T/F:
A heterologous receptor is an autoreceptor.

Back 111

False, a homologous receptor is a receptor for the same neurotransmitter therefore it is aka an autoreceptor

Front 112

What are the 3 different types of autoreceptors?

Back 112

1. Impulse modulating- located on dendrites or cell bodies, decrease chance of AP
2. Synthesis modulating- located on PRE sypnatic terminals- inhibit NT synthesis
3. Release modulating- located on PREsypnatic terminals

Front 113

Antagonist cause _______ stimulation leading to _______ regulation while Agonist cause ______ stimulation leading to _______ regulation

Back 113

Antagonist cause _under_ stimulation leading to _up_ regulation while Agonist cause _over_ stimulation leading to _down_ regulation