Exam 1 Flashcards Preview

Drugs and Disease > Exam 1 > Flashcards

Flashcards in Exam 1 Deck (184):
1

what is pharmacology

scientific study of substances that interact with living systems through CHEMICAL processes

2

chemicals typically bind to _____ and activate or inhibit many normal body processes

regulatory biomolecules

3

drugs are typically what kind of molecules ?

small organic molecules

4

4 main classifications of drugs

1. pharmacological effect

2. chemical structure

3. target system

4. site of action

5

criteria for a good drug?

1. do what it is meant to do
2. no side effects
3. safe
4. easy to take

6

why should drugs work?

drugs = tiny chemicals of simple structure

organism = huge array of chemical reactions that keep the body healthy and functioning properly
- drugs enter this chemical world

7

where do drugs act

upon or within cells

8

3 main molecules targets of drugs

1. lipids/cell membranes
2. proteins (imbedded in membrane or cytosolic)
- receptors/enzymes
3. nucleic acids (DNA/RNA)

9

what happens when lipids are a drugs target?

lipid structure of cell membrane is disrupted

10

order from most common to least common molecular targets of drugs

1. Proteins (enzymes/receptors)
2. Nucleic acids
3. Lipids

11

what protein structure is most important with respect to drug action

tertiary

12

what are the major protein drug target

enzymes

receptors

13

how do enzymes facilitate reactions

1. provide a reaction environment
2. bringing reactants together
3. positioning reactants properly for reaction
4. weakening bonds
5. participating intimately in the reaction mechanism

14

most drugs are enzyme ___(activators/inhibitors)

inhibitors

15

control and communication of cells comes primarily from what?

the brain and spinal column (CNS)

16

in a synapse how are messages transferred

via neurotransmitter/receptor system

17

how do synapses allow for an electrical message sent via nerves to become a chemical message? (allows a potential site for drug interaction

because of the neurotransmitter/receptor system

18

neurotransmitters are usually ___(+/-) charged small molecules

negatively

19

how can drugs increase/decrease neurotransmission

1. stimulate receptor (agonist)
2. block receptor (antagonist)
3. block transport/reuptake of NT
4. block metabolism of NT
5. block synthesis of NT
6. open/close ion channels

20

Nucleic acids as drug targets are drugs that interfere with either ____, ____, or ____ in some way.

replication

transcription

translation

21

typically drug interactions with nucleic acids leads to what

cell death

22

three types of agents that are drugs that act on DNA

1. intercalating cytostatic agents
2. alkylating agents
3. chain "cutters"

23

what do intercalating cytostatic agents do?

insert between strands/layers of base pairs

disrupt the shape of the double helix

prevent replication and translation

24

what do alkylating agents do?

electrophiles attacked by nucleophiles to form strong, covalent bonds to DNA

drugs with 2 alkylating groups can cross-link DNA strands to prevent unraveling

25

what do chain "cutters" do?

agents that cut DNA strands and then prevent DNA ligase from repairing the damage

26

RNA

relays codes for particular proteins from DNA to protein production site (rRNA)

mRNA

27

RNA

constructs protein molecule from message on mRNA-moves along mRNA to "decode" it

rRNA

28

RNA

links triplet code on mRNA to a specific amino acid (different molecule for each AA)

tRNA

29

drugs that interact with RNA with interfere with what?

transcription and translation

commonly see interference with ribosomal action

30

what about a drug and a receptor must be complementary?

functional (chemical) groups

shapes
- chirality is important

31

drugs and receptors interact chemically, intimately, and specifically at the ___ level

atomic

32

what are pharmacodynamic processes

how drugs act on the body

plays a major role in deciding if drug class is appropriate therapy

33

what are pharmacokinetic processes

how the body acts on the drug

absorption, distribution, metabolism and elimination of drugs from the body

important in choosing and administering drugs for particular patients

34

what is the duration of drug action denoted by

1/2 life

35

actions of a drug is terminated by what?

1) dissociation of drug from receptor
2) destruction of a drug-receptor complex (endocytosis)
3) desensitization mechanisms activated

36

receptors must be _1_-specific and _2_

1. ligand-specific
2. change shape

37

what do inert binding sites affect?

distribution and concentration of drug
- drug becomes less available to act and to be metabolized

38

EC50?

effective concentration eliciting a response

39

IC50?

inhibitory concentration = 50% enzyme inhibition

40

ED50?

effective dose in 50% of subjects

41

LD50?

lethal dose that kills 50% of subjects

42

EC50, IC50, ED50, LD50 all relate to what?

Kd

43

EC50, IC50, ED50, LD50 are all measures of what?

potency

44

what is Kd

dissociation constant

measure of receptor binding affinity

45

what is therapeutic index?

toxic/therapeutic conc.

TI=LD50/ED50

or

conc. that kills/conc. that heals

46

does a higher or lower therapeutic index = safer drug?

higher

47

what does potency differentiate?

differentiates compounds based on their concentration-response relationships

48

is potency a precise or relative measure?

relative

49

specific ability of drug to bind to a receptor

affinity

50

affinity is a _1_(relative/precise) measure relating to _2_ responses

1. precise
2. drug-receptor

51

affinity = ?

K1/K2

or

1/Kd

52

relates the magnitudes of the max effects of a series of drugs

efficacy

53

does a more efficacious drug produce a lesser or greater response?

greater

54

what are partial agonists

drugs of low efficacy

appear to bind to receptors, but don't fully activate the system as full agonists

55

4 types of drug antagonism?

1. competitive antagonism (irreversible/reversible)
2. noncompetitive antagonism
3. functional antagonism ("physiologic antagonist)
4. chemical antagonism

56

what is the most common type of antagonist drug

competitive antagonism

57

what is functional antagonism?

represents interaction of two different agonists with opposite pharmacological effects

58

what is chemical antagonism?

direct interaction between agonist and antagonists

59

what are the four major types of transmembrane signaling mechanisms ?`

1. receptors are intracellular
2. receptors on membrane-spanning enzymes
3. receptors on membrane ion channels
4. receptors linked to effector via G-proteins

60

what type of drug agents acts on receptors that are intracellular?

lipid soluble or diffusible agents (steroids or nitric oxide)

61

what kind of receptor would insulin act on

receptor on membrane-spanning enzymes

62

how do receptors on membrane-spanning enzymes work

drug combines with an extracellular receptor which affects intracellular enzymatic activity

63

how do receptors on membrane ion channels work

receptors may directly cause the opening of an ion channel or modify the channel's response to other agents

64

how do receptors linked to effector via G-proteins work

G-protein couples the receptor to its effector

65

what is idiosyncratic response?

an unusual response in an individual

hyp- or hyperactive responses

66

how does drug tolerance occur due to excess stimulation (agonists)?

A cell will remove receptors and decrease their production

67

how does drug tolerance occur due to reduced stimulation (antagonists)

cell will increase receptor population

68

what is anaphylaxis

immediate reaction to a drug
- IgE antibodies --> release histamine and serotonin

69

placebo effect is evident in what percentage of patients

20-40%

70

what is placebo toxicity

patients will experience side effect symptoms of a drug that believe they are taking

71

what causes the primary effect for drugs?

side effects and toxic effects

72

what is the main therapeutic goal of drugs?

to achieve a desired beneficial effect with minimal adverse effects

73

concentration D -->effect/response (receptor level)

what type of pharmacological process?

pharmacodynamic process

74

dose-->concentration at receptor (organismal level)

what type of pharmacological process?

pharmacokinetic process

75

what is the sum reaction of the pharmacodynamic and pharmacokinetic processes?

aka ___ ---> ____

dose --> effect/response

76

what does pharmacokinetics deal with?

deals with drug concentration and how they vary overtime

"fate" of drugs

77

4 pillars of drug-body interactions/processes in pharmacokinetics?

1. absorption
2. distribution
3. metabolism
4. excretion

78

what are the common routes of administration?

Enteral or parenteral

79

route of administration via the GI tract

most common route of administration

least effective

enteral route

80

route of administration other than GI tract

rapid onset/reduced metabolism

parenteral route

81

abbreviation for by mouth

PO
OS

82

cheek pouch?

buccal

83

what does IV stand for

intravenous

84

what does IM stand for

intramuscular

85

what does SC, SQ stand for

subcutaneous

86

what does IA stand for

intraarterial

87

what is intrathecal?

injection into the subarachnoid space (beneath membrane envelope of brain)

88

administering a drug via aerosol or inhalation would be what kind of route?

pulmonary

89

after administration, the drug must be...?

1. absorbed in the blood stream
2. distributed to its target by permeating through barriers/membranes
3. metabolized and/or...
4. eliminated

90

movement of drug from site of administration to the plasma

absorption

91

movement of drug within an organism to the sites of action

distribution

92

what does the rate of drug action depend on

absorption and distribution

93

what is permeation and what are the 4 primary mechanisms

Movement of a drug through system and proceeds through 4 primary mechanisms:

Passive (most common)
1. aqueous diffusion
2. lipid diffusion

Active
3. special carriers (proteins)
4. endocytosis and exocytosis

94

major functions of membranes

1. barriers - contain essential molecules within cells/nuclei/organelles and exclude non-essential molecules

2. support matrix for macromolecules

95

solubility in a lipid (neutral) environment

hydrophobicity/lipophilicity

96

logP = ??

measure of a drug molecules hydrophobicity

logP = lipid/water partition coeffiction

97

what factors should be considered with hydrophobicity/lipidphilicity?

-polarity

- ionizability of molecules (+/-)
- pH

98

pH = ?

-log[H+]

99

Ka = ?

[A- or B][H+]/[AH or BH+]

100

what is the henderson hasselbach equation

pH = pKa + log [Base]/[Acid]

101

are most drugs acids or bases

bases

102

what are 2 special membranes

blood brain barrier (bbb)

placenta barrier

103

characteristics of blood brain barrier (bbb)

- very hydrophobic
- drugs must be highly non polar to pass
- psychoactive drugs
- compromised in very young and old

104

characteristics of placental barrier

- similar to bbb
- hydrophobic
- many drugs readily enter placenta (and may get trapped)

105

what are the major mechanisms to terminate drug action

1. redistribution
2. excretion/elimination
3. metabolism (or biotransformation)

106

metabolism is the most important determinant of _1_ of drug action and _2_ of response

1. duration
2. intensity

107

metabolism alters pharmacological _1_ and _2_

1. activities
2. bioavailabilities

108

metabolism greatly increases the ability to ____ drugs

excrete

109

what are the types of metabolism

inactivation - metabolite is less active (or inactive)

activation - metabolite is more active (Pro-drugs)

combination of activation and inactivation - different activity

110

location of metabolism

liver

111

drug metabolism is also known as what

xenobiotic metabolism
(drug = xenobiotic)

112

goal of xenobiotic metabolism?

hydrophobic molecule --> hydrophilic molecule

want to increase drug excretability and decrease drug activity

113

what happens to drug in phase I of xenobiotic metabolism?

increase functionality (activity)

increase polarity

increase water solubility

114

what happens to drug in phase II of xenobiotic metabolism?

increase size

increase polarity

increate water solubility

115

what phase in metabolism is oxidative?

phase I

116

what phase in metabolism is synthetic?

phase II

117

what reactions happen in phase I metabolism

oxidation

reduction

hydrolysis

118

where does oxidation (and reduction) happen in phase I metabolism

on ER

119

where does hydrolysis take place in phase I metabolism

cytosol

120

what reactions occur in phase II metabolism

conjugation/synthetic

121

where does conjugation/synthetic happen in phase II metabolism

ER and cytosol

122

what enzyme superfamily mediates oxidation in phase I metabolism

cytochrome P450

123

what cytochrome P450 independent enzymes perform oxidation in phase I metabolism

1. flavin monooxygenase
2. amine oxidase
3. dehydrogenases

124

phase I metabolism reactions creates polar _1_ and phase 2 metabolism reactions add _2_ to handles

1. handles
2. polar molecules

125

phase I metabolism reactions make drugs more polar by adding/revealing ____

functional groups

126

phase I

what does N-dealkylation form

amines and aldehydes

127

phase I

what does O-dealkylation form

phenols and aldehydes

128

phase I

what does N-oxidation form

primary, secondary, and tertiary amines

129

major enzymes for the breakdown of neurotransmitters that are primary amines

and

-amine oxidase

130

what happens in phase II metabolism

form new covalent bonds to drug or metabolite via handles

add larger structural/functional units to the handles created in phase I

131

what phase II metabolism reaction is the major route in all mammals?

glucuronidation

132

what enzyme catalyzes glucuronidation (phase II)?

glucuronyl transferase

133

what cofactor is required in glucuronidation (phase II)?

UDPGA

134

phase II

what is happening in glutathione (tripeptide) conjugation

add glutathione (tripeptide) to electrophilic drugs to yield mercapturic acid derivatives

135

what catalyzes sulfation in phase II

sulfotransferase

136

what cofactor is required for sulfation in phase II

PAPS

137

what enzyme catalyzes glutathione conjugation

glutathione transferase

138

what enzymes catalyze amino acid conjugation (phase II)

glutamine-N-acyltransferase

glycine-N-acyltransferase

139

phase II

in methylation, coenzyme _1_ is used to add _2_ to _3_, _4_, and _5_ atoms

1. SAM
2. O
3. S
4. N

140

phase II

in acetylation, _1_ are formed by adding an _2_ group to _3_.

1. inactive amides
2. acetyl (CH3CO-)
3. primary amines

141

phase II

acetylation is catalyzed by what enzyme

acetylase

142

how do we use the sequenced human genome

genetic testing for:
- genetic diseases
- adverse response to specific drugs

measuring gene expression in response to drugs

development of more specific drugs (pharmacogenomics)

143

diagnosis by biochemical markers

what are these biochemical markers

biochemical genetic testing

- loss of enzyme activity
- increase or decrease in a metabolite

144

what form of genetic testing is good for detection of carriers

genetic

145

what form of genetic testing helps with understanding disease pathway

biochemical

146

what form of genetic testing provides a diagnosis before symptoms appear

genetic

147

what form of genetic testing test DNA for causative mutation

genetic

148

what is pharmacogenomics

study of how an individuals genetic inheritance affects the body's response to a drug

149

what holds the promise that drugs might one day be tailor-made for individuals and adapted to each person's own genetic makeup

pharmacogenomics

150

understanding an individual's ___ ____ is thought to be the key to creating personalized drugs with greater efficacy and safety.

genetic makeup

151

Mutations in proteins that metabolize drugs can affect ____

pharmacokinetics

152

Mutations in proteins that are drug targets can affect ____

pharmacodynamics

153

ex vivo = ?

cell based

154

in vivo = ?

viruses and liposomes

155

how could someone watch and follow a drug through the body?

radio labeling drugs --> positron emission

156

what are inborn error of metabolism

recessively inherited enzymopathies

disorders of intermediate metabolism

157

how is inborn error of metabolism inherited

autosomal recessive

158

In the metabolic pathway, what happens if you do not have enough of a functional enzyme?

Failure of formation

159

albinism is what kind of inborn error of metabolism?

failure of formation

(no tyrosinase to produce melanin)

160

Goitrous cretinism is what kind of inborn error of metabolism?

failure of formation

(lack of thyroid hormone)

161

if there is an inborn error of metabolism where there is an accumulation of precursors, what happens if the precursor is soluble (hydrophilic)?

- diffuse increase in bodily fluids and tissues

- increased excretion in urine

162

if there is an inborn error of metabolism where there is an accumulation of precursors, what happens if the precursor is insoluble (hydrophobic)?

- stored in various tissues or tissue organelles

- accumulation leads to progressive problems

163

alkaptonuria is what kind of inborn error of metabolism?

accumulation of precursors

164

phenylketonuria is what kind of inborn error of metabolism?

accumulation of precursor

165

examples of accumulation of precursors insoluble?

lipid storage disease

mucopolysaccharidoses

glycogen storage disease

lysosomal storage disease

peroxisomal disorders

(lets make ghost levitate pronto)

166

Hurler syndrom MPS-1 is what kind of inborn error of metabolism?

accumulation of precursors

167

congenital adrenal hyperplasia is what kind of inborn error of metabolism?

increase alternate products

168

cystinuria is what kind of inborn error of metabolism?

disorder of transport

169

cystic fibrosis is what kind of inborn error of metabolism?

disorder of transport

170

hyperlipidemia is what kind of inborn error of metabolism?

receptor disorder

171

familial gout is what kind of inborn error of metabolism?

excess production

172

inborn errors are individual _1_ but _2_ common

1. rare
2. collectively

173

what kinds of inborn errors of metabolism are there?

1. failure of formation
2. accumulation of precursor
3. increase alternate products
4. disorders of transport
5. excess production
6. receptor disorders

174

advantages of recombinant proteins over those purified from natural sources

1. overproduced
2. human protein
3. decrease viral hazard

175

how are recombinant proteins produced

microbes - yeast/bacteria

animal cells

pharming - introduce human gene behind a whey promoter into a farm animal and purify protein from milk



176

characteristics of using animals cells to produce a recombinant protein

- complex proteins that require secondary modifications

- expensive

- slow

- growth factors (serum)

177

characteristics of using microbes (bacteria/yeast) to produce recombinant protein

- use fermentor

- cheap

- large amounts

178

characteristics of pharming to produce recombinant protein

- introduce human gene behind a whey promoter into a farm animal and purify protein from milk

179

how is insulin produced

microbe

180

examples of recombinant proteins

insulin

erythropoietin - anemia

human growth hormone - dwarfism

tissue plasminogen activator (t-PA) - strokes

clotting factor VIII - hemophilia

181

what are not many protein drugs effective orally?

proteins are digested in the stomach by amide hydrolysis

182

how must blood proteins being injected

IV

183

how can insulin be injected

intraperitoneally (IP)

184

how can proteins targeted for the lungs be administered?

inhaler