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Behavioral Pharmacology > Ch 1: Principles of Pharmacology > Flashcards

Ch 1: Principles of Pharmacology Flashcards

1
Q

Neuropharmacology

A

concerned with drug-induced changes in the functioning of cells in the nervous system

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2
Q

psychopharmacology

A

emphasizes drug induced changes in mood, thinking, and behavior

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3
Q

neuropsychpharmacology

A

goal is to identify chemical substances that act on the nervous system to alter behavior that is disturbed because of injury, disease, or environmental factors

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4
Q

drug action

A

specific molecular changes produced by a drug when it binds to a particular target site or receptor

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5
Q

drug effects

A

alterations in physiological or psychological functions

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6
Q

does a drug’s effects occur just near its site of action?

A

no, the site of action may be very different from the site of drug effect

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7
Q

therapeutic effects

A

drug-receptor interaction produces desired physical or behavioral changes

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8
Q

side effects

A

vary in severity from mildly annoying to distressing and dangerous

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9
Q

specific drug effects

A

based on the physical and biochemical interactions of a drug with a target site in living tissue

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10
Q

nonspecific drug effects

A

those that are based not in the chemical activity of a drug-receptor interaction, but on certain unique characteristics of the individual

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11
Q

placebo

A

a pharmacologically inert compound administered to an individual

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12
Q

do placebos have effects?

A

yes, they can have both therapeutic and side effects

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13
Q

why are placebos important?

A

they are essential in the design of experiments conducted to evaluate the effectiveness of new medications because it eliminates the influence of expectation on the part of the subject

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14
Q

double-blind experiment

A

neither the patient nor the observer knows what treatment the patient has received

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15
Q

Four types of naming conventions for drugs

A

chemical name; generic name; brand name; slang/street name

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16
Q

bioavailability

A

the amount of drug in the blood that is free to bind at specific target sites to elicit drug action

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17
Q

Five parts that make up the pharmacokinetic component of drug action

A
  1. routes of administration
  2. absorption and distribution
  3. binding
  4. inactivation
  5. excretion
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18
Q

routes of administration

A

how/where a drug is administered

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19
Q

absorption and distribution

A

drug passes through cersll membranes and enters the blood plasma where it travels around the body

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20
Q

binding

A

with receptors or with depot binding

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21
Q

inactivation

A

aka biotransformation occurs as a result of metabolic processes in the liver; influences both the intensity and the duration of drug effects

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22
Q

excretion

A

liver metabolites are eliminated from the body with the urine or feces

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23
Q

depot binding

A

binding to plasma proteins or may be stored temporarily in bone or fat, where it is inactive

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24
Q

biotransformation

A

–

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25
Q

enteral

A

methods of of administration use the GI tract; agents administered by these generally slow in onset and produce highly variable blood levels of drug

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26
Q

most common method of enteral administration

A

oral

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27
Q

parenteral

A

other routes of administration that aren’t enteral; injection, pulmonary, topical administration

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28
Q

oral administration (PO)

A

most popular; safe; economical

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29
Q

what must happen for oral administration to be effective?

A

the drug must dissolve in stomach fluids and pass through the stomach wall to reach blood capillaries

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30
Q

absorption

A

movement of the drug from the site of administration to the blood circulation

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31
Q

where are most drugs absorbed when taken orally?

A

small intestine

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32
Q

What can alter absorption when taken orally?

A

food in stomach slows the movement of the drug into the intestine

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33
Q

first-pass metabolism

A

evolutionarily beneficial function because potentially harmful chemicals and toxins that are ingested pass via portal vein to the liver, where they are chemically altered by a variety of enzymes before passing to the heart for circulation throughout the body

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34
Q

Are blood plasma levels stable during oral administration?

A

No–oral administration produces drug plasma levels that are more irregular and unpredictable and rise more slowly than those produced by other methods of administration

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35
Q

rectal administration

A

requires the placement of a drug-filled suppository in the rectum

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36
Q

when is rectal administration beneficial?

A

infants, individuals who are vomiting, unconscious, or who are unable to take medication orally

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37
Q

intravenous (IV)

A

injection is the most rapid and accurate method of administration in that a precise quantity of the agent is placed directly into the blood and passage through cell membranes such as the stomach wall is eliminated

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38
Q

what is method makes over dose most likely?

A

injection– an overdose or allergic reaction can not be easily corrected

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39
Q

intramuscular (IM)

A

injection, which provides the advantage of slower, more even absorption over a period of time

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40
Q

how long does intramuscular absorption typically take?

A

10-30 minutes

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41
Q

intraperitoneal (IP)

A

injection that is rarely used; injected through the abdominal wall into the peritoneal cavity

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42
Q

peritoneal cavity

A

space that surrounds the abdominal organs

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43
Q

subcutaneous (SC)

A

administration, the drug is injected just below the skin and is absorbed at a rate that is dependent on blood flow to the site

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44
Q

subcutaneous implantation

A

commonly use to implant drug-containing pellets–often hormones

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45
Q

two hormonal drugs that can be administered through subcutaneous implantation

A

Implanon andNexplanon–birth control

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46
Q

Inhalation

A

allows drugs to be absorbed into the blood by passing through the lungs

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47
Q

what is the preferred method of administration when oral absorption is slow?

A

inhalation

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48
Q

disadvantages of inhalation

A

damage to the lungs caused by small particles; irritation of the nasal passages

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49
Q

topical

A

application of drugs to mucous membranes generally provides local drug effects

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50
Q

intranasal administration

A

causes local effects but can also have systemic effects, in which case the drug moves across a single epithelial cell layer into the bloodstream avoiding first-pass liver metabolism

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51
Q

what can you bypass with intranasal administration?

A

the blood brain barrier

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52
Q

how can neuropeptides be administered?

A

via intranasal sprays to achieve significant concentrations in the brain

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53
Q

cocaine

A

potent vasoconstrictor–restricting blood flow deprives the underlying cartilage of oxygen, leading to necrosis

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54
Q

transdermal

A

through the skin–administration with skin patches provides controlled and sustained delivery of drug at a preprogrammed rate

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55
Q

disadvantage of transdermal delivery

A

a limited number of drugs are able to penetrate this way

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56
Q

inotophoresis

A

involves applying a small electrical current to the reservoir or the patch. The electrical charge repels drug molecules with a similar charge and forces them through the skin at a predetermined rate

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57
Q

mechanical disruption of the skin

A

small arrays of microneedles coated with drug or vaccine are placed on the skin. The needles penetrate the superficial layer of the skin where the drug is delivered without stimulating underlying pain receptors

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58
Q

stratum corneum

A

superficial layer of the skin

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59
Q

epidural

A

injection used when spinal anesthetics are administered directly into the cerebrospinal fluid surrounding the spinal cord bypassing the BBB

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60
Q

intracranial

A

discrete areas of brain tissue are injected

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61
Q

intracerebroventricular

A

the ventricles–cerebrospinal-fluid filled chambers

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62
Q

infusion pump

A

implanted under the skin of the scalp and can be programmed to deliver a constant dose of antibiotic into the cerebral ventricles

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63
Q

gene therapy

A

refers to the application of DNA, which encodes a specific protein to a particular target site

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64
Q

vector

A

gene delivery system

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65
Q

where are vectors usually injected?

A

directly into the brain region targeted for modification

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66
Q

viral vectors

A

typically chosen for gene therapy because of the special ability of a virus to bind to and enter cells and their nuclei, where they insert themselves into the chromosome to alter DNA

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67
Q

psychoactive drugs

A

drugs that have an effect on thinking, mood, and behavior

68
Q

what dictates absorption?

A

drug concentration which is determined in part by differences in age, sex, body size; the solubility and ionization of the drug

69
Q

what is the single most important factor in determining plasma drug levels?

A

rate of passage of the drug through the various cell layers between the site of administration and the blood

70
Q

what makes up cell membranes?

A

complex lipid (fat) molecules called phosphoipids

71
Q

phospholipids

A

have a negatively charged region at one end and two uncharged lipid tails; they are arranged in a bilayer, with their phosphate ends forming two almost continuous sheets filled with fatty material. Thus the charged heads are in contact with both the aqueous intracellular fluid and the aqueous extracellular fluid

72
Q

what do cell membranes do?

A

prevent most molecules from passing through unless they are soluble in fat

73
Q

passive diffusion

A

high lipid soluble drugs–leave the water in the blood or stomach juices and entering the lipid layers of membranes

74
Q

concentration gradient

A

concentration difference on each side of the membrane

75
Q

what does lipid solubility do?

A

increases the absorption of drug into the blood and determines how readily a drug will pass the lipid barriers to enter the brain

76
Q

partition coefficient

A

estimate lipid solubility; a drug is first mixed with water and then combined with the same volume of oil or a lipid solvent. After settling, the oil and water form layers, which are separated and the amount of the drug found in each layer is compared. The ratio of the amount of drug dissolved in oil divided by its concentration in water is the oil/water partition coefficient

77
Q

what determined water/oil solubility?

A

the extent of ionization of the molecule

78
Q

Oral Administration

A

advantages: safe; self-administered, economical, no needle related complications
disadvantages: slow and highly variable; subject to first pass metabolism; less predictable blood levels

79
Q

intravenous (IV)

A

advantages: most rapid; most accurate blood concentration
disadvantages: overdose danger; cannot be readily reversed; requires sterile needles and medical technique

80
Q

intramuscular (IM)

A

advantages: slow and even absorption
disadvantages: localized irritation at site of injection; needs sterile equiptment

81
Q

subcutaneous (SC)

A

advantages: slow and prolonged absorption
disadvantages: variable absorption depending on blood flow

82
Q

inhalation

A

advantages: large absorption surface; very rapid onset; no injection equipment needed
disadvantages: irritation of nasal passages; inhaled small particles may damage lungs

83
Q

topical

A

advantages: localized action and effects; easy to self-administer
disadvantages: may be absorbed into general ciculation

84
Q

transdermal

A

advantages: controlled and prolonged absorption
disadvantages: local irritation; useful for lipid-soluble drugs

85
Q

epidural

A

advantages: bypasses BBB; very rapid effect on CNS
disadvantages: not reversible; needs trained anesthesiologist; possible nerve damage

86
Q

ionized

A

charged molecules

87
Q

ionization depends on what?

A

the relative acidity/alkalinity (pH) of the solution and an intrinsic property of the molecule (pKa)

88
Q

how is acidity or alkalinity expressed?

A

pH–described on a scale of 1 to 14, with 7 being neutral. Acidic solutions have a lower pH and alkaline (basic) solutions have a pH greater than 7.0

89
Q

pKa of a drug

A

represents the pH of the aqueous solution in which that drug would be 50% ionized and 50% non-ionized.

90
Q

what happens to drugs that are weak acids?

A

they ionize more readily in an alkaline environment and become less ionized in acidic environment

91
Q

what happens to drugs that don’t ionize?

A

the lack of electrical charge makes the drug more lipid-soluble and hence readily absorbed from the stomach to the blood

92
Q

which increases the likelihood of absorption–the small intestine or the stomach?

A

small intestine

93
Q

how long does a drug take to be carried throughout the body?

A

1 to 2 minutes

94
Q

where are high concentrations of drugs found?

A

heart, brain, kidneys, and liver

95
Q

cerebrospinal fluid (CSF)

A

clear, colorless liquid that fills the subarachnoid space that surrounds the entire bulk of the brain and spinal cord and also fills the hollow spaces (ventricles) and their interconnecting channels (aqueducts), as well as the centrally located cavity that runs longitudinally through the length of the spinal cord (central canal)

96
Q

how is CSF manufactured?

A

by cells of the choroid plexus, which line the ventricles

97
Q

what makes up typical capillaries?

A

endothelial cells that have small gaps and larger openings through which molecules can pass

98
Q

intercellular clefts

A

small gaps

99
Q

fenestrations

A

larger openings

100
Q

pinocytotic vesicles

A

part of general capillaries; envelop and transport larger molecules through the capillary wall

101
Q

brain capillaries

A

the intercellular clefts are closed because adjoining edges of the endothelial cells are fused, forming tight junctions. Fenestrations are absent and pinocytotic vesicles are rare

102
Q

what surrounds brain capillaries?

A

astrocyctes—glial feet; by filling the extracellular space around capillaries, these astrocytic glial feel help maintain tight junctions

103
Q

BBB

A

is selectively permeable; does not impede lipid soluble molecules

104
Q

area postrema

A

chemical trigger zone; located in the medulla; vomiting center that causes vomiting when toxic substances are detected in the blood

105
Q

median eminence

A

in the hypothalamus; allows neurohormones manufactured by the hypothalamus to move into the blood traveling to the pituitary gland, which regulate anterior pituitary hrmone secretion

106
Q

placental barrier

A

connects the fetus with the mother’s uterine wall; means by which nutrients obtained from digestion of food, O2, fetal waste products, and drugs are exchanged; lipid-soluble substances diffuse easily and water-soluble pass less easily

107
Q

teratogens

A

agents that induce developmental abnormalities in the fetus

108
Q

examples of teratogens

A

x rays; drugs; maternal infections

109
Q

when is a developing fetus most at risk?

A

each organ system is maximally sensitive to damaging effects during its time of cell differentiation

110
Q

drug deports

A

plasma protein, muscle, fat—drug binding that occurs at inactive sites where no measurable biological effect is initiated

111
Q

is depot binding reversible?

A

yes– the drug remains bound until the blood level drops, causing it to unbind gradually and circulate in the plasma

112
Q

what does depot binding do?

A

has effects on the magnitude and duration of drug binding; reduces the concentration of drug at its site of action; delays the onset of action

113
Q

what can happen because depot binding is nonselective?

A

many drugs with similar physiochemical characteristics compete with each other for these sites. May lead to much higher than expected free drug blood level of the displaced drug, producing an overdose

114
Q

can bound drugs be altered by the liver?

A

no–this prolongs the time that the drug stays in the body

115
Q

how are drugs eliminated from the body?

A

biotransformation (metabolism) and excretion of metabolites that have been formed

116
Q

first order kinetics

A

drug clearance usually occurs exponentially

117
Q

exponential drug elimination

A

a constant fraction (50%) of free drug in the blood removed during each time interval

118
Q

half life

A

the amount of time required for removal of 50% of the drug in blood

119
Q

high binding individuals

A

less free drug so people seem to need higher doses

120
Q

low binding individuals

A

more free drug, so people are more sensitive to the drug

121
Q

goal of a drug regime

A

maintain plasma concentration of the drug at a constant desired level for a therapeutic period

122
Q

steady state plasma

A

the desired blood concentration of drug achieved when the absorption/distribution phase is equal to the metabolism/ excretion phase

123
Q

how long does it take to get to the stead state plasma stage?

A

period of time equal to 5 half-lives

124
Q

zero-order kinetics

A

the drug molecules are cleared at a constant rate regardless of drug concentration

125
Q

biotransformation

A

AKA drug metabolism; chemical changes, most of which happen in the liver

126
Q

how many types of biotransformations are there?

A

2

127
Q

type I (phase I) biotransformations

A

involve nonsynthetic modification of the drug molecule by oxidation, reduction, or hydrolysis.

128
Q

oxidation

A

produces a metabolite that is less lipid soluble and less active, but may produce a metabolite with equal or even greater activity than the parent drug

129
Q

Type II (phase II) biotransformations

A

synthetic reactions that require the combination of the drug with some small molecule such as glucuronide, sulfate, or methyl groups

130
Q

summary of two phases of drug biotransformation

A

produce one or more inactive metabolites, which are water soluble, so they can be excreted more readily than the parent drug. Metabolites formed in the liver are returned to the circulation and are subsequently filtered out by the kidneys, or they may be excreted into bile and eliminated with the feces. Metabolites that are active return to the circulation and may have additional action on target tissues before they are further metabolized into inactive products

131
Q

microsomal enzymes

A

liver enzymes primarily resposible for metabolizing psychoactive drugs, which are located in the smooth endoplasmic reticulum

132
Q

endoplasmic reticulum

A

network of tubules within the liver cell cytoplasm

133
Q

are microsomal enzymes specific?

A

no–they can metabolize a wide variety of xenobiotics

134
Q

xenobiotics

A

chemicals that are foreign to the living organism

135
Q

cycochrome P450 (CYP450)

A

enzyme family responsible for oxidizing most psychoactive drugs, including antidepressants; located in the intestine, kidney, lungs, liver, nasal passages

136
Q

factors that modify biotransformation

A
  1. enzyme induction
  2. enzyme inhibition
  3. drug competition
  4. individual differences in age, gender, genetics
137
Q

enzyme induction

A

when psychoactive drugs are used repeatedly they cause an increase in a particular liver enzyme and can increase the rate of metabolism of all other drugs modified by the same enzyme

138
Q

do enzyme levels ever return to normal after enzyme induction?

A

yes when a drug is terminated there is a gradual return to normal levels of metabolism

139
Q

tolerance

A

some drugs lose their effectiveness with repeated use; may be due to changes in drug metabolism and elimination

140
Q

cross tolerance

A

changes in metabolism and elimination also cause a reduced effect of other drugs

141
Q

enzyme inhibition

A

some drugs directly inhibit the action of enzymes; this reduces the metabolism of other drugs taken at the same time that are metabolized by the same enzyme

142
Q

MAOIs

A

prevent the destruction of certain neurotransmitters by the enzyme monoamine oxidase (MAO); also found in the liver

143
Q

drug competition

A

type of inhibition; occurs for drugs that share a metabolic system

144
Q

genetic polymorphisms

A

genetic variations among individuals that produce multiple forms of a given protein

145
Q

percentage of ethnicities that are slow inactivators

A

44-55% of caucasians and AA
60% europeans
10% asians
5% eskimos

146
Q

ways a drug can be eliminated

A

breath, sweat, saliva, feces, breast milk. urine

147
Q

What is the primary organ for elimination?

A

kidneys

148
Q

process of elimination through urine

A

liver biotransformation of drugs into ionized (water soluble) molecules traps the metabolites in the kidney tubules, so they can be excreted with waste products in the urine.

149
Q

can drugs be reabsorbed after they are broken down by the kidneys?

A

reabsorption from the tubules is pH dependent; if the urine is acidic, the weakly acidic drug will be less ionized and more easily reabsorbed; thus excretion will be less

150
Q

drug disposition tolerance AKA metabolic tolerance

A

occurs when repeated use of a drug reduces the amount of that drug that is available at the target tissue; typically occurs when drugs increase their own rate of metabolism. microsomal enzyme induction –> increased metabolic capacity. All drugs metabolized by the induced enzyme family will show a reduced effect

151
Q

pharmacodynamic tolerance

A

occurs when changes in nerve cell function compensate for continued presence of the drug

152
Q

compensatory up regulation

A

increased receptor number

153
Q

behavioral tolerance (context-specific tolerance)

A

seen when tolerance occurs in the same environment in which the drug was administered, but tolerance is not apparent or is much reduced in a novel environment

154
Q

what does Pavlovian (classical) conditioning play an important role in?

A

drug use and tolerance

155
Q

How drugs become conditioned stimuli

A

psychoactive drugs elicit reflexive effects such as cortical arousal, elevated blood pressure, or euphoria, they can act as unconditioned stimuli, an the drug-taking procedure or stimuli in the environment may become conditioned stimuli that elicit a conditioned response even before the drug is administered

156
Q

what is tolerance due to?

A

learning of an association between the effects of a given drug and the environmental cues that reliably precede the drug effects

157
Q

operant conditioning and rats on a moving belt

A

improved performance over repeated administrations could be identified as a type of tolerance–> learning a new skill

158
Q

state dependent learning

A

tasked learned in the presence of a psychoactive drug may subsequently be performed better in the drugged state than in the nondrugged state

159
Q

explanation for state dependent learning

A

drug effect may become part of the environmental “set;” it may assume the properties of a stimulus itself

160
Q

sensitization (reverse tolerance)

A

enhancement of a particular drug effects after repeated administration of the same dose of drug

161
Q

examples of drugs that induce sensitization and tolerance

A

cocaine and amphetamine

162
Q

what is important in determining sensitization

A

dose dependent and interval between treatments; conditioning

163
Q

pharmacogenetics

A

study of the genetic basis for variability in drug response among individuals. GOAL: identify genetic factors that confer susceptibility to specific side effects or predict good or poor therapeutic response

164
Q

what genetic variability is especially important for neuropsychopharmacology?

A

genetic polymorphisms of the cytochrome P450 enzyme; this is responsible for metabolizing drugs

165
Q

long versus short gene for seratonin

A

long: better response to treatment and are more likely to show remission

Behavioral Pharmacology (11 decks)

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