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Psychopharmacology > Exam 1: Kinetics > Flashcards

Exam 1: Kinetics Flashcards

1
Q

The scientific study of drugs and their effects on a living organism

A

Pharamcology

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2
Q

Neuropharmacology

A

concerned with drug-induced changes in cell functioning in NS

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3
Q

Psychopharmacology

A

emphasizes drug-induced changes in mood, thinking, and behavior

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4
Q

What is the goal of neuropsychopharamacology?

A

identify chemical substances that act on NS to alter behavior. Neurobiology of behavior

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5
Q

Drug ACTION

A

Specific molecular changes produced by a drug when it binds to particular target site/receptor

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6
Q

Drug EFFECTS

A

widespread alterations in physiological/psychological function caused by drug action

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7
Q

Drug-receptor interaction:

1) Favorable effects
2) other effects

A

1) therapeutic effects

2) side effects

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8
Q

Specific drug effects

A

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

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9
Q

Nonspecific drug effect

A

those based NOT on chemical DR but on unique characteristics of the individual

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10
Q

Opposite of placebo effect

A

Nocebo

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11
Q

Pharmacokinetics

A

Body –> Drug

1) Administration
2) Absorption
3) Distribution
4) Biotransfomration/Inactivation
5) Elimination

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12
Q

Pharmacodynamics

A

Drug –> Body

Binding and Action

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13
Q

Bioavailability

A

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

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14
Q

Depot binding

A

drug binds to plasma proteins (IM)

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15
Q

Absorption

A

movement of drug from site of administration to the blood circulation

Absorption = BLOOD CIRCULATION

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16
Q

Agnoist

A

acts like NT (dynamics)

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17
Q

Antagonist

A

blocks NT (dynamics)

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18
Q

Alimentary Canal

A

Mouth down

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19
Q

GI enteral tract (gut)

A

Stomach and intestines.

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20
Q

Eteral administration

A

Stomach/intestine
GI tract/alimentary canal
e.i. oral/rectal

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21
Q

Parenteral administartion

A

all non enteral routes

e.i. topical injection pulmonary

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22
Q

1st pass metbolism

A

portal vein –> liver, reduces drug bioavailability

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23
Q

Bioavailbility

A

[drug] in blood that can interact with targets, determined by kinetics

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24
Q

Drugs that effect thinking mood and behavior

A

Psychoactive drugs

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25
Q

Absorption depends on

A

administration route, absorbing surface, cell layers, drug destroyed by metabolism, solubility/ionization, etc.

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26
Q

Solubility of drugs and absorption

A

lipid soluble = passive diffusion across membrane

greater concentration gradient = rapid

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27
Q

Prodrugs (e.i. Heroin)

A

drug dependent on metabolism to convert inactive drug to active one (BIOACTIVATION)

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28
Q

Properties of drug that allow GI absorption

A

survive gastric enviornment, resist 1st pass, WS, LS

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29
Q

What contribute to gastric degradation of proteins, peptides and drugs

A

Chemical: HCl + Pepsin –> gastric juice

Mechanical: muscle contractions (Peristasis)

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30
Q

Hepatic 1st pass metabolism

A

Intestine –> portal vein –> liver –> hepatic vein –> circulation –> hepatic artery

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31
Q

Ionization depends on

A

pH and pKa

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32
Q

acidity/alkalinity of environment

A

pH

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33
Q

pKa

A

pH of aqueous solution in which drug would be 50% ionized, 50% unionized

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34
Q

Although acid favors stomach, why more in by small intestine?

A

absorption also determined by length of time in contact with absorptive membrane

Larger surface area/slower movement

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35
Q

What drugs can’t be GI tract?

A

highly charged drugs in both acid/basic environments

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36
Q

Absorption rating limiting factor

A

rate at which stomach empties into intestine

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37
Q

GI tract is ___ formed by ___

A

sealed tube formed by Epithelial cells

intracellular space ~4 A
cells tight against each other
hard for drug to leave
Lumen –> Capillaries

Simple columar

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38
Q

Ionized

A

no diffusion water shell

water soluble

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39
Q

Passive/Facilitated rate of diffusion depends on

A

concentration gradient

high = higher rate of diffusion

Passive - lipids, NP
Facilitated - fructose/vitamins

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40
Q

Active transport

A

need energy
[low]> [high]
e.i. glucose, mineral ions, amino acids

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41
Q

Unionized =

A

GI absorption and diffusion

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42
Q

Weak Acid + H+

A

Unionized (LS), absorption

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43
Q

Weak Base + H+

A

Ionized (WS), no absorption

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44
Q

Weak acids best absorbed at

A

Low pH

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45
Q

Weak bases best absorbed at

A

High pH

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46
Q

pH across GI tract

A

Gets higher (less H+)

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47
Q

Acid Ion Trapping

A

ionized after passing into area with higher pH and become trapped there (opposite of best absorption pH)

48
Q

Base Ion Trapping

A

Base ionized and trapped in low pH area

49
Q

_____ maintains higher [unionized molecules] in original compartment promoting faster absorption

A

ion trapping

50
Q

____ of base allows GI absorption

A

deprotonization

51
Q

Small intestine surface area is given by…

A

cylinder, folds, microvilli, villli

52
Q

Capillaries with intestinal villi

A

LS drugs move through lymph vesicle to Lacteal

53
Q

Small Intestine favored by both Weak acids/base becuase

A

surface area
less mucous
longer transit time
high pH for weak bases

54
Q

Distribution

A

moving through blood vessels

55
Q

Artery

A

Thick outer wall
small lumen
thick layer of muscles and elastic fibers

Heart –> Tissue
effects bp

56
Q

Vein

A

think layer of muscle/elastic fibers
Large lumen
thin outer wall

Blood –> heart, no as muscular

57
Q

Capillaries

A

very small lumen
wall is single layer

drug action

58
Q

Does movement from CAPILLARIES/blood to tissue depend on solubility? Why?

A

No, unless bound to protein

Capillaries have a lot of pores

59
Q

Drug redistribution

A

Drug moving from tissues with high vasculature (heart, brain, kidneys, liver) back to plasma to maintain equilibrium

60
Q

Typically Capillary

A

Intracellular - small gaps
Fenestration- larger openings
Pinocytotic vesicles

61
Q

Brain Capillary

A

tight junctions: endothelial cells fused
carrier-mediated transport

astrocytes/glia feet to maintain the barrier, maintain tight junctions.

62
Q

BBB is ___ permeable

A

selectively permeable

lets in lipid soluble
WS by carrier protein
Enzymes made by endothelial/astrocytes can degrade chemicals passing by membrane
Bidirectional

63
Q

Area postrema

A 
chemical trigger zone
BBB free
induces vomiting 
allows WS
works with oral ingestion
located in medulla

WIDE SPACING BETWEEN ENDOTHELIAL CELLS

64
Q

Capillaries have single layer of ___ cells

A

ENDOthelial

65
Q

Capillary structure: continuous

A

intracellular spaces, basement membrane

66
Q

Capillary structure; fenestraed

A

fenstrations, pores in body of cells

67
Q

Capillary: Sinusoid

A

Huge gaps in some capillaries

68
Q

Plasma Protein Binding (PPB)

A

reduces bioavailability/drug effect
induces side effects
extends time of drug in body.

69
Q

PPB: drug interactions

A

free up more due to competition

70
Q

PPB: liver dysfunction

A

increase bioavailability
pass 1st pass

reduces liver’s synthesis of proteins

71
Q

Storage depot binding

A

binding of drug to inactive site

Bone, fat, enamel
decrease bio-available/drug effect

bad effects:
lead/bone
thiopental/fat
tetracycline/enamel

72
Q

Functions of BBB

A

stable environment, prevents access of various chemicals, prevents access of many types of drugs

73
Q

BBB structure mainly determined by

A

tight junctions between endothelial cells

74
Q

BBB structure all parts

A

tight junctions
basement membrane- support
astrocytes release factors that anchor junctions

75
Q

Astrocyte jobs

A
  1. synthesize proteins that support tight junctions between endothelial cells
  2. uptake/degrade molecules that evade BBB
76
Q

Enzomatic barrier

A

glia cells degrade foreign stuff

77
Q

Transcytotic transport where drug and rector in vesicle to go across BBB is used by

A

Insulin/transferrin

78
Q

Biotransformation

A

Alteration in chemical structure of drug molecule by action of enzyme

Most common site: Liver

(also stomach, intestine, blood, kidney, brain)

79
Q

sinusoid

A

irregularly shaped liver blood vessel

allows things to access hepatocytes, large gaps

80
Q

Hepatocytes

A

Contain enzymes needed for drug biotransformation

Connected by tight gap junctions

81
Q

Enzymes

A

proteins with binding sites

reuseable
decrease energy needed for reaction
can break down/add stuff to molecules

82
Q

Phase 1

Nonsynthetic

A

Catabolic - tear things up
(oxidation, hydroxylation, dealkylation, deamination)

SUBTRACTIONS

83
Q

Phase 2

synthetic

A

Anabolic- build things up
(-COOH, -OCCH3, -CH3, -C6H10O7, methyl, amine, carboxyl, glucuronic acid, sulfhydryl)

CONJUGATIONS

84
Q

Cytochrome P450

A

phase 1
mixed function: oxidases

non-specific
inducible

85
Q

inducible

A

make more enzyme or increase affinity of enzyme

86
Q

Transferases

A

phase 12
transfer groups to drug molecule

specific
inducible

87
Q

Do drugs have to go through both phase 1 and 2 or in that order?

A

no

88
Q

Metabolism of Aspirin

A

Phase 1: hydrolysis CP450

Salicyclic Acid (active form)

P2: glucuronic acid transferase

Ether glucuronide
Ester glucuronide

89
Q

_______ is the most common type of P2 conjugation, catalyzed by transferase enzyme: ____

A

glucuronidation

UDPGT

90
Q

1/2 life

A

time for plasma [drug] decline by 50%

91
Q

First Order (exponential)

A

constant % drug removed each interval

Looks like curve

most common type
Rate of metabolism higher at higher plasma concentration of drug

at very high [drug], metabolism becomes zero order

92
Q

Zero Order

A

Constant AMOUNT of drug in blood removed each interval

Rare

e.i. aspirin, ethanol, phenytonin

Rate not effected by plasma [drug]

93
Q

Genetic copies cyto450

A

0 (PM)/ 1 (IM): adverse response, overreaction

2(EM): good

3+ (UM): too many enzyme, don’t respond to medication

94
Q

Factors affecting biotransformation

A 
genetic variation
age
sex
species
illness 
drug history
95
Q

What does excretion

A

kidney

96
Q

Ureter

A

connects kidney to bladder

97
Q

Nephron

A

1.5 million/kidney
functional unit of kidney with renal corpuscle/tubule

H2O leaves descending loop
Na+Cl- leaves ascending limb

98
Q

Renal tubuae

A

in kidney

moves out, gets ride of stuff

99
Q

GLomerulus

A

fist of capillaries in kidney

100
Q

How do water/solutes enter kidney tubules?

A

Bowman’s capsule, surrounds glomerulus

101
Q

_____ too large to enter kidney

A

blood cells/plasma proteins

102
Q

Most drugs that are LS when in kidney are

A

reabsorbed by blood

103
Q

Epithelial Cells:

GI tract vs. Renal Tube

A

GI: simple columner
Renal: simple cuboidal

104
Q

Drug excretion: _______ are excreted in urine, _____ reabsorbed by blood.

A

Unionized (LS) reabsorbed

Ionized (WS) excreted urine

105
Q

Acids excreted faster

A

high pH, ionized

106
Q

Bases excreted faster

A

low pH, ionized

107
Q

pH of kidney tubules

A

4-8 and varies

108
Q

Factors affecting elimination by kidneys

A

acid/base
pKa
pH tubules

109
Q

Anti-Diuretic Hormone (ADH)

A 
Peptide 
synthesized by hypothalamus
stored in posterior pituitary 
facilitates water re-absorption
increases aquaporins at collecting tubules

Increases permeability of luminal membrane to H2O by inserting water channels

increases bp
regulates distal duct in nephron

110
Q

Aldosterone (steroid hormone)

A

Synthesized/release by adrenal gland
acts on collecting tube
facilitates Na+ re-absorption

111
Q

Diuretics that increase urine output: ethanol/caffine

A

Ethanol: inhibit ADH, more fluid out

Caffeine: increase glomerular blood flow rate

112
Q

Steady State Plasma level determined by

A

Half-life

the desired blood [drug] achieved when absorption/distribution = metabolism/excretion phase.

113
Q

microsomal enzymes

A

liver enzyme that metabolize psychoactive drugs

located on smooth ER

lack specificity, metabolize variety of things

ex: CYP450

114
Q

Enzyme induction

A

repeated drug uses causes increase in liver enzyme

speeds up biotransformation of this drug and toerhs

115
Q

Enzyme inhibition

A

repeated drug use causes decrease in liver enzymes, reduces metabolism of drugs metabolized by that enzyme

Psychopharmacology (16 decks)

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