Exam 2 Flashcards
(156 cards)
1
Q
what is the liver the main site for?
A
site of metabolism of nutrients (phase 1&2 of biotransformation)
-DETOXIFICTATION
-1st pass metabolism occurs here
2
Q
what does 1st pass metabolism occur through in the liver?
A
through hepatic portal vein
-GI –> Liver
3
Q
what type of enzymes does the liver contain to help maintain homeostasis?
A
microsomal enzymes
4
Q
what do microsomal enzymes do?
A
-all-purpose binding sites (can bind several molecules in binding sites, not specific)
5
Q
what family are the microsomal enzymes in the liver apart of?
A
cytochrome 450 super family
-over 50 different types
6
Q
what does the cytochrome 450 family do?
A
oxidized psychoactive drugs in phase 1 of biotransformation
-antidepressants, morphine
7
Q
what is enzyme induction?
A
creation of MORE enzymes to reestablish homeostasis
-with repeated use, it increases enzyme synthesis
-can be effected by diet
8
Q
what type of food can create enzyme induction?
A
brussel sprouts
9
Q
what is enzyme inhibition?
A
things that LESSEN the effectiveness of the enzyme
-decrease metabolism
-creates more ‘free’ drug
-can be effected by diet
10
Q
what type of food can create enzyme inhibition?
A
grapefruit
11
Q
which can contribute to tolerance, enzyme inhibition or enzyme induction?
A
enzyme induction
12
Q
what is drug competition?
A
multiple drugs ‘fight’ for same sites and increase drug effects
-more ‘free’ drug
13
Q
what do the kidneys do?
A
filters blood and removes toxins as urine (pH 4.5 - 7.5)
14
Q
what is required for biotransformation and ion-trapping to occur in the kidneys?
A
ionization
15
Q
what does the Koryak tribesman w/ Amanita muscaria mushroom proove?
A
proves that you can feel the effects of the drug a second time after being excreted as urine
16
Q
how can ‘free’ drug stop someone from smoking?
A
when the compounds aren’t ionized (can be done through diet), the nicotine keeps circulating as the ‘free’ drug
-you don’t feel the effects but the drug is still circulating, lessening the cravings
-stress can stop the ‘free’ drug from being free and increase cravings
17
Q
what does ADH (antiduretic hormone) do and what is a common every-day example with ADH?
A
inhibits excretion of water
-alc and caffeine INHIBIT ADH causing you to pee more and become dehydrated
18
Q
how else can a drug be excreted besides through the kidneys?
A
-lungs (breathing alc)
-breast milk (acidic so it ion traps alkaloids)
-skin
-salvia
-bile in feces
19
Q
what is the general relationship between dose and effects?
A
increasing dose, increases effects
-only to a max, then it decrease due to toxicity
-deals with pharmacodynamics (drug interaction w/ target)
20
Q
what are 3 common factors that can impact the dose and effect relationship?
A
size/weight
pharmacokinetics
pharmacodynamics
21
Q
how does pharmacokinetics impact the dose and effect relationship?
A
-protein binding
-cyt 450 differences
-acetylation in phase 2 (rats > humans > dogs)
-conjugation in phase 2 (humans > cats)
22
Q
how does pharmacodynamics impact the does and effect relationship?
A
-NT and receptor distributions vary
23
Q
how does weight impact the dose and effect relationship?
A
-amount of drug per body weight (mg/kg)
-how much it takes to achieve equal blood conc/
24
Q
what does an effective dose produce?
A
produces a biological response
25
what is threshold in dose?
minimum biological response
26
what are the two types of group-dose relationship curves?
-% of pop. responding
-response magnitude
27
when graphing side effects, are they all together on the same curve?
no, each side effect has its own curve
28
which is greater, % of population affected or threshold response?
% population affected
29
what is the response magnitude?
the mean % of max response
30
what is the symbol for effective dose?
EDn
n=% of pop. with effective dose
31
what is the symbol for lethal dose?
LDn
n=% of pop.with lethal dose
32
what is potency?
measured amount needed to produce a certain response
-relative term
-Drug A has the same effect as Drug B but at a lower dose
33
what happens when more of drug is added after max response?
no increase of effects
-might create more side effects
34
what curve would have a higher potency?
lower drug dose with a lower % responding
35
what curve would have greater max efficacy?
higher % responding at a high dose
36
what does the dose-response curve look at?
represent mean for a group
37
what is standard error?
gives an idea of response range for magnitude of response curve
-PROBABILITY not exactness
38
what is the therapeutic index?
effect of dose and % of population responding
-margin of safety
39
what is the equation for therapeutic index?
LD50 / ED50
40
should a big or small number be calculated when the drug is safe when using the therapeutic index?
big number
~100
41
when graphing therapeutic index, do you want the LD and ED lines close together or far apart?
far apart
-you want LD (lethality) to occur at much higher dose
42
what does the slope tell you?
how big the change in effects are when you increase dose
43
what does a steep slope tell you?
large y-axis (R) change
44
what is the type of single drug interaction?
cumulative effects
45
what are the types of multiple drug (2+) interactions?
additive
physiological antagonism
potentiation
46
what is a cumulative single drug interaction?
repeated administration before drug is completely eliminated
-increase of drug in blood conc.
-half life is very relevant
-subjective effects
47
what are subjective effects?
effect goes away but drug is still high in blood conc.
48
what are additive effects?
two different drugs with same effect
-add effects of drugs together
49
what category of drugs are commonly associated with additive effects?
CNS depressants
50
what is physiological antagonism?
two different drugs with opposing effects
51
what is a common example of physiological antagonism?
alc and caffeine
52
what is potentiation in multiple drug interactions?
synergistic (the whole is more than the sum of its parts)
-bigger than additive effects
-hepatoxicity
53
what is hepatoxicity?
nontoxic + toxic = very toxic
toxic + toxic = super duper toxic
54
what causes potentiation in multiple drug interactions?
due to a change in metabolism (biotransformation) or depot binding
55
what is tolerance?
repeated use of same dose of drug (chronic use) decreases the response
-compensatory and homeostatic responses
56
what is metabolic tolerance (drug disposition)?
enzyme induction: more enzyme produced to break down drug
-creates a smaller response
57
what is pharmacodynamic tolerance (neuronal)?
modifications of NT or the NT receptor
-decreases NT synthesis and down-regulates receptors
58
what is behavioral tolerance (associative)?
Pavlovian (classical) conditioning
-conditioned compensatory responses
59
what is acute tolerance (tachyphylaxis)?
occurs b/w 1st and 2nd dose (first nic hit is better than 2nd hit)
-rapid and transient (brief)
-due to NT depletion and the receptors being occupied
60
what is cross tolerance?
tolerance to drugs that work by the same mechanism
61
what category of drugs is tolerance associated with?
depressants
62
what is sensitization?
increase response to same dose of drug
-opposite of tolerance
63
cocaine and amphetamine in sensitization
increase motor activation, reward/motivation
64
what is sensitization NOT explained by?
homeostasis
65
what are nonspecific drug factors?
things that influence drug effects based on individual differences other than drug action
66
what are the four classes nonspecific drug factors?
organism
environment
psychological
task (rate-dependent effects)
67
what are nonspecific factors based on organisms?
weight, sex, age, disease, nutrition, biological rhythms, hormonal states, intraspecies differences, interspecies differences
68
what is a synapse and what are the two types?
communication b/w neurons
-electrical and chemical
69
what are the four types of chemical synapse and what are they?
ligand/receptor
axodendritic: b/w axon terminal and dendrite
axosomatic: axon directly on soma
axoaxonic: involves a third neuron
70
what are the six parts to the synaptic transmission model?
precursor transport
NT synthesis
storage
release
activation
termination
71
what happens at precursor transport?
-NT is loaded into axon terminal
-peptide NT at soma
72
what drives precursor transport?
active transport
73
what happens during NT synthesis?
enzymes and cofactors are loaded into axon terminal
-peptide still at soma
-NT still at axon terminal
74
what are enzymes?
protein that catalyzes a rxn
75
what are cofactors?
donate a portion of itself to the process and becomes apart of NT
76
during storage, where are the molecules stored in and how are they loaded?
stored in synaptic vesicles and loaded by active transport
77
what are the molecules in the synaptic vesicles?
NT, nucleotides (ATP, GTP), and Ca2+
78
what are the synaptic vesicles made out of?
the same lipid bilayer as the cell membrane
79
what are the membrane proteins of synaptic vesicles?
transporter proteins, docking proteins, and ATPase
80
what molecules does a cholinergic vesicle contain?
ATP, GTP, acetylcholine, and Ca2+
81
what process occurs during release?
exocytosis
82
what initiates exocytosis?
action potential
83
how are the reserve pools anchored?
anchored to axon terminal by synapsin-actin linking
84
what is the step by step of release?
-vesicle next to synapse
-action potential reaches vesicle
-Ca2+ INFLUX occurs
-Ca2+ opens voltage-gated channels
-Ca2+ binds to calmodulin
-this activates CaMK2
-CaMK2 phosphorylates synapsin
-synapsin dissociates from vesicle
-vesicles are now free floating and diffuse toward synaptic membrane
85
what fuses the vesicles to the postsynaptic membrane?
SNAPs/NSF
SNARES
Synaptotagmin
86
what do SNAPs and NSF do?
prime for fusion and make sure everything is ready
87
what are the types of SNAPs and NSFs?
SNAPS: alpha, beta, gamma
NSF: ATPase
88
what do SNAREs do?
it is the SNAP receptor that pulls membranes together and intertwines
89
type of vesicle and membrane SNARE?
vesicle: synaptobrevin
membrane: syntaxin, SNAP-25 (not a SNAP)
90
what does synaptotagmin do?
binds Ca2+ and fuses it all together?
91
what are the steps of release when the vesicle fuses with membrane?
-SNAPs/NSF ensure the membrane is ready
-vesicle docks
-SNAREs pull membranes together and intertwine
-Ca2+ binds to synaptotagmin
-Ca bound synaptotagmin fuses with membrane by binding to SNAREs and plasma membrane
92
what occurs at activation?
-NT binds to receptor by diffusing from high conc/ to low con.
-binding changes the conformation of the receptor which changes the post synaptic cell (open/close channel, activate 2d messenger)
93
what are the two types of receptors that a NT binds to a the post synaptic cell?
ionotropic
metatropic
94
what are ionotropic receptors?
channel and binding sites are integrated in same protein
-changes EPSP or IPSP
-rapid desensitization
-acute tolerance (tachyphylaxis)
95
what are metabotropic receptors?
channel and binding sties are in different proteins
-G protein-coupled receptors
-requires GTP
-has neuromodulation (after the NT isn’t binding, it makes adjustments over time)
96
which receptor, ionotropic or metabotropic, is fast and transient (brief)?
ionotropic receptors
97
what are the four ways of termination?
diffusion
enzymatic degradation
reuptake
autoreceptors
98
what is diffusion termination?
-ligand and receptor are bound for temporary amount of time
-receptor becomes inactive and can associate with other ligands
99
what is enzymatic degradation?
cuts up NT so it can't fit in binding sites
100
what is reuptake termination?
-metabolic pumps pump NT back into axon terminal to possibly go back to a vesicles or a glial cell
-if it enters a glial cell (astrocyte) it degrades the NT to be recycled
101
what is autoreceptor termination?
binds same NT they release on the presynaptic cell
-different receptor type and affinity though
102
what are the two types of autoreceptors?
terminal autoreceptor
somatodendritic autoreceptor
103
what is a terminal autoreceptor?
on the presynaptic terminal
-decrease depolarization by manipulating Ca and K channels
-creates an EFFLUX of K+
-decreases NT release
104
what is a somatodendritic autoreceptor?
decreases action potential rate
-decreases NT release
105
for termination to occur, you must have a ___ signal
discrete
106
what happens if channels are continually open during termination?
the ions are at equilibrium
-membrane is no longer polarized and no EPSP/IPSP
107
what does a depolarization block do?
disrupts neural communication and makes the synapse nonfunctional
108
what are heteroreceptors and which type of synapse are they found in?
involving a third neuron
-in axoaxonic synapses
109
what two functions can axoaxonic synapses do?
presynaptic facilitation
presynaptic inhibition
110
what is presynaptic facilitation?
keeps membrane depolarized
-decreases K+ efflux so the K+ molecules can't escape
-axon terminal stays depolarized and Ca2+ channels open
-increasing NT release
111
what is presynaptic inhibition?
-increases K+ efflux
-Ca2+ channels close due to Ca2+ influx
-decreasing NT release
112
what is a binding site?
ligand and receptor interaction
113
what is affinity?
attraction and ability to bind receptor
-physically and electrically
114
what is efficacy?
ability to activate receptor and initiate a biological action
115
drugs can ___ or ___ a NT message
mimic, block
116
what is direct action?
what happens at NT postsynaptic receptor
117
what is indirect action?
what happens at sites other than the NT binding site
118
what is an agonist?
mimics or increases NT effects
-AFFINITY and EFFICACY (binds receptor and activates)
119
what is an antagonist (ANT)?
blocks or decreases NT effects
-only AFFINITY (only binds to receptor)
120
what is a direct agonst?
binds to NT receptor and activates it
121
what is a direct antagonist?
binds to same NT site and takes up a spot so an agonist can't bind
-does not activate receptor
122
what is an indirect agonist/antagonist?
affects NT metabolism, storage, release, reuptake, etc.
123
what is a competitive antagonist?
competes for same site and whoever gets their first gets to bind
-decreases potency
-takes more drug to produce same effect
124
what is a noncompetitive antagonist?
binding occurs at a different site on the receptor (allosteric binding)
-disturbs membrane or other intracellular effects
-example of indirect antagonists
125
what does noncompetitve antagonist affect on a curve?
the max. response produced
126
what is allosteric interactions?
binds at a different site but on same receptor
-potentiation opens the channel more
127
what is a partial agonist?
channel opens part way producing a weaker NT effect
-still activates receptor
128
what is an inverse agonist?
creates opposite effect of NT and completely closes channel
-still activates receptor
129
what is activated when a ligand binds a receptor?
activates EPSP / IPSP or a 2nd messenger
130
can the same NT bind a physically different receptor?
yes!
-it has multiple it can bind to
-it binds on a different part of the NT
-it still is specific for certain ones though
131
what determines how well the receptor can be activated?
the physical fit
132
which form is more active, levo or dextro?
LEVO (left)
133
what is affected when you change the structure of the drug?
affinity, potency, and which receptors it can bind to
134
why can drugs have multiple effects?
it can bind to a variety of receptors
135
what does SSRI stand for?
selective serotonin reuptake inhibitor
136
what does more plus signs mean when talking about a drug and its SSRI ability?
the more active and stronger affinity
137
what are G-proteins?
G-proteins are a transducer
138
what are the two types of G-proteins and what do they do?
Gs: activate/increase activity
Gi: inhibit/decrease activity
139
what are G protein-gated ion channels?
receptor is separate from the effector and indirectly controls the channel
140
what is the speed of G protein-gated ion channels?
relatively fast
-slower than ionotropic though
141
what are 2nd messenger systems?
-effects are slow but long lasting
-converts molecule to make the 2nd messenger (extracellular signal)
142
what is the 1st messenger?
NT
-external signal
143
what are the membrane associated proteins/components?
-receptor proteins
-transducer (transfers)
-primary effector
144
what is an example of an intracellular messenger?
2d messenger
-communicates with a protein kinase or another effector (secondary effector)
145
what are the 2d messengers?
cyclic nucleotides
phosphoinositol
Ca2+ (CaMK)
146
what are the cyclic nucleotides and what is their secondary effector?
cAMP -> PKA
cGMP -> PKG
147
what are the phosphoinositol 2d messengers and what is their secondary effector?
DAG and IP3 -> PKC
-increases Ca2+ inside the cell
148
what is the beta-adrenergic transducer?
G2
149
what is the beta-adrenergic primary effector?
increase of adenylyl cyclase
150
what is the secondary messenger and secondary effector of beta-adrenergic receptor?
increase of cAMP -> increase of PKA
151
what is the transducer of the D2 receptor?
Gi
152
what is the primary effector of the D2 receptor?
decrease of adenylyl cyclase
153
what is the secondary messenger and secondary effector of the D2 receptor?
decrease cAMP -> decrease of PKA
154
what do protein kinases do?
phosphorylates
155
what do protein phosphatases do?
dephosphorylates
156
how does the cell modulate gene expression?
through transcriptional factors
-can increase or decrease transcription
