Pharmacology MT Flashcards
(176 cards)
1
Q
Pharmacology is the study of ______ that interact with ______ through ________ process
A
Pharmacology is the study of substances that interact with living systems through chemical process
2
Q
define medical pharmacology
A
the study of substances used to prevent, diagnose and treat disease
3
Q
_______ is the study of undesirable effects of chemicals on living systems & ecosystems
A
toxicology
4
Q
medical pharmacology studies _____ where as toxicology studies _____`
A
efficacy; side effects
5
Q
Drug –> body is studied via __________
A
pharmacodynamics
6
Q
body –> drug is studied via _________
A
pharmacokinetics
7
Q
________ is the science of drug preparattion. and medical use of drugs in roman times (after 2500 BC)
A
materia medica
8
Q
Francois Magendie & Claude Bernard are known for ..
A
developing methods of experimental physiology and pharmacology
9
Q
The relation of an individuals genetic makeup to their response tot specific drugs is called _________
A
pharmacogenetics
10
Q
What are 3 advances from the field of pharmacogenetics?
A
- understanding that certain diseases are inherited
- genomes of humans, animals and plants have been decoded - options for new research and treatment
- genetic techniques - gene therapy, KO mice
11
Q
A new drug compound requires the discovery of a new ___________ (i.e the pathophysiological process or substrate of a disease condition)
A
new drug target
12
Q
What occurs in in vitro studies and how long does it typically take?
A
Biological products and/or chemical synthesis, optimization (enzymes etc.) combine to form a lead compound.
~ 2 yrs
13
Q
What is evaluated during animal testing? What occurs directly after?
A
Animal testing is the best model of disease for evaluating efficacy, selectivity and mechanism
- directly after: submit to a regulatory body = investigational new drug
~ 2 yrs
14
Q
What does phase 1 of clinical testing evaluate? how many subjects?
A
Is it safe? Pharmacokinetics
20-100 subjects
15
Q
What does phase 2 of clinical testing evaluate? how many subjects?
A
Does it work in patients w/ disease?
100-200 pt.
16
Q
What does phase 3 of clinical testing evaluate? how many subjects?
A
does it work, double blind? (need significant effect)
randomized control trial
1000-6000 pt.
17
Q
the clinical testing phase of drug development takes _- _ years
A
3-4 years
18
Q
______ is an activator of biochemical pathway that mimics endogenous signalling
A
agonist
19
Q
_________ stabilize receptors in an inactive form by shutting down constituent receptor
A
inverse agonist
20
Q
______ inhibits a biological pathway by blocking endogenous signalling.
A
antagonist
21
Q
_______ antagonist compound loosely binds to the same site as the natural ligand and inhibits natural action of ligand
A
competitive
22
Q
_______ antagonist compound binds to _______ on the receptor and inhibits function
A
noncompetitive
23
Q
_______ antagonist causes covalent modification of receptor
A
irreversible
24
Q
Agonists and Antagonists require ___________ to induce change
A
target molecule (receptor)
25
a partial agonist increases ______ (compared to normal) but decreases ______ (compared to full agonist)
effect; effect size
26
Most rapid onset is the characteristic of ______ route drugs
IV
27
- large volumes often feasible
- may be painful
- used for when you cant take meds on daily basis describes which drug route
intramuscular
28
Smaller volumes than IM - may be painful is the characteristic of ______ route drugs
Subcutaneous (SC)
29
most convenient route with a significant first past effect is the characteristic of ______ route drugs
Oral (PO)
30
Less first pass effect than PO is the characteristic of ______ route drugs
Parenteral Rectal (PR)
31
Often very rapid onset (2nd to IV) is the characteristic of ______ route drugs
inhalation
32
Slow absorption used for lack of first pass effect and prolonged duration of action is the characteristic of ______ route drugs
Transdermal
33
The fact that drugs exist in the form of organic and inorganic compounds is important for _______
how the body handles the drug
34
Drug size is an important factor for ______
administration
35
rational drug design describes ...
design based on known structure of ligand & receptor
36
Allosteric Activator + Agonist = ______ response
max
37
Agonist + Competitive inhibitor = _____
Right shift - same max response but don't increase max effect
38
Agonist + Allosteric inhibitor = ______
decrease below the use of a competitive inhibitor
39
What occurs when an agonist binds to a receptor
electrostatic changes = conformational change of receptor
ex. GPCR opening ion channel
40
4 process that are involved in termination of drug action
1. dissociation of drug from receptor = terminate effect (ex. ionotropic receptor)
2. action persists after drug has dissociated (ex. GPCR, phosphorylation)
3. covalent bond - drug receptor complex must be destroyed and new receptors synthesized
4. desensitization mechanisms - receptor mineralization
41
How do receptors determine the drug dose/ conc. & the effect
dose/conc: receptor affinity for a drug
effect: total # of receptors
42
____ is the maximal response that can be produced by a drug
Emax
43
____ is he concentration of drug that produced 50% of maximal effect
EC50
44
What is the eqn for the effect observed at conc. C
45
Constitutive activity describes... and is inhibited by ______
...the fact that some receptors are active w/o being bound to endogenous ligands.. inhibited by inverse agonist
46
____ can be used to measure he potency between different drugs in a log scale
EC50 - the drug conc.(on x axis) which induces a 1/2 max effect (Emax) response
47
responses to low doses usually _____ in _____ proportion to dose. Response increment _______ as dose increases
increase ; direct ; diminish
48
How do we chose among drugs and determine appropriate dosing? (2)
• pharmacologic potency (position dose axis)
• maximal efficacy (end point on response axis)
49
the maximum effect is driven by .... and reduced by increasing the concentration of _____
..the total # of receptors activated ; antagonist
50
Low doses of antagonists affect the agonist concentration effect curve by _______ whereas high dose antagonists cause it to _______
shift to the right ; reduce max response and R shift
51
EC50 is the dose required for ______ to experience 50% ____ effect and is seen in ______
ED50 is the dose required for 50% __________ to obtain the ____ effect and is seen in ______
individual; max; lab tests
of the population; therapeutic; clinical effects
52
IC50 is the measure of the _______of a substance in inhibiting a ____________ by 50%
potency; specific biological or biochemical function
53
You want IC50 to be high when you want to see ____ activity whereas you want EC50 to be high when you want to see _____ activity
decreased; increased
54
if Kd is ___ binding affinity is ____
low; high
55
___ is the concentration (molar) of free drug at which 1/2 amt of possible receptors are bound bound
Kd
56
Kd is _______ (directly or inversely) related to binding affinity
inversely
57
EC50 is generally ____ (lower, higher) than Kd
lower - b/c some spare receptors
58
____ is the maximum number of receptors that can be bound
Bmax
59
spare receptors occur when (2)
1. drug dosent bind long but effect lasts (drug bouncing around to diff receptors)
2. # of available receptors > # of effector molecules `
60
____ is the median effective dose - at which 50% of individuals exhibit the specific effect
ED50
61
____ is the median lethal dose - at which 50% of individuals exhibit a toxic effect
TD50
62
________ relates dose of a drug required to produce a desired effect to that which produced an undesired effect
Theraputic index
63
Theraputic index equation
TI = TD50/ED50
64
A safe drug has a ____ theraputic index b/c need a _____ dose for toxic effects and a ____ dose to be effective (high, low)
high; high; low
65
What are the 4 kinds of transmembrane receptors and how do they work
1. transmembrane receptor protein - acts as an enzyme intracellular when ligand binds outside
2. Transmembrane receptor bound to enzymatic protein (tyrosine kinase)
3. ligand gated ion channel - open or closed w/ ligand binding
4. Transmembrane receptor protein coupled with G protein - modulates second messenger production inside cell
66
How do lipid soluble ligands work?
cross membrane and act on intracellular receptor = stimulates gene transcription via binding to DNA sequences
ex. steroid hormones
67
steroid hormone (lipid soluble ligand) effects occur (when) ______ and last for ________
lag period (hours-days) ; hours-days
68
cytokine receptors are an example of ________
transmembrane protein receptors with intracellular enzymatic activity or stimulate protein tyrosine kinase
69
acetylcholine nicotonic receptor is an example of a ____________. Its effects take ________
ligand-gated transmembrane ion channel; milliseconds (instant)
70
the activated alpha unit in the GPCR ________ resulting in ________
exhanges bound GDP with GTP; dissociation of alpha subunit from beta-gamma dimer
71
The 2 signalling cascades of G protein coupled receptors are _____ & _____ and depends on ______
cAMP and phosphatidylinositol ; alpha subunit type
72
cAMP mediates
_____ in liver
_____ in kidney
____ homeostasis
______ in heart tissue
_______ of smooth muscles
regulation of __________
carb breakdown
water conservation
Ca2+
increased rate of contraction
relaxation
Adrenal and sex steroids
73
Describe the cAMP mechanism (5 steps)
1. GTP activates adenyl cyclase
2. adenyl cyclase converts ATP --> cAMP
3. cAMP stimulates cAMP-dependent protein kinases
4. protein kinases activate/ deactivate further proteins
5. cascade effect
74
Phosphoinositides (PPIs) are membrane bound _____. They regulate (4 processes in cell)
lipids
1. migration
2. proliferation
3. survival
4. diffrentiation
75
phosphatidylinositol is a _____ and mediates the generation of _____ by it's phosphorylation and dephosphorylation
membrane lipid precursor ; PPIs
76
Provide 2 examples of interplay among signalling systems (one opposite, one working together)
1. vasopressor agents contact smooth muscle by phospholipid mediated mobilization of Ca2+ & agents that relax smooth muscle act by elevation of cAMP
2. in the liver cAMP and phosphoinositide work together to stimulate glucose release
77
almost all 2nd messenger signalling involves ______ phosphorylation.
reversible
78
In terms of a signal - phosphorylated = _______ (via _____) dephosphorylation = _________
activation (via kinases); terminates effect
79
_____ is the transfer of drug from its site of administration to the blood stream
absorption
- IV has none b/c direct into blood stream
80
most drugs are absorped by the manner of ______ transport
passive
81
__________ and __________ are important PK parameters
fraction of administered dose ; rate of absorption
82
List 5 factors that affect absorption
1. conc. gradient - drugs move from [high] --> [low]
2. blood flow to absorption site
3. total surface area available for absorption - bigger = more
4. contact time with absorption - more time = more
5. drug properties - lipid solubility, molecular weight, polarity
83
a ______ (charged or uncharged) is hydrophobic and can _______ diffuse across lipid bilayer membranes.
a _____ (charged or uncharged) drug is hydrophilic and cannot diffuse
uncharged; passively
charged
84
most drugs are the salts of _____ acids or bases
weak
85
relative amounts of protonated and unprotonated forms depends on the drug's ______ and the environment's ____
pka; pH
86
The two mechanism that drugs can cross a cell membrane include _______ and _________
passive diffusion; protein-mediated transport (facilitated or active transport) `
87
________ is the fraction of unchanged drug reaching the systemic circulation following any administration
bioavailability
88
______ bioavailability is the amount of drug from a formulation that. reaches the systemic circulation relative to an IV dose
absolute
89
______ bioavailability is the amount of drug from a formulation that reaches systemic circulation relative to a different formulation (non-IV)
relative
- can compare drugs via ratio at relative
90
___________ for the test and reference formulation/route is used to calculate bioavailability
ratio of area under the curve (AUC)
91
For AUC curves _______ is the time in the therapeutic range
duration of action
92
For AUC curves __________ is the conc. for therapeutic benefits
theraputic range
93
For AUC curves _______ is the time to get in the therapeutic range
onset time
94
____ is the max conc of drug found in the body and _____ is the time of Cmax
Cmax; Tmax
95
there are different _____ and ______ of AUC for different routes of administration
shape and size
96
________ is a phenomenon in which a drug gets metabolized at a specific location in the body -results in reduced conc. of active drug when reaching its site of action or systemic circulation
the first pass effect
97
the first pass effect is most toften associated with the _____ but can also occur in ____, ______, _____
liver; lungs, vasculature, GI tract (metabolic enzymes)
98
______ is a # you. can use to calculate how much drug you have in your body if you know the conc. of drug in your body
Volume of distribution (Vd)
99
the _____ the Vd the more likely the drug is found in the tissues of the body.
the ______ the Vd the more likely the drug is confined to the circulatory system
larger; smaller
100
Drugs with Vd:
< /= 4L are ______
4L --> 7L are _____
> 42 are ______
< /= 4L are - confined to plasma
4L --> 7L are - distributed throughout blood
> 42 are - distributed to all tissues in body (esp. fatty)
101
_______ is the time required to change the amount of drug in the body by 1/2 during elimination.
half life
102
half life is relative to ______ and over time _____
Cmax; stays constant ( not dependent on amt of time).
103
_____ is the rate of drug elimination divided by plasma concentration of the drug
clearance (CL)
note: elimination means removal of active drug not excreted.
104
The formula for half life is
half-life = (0.693 • Vd)/ CL rate
- Vd and CL provided
105
______ is the process by which drug reversibly leaves the blood stream (moving b/w body compartments or reaching target receptors)
distribution
106
list 4 factors affecting distribution
1.Organ blood flow
- faster if highly perfused = rapid onsett
2. molecular size
- for extremely large - cant get out of blood
3. lipid solubility
- important for the brain and transport mechanisms
4. plasma protein binding
- bound = inactive - depends on affinity
107
_____ is the conversion of a parent (original) drug to metabolite(s)
metabolism
108
the goal of metabolism is to make the drug ____ polar to ______ renal excretion
more; increase
109
metabolism occurs primarily in the _____ as well as some in the ____, ____, _____, _____
liver; gut, lungs, plasma, brain
110
Phase 1 of metabolism involves _____, ______ and _____ reactions with the. majority being _______
oxidative, reductive, hydrolytic; oxidative
111
phase 1 of metabolism is catalyzed by _________ isoforms. aka hepatic oxidative isoenzymes
cytochrome P450 (CYP)
112
_____ increase enzyme activity = metabolism ______. Cause of many drug-drug interactions that____ potential clinical effects (___ drug)
inducers; speed up ; lower; less
113
____ decrease enzyme activity = metabolism _____. See toxic effects b/c you stay in therapeutic range____ and _____ Cmax
inhibitors; slows down; longer; increase
114
in phase II of meabolism _______ enzymes which are _____ liver enzymes covalently add ____, _____, _____ molecules to parent drug or phase I metabolite to prep for excretion
conjugation; non P50; large, polar, endogenous`
115
List 2 alternative sequences of metabolism
1. some drugs enter phase II directly
2. some drugs skip metabolism all together
116
______ are administered as an inactive drug that relies on metabolism to produce pharmacologically active produce
Produrgs
ex. codeine --> morphine (via CYP2D6)
117
3 pathways of drug excretion in kidney
____ glomular filtration
______ tubular secretion
_______tubular reabsorption
1. Passive glomular filtration - small drugs
2. Active Tubular secrettioon - large drugs + transport proteins
3. Passive tubular reabsorption - reabsorbed back into blood --> urine (pH is key)
118
A carrier mediated process. that is not limited by passive diffusion rules excretes larger drugs by secreting them from the _____ to ______ via ________
liver; intestine; common bile duct.
119
_____ nerves are craniosacral meaning they originate from the ________ regions of the spinal cord
PNS; top and bottom
120
_____ nerves are thoracolumbar meaning they orginate from the ___________ regions fo the spinal cord
SNS; thoracic and lumbar
121
SNS ganglia have ____ chains to the ganglia from the spinal cord vs PNS
shorter
122
most drugs work at the _________ receptors on ________
postganglionic ; target organs
123
Acetylcholine (ACh) is released onto _______receptors at _________ and __________in both PNS and SNS. but only onto _____. receptors in PNS
nicotinic; ganglia; target organs; muscarinic
124
ACh is synthesized from ______ and _______ and stored in synaptic vesicles
Acetyl CoA and Choline
125
Catecholamines NT such as dopamine, NE and Epi are synthesized from ______
tyrosine
126
Nm receptors are found in ______
Nn receptors are found in _____, _____, _____, _____
muscle
ganglia, adrenal, CNS, immune
127
PNS receptors are _______ and have __ subtypes . ____ (more or less) drugs target these receptors and they are important for _________
muscarinic; 5; fewer; drug side effects
128
_________(number of M receptors) cause _____ bladder muscle contraction via increased ____-->____and are ___ (q or i) G protein coupled
M1,M3,M5 ; smooth; PLC --> IP3; Gq
129
_________(number of M receptors) cause _____ heart rate via decreased ___ --> ____ and are ___ (q or i) G protein coupled
M2, M4; decreased; AC --> cAMP; Gi
130
The effects of a _____ (PNS) agonist oppose those of an _____ (SNS) agonist
muscarinic; adrenergic
131
Effects of a muscarinic agonist in
heart -
lungs-
sphincers (GI and bladder)-
Walls (GI and bladder) -
heart
- decreased rate and contraction
lungs
- bronchoconstriction
sphincers (GI and bladder)
- relax (M3)
Walls (GI and bladder)
- contract (M3)
132
In the _____ (PNS or SNS) How does coordinated action lead to urination.
PNS
- M3 (bladder wall) = contract
- M3 (sphicter) = relax
133
____ (PNS or SNS) muscarinic receptors _____ secretion (salivary, respiratory, tears)
PNS; increase
134
to directly stimulate M receptors you use _______
to indirectly stimulate M receptors you use _______ both which ______ Ach
an agonist; acetylcholinesterase (AChE) inhibitors; increase
135
______ (rapid recovery) and _______ (slower recovery) are reversible reaction when cholinesterase is bound (more ACh). Whereas ______ is irreversible
Acetylation (rapid- physiological); Cabamylation (slower - drugs); phosphorylation
136
parasympatholytics (aka anticholinergics) block _______ (PNS or SNS) response/ _____receptors. ex. Atropine
PNS; muscarinic
137
side effects of anticholinergic drugs (ex. atropine)
mouth -
heart -
gut -
bladder -
mouth - dry
heart - tachycardia
gut - constipation
bladder - difficulty urinating
138
_____ receptors in the SNS constrict smooth muscles
alpha - 1. (a-1)
139
a-1 receptors constrict ______ in _____ and most critically on _____ for ______
sphincters; bladder and GI tract; blood vessels; vasoconstriction
140
a-1 receptors are ________ (receptor type) that produce ___ which results in ______ Ca2+. leading to smooth muscle contraction
G-protein coupled; IP3; increased
141
______ receptors in the SNS inhibit presynaptic NE release
alpha - 2 (a-2)
142
a-2 ________(agonist or antagonist) would lead to no NE released into synapse
agonist
143
_____ receptors in the SNS stimulate the heart rate, AV conduction and contraction.
Beta - 1 (B-1)
144
B-1 receptors are ________ (receptor type) that produce ___ which results in ______ Ca2+. leading to increased HR contractility
G-protein coupled; AC/cAMP; more channels
145
B-1 receptors in the ____,____, ____. are only innervated by the ____(SNS or PNS)
liver, kidney, uterus; SNS
146
B-1 receptors in the kidney _____ renin release which causes a _____ in blood pressure
stimulate ; increase
147
_____ receptors in the SNS cause relaxation of smooth muscles
Beta-2 (B-2)
148
B-2 receptors cause _____ (dilation or contraction) in the ____, _____, and (contraction or relaxation) in the walls of ____, ____, ____
dilation; lungs, blood vessels (skeletal muscle)
relaxation; bladder, uterus, GI tract
149
there is a coordinated effect between _____ and B-2 receptors
a-1
150
B-2 receptors are ________ (receptor type) that produce ___ which results in _____
G-protein coupled; AC/cAMP; dilation
151
How does coordinated action of SNS receptors lead to peeing
bladder wall (B-2) contracts
sphincter (a-1) relaxes
152
B-2 receptors in the ____ mediate glucose release by ______ and ________ which _____ blood glucose conc.
liver; gluconeogenesis and glycogenolysis; increases
153
_________ are drugs that mimic sttimulation of the SNS
sympathomimetics
154
sympathomimetics work by 2 mechanisms ...
1. directly activating adrenergic receptors (NE and Epi)
2. increasing amt of NE and Epi in synapse
155
what are the three ways sympathomimetics work to. increase the amt of n.t in the synapse?
1. increase n.t release
2. inhibit reuptake of n.t - inhibit reuptake pumps
3. inhibit metabolism of n.t - enzymes for catecholamine breakdown
156
__________ are drugs that block or reduce sympathetic activity
sympatholytics
157
sympatholytics work by 2 mechanisms..
1. blocking adrenergic recepors (ex. propranolol)
2. decrease amt of epi and NE released into synapse (ex. clonidine)
158
propranolol is a __________ drug that works by .... and acts on ____ receptors
sympatholytic; directly blocking adrenergic receptors; B-1
159
clonidine is a _________. drug that works by ... and acts as an. _____ receptor agonist
sympatholytic; decreasing the amt of SNS n.t released into the synapse; a-2 agonist
160
What are the 2 different iris muscles and how do they affect the pupil when contracted
Circular (sphincter) - contract = constrict pupil
Radial (longitudinal)- contract = dilate pupil
161
Circular (sphincer) contracting resuls from ______(PNS or SNS) stimulation of ____ receptor(s). = ________(constrict or dilate) pupil
PNS; M2, M3; constrict
162
Radial (longitudinal) contracting results from______(PNS or SNS) stimulation of ____ receptor(s). = ________(constrict or dilate) pupil
SNS; a-1; dilate
163
The most common ways to. treat glaucoma are to increase _____ of AH and decrease______ of AH
drainage; production
164
In the PNS ______ receptor(s) stimulation results in ______ ciliary muscle, _____ meshwork and canal = (increased or decreased)_____ drainage
M2, M3; contract; open; increased
165
In the SNS, ____ receptors (increase or decrease) ______AH secretion so ______ drugs are used to (increase or decrease) ______ secretion
B-2; increase; B-2 antagonists; decrease
166
In SNS, _____ receptors (increase or decrease) ____drainage and ______ production of AH so _____ drugs are used
a-2; increase; decrease; a-2 agonists
167
In the PNS side effects of ____ receptor stimulation causes ____ of ciliary muscles = the lens to bulge which improves ____ vision and blurs ___ vision (near or far)
M; contraction; near; far
168
List the PNS and SNS receptors found in the GI tract
M3 - contract walls, relax sphincters
a-1 - contraction of sphincters
B-2 - relaxation of wall
169
List the PNS and SNS receptors found in the heart
M2 - decrease HR and contraction
B-1 - increase HR , AV conduction and contraction
170
List the PNS and SNS receptors found in the blood vessels
a-1 - vasoconstriction
B-2 (in skeletal muscle) - vasodilation
171
List the PNS and SNS receptors found in the bladder
M3- contraction of walls & relax sphincters
a-1 - contract sphincter
172
List the PNS and SNS receptors found in the bladder
M3- contraction of walls & relax sphincters
B-2: relax walls
173
List the PNS and SNS receptors found in the eye
M2, M3 - contraction of circular muscles = constrict pupil
a-1 - contraction of radial muscles = dilate pupil
174
List the PNS and SNS receptors found in the kidney
B-1 - stimulate renin release = increase BP
175
List the PNS and SNS receptors found in the lungs
M: bronchoconstriction
B-2: bronchodilation
176
List the PNS and SNS receptors found in the liver
B-2 - increase glucose release via glycogenolysis and. gluconeogenesis
