Sweep 1 Flashcards
(156 cards)
1
Q
4 types of signaling receptors
A
ligand activated ion channels, g protein, tyrosine kinase receptors, ligand activated transcription factors
2
Q
-zosin
A
alpha 1 blocker
3
Q
-olol
A
beta blocker-
4
Q
-ilol, -alol
A
beta blocker with alpha 1 activity
5
Q
Hyperpolarizing ligand activated ion channet in
A
chlorine
6
Q
depolarizing ligand activated ion channels are
A
not particularly selective (acetylcholine, serotonin, glutamate)
7
Q
ligand activated ion channels in the organelle:
A
IP3 mediated calcium release from ER
8
Q
PIP2 broken down goes to
A
IP3 and DAG
9
Q
——— breaks down PIP2
A
phospholipase C (beta?)
10
Q
What protein helps accelerate G protein phosphorylation activity
A
RGS
11
Q
Affect on ————— - Galphas, Galphai
A
adenylyl cyclase
s = up, i = down
12
Q
What activates cAMP
A
protein kinase A
13
Q
PKA phos leads to
A
stuff happening.
14
Q
Signaling molecules can be embedded in
A
the plasma membrane - GPCRs can liberate them by activating phospholipases
15
Q
Galphai,o
A
increase phospholipase A2, C
16
Q
Phospholipase A2 will produce
A
arachidonic acid
17
Q
arachidonic acid is a source of
A
eicosinoid signaling molecules, prostaglandins
18
Q
IP3 leads to —- release
A
calcium
19
Q
—- complex mediates signalling by calcium
A
calcium calmodulin
20
Q
ca/calmodulin signaling examples
A
NO synthase (relaxes) - endothelial, neuronal
calcium/calmodulin dependent kinase
21
Q
Most isos of protein kinase C regulated by
A
DAG (allows for more efficient binding of calcium)
22
Q
GRK recruited by ———, works by
A
Gbeta, G gamma complex
phosphorylating GPCR, leading to beta arrestin binding, which leads to engulfment.
23
Q
JAK-STAT binding of signalling molecule leads to
A
phosphorylation of receptor by JAK kinase. This leads to 2 stat proteins binding and getting phosphorylated
24
Q
Once phosphorylated, stat proteins
A
dimerize, and then they go to nucleus to induce transcription.
25
STAT domains that can be phosphorylated
SH2, tyrosine. Phosphorylating binds the two together, allowing for dimerization.
26
----------- mediates biological response to cytokines
STAT proteins
27
The larger the partition coefficient, the
more drug to be absorbed.
28
---- transporters kick drug out of cell
ABC
29
---- transporters important for moving organic acids/bases
SLC
30
---- drugs diffuse quickly from blood
lipophilic. Water soluble move through endothelial gaps (slow)
31
Where are there no gaps in endothelium?
BBB
32
Q/C =
Vd - Q = original amount, C = concentration of drug in plasma
33
How many liters of plasma
3
34
How many liters of insterstitial fluid
9
35
How many liters of cells
29
36
Excretion of drugs strategy
make drugs more water soluble.
37
Excretion process
Add or uncover functional group, conjugate
38
----- are membrane bound enzymes that metabolize drugs
microsomes. P450 and cyps here, as well as flavin monooxygenases
39
ways to metabolize
reductiosn, dehalogneation, hydrolysis, glucuronic conjugation
40
Conjugation usually
inactivates drugs, exception is morphine
41
Microsomal enzymes are designed to remove
foreign substances
42
Non-microsomal metabolism occurs when
drug mimics natural substance.
43
Tyramine can lead to
hypertensive crisis when taking MAO inhibitors.
44
Ingestion of grapefruit juice inactivates
CYP3A4 (60% of all met.)
45
Pharmacokinetic tolerance
drug concentration diminished
46
Pharmacodynamic tolerance
drug response diminished
47
Tyramine is an example of
tachyphylaxis. This increases HR and BP by promoting norepinephrine release. Tachy occurs when norepinephrine is depleted.
48
Phase II conjugation by
Nat 1 and 2 nacetyltransferases
49
NATs conjugate
aromatic amines, alcohols, hydroxylamines.
50
Slow acetylators
have drugs stay around longer (NATs). Some good, some bad reactions.
51
Cytochrome p450
CYPs... dummy.
52
CYP2D6 removes
methyl from oxygen.
53
Muscarinic agonists used to treat dry mouth are metabolizedby
CYP2D6. Adverse effects are cholinergic syndrome.
54
CYP2D6 poor metabolizers for codeine
not as much conversion to morphine, not very effective. Ultra metabolizers can experience ab pain.
55
Warfarin metabolized by
CYP2C9
56
CYP2C9 poor metabolizers have bad bleeding issues when taking
warfarin
57
Ryanodine receptors mediate
calcium mediated calciumrelease - differs from IP3.
58
Overactive ryanodine receptors leads to
hyperthermia.
59
Potentiation
second drug with diff activity enhances first drug (ex - improving absorption of drug 2 by drug 1)
60
When digesting alcohol if --------- is allowed to accumulate, you get bad headaches
acetaldehyde.
61
Disulfuram inhibits
acetaldehyde dehydrogenase.
62
Summation
combined activity of two drugs on the same site or similar sites.
63
Additive summation
Drug action is interchangeable when dosed at fractions of their EC50.
64
Infra-additive summation
Less than additive response when dosed as above.
65
Supra-additive
Yield more than additive response when dosed as above.
66
Synergism
combined effect of two drugs greater than maximal effect of either drug alone.
67
Pharmaceutical interactions
When drugs chemically react with each other (rare)
68
Drugs should never be administered with
the same syringe for pharmaceutical interaction reasons.
69
Distribution across plasma membrane can be affected by drugs that:
1. Alter p-glycoprotein activity or levels
2. Alter pH gradients
3. Disrupt membrane barriers
70
beta blockers can
inhibit blood flow to liver by reducing CO, which inhibits clearance of lidocaine.
71
Electrochemical gradient establishment - minor is
sodium potassium atpase pump
72
Electrochemical gradient establishment, major is
potential arising from membrane permeabilities
73
Net efflux of potassium is going to continue until the force
bringing potassium outside is balanced by the electrical force bringing it back in.
74
The ----------- are responsible for maintaining homeostasis
autonomic and endocrine systems
75
Sympathetic ns at effector site:
epi, norepi
76
Somatic at effector site
acetylcholine - nicotinic
77
Parasymp at effector site
acetylcholine - muscarinic
78
Endogenous adrenergic amines
epi, norepi, dopa
79
endogenous adrenergic amines are made in
symp. nerve terminals and adrenal medulla
80
---- receptors are most importnat at presynaptic termini
alpha 2
81
---- inhibit norepi and epi release
alpha 2
82
Norepi/epi when bound will
cause calcium to enter a cell
83
beta 2 on smooth muscle increase
pka, diminish calcium levels, phosphorylate/inhibit mlck
84
----- activates PKA
cAMP
85
----- inhibits MLCK
PKA
86
PKA mediated phosphorylation also activates
potassium channels, which leads to hyperpolarization and reduction in cellular calcium.
87
beta 1 receptors on
cardiac muscle mainly, also some beta 2
88
beta 1 activate
PKA, L-type Calcium channels, increase calcium
89
beta 1 activators can improve
contractility of a failing heart. Can lead to arrhythmias
90
Epi concerns with systemic absorption
arrhythmias
91
Activation of alpha 1 and beta 2 receptors on vascular tissue will lead to
vasoconsttriciton (more alpha than beta)
92
Epi activates
alpha 1, beta 1 and 2
93
norepi doesn't activate
beta 2
94
nor at 0.2microg/kg/min
alpha 1 stimulated, BP increases, reflex bradycardia
95
bradycardia
abnormal slow heart action
96
tachycardia
abnormal fast heart action
97
epi at 0.2microg/kg/min
stimulates all, alpha dominates
98
norepi at 0.1microg/kg/min
stimulates alpha. BPincrease, reflex bradycardia
99
epi at 0.1microg/kg/min
stimulates beta more than alpha, beta 2 dominates. BP decreases
100
Activate beta 1
increas force of contraction, increase rate.
101
Non vascular smooth muscle - Sphincters - relaxation mediated by
alpha receptors with epi/nor
102
Salivary gland norepi/epi net effect
Modest secretion with lots of protein - beta 1 for protein.
103
Epi/norepi does'nt
get into brain
104
Epinephrine for anaphylaxis:
Stimulation of a receptors: Increase blood pressure
Stimulation of b1 receptors: Positive cardiac effects
Stimulation of b2 receptors: Bronchodilation`
105
alpha 2 receptor agonists primarily act in
CNS - inhibit norepi and epi release at presynapse - can be used as msucle relaxant,
106
--- used primarily in heart failure and cardiogenic shock
beta 1 agonists
107
Beta 2 agonists for
respiratory bronchodilation, can also vasodilate and relax uterus
108
non selective alpha antagonists block
transfer mediated feedback loop (alpha 2). Limited use for humans due to side effects
109
phentolamine
non selective alpha antagonist - used to clear up anesthetic effect following dental procedure.
110
patients with pheochromocytoma can benefit from
non selecgive allpha antagonists
111
beta 3 agonists produce
vasodilation
112
beta 2 blockers are nonfavorable due to
airway closure.
113
useful beta blockers are either
beta 1 only or nonselective
114
beta blockers decrease
force of heart contraction and HR and BP decrease renin
115
beta blockers w/o isa (intrinsic sympathomimetic activity)
decrease HR, plasma renin, CO
116
beta blockers with isa
no decrease on cardiac or renin, attenuate agonist driven response.
117
in glaucoma ------- is used to reduce vitrious humor production
beta blockers.
118
beta blockers that get into the brain used for
migraine and tremor from anxiety
119
some antagonist for alpha and beta, used for
hypertension
120
alpha blockers can cause
orthostatic hypotension, so be careful when patients taking drugs for hypertension
121
Patient taking beta blockers more at risk for
hypertensive crisis after anesthetic due to not having beta 2 response to help balance alpha 1.
122
Cholinergic receptors - two types
nicotinic, muscarinic
123
Muscarinic M1,3,5
Linked to Galphaq, which activate DAG, IP3 signaling and contraction
124
Muscarinic M2,4
Linked to galphai, downregulate adenylate cyclase and lead to relaxation
125
Indirect cholinergic agonist
cholinesterase inhibitor
126
Acetylcholine is ---------- for muscarinic and nicotinic
non-selective
127
carbochol favors --------- receptors
muscarinic
128
------- agonists more clinically relevant
muscarinic
129
Odd numbered muscarinic receptors activa
phospholipase C and lead to Ca release and contraction
130
even numbered muscarinic receptors inhibit
adenylcyclase
131
M3 receptors mediate ----------- relaxation
sphincter, but mediate constriction on ciliary muscles (help with drainiage)
132
M2 on heart can
reduce CO
133
Most arteries and veins innervated by
symp adrenergic nerves
134
Some blood vessels are innervated by parasympathetic cholinergic or sympathetic cholinergic nerves. These nerves release
acetylcholine as their neurotransmitter. Coronary arteries are a prominent example.
135
Vascular endothelial cells express
m3 - this increases calcium in endothelial cells, ca/calmodulin leads to NOS upreg. THis leads to vasodilation, as NO increases cGMP production in muscle, which enhances MLCK phosphatase activity
136
M3 on bronchial muscle mediate
contraction
137
Secretory glands - m3 mediates
release of product
138
------------ amine better absorbed than ---------- amine
tertiary, quarternary - tertiary actually can get through bbb
139
Adverse effects of muscarinics
SLUD, Patients with asthma (bronchoconstriction), Cardiovascular disease (vasodilation, reduced cardiac output), ulcer (lacrimation)
140
Anticholinesterases
increase cholinesteerase activity
141
Irreversible anticholinesterases
fatal
142
Anticholinesterases do not produce muscarinic receptor mediated vasodilation
because not much parasymp innervation of vascular endothelium
143
Anticholinesterases can produce vasodilation via
autonomic ganglia
144
Physostigmine (tertiary amine) can produce ------------------ effects through action in the CNS.
vasodilatory
145
Pilocarpine and cevimeline (muscarinic agonists) frequently used to treat
dry mouth (patient needs functional salivary gland).
146
anticholinesterases used to terminate neuromuscular block in
curare like agents
147
Anticholinesterases used to treat
myasthania gravis
148
Anticholinesterases that cross BBB used to treat
alzheimers
149
Using antimuscarinics places target under control of
symp - except for sweat glands, which inhibits sweating and can increase body temp
150
Antimuscarinics can cause eye dilation and lack of
accomodation - would cause serious rise in pressure in glaucoma cases
151
Antimuscarinics can be used to produce
bronchodiilation and help with COPD
152
Antimuscarinics inhibit gastric
motility,secretion at high impractical levels
153
Antimuscarinics block parasymp mediated
secretion
154
Antimuscarinics can be used as
antidote to anticholinesterases, to decrease salivary flow before procedure, treatment of COPD, dilate pupils
155
Nondepolarizing blockers
competitive antagonists of acetylcholine
156
Succinylcholine
depolarizing blocker. Two phases of action, chronic activation of achrs and then deacvitation of sodium channels, long term removal of achrs due to desensitization.
