final material Flashcards
1
Q
what causes catecholamines to be released
A
sympathetic stimulus - usually a fight or flight response
2
Q
what is a catecholamine
A
2 OH + amine on a aromatic ring
3
Q
epinephrine low concentration
A
best B1 agonist
Beta > alpha
B1, B2
not much B3 bc NE
4
Q
beta 1
A
increases heart rate and force of contraction (positive chronotropic and positive inotropic effects, renin release
5
Q
Beta 2
A
bronchodilation, relaxes the smooth muscles (uterine and bronchus), increases vasculature, increases renin
6
Q
Alpha 1
A
acts on more than sympathetic activity, vasoconstriction, contraction of smooth muscles (ureter, uterus, ciliary body), glycolysis/gluconeogenesis
7
Q
alpha 2
A
auto-receptor, negative synaptic loop, decreases synaptic activity, decreases heart rate, vasodilation, inhibits NE, inhibit insulin, stimulates glucagon release
8
Q
epinephrine response at the heart
A
inc heart rate, increase SV, increase CO, increase force of contraction, increase blood pressure
9
Q
epinepherine response at lungs
A
bronchodilation can enhance epi for asthma, BUT high heart rate
10
Q
epi response at vasculature
A
high conc: alpha 1 predominates, vasoconstrict, increases TPR
low conc: B2, decreases TPR, vasodilation
11
Q
epi therapeutic uses
A
not as much vasoconstriction as NE
12
Q
epi in asthma
A
dilates airways
13
Q
epi in conjunction with local anesthetic
A
prolongs action of anesthetic, hangs out longer, vasoconstrictor can be removed from site
14
Q
MOA of epi-pen
A
activates the alpha 1 receptors, lessens the vasodilation and lessens the increased vascular permeability that occurs during anaphylaxis - leads to a loss of intravascular fluid volume and hypotension
15
Q
NE
A
best at increases BP, synthesized and stored in the terminal of the sympathetic post-ganglionic neuron, targets alpha 1, alpha 2, b1, b2
16
Q
NE effect on the heart
A
increases the heart rate and increases the force of contraction and increases the CO
17
Q
NE on lungs
A
no effect, no B2
18
Q
NE on vasculature
A
vasoconstrict - alpha 1
19
Q
NE administered for shock
A
dangerously low blood pressure - admin levophed, dec BP, not enough BV, vasoconstrict because not enough BP, increases peripheral resistance
20
Q
isoproterenol
A
B1 and B2 agonist, decreases peripheral resistance, increases pulse rate, decreases blood pressure
21
Q
dopamine
A
synthesized and stored in the terminal of the SNS postganglionic neuron, concentration dependent
22
Q
low concentration dopamine
A
D1
23
Q
high conc dopamine
A
alpha 1, lowest kd affinity
24
Q
mild conc dopamine
A
B1
25
D1
vasodilator, prominent in mediatic vasculature, renal vasculature, helps regulate renal flow, highest affinity
26
renal dose dopamine
low dose, keeps the renal flow going to preserve kidney function
27
dopamine at the kidney
increases RPF, increases GFR at low and mild dose, starts going away at higher dose
28
dopamine at the heart
increases heart rate, force of contraction
29
dopamine at vasculature
TPR decreases in low conc, TPR increases at high conc
30
therapeutic uses for dopamine
shock, hypotension, poor tissue perfusion, low cardiac output
31
sympathommetics
mimic endogenous catecholamines so they are called sympathomemetics
32
phenylephrine
alpha 1 receptor agonist, opthalmic (dilates), visine (gets red out), constricts vessels
33
naphazoline
alpha 1 receptor agonist
34
oxymetazoline
alpha 1 receptor agonist
35
tetrahydrozoline
alpha 1 receptor agonist
36
alpha 2 receptor agonist
centrally, decreases SNS, decreases HR, TPR, BP
37
clonidine
alpha 2 receptor agonist
38
guanfacine
alpha 2 receptor agonist
39
methyldopa
alpha 2 receptor agonist
40
Dexmedetomidine
alpha 2 receptor agonist
41
upregulation
alpha/b receptors upregulate because not normal stimulation, cause tachycardia because receptors not activated alpha 2 agonist and need more alpha 2 regulation in the frontal cortex
42
dobutamine
B1 receptor agonist, increases heart rate and force of contraction, IV only, can have down regulation and loose effect over time, opposing alpha 1 effect (R,S) eantiomer
43
B2 receptor agonist
bronchodialation
44
(lev)albuterol
SABA - short acting beta agonist, asthmatic episode, not an every day drug
45
terbutaline
B2 receptor agonist
46
salmeterol
long acting beta 2 agonist
47
(Ar)Formoterol
Beta 2 receptor agonist
48
indacterol
long acting beta 2 agonist
49
olodaterol
long acting beta 2 agonist, inhalation administration
50
D1 receptor agonist
selective, fenoldopam
51
alpha 2 receptor dopamine
possible to increase the symp and decrease the para symp - alpha 2 hetero receptor when symp neuron is activated, activity decreases
52
beta adrenergic receptor antagonists
used in CV disorders (hypertension), chronic angina, heart failure, anxiety, migraine headaches, glaucoma, hypertension, angina
53
hypertension and angina - NE
block effect of NE on the heart
| decrease HR, decrease FOC, decrease CO
54
beta blockers therapeutic uses
CV disorders, hypertension, chronic angina, heart failure, anxiety, migraine headaches, glaucoma
55
hypertension and angina- bblockers
block effects of NE on the heart. decreases the HR, decreases FOC, decreases the CO
56
bblocker - RAA system
JG cells secrete renin- B1 receptors
| B2 very powerful vasoconstrictor through Ang 2, can cause vasodilation through blocking of ang 2!
57
heart failure - BBlocker
patients have high levels of catecholamines and excess sympathetic activity - leads to acute coronary syndromes and altered contractility - bblockers very effective!`
58
BBlockers cardioselectivity
B1 over B2, lower kd for B1 over B2
59
BBlockers are great for
COPD (want to avoid B2), diabetes (glucose/glycogen regulation), decrease insulin secretion, tissue sensitivity to insulin
60
Intrinisic Sympathomimetic Activity
partial agonist
61
pindolol
ISA bblocker
62
acebutolol
ISA bblocker
63
labetolol
ISA bblocker, has B2 receptors, causes vasodilation- causes TPR to decrease, B1 antagonist, B2 ISA, alpha 1 block
64
nimidane
normalizes pressure
65
advantages of B1 with ISA
reduce the degree of brady cardia, limits the effects of lipid profile
66
carvedilol
blocks alpha, blocks L-type CC, anti-oxidant
67
elimination of b-blockers
nearly all eliminated in the liver
68
bblockers excreted in the kidney
nadolol, atenolol - used in patients with liver issues who require a bblocker
69
nadalol half life
24 hours. most of all bblockers
70
atenolol half life
12 hours
71
esmolol half life
10 minutes
72
most hepatically cleared bblockers half life
4-6 hours
73
lipids and bblockers
inc LDL and VLDL
| dec HDL
74
CNS and bblocker
drowsiness, fatique, nightmares
75
sexual dysfunction and bblockers
dec libido, erectile dysfunction
76
hypoglycemia and bblockers
masks symptoms of hypoglycemia (which are inc heart rate, shakiness, sweating, SNS increased)
77
bblocker effects on the EKG
dec heart rate, prolonged PR interval, conduction time increase, abrupt discontinuation of bblocker, 2x receptor upregulation (hypertension, tachycardia)
78
glaucoma and bblocker
aqueous humor production
79
thyrotoxicosis bblocker
thyroid hormone increases the expression of beta receptors
80
tremor bblocker
activation of beta 2 receptors cause tremor
81
migraine bblocker
bblocker effective at preventing migraines
82
alpha-adrenergic antagonists (alpha blocker) treatment for
BPH (benign prostatic hyperplasia) and hypertension (last resort)
83
have alpha 1 antagonists demonstrated superiority over other drug classes?
no they have not demonstrated superiority over other drug classes such as ACE inhibitors, B blockers, or thiazide diuretics
84
doxazosin
alpha 1 agonist - discontinued because its inferiority in reducing coronary events
85
prazosin
alpha 1 subtype non-selective reversible competitive antagonist
86
terazosin
alpha 1 subtype non-selective reversible competitive antagonist
87
doxazosin
alpha 1 subtype non-selective reversible competitive antagonist
88
alfuzosin
alpha 1 urinary tract reversible competitive antagonist
89
tamulosin
alpha 1 A reversible competitive antagonist
90
silodosin
alpha 1 A reversible competitive antagonist
91
phentolamine
alpha 1 / alpha 2
92
phenoxybenzamine
irreversible competitive antagonist
93
zosin
non-selective alpha 1 antagonist
94
osin
selective
95
amine
alpha 1/ alpha 2
96
B2 adrenergic agonists and binding sites
affinity- if you want a highly potent agent (low dose)
activation: full agonist or partial agonist
lipophilicity: does play a role in b2 selectivity,
97
B2 adrenergic agonist SAR
NE- B1, alpha 1/2
| Epi- addition of a methyl B2 > b1, alpha 1
98
drawbacks to isoproterenol
short duration of action, increases the heart rate and the force of contraction
99
isoproterenol structure
isopropyl, bulky
100
metaproterenol structure
phenolic groups not a substitute for COMT, more selective than tertbutyl, like isoproterenonol but OH instead of ortho they are meta
101
albuterol
B2>> B1, active eantiomer of albuterol, short acting b2 agonist, t-butyl group, 3 hydroxy methyl, OH on a methyl makes it more selective
102
tertbutyl
B2>b1, like metaproterenol but with a t-butyl group instead of an isopropyl group
103
long acting beta2 agonists
B2 >>> B1
104
salmeterol
long acting beta2 agonists, has the 3-hydroxymethyl group that makes it more selective
105
vilanterol
looks like salmeterol but has 2 Cl- on the ring, partial agonist, binds to exo-site, long chain is like hinges of a door bound to the exo site - long acting beta2 agonists
106
formoterol
long acting beta2 agonists- formic acid attached, lipophillic side chain that fits inside the receptor
107
indacaterol
tautomer, looks like 3-hydroxymethyl, full agonist, either tautomer or could bind to the receptor long acting beta2 agonists
108
olodaterol
bind with the receptor at the active site, has formic acid- long acting beta2 agonists
109
formoterol, indacaterol, olodacterol
QD daily, effecient agonist, fast onset of action 15-45 seconds
110
structure- activity relationship: Long acting B2 agonists
1. aromatic ring: 4-hydroxy group required unless there is a 3,5 biphenolic substitution, better affinity for the b2 receptor- long acting beta agonist
2. 3-hydroxymethyl aromatic substituents
3. ethanol-amine side chain absolute requirement- R configuration for the hydroxyl group is required for receptor activation
4. 3-formidioo - not substrates for COMT
5. basic nitrogen alkyl substitutes-
111
carostyril
has 4 phenol, 3-formamido, hydroxymethyl like, indacaterol - long acting beta agonist
112
beta blocker SAR
aromatic ring containing system and not specific variable, either bridge (beta 1 selective), aromatic side chain
113
non specific beta blockers
ether bridge connectts side chain
114
nadolol
not aromatic, single aromatic ring, nonspecific bblocker
115
pindolol
indole, ISA, nonspecific bblocker
116
metoprolol
H bond acceptor ether b1 selective bblocker
117
atenolol
H bond acceptor carbonyl - b1 selective bblocker
118
bisprolol
b1 selective bblocker H bond acceptor ether
119
esmolol
H bond acceptor ester DOA short, soft drug, fine control of BP
120
structure activity on bblocker SAR
- bulky substituent on nitrogen beta adrenergic side chain
- ether group between aromatic ring and beta adrenergic side chain (contributes to antagonist properties)
- aromatic ring system- non-selective antagonists have a non-specific aromatic system containing group, beta-1 selective agents have the following: single benzene ring, para substituent (H bond acceptor, 1 to 3 atoms from the benzene ring, meta substitution is out)
121
alpha 2 agonists structure
ortho attachments with bridge and cl-
122
structure-activity relationships for alpha 2 agents
- Aromatic ring with 2,6-ortho substituents- all seen with 2,6 Cl- structure
- Bridge- Ch2 or NH
- Basic nitrogen grouping:
- Perpendicular relationship between:
Aromatic ring and basic functional group - not in the same plane
123
yohimbine
alpha 2 antagonist, increases blood pressure on alpha 2
124
hydroxylation is decreased or inhibited by
strong electron withdrawing groups: § CN, SO2R, NO2, CF3, Cl, C=OR (ester, amide)
125
hydroxylation will occur on rings that have ___
electron donating groups attached
126
steric hinderence - what substitutions are favored
meta electronically not favored, ortho may not happen because it can;t get to the site easily, para is the most favored.
127
phase 1 dealkylation via CYP 450 enzymes
carvedilol undergoes dalkylation (removal of a methyl ether), drug is initially oxidized to drug- O-Ch2-OH t
128
side chain oxidation
secondary oxidized over primary - free radical reactions, where oxidation occurs it is governed by the following:
- free radical stability Benzylic > tertiary > secondary > primary
- sterics
