General Flashcards
1
Q
What is the major disadvantage of clinical therapy involving drugs that act on ANS?
A
Lack of specificity
2
Q
Parasympathetics control…
A
cardiac and smooth muscle
gland cells
nerve terminals
3
Q
Parasympathetic presynaptic
A
nicotinic cholinergic
4
Q
Parasympathetic postsynaptic
A
muscarinic cholinergic
5
Q
Sympathetic (sweat glands) postsynaptic
A
muscarinic cholinergic
6
Q
postsynaptic motor neurons
A
nicotinic cholinergic
7
Q
sympathetic (cardiac and smooth muscle, gland cells, nerve terminals) postsynaptic motor neurons
A
adrenergic (alpha and beta)
8
Q
Sympathetic (renal vascular smooth muscle) postsynaptic motor neuron
A
dopamine receptor
9
Q
Adrenal medulla
A
nicotinic cholinergic receptor
releases Epi, NE
10
Q
Cholinergic receptor types
A
muscarinic
Nicotinic
11
Q
muscarinic subtypes
A
M1, M3, M5…Gq coupled
M2, M4….Gi coupled
12
Q
Gq coupled muscarinic receptors
A
M1
M3
M5
13
Q
Gi coupled muscarinic receptors
A
M2
M4
14
Q
Nicotinic subtypes
A
Nm (neuromuscular/muscle type)
Nn (neuronal, or ganglion type)
15
Q
Adrenergic subtypes
A
alpha 1, alpha 2
beta 1, beta 2, [beta 3]
16
Q
Dopamine receptor subtypes
A
D1-D5
17
Q
Other receptors
A
for NANC transmitters
- -NO
- -vasoactive intestinal peptide
- -neuropeptide Y
18
Q
5 key features of neurotransmitter function that provide targets for drug therapy?
A
Synthesis Storage Release Reuptake Degredation
19
Q
If Synthesis and Storage blocked…
A
usually rate-limiting steps, so…
produce long-term effects, but not immediately effective
20
Q
If release blocked…
A
Rapid action and effective
21
Q
If reuptake blocked…
A
Increased synaptic neurotransmitter concentrations (selective or non-selective)
22
Q
If metabolism blocked…
A
reversible or irreversible:
increases transmitter levels
23
Q
If recognition is blocked…
A
Receptor antagonists and agonists…high specificity
24
Q
Sympathomimetic
A
mimicks… effects of impulses conveyed by adrenergic postganglionic fibers
25
Sympatholytic
anti adrenergic...
26
Fundamental difference b/w methods of inactivation of acetylcholine vs. norepinephrine
acetylcholine-->degraded
| NE-->reuptake
27
hemicholiniums
EXPERIMENTAL, NOT CLINICAL
block CHT (that transports Na and choline in)
28
Vesamicol
EXPERIMENTAL,, NOT CLINICAL
blocks VAT
29
Cotransmitters
modulation (enhance or diminish cholinergic activity)
30
Cholinergic Autoreceptors
ACh activates the receptors, but this inhibits further release of ACh
31
Blocking the Ca channels...
inhibits sweating?
32
Metabotropic
function through secondary messanger system
Muscarinic receptors
33
Ionotropic
ion channels
nicotinic
34
M1, M3, M5
Metabotropic
Gq
-->PLC-->IP3-->INCREASES INTRACELLULAR CALCIUM!!!
35
M2, M4
Metabotropic
Gi
blocks adenylate cyclase from making cAMP
inhibitory response
opens K channels (GiRK)
36
nicotinic receptors
ionotropic
increase intracellular Calcium, Na, PKC
amplifies effect
37
If drug not susceptible to cholineterase, then...
improves longevity of drug
| i.e. carbachol chloride and bethanechol chloride
38
metyrosine
inhibits tyrosine hydroxylase
| tyrosine synthesis to dopamine
39
Reserpine
Blocks VMAT
40
Cocaine, tricylic antidepressants
```
block NET
(prevents neurotransmitters from being broken down/ repackaged)
```
41
What process is critical for catecholamine neurotransmission?
reuptake!
42
Phenylephrine
Methoxamine
(receptor affinity)
alpha agonists
| alpha1>alpha2>>>>>>>>>>>beta
43
Clonidine
methylmorepinephrine
(receptor affinity)
alpha agonists
| alpha2>alpha1>>>>>>>>>>>>beta
44
Norepinephrine (receptor affinity)
mixed alpha and beta agonists
alpha1=alpha2
beta1>>beta2
45
epinephrine (receptor affinity)
mixed alpha and beta agonists
alpha1=alpha2
beta1=beta2
46
Does norepinephrine widen pulse pressure?
no
47
Why does epiniephrine widen the pulse pressure?
b/c of beta 2 receptors
48
dobutamine (receptor affinity)
beta agonists
beta1>beta2>>>>>>>alpha
49
isoproterenol
beta agonist
beta1=beta2>>>>>>alpha
50
Albuterol,
terbutaline
metaproterenol
(receptor affinity)
beta agonists
beta2>>beta1>>>>>>alpha
51
dopamine
dopamine agonist
| d1=d2>>beta>>alpha
52
Fenoldopam
dopamine agonist
| D1>>D2
53
ACh and muscarinic receptors have inhibitory effect on...
adrenergic and enteric neuron terminals
54
NE and alpha2 receptors have inhibitory effect on...
adrenergic neuron terminals
55
alpha1 adrenergic receptors
metabotrophic
Gq
GDP-->GTP-->phospholipase C-->IP3-->Calcium!!!-->protein kinase activation
56
beta catechloamine receptors
Metabotrophic
stimulatory
Gs
-->GDP-->GTP-->adenylate cyclase-->cAMP-->protein kinease-->enzyme-PO4-->biologic effect
57
alpha2 adrenergic receptors
Metabotrophic
inhibitory
Gi
-->GDP-->GTP-->BLOCKS adenylate cyclase!!!
58
beta2 agonist effect on smooth muscle
relaxes
| asthma treatment!
59
Ca channel blockers effect on smooth muscle
relaxes
60
COMT
| catechol-O-methyl transferase
drug target
| involved in catecholamine degredation/ synthesis
61
MAO
| monoamine oxidase
drug target
| involved in catecholamine degredation/ synthesis
62
Pheochromocytma
chromaffin tumors typically arising in adrenal glands secreting excessive catecholamines
63
how to diagnose pheochromocytoma
look for urinary catecholamine metabolites metanephrine and vanillylmandelic acid
64
L-DOPA
dopamine precursor
can be used in treatment of Parkinson's
--b/c can cross blood brain barrier (unlike dopamine)
--give w/ inhibitors in the periphery (where we don't want its effects)
65
MAOA inhibitors
block tyramine metabolism
- ->increased tyramine in blood circulation
- ->cheese rxn!! (must avoid many many foods)
66
Desensitization process
1. G-protein coupled receptor
2. drug ligand binds (dynamics of binding somewhat different than endogenous ligand)
3. duration and extent of drug binding causes...
4. accumulation of BETA-ARRESTINS
5. Receptors taken down from cell surface into cell in vesicles
6. fewer receptors means "less bang for the buck"
67
beta-arrestins
proteins involved in desensitization
68
Tachyphylaxis
"loss of activity" in relatively short space of time (tolerance to drug b/c of chronic, constant administration)
- -changes of metabolism
- -clonal expansion of resistant tumor
- -ect
69
what can stimulate glycogenolysis and gluconeogenesis in liver and why?
alpha1 and beta2 receptors in response to hypoglycemia
70
Why are beta blockers a problem for diabetics?
--nonselective beta blockers delay recovery from hypoglycemia in type 1 diabetics
--can interfere w/ counter-regulatory effects by blunting perception of hypoglycemic symptoms (tremor, tachycardia, nervousness)
Beta1-selective antagonist is preferred!
71
Pancreatic beta cells and insulin...
| alpha2 activation significantly...
decreases insulin secretion
72
Pancreatic beta cells and insulin...
| beta-2 activation...
inreases insulin secretion
73
The target tissue and insulin sensitivity...
| beta receptor activation...
increases receptor sensitivity
74
The target tissue and insulin sensitivity...
| beta-blockers
decrease insulin sensitivity
75
The target tissue and insulin sensitivity...
| beta-blockers (vasodilating...3rd generation... drugs
increase insulin sensitivity in pts w/ insulin resistance
76
Hormone sensitive lipase...
| non-selective beta-blockers...
lower HDL cholesterol and increase TGs
| little effect on LDL and total cholesterol
77
alpha1 receptors involved in...
vascular tone
urethral tone
ejactulation process
maintaining contractile state of penile arteries
78
alpha1 receptor blockage can result in...
orthostatic hypotension
relieved symptoms of BPH
sexual dysfunction
persistent priapism
79
Why, when alpha1-receptors blocked by promethazine, does the blood pressure drop, but the heart rate is still able to increase?
the receptors blocked are dominant in vessels but not in heart
80
peripheral anticholinergic effects
no innervation of blood vessels, but there are still receptors
xerostomia caused by ACh inhibition in salivary glands
treatment of hypersalivation
blurred vision; cycloplegia; mydriasis
constipation (b/c inhibition of GI smooth muscle)
IBS
urinary retention secondary to decreased muscle tone
muscarinic agonist or AChE inhibitor
81
NO
vasodilator
| GDP-->cGMP-->smooth muscle relaxation
82
Sidenafil (viagra)
vasodilator
inhibits cGMP break down to GMP
-->prolonged smooth muscle relaxation
83
what can blocking cholinergic and GABAergic pathways connected in hippocampus and basal forebrain complex do?
make us sleepy
84
Drugs w/ anticholinergic activity
1st generation antihistamines
antidepressants
etc.
85
Sumpathetic NS drugs
```
alpha-blockers
beta-blockers
centrally-acting drugs
transmitter depleting drugs
ganglionic blocking drugs
```
86
cardiotonic drugs
beta-agonists
alpha-agonists
muscarinic antagonists
