Chapter 10: Adrenergic Agents Flashcards
modulation of the sympathetic nervous system can be done in 2 ways: ___ and ___
interacting with adrenergic receptors (direct); modulating amount of NE released into synapses (indirect)
t/f alpa ardrenergic receptors have multiple isoforms within each subtype
true
where are a1 receptors located?
vascular smooth muscle, prostate, heart
stimulation of a1 receptors has what physiologic response?
contraction
what is the mechanism of a1 receptors?
couple to gq protein, increase ca, increase contraction
what is the locatio of the a2 receptors?
cns
stimulation of a2 receptors has what physiologic response?
decreased NT release, indirect effect on decreasing heart contraction
what is the mechanism for A2 receptors?
couple to Gi protein, decrease cAMP levels
congestion in allergic rhinitis is caused by
swelling surrounding vascular tissue by immune cells infiltrating the area in response to histamine
stimulating a1 receptors activates the ____ coupled protein, increasing ___ and ___ which increaing intracelluar ___ leading to the smooth muscle contraction
Gq; Dag anf IP3; ca
what is the effect of A1 receptor activation on the sinuses?
constriction of blood vessels, reducing leakiness and infiltration of immune cellls to the area, resulting in congection
phenylephrine is a ____ commonly found in over the counter decongestants like tylenol sinus and is also found in combination products like cold and flu remedies
A1 receptor agonist
the actions of phenylephrine to reduce congestion may have adverse effects in patients with ____
hypertension
blocking the A1 receptor reduces ____ of the prostate and facilitates ____ of the bladder
smooth muscle contraction; voiding
A1A is found in the ___ smooth muscle
prostate
A1B is found in the ___ smooth muscle
vascular
list 2 examples of A1A receptor antagonists
- prazosin
2. tamsulosin
what receptors does prazosin act on?
A1A and A1b adrenergic receptors
what is an off target effect of prazosin?
lowering blood pressure
tamslulosin is more selective for what type of receptor?
A1A adrenergic receptor (no effect on BP)
excessive use of local phenylephrine in nasal spray can cause ___ of the A1 adrenergic receptors
downregulation
if congestion gets worse as a result of down regulation of the A1 adrenergic receptor, will adding more agonist (decongestant drug) help?
NO!
presynaptically in the CNS, stimulation of A2 receptors ___ the release of NT
reduces
A2 receptors are often called ____ receptors
auto
the function of autoreceptors is to reduce ___ by limiting the amount of ___ that can be released in the synapse
over-stimulation; NT
A2 receptors are expressed on the ___ neurons
presynaptic
stimulation of the autoreceptors reduces excitability of the ___ neuron
presynaptic
explain the inhibitory process that follows the activation of an A2 receptor
Gi coupled signalling cascade is activated, inhibiting adenyl cyclase and reducing cAMP and reduced opeining of Ca channels whcih prevents the release of NE vessicles
clonidine is an example of an A2 adrenergic receptor ___
agonist
what is the function of clonidine?
stimulates A2 receptors to reduce the amount of released of NE
what is the therapeutic use of clondidine? In what patients does it work best in?
lower bp ; those not responding to other antihypertensives
which of the beta receptors are more widespread in the body?
B2
B1 receptors are located in the ___
heart
both B receptors cause the increase in production of ___
cAMP
both B receptors are coupled to what G protein?
Gs
stimulation of B 1 receptors causes
increased heart rate and contractility
what the effect of lung B2 stimulation?
bronchodilation
what is the effect of smooth muscle B2 stimulation?
relaxes
what is the effect of liver b2 stimulation?
glycogenolysis
NE, E and dobutamine are examples of B1 ____
agonists
dobutamine is a ___ B1 agonist that can be used in emergency situations to increase ___
synthetic; cardiac output
in cardiac cells, the increae in cAMP activates ___
PKA
what is the effect of PKA on cardiac cells?
phosphorylate voltage-gated ca channels, which increases the amount of Ca that enters the cells during membrane depolarization, therefore greater cardiac output
epinephrine causes an increase in the mean ____ bp
arterial
blocking B1 with propranolol prevents the actions on epinephrine in the ___ but not in the ___
cardiac muscle; blood vessels
competitive antagonists of B adrenergic receptors are typically called ___
beta blockers
the clinical use of propranolol has declined and selective b blockers like ___ are on the rise
metroprolol
metoprolol and other selective B blockers are preferred because they …
act in cardiac tissue and have fewer unintended effects
propranolol is a ___ beta blocker
non-selective
metoprolol is a ___ B blocker
selective
____ was one of the first clinically available B blockers for hypertension
propranolol
propranolol is very ____ , has a high ___ and can enter the ___
lipophillic, Vd; CNS
metoprolol has ___ agonist activity
inverse
topical b blockers in the form of eyedrops are used for treatment of ___ . Is this a common course of treatment for this condition?
glaucoma ; no but it used to be very popular
what are the 2 effects of using topical b blockers in glaucoma?
- decreases aq humour production
2. decreases IOP
give an example of topical beta blocker used in the treatment of glaucome
timolol
which beta receptor is suggested to be the path to lowering IOP in the use of timolol?
B2
timolol is a ___ B blocker
non-selective
in the lungs, modulation of B2 receptors is important to treating conditions such as ___ and ___
asthma and COPD
B2 are expressed extensively in the ____
lungs
endogenously, ___ has a higher affinity for B2 receptors than ___
E; NE
when the symapthetic system is activated, much of the response in the lungs is due to what NT?
epinephrine
____ is used to treat bronchoconstriction in anaphylactic shock
epinephrine
epinephrine has actions at A1 and B1 receptors, so to decrease bronchocondtriction, there are also significant cardiovascular effecst, why is this not too big of an issue?
half life of epinephrine is short, so effects are not prolonged
what is salbutamol?
synthetic B2 receptor agonist that is inhaled to cause bronchodilation
where does salbutamol act?
locally in the lungs
the action of salbutamol occurs ____
rapidly
when is salbutamol administered?
at onset of symptoms in patients with asthma
B2 agonists such as salbutamol are typically called ____ medications for the treatment of asthma
rescue
pseudophedrine is an example of a ___ adrenergic receptor agonist
mixed
pseudoephedrine can be found in some OTC ____ products, but has been controllled due to it being a starting material for making ___
cold and decongestant; methamphetamine (crystal meth_
the primary therapeutic target of pseudoephedrine is ___ receptors to cause ___
A1; vasoconstriction
pseudoephedrine also targets ___ receptors, which increases cardiac output
beta
the effect of pseudoephedrine on B receptors can be problematic for patients with ___
hypertension
t/f blocking both A and B receptors reduces BP more than if only one was activated alone
true
Carvediol is an ____ of B1, B2 and a1 receptrs
antagonist
what is the primary action of carvediol?
lower bp
carvediol binds reversibly or irreversibly?
reversibly
what is the order of receptor affinity from highest to lowest in carvediol ?
B1, A1, B2
blocking B2 may worsen they symptoms of __ and ___
asthma and COPD
blocking A1 may worsen the symptoms of ___
orthostatic hypotension
what patients should not take carvediol?
patients with asthma, COPD and hypotension
___-like drugs are structurally similar to catecholamines, thus are good substrates for catecholamine transporters
amphetamine
what is the action of amphetamine/
enters presynaptic cell ny NET, taken into the NE vessicles by VMAT and then displaces NE from the vessicle and accumulate in the cytoplasm until it is passively released into the synapse
are action potentials required for amphetamine to cause release of NE?
no
adderall is the amphetamine available as an RX for patients with
ADHD
speed is an example of an ___
amphetamine
when acting on the CNS, amphetamine in most people casues a ___
rush or a high
___ and ____ block the NET transporter, preventing NE reuptake into presynaptic neuron
cocaine and atomoxetine
therapeutically, atomoxetine is another Rx option for
ADHD
