adernergic agonists Flashcards
where can you find adrenergic receptors?
post synaptic in the sympathetic effector organs
or pre synaptic on the neuron
what are the steps of neurotransmission at the adrenergic neurons?
The process involves 5 steps: synthesis, storage, release, and receptor binding of norepinephrine, followed by removal
what are the two types of adrenergic receptors and how where they classified
alpha (a) and beta (b)
alpha has high affinity for epinephrine>norepinephrine>isoproterenol
beta has high affinity for isoproterenol>epinephrine>norepinephrine
where are alpha1 receptors located and what G protein do they activate
found on thr postsynaptic membrane if the effector organs.
they activate Gq protein—–> phospholipase C which increase IP3 and DAG
where are alpha 2 located and what result from their activation?
they are located on the sympathetic and parasympathetic presynaptic nerve endings.
they control the release of norepinephrine (inhibitory heteroreceptors) and acetylcholine (inhibitory heteroreceptors).
they work by GI protein—–inhibits adenylyl cyclase—–fall in cAMP levels.
MAO—-when norepinephrine binds to the alpha2 receptors it sends an inhibitory signal to stop the release of norepinephrine (auto inhibition) or acetylcholine (hetero inhibiton)
what are the further subdivisions of alpha receptors
alpha1—-a,b,c,d
alpha2—–a/b/c
what are the differences between beta1 and beta2 receptors
beta 2 has a higher affinity for epinephrine than norepinephrine while beta1 has the same affinity
what is the G protein for beta receptors
Gs proteins——-activates and increases adenylyl cyclase—–more cAMP
remember that
Adrenergically innervated organs and tissues tend to have a predominance of one type of receptor.
example: skeletal muscles have both a1 and B2 but B2 predominantes
Other tissues may have one type of receptor exclusively, like the heart which have B1 only
what does the simulation of ALPHA1 leads to
vasoconstriction
increased peripheral resistance
increased blood pressure
mydriasis (dilated pupils)
increased closure of internal sphincter of the bladder
what does alpha2 activation leads to
inhibition of norepinephrine and acetylcholine and insulin release
what does the activation of beta1 receptors lead to
tachycardia
increased lipolysis
increased heart contractility
increased release of renin
what does the activation of beta2 lead to
vasodilation
decreased peripheral resistance
bronchodilation
increased glycogenolysis
increased glucagon
relaxed uterine smooth muscle
what are the three mechanisms that explains the desensitization of adrenergic receptors
1) sequestration of the receptors so that they are unavailable for interaction with the ligand
2) down-regulation, that is, a disappearance of the receptors either by destruction or by decreased synthesis
3) an inability to couple to G-protein, because the receptor has been phosphorylated on the cytoplasmic side.
what do adrenergic agonists look like and what are the important structural features
they look like b-phenylethylamine derivatives
•1) the number and location of OH substitutions on
the benzene ring
•2) the nature of the substituent on the amino
nitrogen.
what are the properties of catecholamines
high potency
rapid inactivation
poor penetration into the cns
how do non-catecholoamines differ from catecholamines
they lack the catechol hydroxyl groups
have a longer half life
cant be inactivated by COMP
can go through theCNS
what does the subsititutions on the amine nitrogen determine
the Beta selectivity
answer the following about Epinephrine
is it a direct or indirect acting
where is it secreted from
compare the actions at low and high dose
what are the effects on the
heart,renin,arterioles,bp,respiratory,blood sugar
what are the therapeutic uses
what are the side effects
- direct acting
2.from the adrenal medulla
3.at low doses effects beta receptors (vasodilation), at high doses effects the alpha receptors (vasoconstriction)
4.increases the contractility(b1)
increases heart rate (b1)
increases cardiac output and oxygen consumptions
increases renin releases
vasodilators
increases systolic bp while lowers diastolic
powerful bronchodilation
hyperglycemia (increased glucagon and glycogenolysis)
increased lipolysis
5.used for bronchospasm, anaphylactic shock, cardiac arrest,improving local anesthesia at low conc( by causing vasoconstriction at the site of injection thus reducing the systemic absorption and giving a longer effect) , and intraocular surgery to maintain mydriasis
6.cns effects that include anxiety, fear, tension,headache, and tremor.
cardiac arrhythmias
pulmonary edema
have an increased CV actions with patients with hyperthyroidism
Inhalation anesthetics also sensitize
the heart to the effects of epinephrine, which may lead to tachycardia
increases the release of endogenous stores of glucose. In diabetic patients, dosages of insulin may have to be increased
can be given by IV, SC and inhalation
answer the following about norepinephrine
is it direct acting?
affinity for what receptor?
what are the actions
what is the drug interaction with atropine
what are the therapeutic uses
how is it given\ what is the duration
what are the side effects
- yes
- alpha
- a) vasoconstriction
b) baroreceptor reflex ( causes a reflex bradycardia effect) - when atropin is given before norepinephrine it causes tachycardia
- used for treating shocks like septic shocks
- given by IV lasts for 1-2 mins
- similar to epinephrine, can cause blanching and sloughing of the skin along the injected vein due to it bring a potent vasoconstrictor, If extravasation occurs, it can cause tissue necrosis
answer the following about Isoproterenol
is it direct acting
stimulate which receptors
is it used therapeutically
what are the effects
what are the side effects
- direct acting synthetic
- beta 1 and 2
- rarely used due to it nonselectivity
- on the heart—-it increases the HR, contractility and output
on the arterioles of skeletal muscle& peripheral
resistance——-dilates the artioles and decreases the resistance
slightly increases the systolic BP and greatly reduces the diastolic BP
it is a potent bronchodialter and may be useful in AV shock
- similar to Beta receptor-related side effects of epinephrine
answer the following about Dopamine
which receptors are activated by it
what are the effects on high and low doses
it binds to D1 and D2 where are they located and what are the effects
what are the actions
what are the therapeutic uses
what are the side effects
- alpha and beta
- at high doses—-causes vasoconstriction (alpha)
at low —- causes tachycardia (beta)
note: its similar to norepinephrine - they are located in the peripheral mesenteric and renal vascular beds, where binding of dopamine produces vasodilation. D2 receptors are also found on presynaptic adrenergic neurons, where their activation interferes with norepinephrine release.
- on the CVs—–low dose—-beta1 stimulation
at high dose—-alpha 1 stim—vasoconatruction
on the renal and visceral—dilation of the renal arterioles—increses bloodflow (by effecting the D receptors)
5.cardiogenic and septic shocks, and hypotension and severe HF
6.has the same effects as sympathetic stimulation such as nausea,hypertension,arrhythmias by its short lived due to the rapid metabolizim by MAO and COMT
answer the following about Fenoldopam
agonist of what receptor
what is the clinical use
what is the effect on the arterioles, and mesenteric arteries?
what is the half time after IV
- D1
- used ad a vasodilator to treat sever hypertention
- dilates them
- 10 mins
extra notes from the book
R-isomer is active
Headache, flushing, dizziness, nausea, vomit and tachycardia( due to vasodilation
answer the following about Dobutamine
is it synthetic
agonist to what receptor
what are the major effects
what are the therapeutic uses
what are the adverse effects
- yes
- majorly Beta1 but with minor Beta2 and Alpha1 effects
3.increses heart rate and cardiac output
- It is used to increase CO in acute CHF as well as for inotropic support after cardiac surgery.
5.the same as those for epinephrine.
• Avoid in atrial fibrillation because it increses AV conduction
tolerance my be developed
answer the following about oxymetazoline
its a direct synthetic agonist to what receptor
what are the efffects
found in what?
what is the MAO
what are the side effects if it entered the systemic circulation
what are the long term side effects
- alpha 1 and 2
- vasoconstrction and decreases congestion
3.found in many over-the-counter nasal spray
decongestants, as well as in ophthalmic drops for the relief of redness of the eyes associated with swimming, colds, and contact lenses.
4.stimulates the the alpha receptors on the blood vessels supplying the nasal mucosa and conjunctiva and causing vassoconstriction
5.nervousness, headaches, and trouble sleeping (cns)
6.Use for greater
than 3 days is not recommended, as rebound congestion and depen-
dence may occur.
answer the following about phenylephrine
• It is a direct-acting drug that binds primarily to which α receptors?
• What is its effect on blood vessels and systolic and diastolic BP?
used for the treatment of what
used in nasal and ophthalmic solutions for what
- alpha 1
- vasoconstrictor that raises both systolic and diastolic blood pressures. It has no effect on the heart itself but, rather, induces reflex bradycardia
- used to treat hypotension
4.nasal decongestant and for mydriasis
note— has been replaced by pseudoephedrine due to the misuse to make crystal meth (walter white)
answer the following about Midodrine
its a prodrug of what
agonist to what receptor
used for what
whats the dose
- desglymidodrine
2.selective alpha1
- acts in the periphery to increase arterial and venous tone. Midodrine is indicated for the treatment of orthostatic hypotension.
4.3 times daily
answer the following about Clonidine
agonist to what receptor
used for what disease
what are the other uses
how How does Clonidine decrease sympathetic outflow to the periphery?
- alpha 2
2.used in managment of ADHD
3.the treatment of hypertension. It can also be used to minimize symptoms of with drawal from opiates, tobacco smoking, and benzodiazepines.
4.Clonidine acts centrally on presynaptic~ receptors to produce inhibition of sympathetic vasomotor centers, decreasing sympathetic outflow to the periphery.
answer the following about Albuterol ,metaproterenol& terbutaline
what are the uses
what are the side effects
what happens when they are systemically administered
- they are SABA bronchodilators (metered dose MDI)
- tremor, but patients tend to develop tolerance to this effect. Other side effects include restlessness, apprehension, and anxiety.
3.tachycardia or arrhythmia (due to B1 receptor activation), especially in patients with underlying cardiac disease
answer the following about Salmeterol and formoterol
what are the used for
how do they differ from SABA
are they used as monotherapy
1.they are LABA
- the dose last longer
- not recommended as monotherapy but are
highly efficacious when combined with a
corticorsteroid.
answer the following about Mirabegron
•Is an agonist at which receptor?
•What is its effect on the urinary bladder?
•It is used for patients with what disorder?.
•It may increase BP and should not be used in patients
with uncontrolled HTN.
•Dose higher than (200 mg) are not recommended why?
- beta 3
- relaxes the detrusor smooth muscle and creases the capacity
3.overactive bladder
4.It increases levels of digoxin and inhibits the CYP2D6 isozyme, which may enhance the effects of other medications metabolized by this pathway for example, metoprolol
answer the following about amphetamine
is it direct acting?
what are the CNS effects
whats the bp effect
what is the mao
- no, indirect acting
2.stimulates the brain and abused by drug abusers
- increases the bp and heart rate
4.by increasing the release of catecholamines such as dopamine and norepinephrine
answer the following about tyramine
is it direct acting
is it clinically useful
where is it found
how is it metabolized
whats the moa
What happens if a patient taking is MAOIs and takes it
- no, indirect
2.no
- in fermented food
4.oxidized by MAO in the GIT
- increases the release of catecholamines
- it can precipitate serious vasopressor episodes
answer the following about Cocaine
is it indirect
what the moa
- yes
- blocks the sodium-chloride dependent norepinphrine transporter thats required for uptake of norephinphrine
cause norepinephrine accumulates in the synaptic space
resulting in enhancement of sympathetic activity
• Therefore, small doses of the catecholamines produce greatlymagnified effects in an individual taking cocaine.
• In addition, the duration of action of epinephrine and
norepinephrine is increased
answer the following about ephedrine and pseudoephedrine
what does mixed agonist means
why do they have a long duration
can they get into the cns
whats the effects
1.They not only enhance release of stored norepinephrine from nerve endings but also directly stimulate both a and p receptors
- they are are poor substrates for COMT and MAO. Therefore, these drugs have a long duration of action.
- yes ephidrine more the pseudo
4.Ephedrine raises systolic and diastolic blood pressures by vasoconstriction and cardiac stimulation and it is indicated in anesthesia-induced hypotension. Ephedrine produces bronchodilation, but it is less potent and slower acting than epinephrine or isoproterenol.
Oral pseudoephedrine is primarily used to treat nasal and sinus congestion.
thier usage has been limited due to the usage in making crystal meth
