test 4 Flashcards
How are adrenoceptors activated?
Through norepi or epi
What do adrenoceptors act on?
Act on neurons that release norepi
What does administration of epi cause?
Produces similar effects of stimulation of sns
Sympathetic response
What do alpha 1 receptors act on?
Vascular smooth muscle
Genitourinary smooth muscle
Intestinal smooth muscle
Heart
Liver
What do alpha 1 receptors do to the vascular smooth muscle?
Contraction
What do alpha 1 receptors do to the genitourinary smooth muscle?
Contraction
What do alpha 1 receptors do to the intestinal smooth muscle?
Relaxation
What do alpha 1 receptors do to the heart?
Increase intropy and excitability
What do alpha 1 receptors do to the liver?
Glycogenolysis and gluconeogenesis
What do alpha 2 receptors act on?
Platelets
Pancreatic beta cells
Nerves
Vascular smooth muscle
What do alpha 2 receptors do to platelets?
Aggregation
What do alpha 2 receptors do to the pancreatic beta cells?
Decrease insulin secretion
What do alpha 2 receptors do to nerves?
Decrease NE release
What do alpha 2 receptors do to vascular smooth muscle?
Contraction
What do Beta 1 cells act on?
Heart
Renal juxtaglomerular cells
What do beta 1 cells do to the heart?
Increase chronotropy and intropy
Increase AV node conduction velocity
What do beta 1 cells do renal juxtaglomerular cells?
Increase renin secretion
What do beta 2 cells act on?
Smooth muscle
Liver
Skeletal muscle
What do beta 2 cells do to smooth muscle?
Relaxation
What do beta 2 cells do to liver?
Glycogenolysis
Gluconeogenesis
What do beta 2 cells do to the skeletal muscle?
Glycogenolysis and K+ uptake
What receptor is the main cause of ateriole constriction and eye muscle contraction?
Alpa 1
What receptor causes the heart to increase rate and force?
Beta 1
What receptor causes the lungs to relax?
Beta 2
What receptor is responsible for decreased activity of intestines and dilation of skeletal muscle?
Beta 2
What are alpha 1 agonists used for?
Shock/hypotension
Nasal decongestant
What are alpa 1 antagonists used for?
Antihypertensives
BPH
What are alpha 2 agonists used for?
Antihypertensives
Glaucoma
Analgesia
Sedatives
What are alpha 2 antagonists used for?
We do not use them clinically
What are Beta 1 agonists used for?
There are none
What do we use Beta 1 antagonists for?
Antihypertensives
Antiarrhythmics
What are beta 2 agonists used for?
Bronchodilators
Glaucoma
What are beta 3 agonists used for?
Weight loss
What are beta 2 antagonists used for?
They are not used clinically
What does stimulation of the alpha 1 receptor cause?
Vasoconstriction
Increased peripheral resistance
Increased blood pressure
Mydriasis
Closure of the sphincter of bladder
What does stimulation of the alpha 2 receptor cause?
Inhibition of norepinephrine release
Inhibition of ACH release
Inhibition of insulin release
What does stimulation of the beta 1 receptors cause?
Tachycardia
Increased lipolysis
Increased myocardial contractility
Increased release of renin
What does stimulation of the beta 2 receptors cause?
Vasodilation
Decrease of peripheral resistance
Bronchodilation
Increased glycogenolysis
Increased release of glucagon
Relaxed uterus
What happens to catechols when they are exposed to air?
They are oxidized and the solution darkens to a highly colorized product
How are catechols metabolized?
By COMT
What are the non selective alpha 1 agonists?
Norepi and epi
Why arent NE and E used clinically alot?
They have limited clinical uses due to selectivity issues and oral bioavailability
Which is used more often? EPi or NOrEpi
EPI
Why is epi used?
For trauma (stimulation of the Beta 1 - heart muscle) - hypotension
What are the selective alpha 1 agonists?
Phenylephrine
Metaraminol
Methoxamine
Tetrahydrozoline
Oxymetazoline
Why do selective alpha 1 agonists have limited cardiac stimulation?
They are selective so they have little cardiac activity
What are alpha 1 selective agonists used for?
Nasal decongestants
Red eye
Why do selective alpha 1 agonists last longer in the body than E and NE?
They have a longer duration of action due to less catechol activity
What are alpha 2 agonists mainly used for?
Hypertension, sedative, and epidural enhancer
What are the alpha 1 selective agonists?
Clonidine, apraclonidine, brimonidine, Tizanidine, Guanfacine, Guanabenz, Methyldopa
What are apraclonidine and brimonidine used for?
Glaucoma and have little systemic effect
What is methyldopa used for?
Antihypertensive during pregnancy (metabolized into active compound = methylnorepinephrine)
What are the beta 1 agonists?
Dopamine and its analogues
What does Beta 1 agonism do?
Increased contractile force of the heart
Cardiac stimulation
We want to avoid this
When are beta 1 drugs used?
As a cardiac stimulant post surgery
What are Beta 2 agonists used for?
Bronchodilation
Short acting and long acting
Asthma
COPD
What kind of drug is isoproterenol?
Beta 2 short acting agonist
Why is isoproterenol not used?
It has beta 1 type side effects due to an isopropyl group as the amine side chain
Has a catechol that makes it unstable
What kind of drug is albuterol?
Short acting beta 2 agonist
Why is levalbuterol 4 times more potent than albuterol?
It is the pure isomer and not the racemic mixture but it is more expensive and time consuming to make
What kind of drug is salmeterol with flucticasone (Advair)?
Long acting Beta 2 agonists
What makes a beta 2 agonist long acting?
Much higher LogP due to a long lipophilic side chain
What kind of drug is formoterol with budesonide (symbicort)?
Long acting beta 2 agonist
4 times more potent than advair
What makes a drug a mixed acting sympathomimetic?
It is a drug that acts both directly and indirectly (directly activates receptor and causes release of NE)
What are mixed acting sympathomimetics used for?
Nasal decongestant (Sudafed)
What drugs are alpha 1 selective antagonists?
Prazosin, Terazosin, Tamsulosin, Doxazosin, Alfuzosin, Sildosin
What do alpha 1 A receptors do?
Decrease smooth muscle contraction of the prostate while B is vasculature
What kind of drug is Yohimbe?
Alpha 2 agonist
What does yohimbe do?
induce hypertension
Increase heart rate
No clinical use but can be used for impotence and orthostatic hypotension
What do Beta 1 antagonists do?
Decrease contractile force and decrease blood pressure
What is the difference between olols and alols?
Olols are for aryloxypropanolamines
Alols are for arylethanolamines
What do beta blocker do to decrease blood pressure?
They compete with catecholamines for Beta 1 and 2 binding to treat hypertension
What are olols used for?
Glaucoma and hypertension
What are the ADRs of non selective beta blockers?
Fatigue
Bronchoconstriction
Sexual dysfunction
Arrhythmias from withdrawls
What pneumonic device can you use to see if the beta blocker is selective “clean” or not?
BEAM (if they start with these letters they are clean as well as Nebivolol and except Metipranolol)
What enzyme converts tyrosine to L DOPA
Tyrosine hydroxylase
What molecule inhibits tyrosine hydroxylase?
Alpha methyl tyrosine
What enzyme converts LDOPA to dopamine
Dopa decarboxylase
What molecule inhibits dopa decarboxylase?
Carbidopa
What enzyme converts dopamine to norepinephrine?
Dopamine beta hydroxylase
What takes up dopamine into vesicles?
VMAT
What inhibits VMAT?
Reserpine
Why do you need to transport dopamine into a vesicle?
MAO will degrade the dopamine in the cell
What enzyme converts NE to E?
Phenylethanolamine N Methyl transferase
What produces E?
adrenal medullary cells
What are the two ways to terminate catecholamine neurotransmission?
Reuptake
Diffusion away from synapse
What is the major way to terminate catecholamine neurotransmission?
Presynaptic reuptake
What blocks reuptake of catecholamines?
Cocaine and antidepressants and amphetamines
What does COMT do?
Metabolizes NE, E, and DA and is excreted into the urine and not reuptaked
What kind of G protein is alpha 1?
Gq
What kind of G protein is alpha 2?
Gi
What kind of G protein is beta?
Gs
What does alpha 2 activation do inside of the cell?
Inhibits adenylate cyclase (decrease PKA and CAMP and increase K+ so it hyperpolarizes the cell to inhibit it)
What does alpha 1 activation do inside the cell?
Increase phospholipase C (Increase IP3, DAG, Ca2+ from ER)
What is unique of the beta 2 variant of agonist potency?
Beta 2 - epinephrine has much greater effect than NE unlike others where they are the same
What does systolic tell you?
Strength and volume of cardiac output
What does diastolic tell you?
Peripheral vascular resistance
What does mean arterial pressure tell you?
Tissue perfusion pressure
Monitered by baroreceptors
Heterologous
PKA
Homologous
Beta arrestin
BARK
What class is epinephrine and norepinephrine in?
Nonselective adrenergic neurotransmitters
What does reserpine do?
Blocks VMAT
VMAT takes up neurotransmitters into vesicles so they are not degraded by MAO so this would reduce the amount of neurotransmitters available
What class of drug is amphetamine?
Indirect acting sympathomimetic
Why is NE and E not typically used in clinical settings?
They have selectivity issues and oral bioavailability issues
Which is used more, E or NE?
E
When is epi used?
During trauma situations (trauma based hypotension
What class of drug is Phenylephrine?
Alpha 1 selective agonist
What is phenylephrine used for?
Nasal decongestant
Sudafed PE
What class of drug is Tetrahydrozoline?
Selective alpha 1 agonist
Visine
What is tetrahydrozoline?
Reduce red eye
What class of drug is oxymetazoline?
Selective alpha 1 agonist
Afrin
What does oxymetazoline do?
Used as a nasal decongestant
Why do selective alpha 1 agonists have little or minimum cardiac stimulation?
Because they are not selective to the beta receptors (beta1) that stimulates the heart
Why do selective alpha 1 agonist have a longer duration of action compared to E and NE?
Because they do not have catechols so are not sucseptible to COMT
What class of drug is clonidine?
Selective alpha 2 agonist
Catapres
Why is clonidine considered a flag ship compound?
It was used as an alpha 1 nasal decongestant but they noticed a significant reduction in blood pressure so they found alpha 2 activation
What do alpha 2 receptors primarily do when stimulated?
Decrease the amount of NE released into the cleft
What class of drug is apraclonidine?
Selective alpha 2 agonist
Iopidine
What is apraclonidine used for?
eye drops for glaucoma
What class of drug is brimonidine?
Selective alpha 2 agonist
Alphagan P
What is brimonidine used for?
Glaucoma
What class of drug is Guanfacine?
Selective alpha 2 agonist
Tenex, Intuiv
What class of drug is alpha methyldopa?
Selective alpha 2 agonist
Aldomet
What is alpha methyldopa used for?
Antihypertensive during pregnancy
It is metabolized into methylnorepinephrine
What class of drug is Dobutamine?
Beta 1 agonist
What is dobutamine used for?
Only used as a cardiac stimulant post surgery
What do you need for beta 2 selectivity?
A t butyl or greater group on the amine
an OH on the beta carbon
What class of drug is Isoproterenol?
Short acting beta 2 agonist
Why is isoproterenol not a good drug?
It has beta 1 side effects due to the isopropyl group on the amine
It has a catechol so it is not stable
What class of drug is albuterol?
short acting beta 2 agonist
Proventil, Ventolin, ProAir
What class of drug is levalbuterol?
Short acting beta 2 agonist
Xopenex
What is the difference between levalbuterol and albuterol?
albuterol is a racemic mixture
levalbuterol is the pure active isomer which makes it 4 times for potent as a bronchodilator
What is albuterol and levalbuterol used for?
it is a rescue inhaler so for acute symptoms
What class of drug is salmeterol?
Long acting beta 2 agonist
With fluticasone = Advair
Without = serevent
What is Salameterol used for?
Chronic or daily use for asthma and COPD
NOT FOR ACUTE SYMPTOMS
What class of drug is formoterol?
LABA
What makes a beta 2 agonist long acting?
It has a lipophilic long side chain that interacts with the exosite so the drug can keep interacting over and over with the binding site or active site
What is the main difference between formoterol and salmeterol?
faster onset for formoterol
What class of drug is pseudophedrine?
Mixed acting sympathomimetic
What is the main side effect of pseudophedrine?
Increase in blood pressure from indirect activity
What class of drug prazosin?
Alpha 1 selective antagonist
Minipres
What is Minipress used for?
Hypertension and BPD (not FDA approved for BPH)
What is the difference between alpha 1 A and alpha 1 B?
Alpha 1 a has selectivity for the prostate (used for bph)
Alpha 1 B has selectivity for the vasculature (hypertension)
What is the USAN for quinazolines?
Azosin
What class of drug is terazosin?
Selective alpha 1 antagonist
Hytrin
What is Hytrin used for?
Hypertension and BPH
What class of drug is tamsulosin?
Selective alpha 1 antagonist
Flomax
What is tamsulosin used for?
BPH
What class of drug is doxazosin?
Selective alpha 1 antagonist
Cardura
What does doxazosin treat?
BPH mainly
What class of drug is Alfuzosin?
Selective alpha 1 antagonist
Uroxatral
What is alfuzosin used for?
BPH
What class of drug is silodosin?
Selective alpha 1 antagonist
What is silodosin used for?
BPH
What class of drug is yohimbine?
Alpha 2 antagonist
Herbal not FDA approved
What does yohimbine treat off label?
Impotence
orthostatic hypertension
What do selective beta 2 blockers treat?
Glaucoma and hypertension
What is added to the drug for it to be an antagonist?
A bulky side chain
What are the adr’s of selective beta blockers?
Fatigue
Bronchoconstriction
Sexual dysfunction
Arrhythmias upon withdrawls
what pneumonic device is used to see clean beta blockers?
BEAM
Plus Nebivolol
What is the rate limiting step for making neurotransmitters?
Tyrosine to LDOPA through tyrosine hydroxylase
How do you get from LDOPA to Dopamine?
DOPA decarboxylase
How do you get from dopamine to Norepinephrine?
Dopamine Beta Hydrolase
How do you get from NE to E?
Phenylethanolamine N methyl transferase
What are the two ways to terminate catecholamine neurotransmission?
Reuptake (presynaptic is major)
Diffusion away from the synapse
What drugs block reuptake?
Antidepressants and Cocaine
What metabolizes E, NE, and DA and excretes it in the urine?
COMT
Why is alpha 2 receptor considered an autoreceptor?
it is inhibitory and is on the presynaptic neuron unlike the others which are on the postsynaptic neuron
How do alpha 2 receptors create an inhibitory response?
Increase K currents to hyperpolarize the cell
What kind of G coupled receptor is alpha 1?
Gq
What does Gq alpha 1 receptor do in the cell?
Increase IP3, DAG, Ca2+, and turns on phospholipase C
What kind of G coupled receptor are the beta receptors?
All are Gs
Which has a greater effect on beta 2, E or NE?
E
What does systolic pressure measure?
Cardiac output
What does diastolic pressure measure?
PVR
What is mean arterial pressure?
Tissue perfusion pressure monitered by baroreceptors
Why does phenylephrine help with nasal decongestion?
The mucosal membranes are highly vascularized and if you constrict the vasculature, it reduces the pressure in the nose
What are two off label uses for clonidine?
Sedative
Epidural enhancer
What kind of spacer does clonidine and its derivatives have?
An N and C spacer
What are the three major determinants of action of a drug?
Relative potency of amine or drug (is it alpha or beta)
Dominant tone
Reflex and other homeostatic adjustments
What is the main difference between reuptake 1 and 2?
Reuptake 1 has a high affinity for NE but is slow
Reuptake 2 has a low affinity for NE but is fast (protective mechanism if there is too much NE in the cleft)
What are the two ways a receptor can be desensitized?
Changes in the receptor or receptor coupling
Receptor sequestration (tachyphylaxis)
What is inotropic?
Contractile force
What is chronotropic?
Increase in hr and conduction velocity
What is the core drug structure of sympathomimetics?
Phenylethanolamine
What kind of drug is amphetamine?
Indirect acting sympathomimetic
How does amphetamine cause an increase in calcium release?
Taken in by VMAT and moves NE out into the cytosol. It is a weak MAO inhibitor so it also inhibits the break down of NE and E
What is the main difference between amphetamine and tyramine?
It is Calcium independent it is metabolized by MAO
What kind of drug is methylphenidate?
Psychostimulant
Indirect agonist
What kind of drug is Concerta?
Psychostimulant
indirect agonist
How does concerta work in terms of delayed release?
Causes osmotic release
Immediate release and then the device delays release to different compartment
What is phentermine (adipex P) used to treat?
Obesity
What drug is a mydriatic agent but wont cause cycoplegia (cilliary muscle constriction)?
Phenylephrine
Alpha receptors are not on the cilliary muscle
What drug causes an increase of blood pressure and reflex bradycardia?
Phenylephrine
How do you stop reflex bradycardia from phenylephrine?
Add a ganglionic blocer
no ACh on heart so no reflex bradycardia
What class of drug is midodrine (orvaten)?
Alpha 1 agonist
What is midodrine used to treat?
Orthostatic hypotension
What class of drug is hydroxyamphetamine and tropicamide (Paremyd)?
Alpha 1 agonist
What does hydroxyamphetamine and tropicamide (Paremyd) treat?
It is a mydriatic agent so glaucoma
What class of drug is Droxidopa (Northera)?
Alpha 1 agonist
What is Droxidopa used to treat?
Orthostatic hypotension (neurogenic)
Prodrug of NE and E, Metabolized into neurons by the DOPA decarboxylase
What kind of drugs are imidazolines?
Alpha 1 agonist
What are the main side effects of clonidine?
Dry mouth
What kind of drug is Precedex/dexmedetomidine?
Alpha 2 agonist
Sedative for ICU
