test 1: lecture 13 Flashcards
⍺1 adrenergic agonists will cause — in the heart
nothing, no ⍺1 receptors in the heart
phenylephrine (Neo-Synephrine), oxymetazoline (Dristan), tetrahydrozoline (Visine)
what are some ⍺1 adrenergic agonists
phenylephrine (Neo-Synephrine), oxymetazoline (Dristan), tetrahydrozoline (Visine)
what will ⍺1 adrenergic agnosists due to vasculature
vasoconstriction
this will trigger vagal effect and bradycardia
phenylephrine (Neo-Synephrine) is used for —
tetrahydrozoline (Visine) is used for —
nasal decongestant
eye redness
both are ⍺1 adrenergic agonists that cause vasocontriction and then vagal reflex
Activation of presynaptic α2 receptor causes —
decreased NE release from neurons
clonidine (catapres) is a —
⍺2 adrenergic agonist → causes hypotension
binds to presynaptic ⍺2 receptor and causes decrease in NE release
will also attach to autoreceptors within the CNS, that will decrease SYM outflow to periphery
Also stimulate postsynaptic α2 receptors in periphery on VSMC → vasoconstriction
what are two ⍺2 adrenergic agonists?
clonidine
xylazine
cause decreased NE release, decreased SYM outflow in the brain, cause vasoconstriction on vascular smooth muscle cells
Postsynaptic α2 receptor activation on VSMC in certain vascular beds result in — and a potential increase in —
vasoconstriction
BP
clonidine(catapres) and xlyazine (rompun) are ⍺2 adrenergic agonists
biphasic response of ⍺2 adrenergic agnoists
brief initial pressor (hypertensive) effect that is gradually reverses to hypotension
2B postsynaptic ⍺2 receptors on VSMC cause inital vasoconstriction→HTN
2A ⍺2 activation in the CNS reduces SYM tone causing low BP
2A ⍺2 activation of the presynaptic receptor located on peripheral sympathetic nerve terminals innervating vascular smooth muscle augments vasodilation
drug used to treat HTN
clonidine (catapres)
xylazine
⍺2 agonist that causes sedation and analgesia
because it binds to a2 receptors in the brain
what is rebound hypertension from a2 agonists
a2 on nerve stops NE release, smooth muscle cell increases receptors looking for NE, when you stop drug the extra receptors lead to bigger response
= vasoconstriction
rebound effect of a1 agonists
nasal spray
chronic use of a1 agonist, will cause decrease in a1 receptors. if you stop drug quickly, normal amount of NE will be released but there is now lower # of a1 receptors. This leads to leaky vessels and nasal congestion
nonselective B adrenergic agonists (B1/2) are used for —
B>a receptors
B1=B2
CHF → B1 increases cardiac contractility and CO
B2 activation causes brochodilation, used to treat asthma
isoproterenol (isuprel)
isoproterenol (isuprel) is a —
Nonselective β Adrenergic Agonists (β1/2)
isoproterenol (Isuprel) is used to treat
CHF: B1 activation causes increased cardiac contractility and increased CO
asthma: B2 activation leads to bronchodilation
B1/2 have B>a, with B1=B2
Nonselective β Adrenergic Agonists (β1/2)
B1 agonist is used to treat
short term CHF
increases force of cardiac contraction but does not effect HR
dobutamine (dobutrex)
dobutamine (dobutrex) is what type of drug
B1 adrenergic agonist
increases force of cardiac contraction but has minimal effect on HR
treatment of short term CHF
— are b2 adrenergic agonists
albuterol (Salbutamol)
Metaproterenol
B2>B1 at low dose
β2-stimulation ↑ bronchodilation and other smooth muscle relaxation
prevent premature labor by relaxing uterine smooth muscle
albuterol is used for
β2 Adrenergic Agonists
B2>B1 at low dose
β2-stimulation increased bronchodilation and other smooth muscle relaxation
Also used to prevent premature labor by relaxing uterine smooth muscle
if you give high dose albuterol what will happen
spillover to B1 receptors
albuterol is a B2 agonist that causes bronchodilation and other smooth muscle relaxation
— is a B3 Adrenergic Agonists
myrbetric (mirabegron)
B3 receptors are in brown fat, β3 receptor stimulation leads to increased lipolysis (fat breakdown)
B3 are also in bladder can be used to treat overactive bladder (OAB)
myrbetric (mirabegron) is what type of drug
β3 Adrenergic Agonists
used to treat overactive bladder
Sympathetic action on bladder causes relaxation of detrusor muscle and therefore a decrease in urge to urinate
what does myrbetric(mirabegron) do
Sympathetic action on bladder causes relaxation of detrusor muscle and therefore a decrease in urge to urinate
B3 agonist
how does tyramine and amphetamines get into the neuron?
presynaptic plasma membrane transporters
these are indirectly acting synpathomimetics
why dont ‘Indirectly acting’ sympathomimetics induce release of EPI from Adrenal gland?
indirectly acting symoathomimetics need to be transported into the cell by receptor: they then increase NE release
adrenal gland chromaddin cells do not have a way to reuptake EPI
tyramine and amphetamines are indirectly acting sympathomimetics that cause release of NE in nerve
indirectly acting sympathomimetics will be transported into the nerve terminal and cause
inreased release of endrogenous catecholamines (NE)
tyramine and amphetamine
what are three catecholamine reuptake inhibitors
cocaine
imipramine (impril)
amitryptyline (amitril)
allow NE,DA and serotonin to stay in synapse for longer, acts as antidepressants
how do reuptake inhibitor sympathomimetics work?
allow NE,DA and serotonin to stay in synapse for longer, acts as antidepressants
cocaine
imipramine (impril)
amitryptyline (amitril)
how do mixed acting sympathomimetics work?
Cause release of endogenous catecholamines and ALSO bind directly to adrenergic receptors
ephedrine
Adverse effect: Potential hypertension and cardiac arrhythmias
ephedrine
mixed acting sympathomimetics
Cause release of endogenous catecholamines and ALSO bind directly to adrenergic receptors
can cause: increase HTN, decreased bladder sphincter incompetence, increased bronchodilation for treatment of asthma
Adverse effect: Potential hypertension and cardiac arrhythmias
sudafed (pseudoephedrine) is a —
mixed acting sympathomimetic
Cause release of endogenous catecholamines and ALSO bind directly to adrenergic receptors
can also be used to make meth
phenylephrine (sudafed-PE)
is a mixed acting sympathomimetic
Cause release of endogenous catecholamines and ALSO bind directly to adrenergic receptors
can not be used to make meth!
what does guanethidine do?
decreases NE release from nerve terminal
guanethidine accumulates and replaces NE in vesicle
High doses cause TRIPHASIC effect
(1) Transient hypertension due to displaced NE
(2) Drop in BP due to decrease NE release
(3) Progressive drop in BP and cardiac output
used an an anti-hypertensive
GuaNEthidine prevents NE (norepinephrine) release
bretylium
blocks transmitted release by stopping release of NE vesicles
different from guanethidine which accumulates and replaces NE in vesicle
No BBB cross
no affect on EPI release form adrenal medulla cause it needs plasma membrane transporter to get into nerve
clonidine
a2 agonist
binds to a2 on presynaptic nerve, which stops NE release
reserpine
Blocks the uptake of DA and NE into synaptic vesicles by VMAT
Does not require transporter to enter cells
may also cause lower EPI in adrenal gland
long acting tranquilizer in horses
— blocks DA and NE uptake by VMAT into vesicles and does not need transporter to get into cells
reserpine
leads to decreased NE, cause cytoplasmic NE will get broken down by MAO
can also decrease EPI in adrenal gland
⍺-methyl-DOPA
false transmitter
gets into cell without transporter
cell thinks it is a normal DOPA and turns it into a-methyl-NE and released in the vesicle with normal NE
a-methyl-NE will not bind as strongly to a1 but will also bind to a2 autoreceptors→ decreases release of NE from the cell
a-methyl-dopa will use up the enzymes that usually make NE, will lead to smaller amount of NE released
— is a false transmitter release
α−methyl-DOPA
gets into cell without transporter
cell thinks it is a normal DOPA and turns it into a-methyl-NE and released in the vesicle with normal NE → a-methyl-dopa will use up the enzymes that usually make NE, will lead to smaller amount of NE released
a-methyl-NE will not bind as strongly to a1 but will also bind to a2 autoreceptors→ decreases release of NE from the cell
what are two things that block NE synthesis in the cell
α-CH3-p-tyrosine
NE at high doses
— inhibits tyrosine hydroxylase enzyme
α-CH3-p-tyrosine
— are MAO inhibitors
pargyline
moclobemide
Used as antidepressant. It blocks degradation of DA and Serotonin in CNS too
what is cheese syndrome
thyramine is found in cheese and wine, is usually degraded by MAO
if you use antidepressents like pargyline and moclobemide which inhibit MAO, can lead to build up of thyramine
can lead to hypertensive crisis
5 uses of a- adrenergic receptor blockage
hypertension: decreased a1 vasoconstiction leads to decreased peripheral resistance
CHF: lower arterial pressure improved CO
peripheral vascular disease (raynauds)
benign prostatic hyperplasia: decreases tone of prostate and urethral sphincter allows urinartion
shock: decrease shock mediated vasoconstriction to increase organ perfusion and fluid replacement
— are irreversible ⍺ receptor blockers
dibenamine
phenoxybenzamine
phenoxybenzamine and
dibenamine are — and work —
irreversible ⍺ receptor blockers
will bind nonselectively to a1 and a2 and break receptors
will need to wait for body to make new a1 or a2 receptors
— is a reversible ⍺ receptor blocker
phentolamine (regitin)
how does phentolamine (regitin) work
reversible ⍺ receptor blocker
a1=a2
if you block a2 autoreceptor that causes increased release of NE, which will trigger B1 in the heart and can lead to tachycardia
prazosin (minipress)
selective ⍺1 blocker
a1»a2
will block a1= decrease BP
does not affect a2 at low dose so no extra release of NE and no tachycardia (this is what happens with reversible ⍺ receptor blocker, phentolamine (regitin)
tamsulosin (flomax)
selective ⍺1 blocker
works on α1A- in urinary tract
used to improve urinartion with men you have Benign Prostatic Hyperplasia (BPH) → relaxes muscle
yohumbine
selective ⍺2 blocker
(only 40:1 a2>a1= high spill over)
will block a2 which causes increase of NE relased
this leads to increased HR and vasocontraction down stream
used to reverse xylazine induced sedation
yohimbine will reverse —
xylazine-induced sedation
yohimbine is a ⍺2 blocker
xylazine is a ⍺2 agonist
side effects of ⍺ receptor blockage
Postural Hypotension
* Block of α1 -mediated reflexive vasoconstriction upon standing → venous pooling → syncope
reflexive trachycardia
* a2 block will increase NE and cause tachycardia through B1
nasal stuffiness
* Block sympathetic tone on vessels in the nose leasing to increased in fluid leakage
beta blockers are used for
Afib
HTN- will decrease BP
Angina:
Anxiolytic: stop tremors and anxiety
glaucoma: decrease production of aqueous humor in the eye
propranolol(inderal)
non selective B blocker
B1=B2
decreases HR, contractility and CO
Membrane stabilization effect at high doses
large withdrawal and rebound effect
propranolol (inderal) withdrawal effect
non-selective B blocker
pindolol (calvisken)
nonselective B blocker
partial agonist: less withdrawal syndrome, less reduction in heart rate, but at high dose will cause increased HR,BP and brochodilation
timolol (timoptic)
B blocker
nonselective B1=B2
less membrane stabilization
used for wide angle glaucoma
metoprolol (lopressor)
selective B1 blocker
As potent as propranolol at β1 but 100X less potent at β2 Little effect on adrenergic β2 -mediated effects Cardioselective cause hitting B1 not B2
butoxamine
selective B2 blocker
Selective for blocking smooth muscle relaxation
No pronounced cardiac effects (No β1 action)
side effects of B blocker
cardiac failure: in CHF patients
bradycardia from decreased SYM to SA node
Bronchial asthma: cause bronchoconstriction
diabetics using oral hypoglycemics: B2 is needed to release EPI which causes release of glucose from liver, B blocker would cause hypoglycemic shock
