Lectures 9 and 10- Adrenergic pharm Flashcards
what is the minor component of establishment of resting potential (electrochemical gradient)?
ion flux from Na/K ATPase pump activity
what is the major component of establishment of resting potential (electrochemical gradient)?
potential arising from different membrane permeabilities of Na and K (K channels leaky)
K is … more permeable than Na
100x
excitable cells have special membrane proteins that are specific channels for Na and K. These proteins are called …. channels because they can be open or closed based on potential difference across the membrane.
The channel for Na responds … to changes in voltage and the K channel responds …
voltage gated
faster
slower
APs in cardiac tissue are much … than in nerve or skeletal muscle
slower
simplified timeline of AP
- Na enters through ligand gated channels. cell begins to depolarize
- threshold depolarization is reached causing voltage sensitive Na channels to open
- depolarization spreads
- K channels open (slower)
- Na and K close. system back to hyperpolarized resting state
synaptic transmission timeline
- Ap in nerve terminal opens calcium channels
- calcium entry causes vesicle fusion and transmitter release
- receptor channels open, Na enters the postsynaptic cell and AP resumes
the ganglia in the sympathetic system are close to the … in a chain
spinal cord
the ganglia in the parasympathetic system are close to
the target organ
sympathetic innervation comes from which part of the spinal cord?
thoracolumbar
parasympathetic innervation comes from which part of the spinal cord?
craniosacral
postganglionic fibers in the sympathetic system are
long
postganglionic fibers in the parasympathetic system are
short
is there more branching in the symp or parasymp system
sympathetic
alpha1 (some alpha2) receptors on … cells increase calcium, increase activity of a MLCK, increase myosin light chain phosphorylation and increase muscle contractility
smooth muscle
phosphorylated … is essential for muscle contraction
MLC
… receptors are most important at presynaptic termini, they inhibit epi and norepi release (CNS and PNS)
alpha2
alpha2 … enhance CNS response
antagonists
alpha2 … attenuate CNS response
agonists
alpha2 antagonists … HR
alpha2 agonists … HR
increase
decrease
vasoconstrictor or vasodilator? a1 agonist a1 antagonist a2 agonist a2 antagonist
vasoconstrictor
vasodilator
vasodilator
vasoconstrictor
… receptors on smooth muscle cells increase PKA, phosphorylate and inhibit MLCK, diminish calcium levels and inhibit MLCK, diminish phosphorylation of MLC and decrease muscle contractility
beta2
cAMP activates … which in turn inhibits MLCK
PKA
PKA mediated phosphorylation also activates … which leads to hyperpolarization leading to reduction in cellular calcium producing smooth muscle relaxation because MLCK activity is attenuated
K channels
… receptors on cardiac muscle cells activate PKA, activate L type calcium channels, increase calcium levels and increase muscle contractility
b1
the … receptor is the dominant receptor in cardiac muscle. drugs that activate this receptor improve contractility of heart, increase HR and excess stimulation can results in arrythmias
b1
activation of the … receptor leads to vascular and non vascular smooth muscle relaxation. (reduce BP, broncodilation, reduce uterine contraction)
b2
there are a large number of … receptors relative to … receptors on vascular smooth muscle. activation of these will lead to vasoconstriction
a1
b2
epi’s actions in an emergent situation
stim alpha: increase BP
stim b1: positive cardiac effects
stim. b2: bronchodilation
methoxamine, phenylephrine, levonordefrin, midodrine, oxymetazoline, metaraminol are all
alpha1 receptor agonists (increase BP)
denopamine, dobutamine, xamoterol, isoprenaline are all
b1 receptor agonists (treat heart failure)
albuterol, pirbuterol, isoprenaline, formoterol, clenbuterol are all
b2 receptor agonists (smooth muscle relax)
… is used to reverse soft tissue numbness after administration of local anesthetics with vasoconstrictors. injected when pain relief is no longer needed
phentolamine
beta blockers will …. renin release from kidney
diminish
ISA stands for
intrinsic sympathomimetic activity (partial agonist)
beta blockers without ISA…
decrease HR, decrease renin activity, decrease CO
beta blockers with ISA
do not depress cardiac fxn or renin activity but do attenuate agonist driven increases
beta blockers can also reduce vitreous production to treat …
glaucoma
beta blockers that get into the CNS can be used to treat … and …
migraine
tremor associated anxiety
2 blockers that are alpha receptor and beta receptor antagonists
labetalol
carvedilol
…. is 7x more potent as a beta blocker, ISA activity, used in long term management of HTN
labetalol
…. no ISA activity, effective in tx of CHF, antioxidant activity
carvedilol
clonidine causes
xerostomia
cholinergic receptors comes in 2 types:
nicotinic and muscarinic
odd numbered muscarinic receptors (M1,M3,M5) are linked to …
Gaq (activate DAG and IP3 signaling)
even numbered muscarinic receptors (M2, M4) are linked to ….
Gai (inhibit adenylate cyclase)
cholinergic agonists can either be … or …
direct acting
indirect acting
direct cholinergic agonists bind to ….
muscarnic or nicotinic AcCH receptor or both
indirect acting cholinergic agonists are ….
cholintesterase inhibitors (acetylcholine will stick around longer)
hydrolysis by cholinesterase has a profound effect on the duration of action of ….
cholinergic agonists
acetylcholine is hydrolyzed …. and has the … duration of action
rapidly
shortest
methacholine is hydrolyzed…. somewhat …duration of action (compared to acetylcholine)
slower
longer
carbachol is … hydrolyzed so longer duration of action
not
which are more clinically relevent? muscarinic or nicotinic agonists?
muscarinic
does acetylcholine affect muscarinic or nicotinic specificity ?
non selective
does carbachol favor muscarinic or nicotinic receptors
nicotinic
does methacholine favor muscarinic or nicotinic receptors
muscarinic
