Pharmacology - Shock Part 1 Flashcards
define shock
inadequate tissue perfusion due to hypotension. ultimately leads to organ system failure
in shock, there is an imbalance between what 2 things
oxygen supply and oxygen demand
name 4 types of shock
hypovolemic
distributive
obstructive
cardiogenic
formula for blood pressure
how do each of the components relate to shock
BP = CO * SV
in shcok patients, vasopressors work to increase the stroke volume and inotropes work to increase the heart rate and thus increase cardiac output
3 classes of pharmacotherapy used for shock
catecholamines
vasopressin
PDE inhibitors (milrinone)
“inotrope” means increase in ____
contractility
result of ligand binding to a1 vs a2
a1 - Gq couples. IP3, DAG, increase intracelllar calcium
a2 – Gi coupled. inhibition of AC and decreased cAMP
true or false
a1 receptors are mainly located in the smooth muscle
true
result of ligand binding to B1 vs B2 vs B3
B1 - increased AC and cAMP
B2 - increased AC and cAMP
B3 - Increased AC and increase cAMP
result of ligand binding to D1 and D5 dopamine receptors
what about all other dopamine receptors
increased AC and increased cAMP
all other - inhibition of AC
where are D1 and D5 receptors mainly located
in the renal (kidney) vasculatorue
true or false
ligand binding to a2 decreases blood pressure
true
true or false
ligand binding to b1 causes smooth msuscle relaxation
true
what occurs with ligand binding to b1
increased force and rate of contractility of the heart
also stimulates the release of renin
rate limiting step of NE synthesis
conversion of tyrosine to dopa by tyrosine hydrxylase
name 2 NE reuptake inhibitors
what is their effect on blood pressure
cocaine, tricyclic antidepressants
increased BP because NE is staying in the synaptic cleft for longer and exerting its effect
how do cocaine and the tricyclic antidepressants inhibit the reuptake of NE
by inhibiting NET (nor epi transporter)
effect of reserpine on blooc pressure
decreased blood pressure bc reserpine inhibits VMAT – the transporter that takes dopamine into the vesicle. ultimately the synthesis of NE is inhibited
in most sympathetic postganglionic neurons, _____ is the final product
in what places is it sometimes converted into something else
NE
in the adrenal medulla and some areas of the brain - NE is converted to epinephrine (bc NE is too hydrophilic to cross BBB ! CH3 is added to form epi)
effect of amphetamine on norepinephrine
enhances NE and dopamine neurotransmission
by inhibiting MAO
name 3 indirectly acting mixed sympathomimetics
tyramine, amphetamines, ephedrine
what is COMT and can it be taken orally
catechol-O-methyltransferase - an enzyme that breaks down catecholamines
cannot be taken orally bc it will be oxidized
2 methods in which noradrenergic transmission is terminated
-simple diffusion away from the receptor site and to the liver/plasma for metabolism
-reuptake into the nerve terminal through NET (cocaine blocks!)
name 2 alpha agonists — 1 is more selective for alpha 1 and one is more selective for alpha 2
alpha 1 - phenylephrine
alpha 2 - clonidine
name 2 MIXED ALPHA AND BETA AGONISTS
which doesnt affect B2 (the lungs) as much
norepinephrine and epinephrine
norepi doesnt affect B2 as much
name 2 b agonists
state their selectivity
dobutamine
isoproterenol
dobutamine is a more selective B1 agonist
isoroterenol is a more selective B2 agonist
true or false
dopamine is a dopamine agonist
true
true or false
dopamine is much more selective for the D1 receptor over D2
false - equal D1 and D2
rank the following according to their affinity to the alpha receptor:
epinephrine
isoproterenol
norepinephrine
most selective for alpha - norepinephrine
epinephrine
least selective for alpha - isoproterenol
OPPOSITE FOR BETA – isoproterenol is most selective for beata
true or false
a1 is gs-coupled
FALSE - GQ
true or false
all 3 beta receptors are Gs-coupled
true
a2 receptor is ___ coupled
Gi
substitution of _____ INCREASES beta receptor activity
nitrogen
true or false
substitution of N decreases beta receptor activity
false - increases
dobutamine has
name 2 inotropes
dobutamine
milrinone
name 3 vasopressors
phenylephrine
vasopressin
angiotensin II
true or false
NE can be called either a hormone or a neurotransmitter
true
vasopressor of choice for septic/cardiogenic shock
norepinephrine
structurally how does NE differ from epinephrine
NE has no methyl group on the nitrogen - epinephrine does
true or false
NE has a short half life
therefore…..
true
requires continuous IV infusion
true or false
NE constricts only ateriolar beds
false - both arteriolar and venous
the NE IV infusion is titrated to….
blood pressure control
true or false
NE does not cross the placenta
FALSE - it does
cannot give in pregnancy unless emergency
does NE cross the BBB
no
2 metabolic enzymes of NE
which metabolite is still active and which is inactive
COMT - still active
MAO - inactive
2 liabilities of NE
local ischemia due to severe vasoconstriction
hypertensive
to give NE and other vasoconstrictors what vein should be used
large central veins - avoid local
as mentioned, NE can cause ischemia. this could progress to what? what is treatment?
gangrene
phentolamine
2 contraindications NE
pheochromocytoma
arrhythmias (can make worse)
important consideration when giving NE for hypovolemic shock
dont give without fluid replacement
MAO/tricyclic antidepressants + vaspressors like NE
increased NE/vasopressor response
B blockers + vasopressors like NE
increased vasopressor response
A blockers + vasopressors like NE
decreased vasopressor response
true or false
NE + ergot vasocontrictors woll increase the effect of NE
true
sodium bicarb + pressors (like NE)
decreased response bc of acid-base interaction
atropine + pressors like NE
good – blocks the reflex bradycardia from NE.
increases pressor response
diuretics + vasopressors like NE
decreased pressor response
cyclopropane and other general anesthetics + NE/vasopressors
enhanced arrhythmia liability
phenylephrine is mostly a _____ ateriolar vasoconstrictor
a1
phenylephrine is used systemically to do what
what about topically?
elevate peripheral resistance in shock patients
topically - decongestant (nasal and ophthalmic)
true or false
phenylephrine constricts eye pupils
false - dilates - for the retina to be visualized
place in therapy for phenylephrine in septic shock patients
SECOND LINE to NE for septic shock
AEs of phenylephrine
reflex bradycardia (bc increases BP!)
hypertension, arrhythmias
1 situation in which phenylephrine is CONTRAINDICATED
in patients with narrow angle glaucoma (wide is okay)
true or false
phenylephrine has no issue with diabetic patients
FALSE - use precaution. increases glucose
phenylephrine should be used with precaution in hyper or hypothyroidism
hyper
which dosage form of phenylephrine should be used in infants
nasal spray
how should phenylephrine be stored? when can you not use it?
in a light resistant container
dont use if discolered - forms adrenochromes (inactive)
