Pharmacology - Shock Flashcards
a clinical syndrome characterized by a perfusion of tissues is known as
shock
shock is usually associated with
hypotension
failure of organ systems
is shock a life threatening impairment
yes
what is life threatening about shock
lack of o2 and nutrients to the organs of the body
how can shock be managed?
fluids
determining root cause
blood pressure and HR
BP =
CO x SVR
CO is dependent on ___ in shock management
inotropesS
SVR is dependent on ____ in shock management
vasopressors
pharmacotherapy of shock includes
catecholamines
vasopressin
phosphodiesterase inhibitors - milrinone
what are the types of adrenoreceptors
alpha 1 and 2
where are alpha 1 receptors located
post synaptic effect cells - especiall y smooth muscles
what is the result of ligand binding to alpha 1 receptors
Gq - formation of IP3 and DAG
increased intracellular calcium
where are alpha 2 receptors located
pre synaptic adrenergic nerve terminals, platelets, lipocytes, smooth muscle
what is the result of ligand binding to alpha 2 receptors
GI
Inhibition of adenylyl cyclase, decrease cAMP
what are the beta adrenoceptors
beta 1, 2, 3,
what is the result of ligand binding of beta 1 adrenoceptors
stimulation of adenylyl cyclase, increased cAMP
where are beta 1 receptors located
in the post synaptic effect cells especially heart, lipocytes, brain, presynaptic adrenefic and cholinergic nerve terminals, juxtaglomerular apparatus of renal tubules and ciliary body epithelium
where are beta 2 receptors located
post synaptic effector cells, smooth muscle - bronchi and cardiac muscle
what is the result of ligand binding to beta 2 adrenoceptors
stimulation of adenylyl cyclase and increased cAMP which activates cardiac Gi under some conditions
where are beta 3 adrenoceptors located
post synaptic effector cells especially lipocytes, heart
what is the result of ligand binding of beta 3 adrenoceptors
stimulation of adenylyl cyclase and increased cAMP
what are the types of dopamine receptors
d1, d5, d2, d3, d4
which dopamine receptors are located in the brain, effector tissues, and especially smooth muscle of the renal vascular bed
D1, D5
D1 and D5 dopamine receptors lead to the _____ with ligand binding
stimulation of adenylyl cyclase and increased cAMP
D2 dopamine receptor binding leads to
inhibition of adenylyl cyclase , increased potassium conductance
alpha 1 receptor actions are ____ when innervated
contractions
alpha 2 adrenergic and cholinergic nerve terminals led to ____ when innervated
inhibition of transmitter release
what beta adrenoceptors are found in the juxtaglomerular cells
beta 1
what are the actions when beta 1 adrenoceptors are innervated
increases fore and rate of contraction
increases renin release
which beta receptor promotes smooth muscle relaxation? and where
beta 2
repspiratory, uterine and smooth muscle
d1 receptors when innervated
dilate renal blood vessels
what is the final product in most sympathetic postganglionic neurons
norepinephrine
in the adrenal medulla and certain areas of the brain some NE is converted to
epinephrine
in dopaminergic neurons, synthesis terminates wtih
dopamine
_____________ inhibits monoamine oxidase and enhaces NE and dopamine neurotransmission
amphetamine
termination of noradrenergic transmission results from what processes
simple diffusion away from receptor site
reuptake into the nerve terminal by NET or intro peri synaptic glia or other cells
phenylephrine has an affinity for
alpha agonists , a1
NE and Epinephrine have an affinity for
mixed alpha and beta agonists
dobutamine and isoproterenol have an affinity for
beta agonists
dobutamine has a greater affinity for
beta 1
T or F NE has a greater affinity for a1 than a2
F, =
which dopamine agonists has an equal affinity for D1 and D2
dopamine
what is known as the primary transmitter
norepinephrine
what are the indirectly acting and mixed sympathomimetics that release stored transmitter from noradrenergic nerve endings by a calcium independent process
tyramine, amphetamines, and ephedrine
phenylephrine lacks an -oh group which impacts its activity by
decreases sympathomimetic activity
ephedrine lacks 2 -oh groups which impacts its activity by
increasing its distribution in the CNS
ephedrine, amphetamine and methoxamine have a methyl substitution on alpha carbon leads to
decreased oxidation by MAO
is dobutamine beta 1 or beta 2 selective
beta 1
terbutaline is beta 2 or beta 1 selective
beta 2
substitution on ___ increases beta receptor activity on dobutamine and terbutaline
N
the vasopressor of choice for septic and cardiogenic shock is
norepinephrine
how does norepinephrine differ from epinephrine
by the absence of a methyl group on the nitrogen atom
norepinephrine is indicated for
blood pressure control in certain acute hypotensive states
myocardial infarction
septicemia
blood transfusion
drug reactions
norepinephrine is used as an adjunct in the treatment of
cardiac arrest
profound hypotension
norepinephrine is a direct acting
adrenergic agonist
what is the mechanism of acting of norepinephrine
constricts arteriolar and venous beds to elevate both systolic and diastolic BP
norepinephrine has major alpha 1 and small beta 1 activity and used in
reversing vascular shock with bradycardia
what is the onset of norepinephrine
quick onset
how is norepinephrine administered
short duration requires continuous IV infusion 1-2 min
T or F norepinephrine crosses the placenta and the blood brain barrier
F, crosses the placenta not the blood brain barrier
how is NE metabolized?
COMT - normetanephrine which is active
MAO - vanilylmandelic acid which is inactive
what are the ADR of norepinephrine
leads to tissue hypoxia
HA
palpitation, bradycardia, hypertension, arrhythmia
N,V
loca VC and tissue necrosis extravasation ischemia could progress to gangrene
avoid local vein, use large vein
what are CI of norepinephrine?
arrhythmias
pheochromocytoma
in hypovolemic shock, dont give with fluid replacement
norepinephrine should be taken with caution in patients who are
pregnant
lactating
peripheral vascular disease
DDIs with norepinephrine
MAO-Inhiibitors , tricyclic antidepressants which increase pressor response
beta blockers increase pressor response
alpha blokers decrease pressor response
ergot vasoconstrictors increase pressor response
sodium bicarbonate a-b int decreases response
atropine increases heart rate
diuretics decrease pressor
cyclopropane and general anesthetics enhance arrhythmia liability
phenylephrine is uses systemically but best know for its
local applications in nose drops, eye drops, and cough preps as a decongestant
phenylephrine is mostly a _____ agonist
alpha 1, arteriolar vasoconstrictor
when phenylephrine is used systemically it is used to ______ in vascular shock
elevate PR
_____ is a second line agent to NE in septic shock
phenylephrine
what are the ADR of phenylephrine
CNS HA, weakness, dizziness
CV reflex bradycardia, lowered CO, ischemia, HTN, arrhythmias
EENT stinging, lacrimation, blurred vision
Skin pruritis
phenylephrine is CI in pts with
narrow angle glaucoma
which patients should take phenylephrine precautiously
severe HTN
diabetes - increases glucose
hyperthyroidism
elderly - coronary pt
severe ASHD - compromised o2 delivery
cardiac disease - o2 delivery problem
infants - use nasal spray
extravasation ischemia
DIs with phenylepinephrine
increased pressor effects with MAOinhibitors and tricyclic antidepressants
phenylephrine has storage instructions. what are they?
they should be stored in a light resistant container
do not use if discolored because forms adrenochromes (inactive)
what is released endogenously in the emergency reaction from the adrenal medulla?
epinephrine
epineprhine is used in the emergency treatment of
allergic reactions
including anaphylaxis
induction and maintenance of mydriasis during intraocular surgery
what are the dosage forms for epinephrine
iv infusion or im in the thigh
what is the onset of epinephrine
quick onset - seconds
short duration - minutes
which action of epinephrine requires a high dose
pressor amine to treat vascular shock
what action of epinephrine requires low doses
positive inotrope and chronotrope for heart to treat cardiogenic shock
vasodilation of cerebral coronary and renal dopaminergic receptors
epinephrine’s response is dose related, which receptor response is high dose
alpha 1 VC
epinephrine’s response is dose related, which receptor response is low dose
beta 1 cardiac stimulant and beta 2 vasodialator
what are the uses of epinephrine
cardiac arrest - cardiogenic shock
hemostasis - hemorrhagic shock
anaphylaxis - IM epi
opthalmic . nasal
asthma
what are the ADR of epinephrine
CNS - tremors, anxiety, depression, insomnia, hA CONVULSIVE SEIZURES
EENT - dry nose, irritation of nose and throat
CV - palpitations, tachy, HTN, chest pain, arrhythmias,
GI - anorexia, NV
Resp - depression high dose
Extravasation ischemia
Epinephrine is CI in
narrow angle glaucoma
______ and _____ are used to retain water, and increase blood volume to treat shock
vasopressin
desmopressin
how many amino acids make up vasopressin a
9 amino acids
what is the moa of vasopressin
retains water
from posterior pituitary hormone
vasoconstrictor at high doses
what is the therapeutic use of vasopressin
septic shock
esophageal varices with GI bleeds
diabetes insipidus
prevents post op abdominal distention
what are the ADR of vasopressin
CV - increased BP, brady, arrhythmia, venous thrombosis, VC with high dose, anginal pain
CNS fever vertigo pounding head
derm - uticaria pallow
GI NV adb pain flatulence
NM skeletal muscle tremor
misc diaphoresis MI
what type of receptors are involved in the MOA of vasopressin
GPCRs
V1a,b act on which coupled receptors
Gq - peripheral and brain
V2 act on which coupled receptors
Gs - peripheral , kidneys
what is the mechanism of action of desmopressin
retains water in the body by altering the collecting duct membrane to water
VC at high doses, elevates factor 8 and von willebrand factor
desmopressin is a vasopressin analogue but with
greater hemostatic activity
what is the therapeutic use of desmopressin
increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines
hemostatic, antihemophilic to control bleeding in hemophilia, von willebrand disease, thrombocytopenia
treat diabetes insipidus
what are the ADRs of desmopressin
CV - FACIAL FLUSHING
CNS - dizziness and HA
GI - abd cramps, N
local pain at inj site
angiotensin II is made up of __ amino acids
8
angiotensin II is available as which dosage form
IV
Angiotensin II is used to treat
septic and other distributive vasodilatory shock in adults
what are the AE of angiotensin II
thromboembolic events DVT
thrombocytopenia
tachycardia
drugs that increase HR and force such as NE, EPI, ISO are CI in
obstructive cardio myopathy with HF
because blood vessels exiting the heart rate are narrowed and increase HR and force will only further damage of th heart and increase HF
dopamine and dobutamine are both ___ inotrope
positive
dopamine is a positive inotrope with ____ pressor effects
alpha 1
dobutamine is a positive inotrope with ____ vasodialator effects
beta 2
dopamine is used in
cardiogenic and vascular shock
dobutamine is used in
cardiogenic shock with HTN
T or F dopamine is synthetic
F, dopamine is natural and dobutamine is synthetic
dopamine is considered a ____ EPI with dopamine receptor activity
weak
dobutamine is a ___ derivative
ISO
dopamine must be administered via
IV
what must be used when administering dopamine
an infusion pump to control rate
what is the mechanism of action of dopamine
“less potent epi”
inotropic action - beta 1, cAMP mediated increase in myocardial Ca++ availability - low dose
chronotropic - beta 1 stimulation - low dose
vasopressor - alpha 1 vasoconstriction - high dose
moderate dose of dopamine effects are active on
alpha 1 and beta 1
T or F dopamine crosses the BBB
F does not, widely distributed
how is dopamine metabolized
in the liver, kidney, plasma by MAO and COMT
how is dopamine excreted
renally
dopamine is CI in
tachyarrhythmias
pheochromocytoma
ventricular fibrillation
what is a key side effect of dopamine?
metabolic - hyperglycemia
misc extravastion ischemia at injection site
CNS HA
CV ectopi beats, tachy, anginal pain, palpitations, hypotension, brady, conduction disturbances, HTN, VC, widening QRS complex
GI NV
resp dyspnea, asthmatic episodes
dobutamine is a _____ analogue
isoproterenol
what is the mechanism of action of dobutamine
a potent beta 1 agonist positive inotrope and chronotrope increasing CO
with a new vasodilator or unloading effect on the heart
what are the ADR of dobutamine
CNS - anxiety HA dizziness
CV tachy palpitations PVCs HTN angina
GI heartburn NV
ms Muscle cramps
DI for dobutamine is
all antiHTN drugs (decreases bP)
name a bipyridine drug
milrinone
what is the mechanism of action of milrinone
inhibits phosphodiesterase 3, the enzyme that degrades CAMP
elevated cAMP leads to increased calcium availability at cardiac muscle increasing inotropic and chronotropic activity
relaxes vascular smooth muscle causing vasodilation which serves to unload the heart
decreases blood viscosity
what is a caution of the positive inotropic an chronotropic activity of milrinone
positive inotropic effects are beneficial
chronotropic increases HR which can be o2 wasting and precipitate anginal pain
milrinone is metabolized to
glucuronide
a majority of milrinone is metabolizes to
nothing, remains unchanged
how is milrinone eliminated
renally
what is the dosage form of milrinone
IV continuous infusion
____ % of milrinone is protein bound
70
what is a DDI of milrinone
forms a precipitate with IV furosemide
what are the ADR of milrinone
CV - cardiac arrhythmias, hypotension, Vtach, anginal chest pain
CNS HA
HEMA thrombocytopenia
hypotensive liability
what is the duration of therapy of milrinone
5 days
