ANS pharmacology and pathophysiology Flashcards
how is phenylephrine metabolized
MAO
2 examples of mixed function alpha and beta agonists
labetalol
carvedilol
cholinergic agonists (3)
nicotine
bethanechol
physostigmine
direct vasodilators/nitrodilators (3)
nitroprusside, NTG, hydralazine
does PAP increase with phenylephrine
yes d/t pulmonary vasoconstriction and increase in venous return
in the event of a neo OD, what is the drug you give and the drug you AVOID
give: a2 antagonist such as phentolamine
avoid: beta antagonists- can cause pedema
elimination half life of clonidine
8 hours
elimination half life of dexmedetomidine
2 hours
MOA of clonidine
inhibits NE release causing vasodilation and diminishing sympathetic outflow, decreasing HR and BP
sedation via locus coeruleus
pain modification and analgesia via dorsal horn of SC
clinical uses for clonidine (3)
treating HTN
controlling opiate and nicotine withdrawal manifestations
dx of pheochromocytoma
isoproterenol and
airway resistance
metabolism
receptor binding
gtt dose
primary use
airway resistance: decreased
metabolism: COMT
receptor binding: B1>B2 (.015-.15mcg/kg/min)
primary use: drug pacing. less commonly used now
dobutamine and
airway resistance
metabolism
receptor binding
primary use
airway resistance: no change
metabolism: COMT
receptor binding: B1>B2>A1 (2-20mcg/min)
primary use: cardiogenic shock, stress test
epinephrine IV infusion dose
.01-.2mcg/kg/min
systemic effects of catecholamines include
NE receptors it effects
mostly A1 and B1, minimal B2
IV infusion dose of NE
.1-.22mcg/kg/min
NE is first line therapy in
distributive shock
isoproterenol is derived from
dopamine
short acting B2 agonist inhalers include (3)
albuterol
levalbuterol
terbutaline
long acting B2 agonist inhalers include (2)
salmeterol
formoterol
which adrenoreceptor agonist is metabolized by the liver
ephedrine
what is the alpha antagonist family of drugs usually used to treat (4)
HTN
HF
BPH
pheo
MOA of phenoxybenzaprine and use/route of admin
non selective non competitive alpha antagonist that blocks NE and epi, lowering PVR and BP
HR may increased d/t increase in free, unbound NE
almost exclusively used in pheo’s preop to decrease BP
PO!!
what terminates the clinical effect of phenoxybenzaprine
since its irreversible, only the synthesis of new receptors can terminate its effect
best tx for phenoxybenzaprine induced severe hoTN
vasopressin and fluids.
MOA of phentolamine and route of admin (and what reflex it elicits)
noncompetitive non selective alpha antagonist
action can be overcome using an alpha agonist though such as neo or NE
potent rapidly acting vasodilator that causes baroreceptor mediated reflex tachycardia and should be used with caution in CAD patients
IV!!
DOA of phenozybenzaprine versus phentolamine
phentolamine has a much shorter half life of <10 minutes
phentolamine clinical use
can be used to tx extravasation from NE or epi
phentolamine has an affinity for which random receptor
5HT- causes stomach acid secretion and mast cell degranulation
prazosin receptors, MOA, SE
highly selective a1 receptor antagonist with an affinity for a1>a2 1000:1
decreases PVR in arterioles and veins, which increases venous capacitance and decreases preload and BP with little change in HR
SE: postural/orthostatic HoTN
3 analogs of prazosin (a1 selective antagonist) include
terazosin
doxazosin
tamsulosin
terazosin as compared to prazosin
less potent, longer acting, mainly used to tx prostate hypertrophy
doxazosin and tamsulosin as compared to prazosin
weaker vascular effects, primarily used in treating prostate hypertrophy. anesthetic induced HoTN can still be exacerbated
yohimbine receptor affinity, MOA, uses (5)
selective a2 adrenergic antagonist
increases PSNS activity and decreases SNS activity
used for ED, athletic performance, weight loss, HTN, diabetic neuropathy
propanolol receptor affinity, MOA, SE
nonselective B1/B2 antagonist that inhibits actions of NE, epi, dopa, dobut, and isoproterenol
possesses membrane stabilizing effects at high doses which means it also acts as an anti arrhythmic
SE: B2 related: bronchoconstriction, hypoglycemia, peripheral vascular constriciton. may aggravate raynaudus
(selective: A-N. non selective: O-Z. alpha: not -olol)
non selective beta adrenergic antagonist examples include (5)
carvedilol
pindolol
nadolol
sotalol
timolol
(selective: A-N. non selective: O-Z. alpha: not -olol)
non selective BB with very long half life
nadolol
non selective BB with simpathomimetic effects
pindolol–>weak beta agonist effects, associated with less HR slowing/HoTN
(selective: A-N. non selective: O-Z. alpha: not -olol)
metoprolol receptor selectivity, MOA, uses (4), SE
B1
limits HR increase, useful in patients with ischemic disease
used in patients with angina, HF, afib, HTN
(selective: A-N. non selective: O-Z. alpha: not -olol)
esmolol receptor selectivity, uses, onset and DOA,
B1 selective
uses: preventing acute increases in HR intraop
onset/DOA: swift onset, DOA <15 min, can titrate to effect
(10-80mg bolus or 50-330mcg/kg/min)
(selective: A-N. non selective: O-Z. alpha: not -olol)
atenolol receptor selectivity, MOA, uses, onset, DOA
receptor selectivity: B1 receptor antagonist, synthetic
uses: prevents increase in HR, decreases electrical conductivity and inotropy from release of NE
increases cardiac work and decreases O2 demand
DOA: 25-200mg BID to reach full effect in 1-2w (IV or PO)
labetalol receptor selectivity, MOA, uses, onset, DOA, SE
adrenergic antagonist with a1 and non selective B adrenergic activity (B>a 7:1)
MOA: a1 antagonism vasodilates and decreases PVR. b1 antagonism can cause mild decrease in HR, B2 antagonism can cause bronchospasm
can decrease HR without causing baroreceptor reflex
uses: primary for acute HTN (make sure HR is ok because bradycardia will be exacerbated)
doa: t1/2 6 hours. metabolized by liver, eliminated by kidney.
(selective: A-N. non selective: O-Z. alpha: not -olol)
carvedilol receptor selectivity, MOA, uses (4), other
receptor selectivity: a1, non selective B1/B2
MOA: vasodilation with modest HR reduction
uses: HF, LV dysfx, HTN, acute MI
has anti oxidant and anti inflammatory properties
methacholine MOA/use
m3 receptor agonist that evokes bronchospasm, increases airway secretions, impairs peak expiratory flow rates
administered to ID if patient has reactive aw disease when they dont have any clinical outward signs of asthma
bethanachol MOA/use
selective m3 agonist for GI/urinary tract and is used postop to tx urinary retention
2 cholinergic agonists that produce miosis and can maybe help with glaucoma
carbamycholine
pylocarpine
which commonly used anticholinergic is a quaternary amine
glyco (aka does not cross BBB)
muscarinic (anticholinergic) toxicity tx
physostigmine 1-2mg IV
effects of CCB’s on myocardium
decrease in after load, preload, contractility.
increase in diastolic perfusion, decrease in exercise vasoconstriction or spasm
heart and VSMC’s have two types of calcium channels. what are they and what do our CCB’s target
transient (T) form and long (L) form
our CCB’s target the L form
what are CCB’s used to treat (5)
HTN, arrhtyhmias, PVD, cerebral vasospasm, angina
3 classes of CCB’s and examples
- dihydropirodines: nifedipine, nimodipine, nicardipine, clevidipine
- benzothiazepines: diltiazem
- phenylalkamines: verapamil
two best CCB’s for HR control and why
verapamil and diltiazem (class 4 anti arrhythmic that suppress SA node discharge/AV node conduction)
order of CCB’s to use for control of contractility (4)
verapamil>nifedipine>diltiazem>nicardipine
CCB used for cerebral vasospasms
nimodipine
two best CCB’s to decrease SVR
nicardipine (good coronary anti spasmodic) and nimpodipine
do CCB’s produce greater relaxation of arterial or venous smooth muscles?
aterial
best CCB for supra ventricular arrhythmias
verapamil (or dilt)
does carvedilol have any negative chronotropic or inotropic effects?
nope
half life of clevidipine and reflex that may occur
~2 minutes, baroreceptor mediated increase in HR
NTG primary site of dilation, MOA, uses, cautions
dilates venules primarily at low doses. as dose increases, dilates arterioles and increase in HR is seen
MOA: NO. arterial CO and BP decrease r/t decreased preload. improves O2 supply/demand
uses: first line for cardiac ischemia d/t dilation of both normal AND stenotic arteries
cautions: when using a NO liberation drug like sildenafil d/t severe HoTN
sodium nitroprusside (SNP) site of dilation, dose caution, byproduct
ultra short acting NO donor with potent venous and arteriolar dilation activity which decreases after load AND preload
do not exceed 500mcg/kg and dont give any faster than 2 min
coronary steal, reflex tachycardia (B1 antagonist can help)
cyanide is produced after SNP admin which can inhibit aerobic metabolism. also binds with HGB forming metHGB and binding to sulfur to form thiocyanate
hydralazine site of action (4), MOA, SE
result of activation of Ktp channels resulting in increased Ca2+
causes dilation in cardiac, cerebral, splanchnic, and renal vasculature leading to reduced SVR and BP. preserves LV preload and does not dilate venous capacitance vessels
tachycardia (B1 antagonist can help) r/t baroreceptor reflex activity
minoxidil SE’s that are weird and what its now used for
has bad reflex tachycardia so have to give B1 antagonist with it
hypertrichosis (hair growth), salt and water retention.
now used to tx scalp hair loss
examples of PDE5 inhibitors (3)
sildenafil
tadalafil
vardenafil
MOA of PDE5 inhibitors
increase level of cGMP and target lungs and penis
no cGMP breakdown means increase in NO vasodilation. which relaxes smooth muscles and increases BF
promote pulmonary vasodilation and decrease p.artery pressure
examples of PDE4 inhibitors
roflumilast
apremilast
ibudilast
MOA of PDE4 inhibitors
increase cAMP, targeting airway skin and immune system
can cause smooth muscle relaxation in those with hyper reactive airways
useful in skin, bowel, joint inflammation
examples of PDE3 inhibitors
milrinone and cilostazol
MOA of PDE3 ihibitors
increase cAMP and cGMP and are useful in CV disease
increased inotropy with VSMC relaxation= indicators
promote relaxation in peripheral vessels to help with intermittent claudication
prevent platelet aggregation for thrombosis and prophylaxis
theophylline
increases cAMP in airways and is useful in patients with asthma and COPD
V1 receptors mediate
CV effects such as SVR
V2 receptors mediate
function in kidneys and ADH
V3 receptors are found in
pituitary gland and regulate autocoids (biological factors that act as local hormones)
vasopressins major endogenous roles include (3)
water, osmolar, and BP homeostasis
overview of RAAS loop
- renin acts on angiotensinogen (produced by liver) circulating in blood to produce angiotensin 1
- ACE (found in lung) removed 2 amino acid residues from angiotensin 1 to produce angiotensin 2
- angiotensin 2 acts on renal tubules to increase Na/H2O reabsorption and stimulate K excretion
role of angiotensin 2 on angiotensin receptor types 1 and 2
AT1: potent vasoconstrictor of kidney and mesenteric arterioles
AT2: regulates vascular response, cardiac growth response, and fibrotic response in other tissues
what triggers release of epi and NE from adrenal medulla
AT2
what is stimulated by AT2 to amplify Na reabsorption and K excretion
aldosterone
ACEI clinical uses (4)
HTN, CHF, mitral regurg, LV dysfx
ACEI effects include
decrease generation of angiotensin
reduce LV after load, reducing arterial vasomotor tone
cause plasma aldosterone levels to fall
decrease water and sodium retention
block breakdown of bradykinin (endogenous vasodilator)
decrease concentration of LDL cholesterol
does not impair baroreceptors (so orthostatic HoTN isn’t an issue)
renal protective effects in DM patients
SE of acei’s (5)
dry cough
hyperkalemia
fatigue
renal dysfunction
angioedema
which acei is a pro drug
elanapril (elanaprat is pro drug)
MOA of ARB’s
have affinity for AT1 receptor which inhibits AT2 from exerting its effect (better than ACEI’s do)
characteristics of ANS modification from volatile agents include (6)
GABA-A receptor agonism (chloride conductance)
altered myocardial Ca2+ function –> myocardial depression
altered Ca2+ function im VSMC–> vasodilation
depression of baroreceptor reflex
antagonism of SA node automaticity (can lead to nodal rhythm)
impairs ventilatory response to CO2 and O2
uncoupling of cerebral BF auto regulation (usually >.5MAC)
inhaled agents decrease (4)
CO, BP, CI, SVR
how to inhaled agents promote anti arrhythmic effects
prolong QT interval by inhibiting K reflux to allow for repolarization
propofol MOA and SE
GABAa receptor agonist
depression of baroreceptor reflex, mild bronchodilation
etomidate MOA and SE
GABAa receptor agonist
vasoconstrictor reducing CBF and ICP
does not block SNS response to laryngoscopy
minimal changes in HR SV and CO
midazolam MOA and SE
GABAa receptor agonist
induction dose can decrease BP and SVR, dose dependent decrease in respiratory drive and aw reflex.
when used as sedative, produces anxiolysis without significant CV or respiratory effect
MOA of class 1B antiarrhythmics (lidocaine being the standard drug)
suppress automaticity by increasing electrical stimulation threshold of ventricle and his purkinje system and inhibiting spontaneous depol during diastole
resting HR of transplanted heart
100-120 (set by SA node)
digitalis effect on recipient heart
increase of contractility due to its direct cardiac effects
verapamil effect on recipient heart
AV node block due to direct effect
effect of BB on recipient heart
increased antagonist effect
which reflex is intact with recipient heart
bainbridge since its SA node mediated
Paraganglioma overview
neuroendocrine tumors that arise from neural crest cells. in adrenal locations (like pheos) but rarely secrete vasoactive substances. when they do, its usually norepinephrine.
can also secrete serotonin or kallikrein which will produce sx including carcinoid like sx like bronchoconstriction, diarrhea, HA, flushing, HoTN
histamine/bradykinin release: bronchoconstriction/HoTN
located usually: lung, head, neck, CA, glossopharyngeal nerve, jugular vein, middle ear.
small tumors can be radiated or embolized
anesthetic concern: cranial nerve paragangliomas can cause swallowing impairment, aspiration, aw obstruction
surgical dissection of one near IJ increases risk of air embolism
MSA overview
degeneration and dysfx of diverse CNS structures such as basal ganglia, cerebellar cortex, locus coeruleus, pyramidal tracts, vagal motor nuclei
-autonomic dysfx predominating is usually from locus coeruleus, intermediolateral column of SC, and peripheral autonomic neurons and manifests as orthostatic HoTN
MSA s/sx
urinary retention
bowel dysfunction
impotence
postural HoTN
pupillary reflexes can be sluggish
control of breathing abnormal
baroreceptor reflex failure
MSA anesthetic considerations
bradycardia r/t HoTN best treated with atropine/glyco
s/sx light anesthesia harder to ID because SNS less reactive
any anti parkinson meds should be continued in preoperative period
BB’s with first letter a-n are
BB’s with first letter o-z are
cardioselective (B1)
non selective (B1/B2)
BB’s with intrinsic sympathomimetic activity or partial agonists mnemonic
Buci and Celi took Cart Pin and Pen to Ace Lab
Bucindolol
Celiprolol
Cartelol
Penbutolol
Acebutalol
Labetalol
BB’s with membrane stabilizing or na+ blocking action (anti arrhythmic activity/LA activity) mnemonic
professor meto took pin to ace lab
propanolol (max MSA)
metoprolol
pindolol
acebutolol
labetalol
