cardiac pharm - adrenergic agents Flashcards
what are the CNS neurotransmitters
epi, NE, dopamine, serotonin, GABA, Ach
what are the natural catecholamines
epi, norepi, dopamine
what are the synthetic catecholamines
isoproterenol and dobutamine
what is the potency of catechols at alpha receptors
NE>epi>isoproterenol
what is the potency of catecholamines at the beta receptors
isoproterenol > epi > norepi
where are alpha 1 receptors found and what does activation cause
vasculature, gut, heart, glands
activation causes vasoconstriction and relaxation of the GI tract
where are alpha 2 receptors found and what does activation cause
found pre-synaptically in peripheral vascular smooth muscle, coronaries, brain
activation causes inhibition of NE release and inhibition of SNS outflow leading to decreased BP and HR and inhibition of CNS activity
found post-synaptically in coronaries, CNS
activation causes constriction and sedation and analgesia
where are beta one receptors found and what does activation cause
found in myocardium, SA node, ventricular conduction system, coronaries, kidney.
activation causes increase in inotropy, chronotropy, myocardial conduction velocity, coronary relaxation, and renin release
where are beta 2 receptors found and what does activation cause
found in vasc, bronchial, and uterine smooth muscle, smooth muscle of skin, myocardium, coronaries, kidneys, GI tract
causes vasodilation, bronchodilation, uterine relaxation, gluconeogenesis, insulin release, potassium uptake by cells
what are the 2 synthetic non-catechols
ephedrine and phenylephrine
is ephedrine indirect or direct acting
both
is phenylephrine direct or indirect acting
direct
what is a side effect of repeated doses of ephedrine
tachyphylaxis (aka rapidly diminishing response to successive doses of drug, rendering it less effective)
what is a side effect of phenylephrine related to HR
reflex bradycardia
what is the pressor of choice for OB
phenylephrine
describe alpha1 second messenger/output
- phospholipase C activated
- you get inositol triphosphate (IP3) and diacylglycerol (DAG)
- activates protein kinase C which increases free Ca2+
- Calmodulin activation = increased CB formation = contraction
vasoconstriction
describe alpha 2 second messenger/output
- inhibits adenylate cyclase
- decreased CAMP
- increased K conductance (hyperpolarization)
decreased norepi release
describe beta 1 and 2 second messenger/output
- activated adenylate cyclase
- increased CAMP
- increased kinase activation and phosphorylation
relaxes smooth muscle and stimulated cardiac contractility
what does the alpha 1 receptor activation do at the iris
contraction of radial muscle = dilates pupil = mydriasis
what does alpha 1 do at the prostate and uterus
contract
what is alpha 2’s affect on platelets
aggregation
what is alpha 2s action on vascular smooth muscle
post-synaptic = contraction
pre-synaptic = dilation
beta 1 role at kidneys
stimulation of renin release
beta 2 role at mast cells
decreased histamine release
beta 2 role at pancreas
increased insulin release
beta 2 role at liver
glycogenolysis
what does beta 2 activation do to potassium
increases potassium uptake
dopamine 1 receptor location and action
at smooth muscle
post synaptic: dilates renal, mesenteric, coronary, cerebral blood vessels
dopamine 2 receptor location and action
at nerve endings
pre synaptic: - modulates transmitter release, nausea and vomiting
what does the joint national committee on prevention, detection, and treatment of high blood pressure say is a normal BP
SBP <120
DBP<80
age 18-59 with no co-morbidities and 60 or older with diabetes and/or chronic kidney disease <140/90 is ok
age 60 or older with no diabetes or chronic kidney disease <150/90 is ok
what is the first line treatment of hypertension
thiazide diuretic
hypertensive urgency
DBP >120 with evidence of progressive end organ damage
goal: decrease DBP to 100-105 within 24 hours (clonidine)
hypertensive crisis
DBP > 120 with evidence of end organ failure
goal: decrease DBP to 100-105 ASAP
(nitroprusside, nitroglycerin, labetalol, fenoldapam)
name the alpha antagonists and whether they are competitive or non-competitive
competitive: phentolamine, prazosin, yohimibine
covalent bond/non-competitive: phenoxybenzamine
name the non-selective alpha receptor antagonists
phenoxybenzamine
phentolamine
name the alpha 1 selective antagonists
prazosin, terazosin, doxazosin, alfuzosin, tamsulosin
name the alpha 2 selective antagonist
yohimbine
tolazoline
what are the mixed alpha and beta antagonists
labetalol and carvedilol
what are the non selective beta antagonists (first generations)
Propanolol nadolol penbutolol pindolol timolol
what are the second generation beta one selective antagonists
acebutolol atenolol bisoprolol esmolol metoprolol
what are the third generation non selective beta antagonists
carteolol
carvedilol
bucindolol
labetolol
what are the third generation beta 1 selective antagonists
betaxolol
caliprolol
nebivolol
name a beta antagonist more selective for beta 2
butoxamine
what are the CV effects of alpha 1 antagonism
decreased PVR and lowered BP
postural hypotension due to failure of venous constriction upon standing
what are the CV effects of alpha 2 antagonism
increased NE release from nerve terminals results in tachycardia due to stimulation of beta receptors in the heart
GU effects of alpha antagonists
blockade in prostate and bladder cause muscle relaxation and ease micturition
\aka you can pee easier
alpha antagonist eye effect
miosis
alpha antagonist airway effect
increased nasal congestion
phenoxybenzamine moa
binds covalently to alpha 1 and 2 receptors (nonselective, however more affinity for 1) to cause decreased SVR and vasodilation with less associated tachycardia
pharmacokinetics of phenoxybenzamine
pro drug with 1 hour onset time
long acting with elimination half time of 24 hours
phenoxybenzamine uses
for pheo patients in preop
raynauds
preop dose of phenoxybenzamine for patients with pheo
0.5-1 mg/kg
phentolamine moa
non selective alpha antagonist that produces a decrease in SVR and vasodilation and causes reflex mediated AND alpha-2 associated increases in HR and CO
uses of phentolamine and associated doses
intraoperative management of hypertensive emergency (30-70 mcg/kg)
- pheochromocytoma manipulation
- autonomic hyperreflexia
extravascular administration of sympathomimetic agents (2.5-5 mg)
tola said you may see a drip in the OR of 0.1-2mg/min
prazosin moa
selective alpha 1 antagonist that is less likely to cause tachycardia and dilates both arterioles and veins
uses of prazosin
preop prep of patients with pheo
essential HTN (combined with thiazides)
decreasing afterload in patients with heart failure
Raynauds
why do people use yohimibine
it is an alpha 2 selective blocker that increases release of norepi from post-synaptic neuron and is used for orthostatic hypotension and impotence/ED
what are terazosin and tamsulosin and what are my biggest concerns
long acting selective alpha 1 antagonists that are effective in prostatic smooth muscle relaxation
orthostatic hypotension is biggest concern so prescribers should start slow so patients can adjust
when was propanolol released according to that graph?
1965ish
might be a good bonus
what do beta receptor antagonists do
disallow sympathomimetics from provoking a beta response on the heart, airway, blood vessels, JG cells, and pancreas
beta antagonist effects on heart
bradycardia, decreased contractility, decreased conduction velocity, improve O2 supply and demand balance
beta antagonist effects on airway
bronchoconstriction and bronchospasm
beta antagonist effects on the blood vessels
vasoconstriction in skeletal muscles, increase PVD symptoms
beta antagonist effects on JG cells
decreased renin release which is an indirect way of decreasing BP
beta antagonist effects on pancreas
decreased stimulation of insulin release by epi/norepi at beta one
and then beta 2 antagonism can mask symptoms of hypoglycemia
beta antagonist moa
selective binding to beta receptors
competitive and irreversible inhibition - aka large doses of agonists will overcome antagonism
what happens to the beta adrenergic receptors in patients who chronically take beta antagonists
upregulation - so if we stop them suddenly perioperatively, expect hypertension/tachycardia
which beta blocker would you choose for patients who have asthma, copd, smoking hx
an alpha 1 selective like metoprolol
what is the elimination half life of esmolol
10 minutes
what is the T1/2 of metop
3-4 hours
what is the T1/2 of labetalol
5 hours
what do we use beta blockers for
treatment of hypertension management of angina decrease mortality in treatment of post MI patients suppression of tachyarrythmias prevention of excessive SNS activity
what are some relative contraindications to beta blockers
pre-existing AV heart block or cardiac failure
reactive airway disease
diabetes without BS monitoring
hypovolemia (d/t decreased CO and BP)
how should you give adrenergic antagonists to patients with pheo
give an alpha antagonist before you give a beta antagonist
otherwise you will drop their heart rate and they will still be working against a crazy afterload
what detrimental CV effect can happen when you take a beta antagonist and inhalational agents
hypotension
beta antagonism and IOP
these decrease aqueous humor production so good for patients with glaucoma because IOP is decreased
timolol
what happens to your lipid panel with beta antagonists
can cause decreased concentration of HDL which may increase risk for CAD
(chronic use)
propanolol moa
nonselective beta antagonist which decreases HR and contractility at beta 1 and increases vascular resistance at beta 2
concerns for patients taking propanolol chronically
decreased clearance of amide LAs d/t a decrease in hepatic blood flow inhibiting metabolism in liver - risk for LA toxicity
decreased pulmonary clearance of fentanyl (both are basic lipophilic amines)
what is the HR goal for propanolol
55-60
propanolol cardiac effects
decreased hr, contractility, co
increased PVR, coronary vascular resistance
also decreased renin release
dose of propanolol
0.0k mg/kg IV or 1-10 mg
give slowly 1mg q5min
protein binding of propanolol
90-95%
metabolism of propanolol
significant 1st pass effect (90-95%)
metabolized in liver
elimination half time of propanolol
2-3 hours and will be increased in low hepatic blood flow states
metoprolol moa
beta one selective but dose related
metabolism and elimination of metoprolol
first pass effect (60%)
metabolized in liver
elimination half time = 3-4 hours
dose of metop
PO = 50-400 mg IV = 1-15mg max
dose of metop
PO = 50-400 mg IV = 1-15mg max
atenolol moa
most selective beta 1 antagonist and thought to have the least CNS effects
advantageous to those who need beta 2
pharmacokinetics of atenolol
given PO
NOT metabolized in liver
excreted in renal system and so elimination half time is increased in patients with renal disease (normally 6-7 h)
uses of atenolol
antihypertensive
also given to people who get nervous public speaking
esmolol moa
rapid onset and short duration beta 1 selective blocker
onset of action of esmolol
60 second
duration of action of esmolol
10-30 minutes
metabolism of esmolol
plasma esterase
these aren’t the same ones that metabolize succ so there is no effect
does esmolol cross BBB or placenta
NO it has poor lipid solubility
esmolol used for
to treat HTN and tachycardia associated with DL
pheo surges
thyrotoxicosis
thyroid storm
side effects of timolol eye gtts
hypotension and bradycardia and increased airway resistance
Nadalol moa/pk
non selective beta blocker with no significant metabolism
renal and biliary elimination
T1/2 of 20-40h so they only take it 1x a day
betaxolol considerations
cardioselective beta one blocker
elimination half time = 11-22h
single dose daily for HTN
topical for glaucoma with less risk of bronchospasm than timolol so good choice for patients with glaucoma and asthma
labetalol moa
combined alpha and betal non-selective antagonist
IV B:A = 7:1
PO B:A = 3:1
decreases systemic BP via alpha 1 with attenuated reflex tachy via beta 2 blockade
so decreased HR, SVR, and BP with unaffected CO
PK of labetalol
conjugation with glucuronic acid, <5% recovered unchanged in urine
elimination half life of 5-8h - prolonged in liver disease but not affected by kidney disease
when is the max drop in BP after IV admin of labetalol
5-10 minutes after admin
dose of labetalol
0.1-0.5 mg/kg IVP
usually give 5 mg at a time for mild hypertension in OR
what do we use labetalol for
intraoperative HTN and hypertensive crisis
can be used in hypotensive technique without an increase in HR
side effects of labetalol
orthostatic hypotension, bronchospasm, heart block, CHF, bradycardia
centrally acting agents moa
centrally acting partial alpha 2 agonists, acting at CNS non-adrenergic binding sites and alpha 2
reduce sympathetic outflow from vasomotor centers in the brain stem
uses for alpha 2 agonists
htn induce sedation decreased anesthetic reqs improve periop hemodynamics analgesia
what is clonidine
a centrally acting alpha 2 agonist that decreases BP and CO due to decreased HR and peripheral resistance`
risk of abrupt cessation with clonidine
rebound hypertension - so continue periop
side effects of clonidine
brady sedation dry mouth impaired concentration nightmares depression vertigo EPS lactation in men
PK of clonidine
given PO or TD patch
50/50 hepatic metabolism and renal excretion
withdrawal syndrome of clonidine
occurs with doses >1.2 mg/day
18h after d/c of last dose
lasts for 24-72 hours
treatment = rectal or TD clonidine
ephedrine dose
5-10 mg IVP
phenylephrine dose
100mcg/ml increments IVP
15mcg/min gtt
epi dose
1-20 mcg/min
dopamine dose
low (dopa) = 3-5 mcg/kg
medium (beta) = 6-10 mcg/kg
high (alpha)= >10 mcg/kg
dobutamine dosing
1-20 mcg/kg/min
