Cardiovascular agents II part 2 Flashcards
Phenoxybenzamine is a
non-selective (binds covalently) alpha antagonist alpha 1 activity> alpha 2
less alpha 2, so less associated tachycardia with decrease in SVR & cause vasodilation
Phenoxybenzamine is used for
preoperative control of BP in patients with pheochromocytoma (0.5-1.0 mg/kg) & for patients with Raynaud’s disease
PO medication
Phenoxybenzamine onset time & duration of action
1 hr. onset
elimination half-time of 24 hours (long-acting)
pro-drug- inactive substance until it is converted to something that works in the body
Prazosin is considered a
selective alpha 1 antagonist
less likely to cause tachycardia
dilates both arterioles & veins
Prazosin is used for
pre-op preparation of patients with pheochromocytoma, essential HTN (combined with thiazides), decreasing afterload in patients with HF
Raynaud phenomenon
Phentolamine is a
non-selective alpha antagonist
Phentolamine is used for
intraoperative management of hypertensive emergencies (30-70 mcg/kg): pheochromocytoma manipulation & autonomic hyperreflexia
used subcutaneously for extravascular administration of sympathomimetic agents (2.5 to 5.0 mg)
Phentolamine causes
peripheral vasodilation and a decrease in SVR
reflex mediated and alpha 2 associated increases in HR & CO
Yohimibine is a
alpha 2 selective blocker
Yohimibine is used for
orthostatic hypotension & impotence
Yohimibine causes
increased release of norepi from post-synaptic neuron
Terazosin & tamsulosin are
long acting selective alpha 1 antagonists that are effective in prostatic smooth muscle relaxation
The biggest concern with terazosin & tamsulosin include
orthostatic hypotension
Beta blockers work at
phase 4 to block antiarrhythmic effects due to excessive catecholamines
decrease HR, workload on heart, and increase time for CPP
Beta adrenergic receptor antagonists work on the heart to cause
bradycardia, decreased contractility, decreased conduction velocity, and improve O2 supply and demand balance
Beta adrenergic receptor antagonists work on the airway to cause
bronchoconstriction and can provoke bronchospasm in patients with asthma or COPD
Beta adrenergic receptor antagonists work on the blood vessels to cause
vasoconstriction in skeletal muscles, increased PVD symptoms
Beta adrenergic receptor antagonists work on the juxtaglomerular cells to cause
decreased renin release–> indirect way of decreasing BP
Beta adrenergic receptor antagonists work on the pancreas to cause
decreased stimulation of insulin release by epi/norepi at beta 2 and then mask symptoms of hypoglycemia beta 1
Beta adrenergic receptor antagonists work by
selective binding to beta receptors (influence inotropy, chronotropy)
competitive and reversible inhibition- large doses of agonists will completely overcome antagonism
Chronic usage of beta antagonists is associated with
increased number of receptors (up-regulation)
if you have sudden stop perioperatively they’d have more of a response to SNS stimulation
Non-selective beta adrenergic antagonists include
propranolol, nadalol, timolol, pindolol
Beta 1 adrenergic antagonists include
metoprolol, atenolol, acebutolol, betaxolol, esmolol
large doses lose selectivity
Clinical uses of beta blockers include
treatment of hypertension, management of angina, decrease mortality in tx of post MI patients, used periop & preop for pts at risk for MI, suppression of tachyarrhythmias, prevention of excessive sympathetic nervous system activity
Relative contraindications to beta blockers include
hypovolemia (if you drop HR then cannot keep up CO)
diabetes mellitus (without BS monitoring) can mask s/s of hypoglycemia
reactive airway diseaes
pre-existing AV heart block or cardiac failure
Side effects of beta blockers include
CV system- decrease HR, contractility, BP
exacerbation of peripheral vascular disease (block of beta 2 vasodilation)
airway resistance- bronchospasm
metabolism- alter carbohydrate and fat metabolism, mask hypoglycemic increase in HR
distribution of extracellular K-inhibit uptake of K into skeletal muscles
May have decreased BP with anesthetics
Nervous system- fatigue, lethargy
N/V & diarrhea
Eye- reduction in IOP d/t decreased aqueous humor production
decreased concentration of HDLs have been seen with chronic use that may increase risk for CAD
Propranolol is considered
the prototype & is a non-selective beta blocker
Propranolol has (CV effects)
decreased HR & contractility (B1) and increased vascular resistance (B2)
Propranolol goes through
extensive 1st pass effect
With patients who have been treated chronically with propranolol,
there is decreased clearance of amide local anesthetics & decreased pulmonary clearance of fentanyl
Propranolol is administered with a goal of
55-60 bpm
Cardiac effects of propranolol include
decreased HR, contractility, decreased CO
the above effects are especially prominent during exercise and sympathetic outflow
blockade of beta 2 receptors–> increased PVR, increased coronary vascular resistance
reduction in renin release (mainly through B1 antagonism)
Propranolol is metabolized
in the liver
& highly protein bound
Propranolol has elimination half time of
2-3 hours
Propranolol dosage is
oral dose much larger than IV dose b/c undergoes significant first pass effect- 0.05 mg/kg IV or 1-10 mg (give slowly 1 mg q 5 min)
Propranolol decreases clearance of
amide LAs due to a decrease in hepatic blood flow inhibiting metabolism in the liver- risk of systemic toxicity of amide local anesthetics
Metoprolol is a
beta 1 selective (inotropic & chronotropic)
selectivity is dose related
Metoprolol undergoes
significant first pass effect
Metoprolol is metabolized
in the liver
The elimination half time of metoprolol is
3-4 hours
The dosage of metoprolol is
PO 50-400 mg
IV 1-15 mg (max dose)
With metoprolol the beta 2 receptors
remain intact- bronchial dilation, vasodilation, and metabolic effects
patients with asthma would benefit from this selectivity
Atenolol is the
most selective beta 1 antagonist and though to have the least CNS effects
Atenolol elimination half time is
6-7 hours
Atenolol is used for
oral drug to treat HTN (long lasting antihypertensive effects) & advantageous to those who need beta 2 receptor activity like asthmatics
Metabolism for atenolol
not metabolized in the liver, excreted via renal system, therefore elimination half life is increased markedly in patients with renal disease
Esmolol is
a short duration beta 1 selective beta blocker
has a rapid onset
Esmolol (availability, onset of action, elimination half time & duration of action)
availability : IV
Onset of action: 60 seconds
elimination half time is 9 minutes
Duration of action is 10-30 minutes
Esmolol is metabolized by
plasma esterase (less than 1% of the drug is excreted unchanged in the urine) not the same esterases as plasma cholinesterases responsible for metabolism of succinylcholine (no effect on succinylcholine metabolism or duration of action)
Esmolol has poor
lipid solubility & does not cross the BBB or placenta
Esmolol is used to treat
hyperdynamic effects of- pheochromocytoma, thyrotoxicosis, and thyroid storm
useful in treating HTN & tachycardia associated with laryngoscopy
Treatment of hypotension includes
sympathomimetics- ephedrine, phenylephrine, vasopressin, epinephrine, norepinephrine, dopamine, dobutamine
Side effects of centrally acting partial alpha 2 agonists include
bradycardia, sedation, xerostomia (dry mouth), impaired concentration, nightmares, depression, vertigo, lactation in men, EPS
Clonidine results in
BP reduction from decreased CO due to decreased HR and peripheral resistance
rebound hypertension with abrupt cessation
Centrally acting agents are metabolized via
hepatic metabolism and renal excretion
Centrally acting agents are available as
PO or transdermal patch
Withdrawal symptoms with centrally acting agents include
occurs with doses >1.2 mg/day
occurs 18 hours after acute discontinuation of drug
lasts for 24-72 hours
treatment rectal or transdermal clonidine
Perioperative use of beta-blockers indicates
that beta blockers should only be given if patient is already on beta blockers and hasn’t already taken it prior to surgery
Clinical uses of centrally acting agents include
hypertension, induce sedation, decrease anesthetic requirements, improve perioperative hemodynamics, and analgesia
The mechanism of action of centrally acting agents includes
reduce sympathetic outflow from vasomotor centers in the brain stem; centrally acting selective partial alpha 2 adrenergic agoists
The site of action of centrally acting agents
CNS non-adrenergic binding sites and alpha 2 receptor agonism
Labetalol is used to treat
intraoperative HTN and hypertensive crisis
can be used in hypotensive technique without an increase in HR
Labetalol causes a
decrease in systemic BP via alpha 1 with attenuated reflex tachycardia (beta 1 blockade)
decreased BP, SVR, HR; CO is unaffected
Labetalol side effects include
orthostatic hypotension, bronchospasm, heart block, CHF, and bradycardia
Timolol is considered to be a
non-selective beta blocker
Timolol is used to treat
glaucoma- decreases intraocular pressure by decreasing production of aqueous humor
Timolol side effects include
eye drops can cause decreased BP, HR, and increased airway resistance
Nadolol is considered to be
non selective beta blocker
Nadolol metabolism and elimination half-time
no significant metabolism (renal/biliary elimination)
20-40 hrs take 1x daily
Betaxolol is considered to be a
cardioselective beta 1 blocker
Betaxolol elimination half-life is
11-22 hours
Betaxolol is used for
HTN
topical useful for glaucoma with less risk of bronchospasm as seen with timolol so good alternative choice in asthmatics with glaucoma
Labetalol is considered to be a
combined non-selective antagonists
alpha 1, beta 1 & beta 2 receptors
IV: beta to alpha blockade 7:1
PO: beta to alpha blockade 3:1
Labetalol is metabolized via
conjugation of glucuronic acid; <5% drug recovered unchanged in the urine
The elimination half time is
5 to 8 hours; prolonged in liver disease not affected by renal dysfunction
The maximum drop in blood pressure with labetalol occurs
5-10 minutes after IV administration
Labetalol is usually given
5 mg at a time for mild hypertension in the OR
Precautions with taking timolol/brimonidine
bronchospastic disease, diabetes mellitus, glaucoma-angle closure, myasthenia gravis, hepatic/renal impairment, pregnancy/lactation, thryodoxicosis
Contraindications with taking timolol/brimonidine
sinus bradycardia, cardiogenic shock, hypersensitivity to drug and/or its components, heart failure uncompensated, heart block 2nd or 3rd degree, severe COPD/asthma, MAO inhibitor use with or within 14 days
Indications for brimonidine/timolol include
to lower IOP such as open-angle glaucoma and ocular hypertension
