alpha antagonists and beta antagonists test 2 Flashcards
endogenous catecholamines (3)
epinephrine
norepinephrine
dopamine
CNS neurotransmitters (6)
epinephrine norepinephrine dopamine serotonin GABA acetylcholine
synthetic catecholamines
isoproterenol
dobutamine
catecholamine affinity for alpha receptors in order
norepinephrine>epinephrine>isoproterenol
catecholamine affinity for beta receptors in order
isoproterenol>epinephrine>NE
a1 physiology: which synapse, organs, action
postsynaptic
vasculature, heart, glands, gut
vasoconstriction
a2 physiology: which synapse, organs, action
presynaptic: found in peripheral vascular smooth muscle, coronaries, brain
inhibition of NE release, decrease in BP and HR
postsynaptic (less often): coronaries, CNS. constriction, sedation, analgesia
b1 physiology: organs, action
myocardium, SA node, ventricular conduction system, coronaries, kidney
increase in inotropy, chronotropy, myocardial conduction velocity, coronary relaxation, renin release
b2 physiology: organs, action
vascular, bronchial, uterine smooth muscle, smooth muscle in the skin, myocardium, coronaries, kidneys, GI tract
vasodilation, bronchodilator, uterine relaxation, gluconeogenesis, insulin release, potassium uptake by the cells (because decreased intracellular calcium activates potassium channels and hyperpolarize cell)
ephedrine MOA, action, dose, DOA, SE
mostly indirect action by increasing catecholamine release, also direct. acts on alpha and beta
vasoconstriction, HR increase, inotropy increase. used to increase BP
5-25mg, give in increments of 5-10mg
DOA 15m-1h
SE: tachyphylaxis
phenylephrine MOA, uses, dose, DOA
direct a1 agonism
used to increase BP, also used for nasal intubations (nasal spray)
bolus of 50mg or 100-200mcg depending
infusion ranges from 20-100mcg/min
DOA 5-20min
SE: baroreceptor mediated reflex bradycardia
a1 signal, 2nd messengers, physiologic response example
excitatory blood vessels
1. PLC activated 2. IP3&DAG 3. PKC and increased free Ca2+ versus?
2. increased calcium, increased ca calmodulin activation, increased actin/myosin interaction, smooth muscle contraction
smooth muscle vasoconstriction
a2 signal, 2nd messengers, physiologic response example
inhibitory, blood vessels pre synaptic, CNS post synaptic
1. inhibit adenylate cycle 2. decrease cAMP 3. increase K conductance
decreased cAMP increases smooth muscle contraction and increased K creates hyperpolarization
B1,2,3 signal, 2nd messenger output, physiologic response examples
excitatory or inhibitory, depends on cAMP actions
- activate adenylate cyclase to increase cAMP
- increased intracellular cAMP relaxes smooth muscle BUT stimulates cardiac contractility
where are a1 adrenoreceptors found and what is their action (5)
- most vascular smooth muscle, contraction
- iris, contraction (which dilates pupils), mydriasis
- pilomotor smooth muscle, erects hair)
- prostate and uterus, contraction
- heart, increased force of contraction
where are a2 adrenoreceptors found and what is their action (5)
- platelets, aggregation enhancement
- adrenergic and cholinergic nerve terminals, presynaptic, inhibits transmitter release so decreases BP and HR
- vascular smooth muscle, contraction (postsynaptic) or dilation (presynaptic, CNS)
- GI tract, relaxation (presynaptic)
- CNS, sedation and analgesia via decreased SNS outflow from brainstem
where are B1 receptors found and that is their action
heart, kidneys. increases force and rate of contraction, chronotropy and inotropy, stimulation of renin release
where are B2 receptors found and what is their action (6)
- respiratory, uterine, vascular, GI, GU (visceral smooth muscle), promoted smooth muscle relaxation
- mast cells, decreases histamine release
- skeletal muscle, potassium uptake, dilation of vascular beds, tremor, increased speed of contraction
- liver, glycogenolysis
- pancreas, increased insulin secretion
- adrenergic nerve terminals, increased release of NE
where are B3 receptors found and what is their action
fat cells, activates lipolysis, thermogenesis
classes of drugs to treat hypertension
SNS antagonists (B, alpha, mixed, centrally acting a2) RAAS antagonist (ACEI, ARB, diuretics) endothelium derived mediator and/or ion channel modulators (direct vasodilators, CCB, K channel opener)
hypertension first line therapy
thiazide diuretic unless there is a compelling indication
tx goal for 18-59 with no co morbidities or >60 with DM or CKD
140/90
tx goal for >60 with no DM or CKD
150/90
hypertensive urgency threshold, goal, drug of choice
DBP >120 without end organ damage
goal: decrease DBP to 100-105 within 24h
clonidine
hypertensive emergency threshold, goal, drug of choice
> 120 DBP with evidence of end organ failure
goal: decrease DBP to 100-105 ASAP
drugs: nitroprusside, nitroglycerin, labetalol, fenoldapam
competitive alpha antagonist examples (3)
phentolamine, prazosin, yohimbine
covalently bound alpha antagonists
phenoxybenzamine (DOA long)
clinical uses of a1 antagonists (3)
HTN, BPH, Pheochromocytoma
which alpha antagonists are a1 selective
prazosin, terazosin, doxazosin, tamulosin
which alpha antagonist has moderately higher affinity for alpha 1 than alpha 2
phenoxybenzamine
which alpha antagonist has equal affinity for a1 and a2
phentolamine
which alpha antagonists have higher affinity for a2 than a1
yohimbe, tolazoline
name the mixed alpha and beta antagonists and their affinity for the receptors
labetalol, carvidelol
b1=b2>a1>a2
which beta antagonists are selective for b1
metoprolol, atenolol, esmolol
which beta antagonists have equal affinity for B1 and B2
propanolol, nadolol, timolol
which beta antagonist is beta 2 selective
butoxamine
first generation non selective beta antagonists
nadolol, penbutolol, pindolol, propanolol, timolol
third generation non selective beta antagonists
carteolol, carvedilol, bucindolol, labetalol
GU, eye, nasal effects of alpha antagonists
blockade in prostate and bladder cause muscle relaxation and ease micturition
miosis
increased nasal congestion
Phenoxybenzamine binding, receptor affinity, action, onset, t1/2, uses, dosage
binds covalently
non selective but greater affinity for alpha 1 than alpha 2 (less associated tachycardia with decrease in SVR)
decreases SVR, vasodilation
onset 1h (slow, not great for OR)
t1/2 24h (long acting)
used preop for control of BP in patients with pheochromocytoma, will start them on this 1-2w pre surgery at .5-1mg/kg
used for patients with raynauds
Phentolamine receptor affinity, MOA, uses
non selective alpha antagonist
produces peripheral vasodilation and decrease in SVR
reflex mediated and alpha 2 associated increases in HR and CO
used: intraop management of hypertensive emergencies at 30-70mcg/kg
pheochromocytoma manipulation
autonomic hyperreflexia, tamps this.
SQ for extravasation 2.5-5mg
Prazosin receptor affinity, actions, uses
selective a1 antagonist
less likely to cause tachycardia
dilates both arterioles and veins
used: preop preparation of patients with pheochromocytoma, essential HTN (combined with thiazides), decreasing after load in patients with heart failure, raynauds (PO drug)
Yohimbine receptor affinity, action, uses
(not used so much anymore)
alpha 2 selective blocker
increases release of NE from post synaptic neuron
used with orthostatic hypotension, impotence
Terazosin and Tamulosin receptor affinity, action, uses, t1/2 consideration, SE
long acting selective alpha 1 antagonist, particularly effective in prostatic smooth muscle relaxation
varying t1/2
orthostatic hypotension biggest concern
Beta antagonist mechanism of action, receptor effect
competitive and reversible inhibition, large doses of agonists will completely overcome antagonism.
chronic use associated with up regulation of receptors
clinical uses of BB’s
tx of HTN
management of angina
decrease mortality in treatment of post MI patients
used periop and preop for pts at risk of MI
suppression of tachyarrhythmias
prevention of excessive SNS activity
BB relative contraindications
pre existing heart block or cardiac failure
reactive airway disease
DM (without BS monitoring)
blunts response to hypovolemia, so dont give during hypovolemia
BB SE’s
- decrease HR, contractility, BP
- exacerbation of peripheral vascular disease (block of B2 vasodilation)
- airway resistance, bronchospasm
- metabolism, alter carbohydrate and fat metabolism, mask hypoglycemia increase in HR
- distribution of extracellular potassium, inhibit uptake of potassium into skeletal muscles
- interaction with anesthetics, may have decreased BP with IA’s
- nervous system fatigue, lethargy
- N/V/D
- eye- reduction in IOP (esp if pt has glaucoma) d/t decreased aqueous humor production
- decreased concentrations of HDL’s have been seen with chronic use that may increase risk for CAD
Propanolol receptor selectivity, CV effects, alternative concerns, tx goal, dosing, protein binding, metabolism, interaction with other drugs
non selective BB
decreased HR and contractility, CO. increased vascular resistance, due to decreased O2 demand, this is ok. reduction in renin release
extensive first pass effect
goal: 55-60bpm
oral much larger than IV dose r/t 1st pass effect (but still give PO more than IV)
.05mg/kg IV or 1-10mg (give slowly 1mg q5m)
90-95% protein bound
metabolized in liver
t1/2 2-3h (will be increased in low hepatic BF states)
concerns with patients who have been treated chronically- decreases clearance of amide LA’s due to decrease in hepatic BF inhabiting metabolism in liver, risk of systemic toxicity of amide local anesthetics, decreased pulmonary clearance of fentanyl (both are lipophilic amines)
Metoprolol receptor selectivity, dose, dosing consideration, metabolism, onset, t1/2, route of administration, patient population that would benefit
beta 1 selective (selectivity is dose related) 60% goes through first pass PO 50-400mg IV 1-15mg (max dose) onset 3min t1/2 3-4h metabolized by liver beta 2 receptors remain intact (bronchodilation, vasodilation, metabolic effects)
Atenolol receptor affinity, t1/2, excretion, uses
most selective B1 antagonist, thought to have least CNS effects
t1/2 6-7h, increases markedly in patients with renal disease
excreted via renal system
PO for HTN, long lasting HTN effects, good for pts with lung disease
Esmolol receptor affinity, onset, t1/2, DOA, metabolism, uses:
b1 selective antagonist
onset 60 seconds
t1/2 9 min
DOA 10-30min
metabolism plasma esterase
poor lipid solubility, does not cross BBB or placenta
useful in tx HTN and tachycardia associated with laryngoscopy. also useful for hyper dynamic effects of pheochromocytoma, thyrotoxicosis, thyroid storm
Timolol receptor affinity, uses
non selective BB
used to tx glaucoma, decreases intraocular pressure by decreasing production of aqueous humor
eye drops can cause decreased BP and HR and increased airway resistance
Nadolol receptor selectivity, metabolism, t1/2, how often to take, use
nonselective BB
no significant metabolism (renal/biliary elimination)
t1/2 20-40h take 1x daily
good for esophageal varices
betaxolol receptor selectivity, t1/2, how often to take, uses
b1 selective
t1/2 11-22h
single dose daily for HTN
topical, useful for glaucoma, with less risk of bronchospasm as seen with timolol, so good alternative choice in asthmatics with glaucoma
labetalol receptor affinity, metabolism, t1/2, max drop in BP time, dose
combined non selective antagonists (alpha 1, B1/2)
metabolism: conjugation of glucoronic acid
t1/2: 5-8h, prolonged in liver disease but not affected by renal dysfx
max drop in BP 5-10min after IV admin
dose .1-.5mg/kg, usually 2.5-5mg at a time for mild HTN in OR)
labetalol uses
decreases systemic BP with attenuated reflex tachycardia. decrease in BP SVR and HR but CO unaffected
used to tx intraop HTN and HTN crisis
can be used in hypotensive technique (not super popular anymore)
centrally acting agents MOA, site of action, clinical uses
reduce sympathetic outflow from vasomotor centers in brain stem. selective partial alpha 2 adrenergic agonist.
site of action: CNS non adrenergic binding sites and a1 receptor agonism
clinical uses: HTN, sedation, decrease anesthetic requirements, improve periop hemodynamics, analgesia
Clonidine effects, SE, route of admin, metabolism, excretion
BP reduction from decreased CO due to decreased HR and peripheral resistance. rebound HTN with abrupt cessation happens. sedative property dissipates over time
SE: bradycardia, sedation, xerostomia, impaired concentration, nightmares, depression vertigo, EPS, lactation in men
avail as PO or transdermal patch
hepatic metabolism
renal excretion
withdrawal syndrome of centrally acting agents
occurs with doses >1.2mg/day
occurs 18 hours post acute d/c of drug
lasts 24-72h
tx is rectal or transdermal clonidine
