Blockers Flashcards
Cells in the (xxxxx) synthesize and secrete norepinephrine and epinephrine.
adrenal medulla
Following release into blood, these hormones bind (XXXXXX) receptors on target cells, where they induce essentially the same effects as direct (XXXXXX) nervous stimulation.
adrenergic
sympathetic
Ratio for norepinephrine and epinephrine in the adrenal medulla?
80% is epi
20% is NE
How is norepinephrine made?
Tyrosine
DOPA
Dopmaine
Norepinephrine
How is Epinephrine made?
Tyrosine
DOPA
Dopmaine
Norepinephrine
What enzyme is responsible in making Tyrosine into DOPA?
tyrosine hydroxlase
what enzyme is responsible in making DOPA into Dopamine?
DOPA decarboxylase
What enzyme is responsible in making Dopamine into Norepinephrine?
Dopamine B-hyroxylase
What enzyme is responsible for making Norepinephrine into Epinephrine?
phenylethanolamine N-methyltransferase
Norepinephrine and Epinephrine are metabolically degraded by what two compounds?
MAO and COMT
Acetylcholine is broken down by what enzyme? How is it metabolized? What are the two compounds it is broken down into??
Acetylcholinesterase
Acetate + Choline
Norepinephrine and Epinephrine are both ultimately broken down into what compound?
Vanillymandelic Acid (VMA)
The metabolic pathway in the nerve endings for the breakdown of epi and norepi?
MAO to COMT
The metabolic pathway in the liver for the breakdown of epi and norepi?
COMT and MAO
Alpha 1 postsynaptic receptor stimulation causes what?
-Mydriasis (pupillary dilation d/t contraction of radial eye muscles) (fight or flight, you need to let more light in)
-Bronchoconstriction (through AcH)
-Vasoconstriction
-Uterine contracture
(male ejaculation)
-Contraction of sphincters of GI/GU tract
What g protein receptor is alpha 1 post synaptic?
Gs
Alpha 2 pre synaptic receptor stimulation causes?
- Some vasoconstriction of vascular smooth muscle
- Decreased N.E. release
- Sedation (how precedex works, 1600x more specific than clonidine)
- Sympathetic outflow (decreases)
- -Peripheral vasodilation
- -Lowers BP
- Inhibit insulin release from Islet cells (beta cells) (more glucose)
what g protein receptor is alpha 2 pre synaptic?
Gi
What are the non-selective alpha antagonist?
phentolamine
phenoxybenzamine
tolazoline
If it ends in -ine it is non slective
What are the selective alpha 1 antagonist?
Prazosin
Terazosin
Doxazocin
Tamsulosin
What is a selective alpha 2 antagonists?
Yohimbine
What does beta 1 receptor stimulate?
Chronotorpic (increase HR)
Dromotropic (increase conduction)
Inotropic (increase contractility)
What does beta 2 receptor stimulation cause? non cardiac
- Relaxes smooth muscle
- Bronchodilation
- Vasodilation (b/c there are some beta 2 in the periphery, mostly alpha receptors)
- Relax uterus/bladder/gut
- increase Glycogenolysis, lipolysis, gluconeogenesis (making glucose from aminoacids & from the glycerol portion of fat), insulin hypoglycemiagluconeogenesis).
- Activation of Na/K pump
- –K goes intracellular (can produce hypoK & dysrhythmia)
What are non selective beta antagonists?
propranolol
timolol
nadolol
pindolol
If the name starts after N is nonslecetive
what are selective beta 1 antagonists?
atenolol
esmolol
metoprolol
If the name starts between A-M it is selective
Alpha antagonists Inhibits action of NE at (XXXXX) synaptic receptors (reversible or irreversible)
post
NE is release presnyaptically, the alpha antagonist will inhibit the presynaptic site to prevent the release of NE. Therefore NE cannot stimulate postsynaptic. Will block pre and post synaptic alpha receptors.
Alpha antagonists Attenuates sympathetic responses which two places in the body?
heart, peripheral vasculature
true or false?
Alpha antagonists dont produce orthostatic hypotension, baroreceptor reflex tachycardia
False
Alpha antagonists MAY produce orthostatic hypotension, baroreceptor reflex tachycardia
true or false?
α blockade inhibits epinephrine’s effect on insulin secretion
True
α blockade inhibits epinephrine’s effect on insulin secretion
What is reversible inhibition?
- Competitive binding at receptor site**
- Effects of inhibition may be overcome by administering sympathomimetic
Competitive, if you give more of the stimulant you should be able to overcome the effect, this is for reversible
You wont be able to do that if it is irreversible
What is irreversible inhibition?
- Covalent binding at receptor site**
- Inhibition may not be overcome by admin of sympathomimetic-insurmountable
- Metabolism of drug required to terminate blockade response
What is a reversible inhibitor that produces peripheral vasodilation, produces baroreceptor-mediated increase in HR and CO as well as dysrhythmia and angina as side effects?
Phentolamine
what is the onset and duration of phentolamine?
onset of 2 min and duration is 10-15min
what are the clinical uses of phentolamine?
Acute Hypertensive emergencies
–Pheochromocytoma- intra op management
–Autonomic Hyperreflexia
30 to 70 mcg/kg IV (prompt/transient dec in BP)
Drip may be desirable to maintain steady state
How do you treat a dopamine extravasation?
Local infiltration of phentolamine-containing solution (2.5 to 5mg in 10ml)
What is pheochromocytoma?
tumor of chromaffin cells of the adrenal medulla
4 to 1 NE to epi
what are the symptoms of pheochromocytoma?
- increase hr
- increase blood pressure/orthostatic blood pressure
- increase anxiety
- decrease weight
- diaphoresis
Is Phenoxybenzamine
Selective or non selective?
irreversible or reversible inhibitor?
what kinda of bond?
Phenoxybenzamine is a non-slective irreversible inhibitor, covalent binding
what is the onset and half-life of Phenoxybenzamine?
slow onset of up to 60 minutes
prolonged half-life of 24 hours
true or false?
Phenoxybenzamine does not have an cumulative effects with repeated doses.
False
Phenoxybenxamine has cumulative effects with repeated doses
what are the non cardiac effects of Phenoxybenzamine?
Non cardiac effects: miosis, nasal stuffiness, sedation
What does Phenoxybenzamine cause hypotension?
Profound hypotension in presence of hypovolemia, blood loss, vasodilators & inhalation agents (b/c this will cause vasodilation as well)
What are the clinical uses of Phenoxybenzamine?
Clinical Uses Preop BP management in Pheochromocytoma begin treatment 2 weeks prior to surgery Inoperable Adrenal tumors Raynaud’s Disease (bad peripheral constriction)
What is Yohimbine?
- –Selective α₂ antagonist @ presynaptic receptors (increases release of NE)
- –Enhances release of NE
What are the clinical uses of Yohimbine?
Clinical Uses:
idiopathic orthostatic hypotension
Impotence (former treatment)
Does Prazosin work pre or post synaptic?
Selective post-synaptic α₁ antagonist
Reflex tachycardia is less common because drug has no inhibitory effect on α₂ receptors
How is Prazosin metabolized?
Prazosin is hepatically metabolized
what is the onset and duration of Prazosin?
PO
onset of 30 min
duration of 4-6 hours
What are the clinical use of Prazosin?
- HTN
- Raynaud’s Disease (b/c it’s a vasodilator)
- Benign Prostatic Hypertrophy- decrease tone of the prostate & bladder neck (Doxazosin, Terazosin, Tamsulosin preferred)
true or false?
beta antagonists Inhibition is competitive & reversible
true
beta antagonists Inhibition is competitive & reversible
what body parts do beta antagonists effect?
beta antagonists Effects cardiac & smooth muscles of airway and blood vessels
Should you Continue β blockers during periop period to avoid SNS hypersensitivity?
Yes
Continue β blockers during periop period to avoid SNS hypersensitivity
β₁ cardioselectivity is well suited for what kind of patients?
β₁ cardioselectivity is well suited for asthma patients
β₁ cardioselectivity is ideal for treating what?
β₁ cardioselectivity Ideal for treating essential HTN because no vasodilation of peripheral blood vessels
what are the effects of β₁ cardioselectivity blockers??
- Decreases chronotropic, dromotropic, & inotropic effects
- Decreases myocardial O₂ demand & myocardial ischemia
What is Propranolol (Inderal)?
- Beta blocker prototype drug
- Non-selective pure antagonist
What are the cardiac effects of Propranolol (Inderal)?
- dec HR, contractility & CO
- inc peripheral vascular resistance & coronary vascular resistance
- Inc myocardial O₂ requirement but offset by bradycardic O₂-sparing effect
What is the meabolism and half time for Propranolol?
- Extensive hepatic first-pass metabolism limits bioavailability
- First-pass varies widely in patients accounting for wide dose range 40-800mg/day PO
- Elimination half time 2-3 hrs
What is Propranolol drug interactions with Amide Local anesthetics?
- Decreases clearance of Amide Local Anesthetics D/T decreased hepatic blood flow & inhibition of liver metabolism (Ex: Bupivacaine clr decreased by 35%)
- Inc susceptibility for systemic Amide local anesthetic toxicity
What is Propranolol drug interactions with Opioids?
- Pulmonary first-pass uptake of Fentanyl is HIGHLY DECREASED in pts taking propranolol**
- 2-4 times as much injected Fentanyl enters systemic circulation right after injection (higher chance of Fentanyl overdose)
- This response reflects ability of one basic lipophilic amine (propranolol) to inhibit pulmonary uptake of another basic lipophilic amine (fentanyl)
What is Metoprolol? and what does it prevent?
β₁ selective, prevents inotropic & chronotropic responses to beta stimulation
Becomes nonselective at high doses-Selectivity is dose related
Metoprolol is well suited for what type of patients?
Suited for COPD/PVD pts because NO β₂ activity at normal dose (2-15mg IV).
What is the half-life of Metoprolol?
High first-pass
Half-life 3-4 hrs
What is Atenolol (Tenormin)?
- Most selective Beta1 Blocker
- Periop Tx decreases incidence of post MI in CAD pts
- does not potentiate insulin-induced hypoglycemia seen with nonselective Beta blockers, may administer with caution
How is Atenolol (Tenormin) metabolized, excreted, and half-time?
Little to no hepatic metabolism
Renal excretion
Elimination half-time 6-7 hrs
What is Esmolol?
IV only, rapid onset, short acting β₁ antagonist (0.5mg/kg)
What is Esmolol useful for?
Tx HTN & tachycardia in response to intra-op noxious stimulation & intubation (eg 150mg IV 2min before Laryngoscopy)
What are the clinical uses for Esmolol?
- Electroconvulsive therapy (ECT)
- Pheo
- Thyrotoxicosis
- PIH (pregnacy induced htn)
- Epi- or cocaine-induced cardiac toxicity
What is the half-life and metabolism of Esmolol?
Elim half-time 9 min- rapid hydrolysis in blood by plasma esterases**, independent of liver, renal, hepatic function
Poor lipid solubility limits crossing into CNS/placenta
What is the dose of Esmolol?
Dose: 0.5mg/kg (peaks 5min**). Return of HR to pre-drug level within 10-30min
What are Labetolol/carvdilol?
Labetolol/carvdilol-selective α1 and nonselective β antagonist
What is the potency ratio for Labetolol/carvdilol?
β to α blocking potency ratio 7:1 for IV route 3:1 PO for Labetaolol.
Carvediolol only available PO 10:1
What is the onset and elimination half time?
-Onset 5- 7 min
-Elimination half time 5-7 hours, prolonged in
liver disease
–α1 blockade lowers BP, β blockade
—-blunts reflex tachycardia
What are the clinical uses for Labetolol?
- Hypertensive emergencies
- Rebound HTN d/t clonidine withdrawal
- Angina pectoris
- Pheochromocytoma (when they remove this)
- HR control intra-op
- Repeated doses 20-80mg IV every 10 min**
- Orthostatic hypotension most common S/E
What are the Side Effects: β antagonists?
- Dependent on selectivity & intrinsic sympathomimetic activity
- Affects airway resistance, carbohydrate & lipid metabolism
- May cross BBB & placenta
- GI: N/V/D (PO)
What are the Contraindications to β Blockade?
- Sinus or AV node dysfunction, heart block
- Hypotension
- Decompensated heart failure
- Severe reactive airway disease
What does alpha and beta stimulate do with insulin?
Beta 2 stimulates Beta islet cells , which increase insulin release
Alpha 2 decrease insulin release
