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Name 4 catecholamines
Epinephrine, Norepinephrine, Dopamine, Dobutamine, Isoproterenol
Epinephrine's affinity for alpha & beta receptors
What blood pressure response will you see with stimulation of alpha receptors in the blood vessels?
Increased Diastolic BP
What blood pressure response will you see with stimulation of beta receptors in the CV system?
Increased Systolic BP
What response in the heart will you see from Epinephrine?
Positive inotropy, Positive chronotropy
What beta-2 activation response will you see in the skeletal muscle blood vessels with Epinephrine?
Skeletal muscle vessels dialate
Dosing of Epinephrine?
Asystole = 1mg IV q 3-5min
Hypotension = 1-10 mcg/min IV infusion
Bronchodilator = 0.1-0.5mg IM/SQ q 10-15 min
How is Epi metabolized?
Quick metabolism by COMT & MOA enzymes
Norepi's affinity for Alpha & Beta receptors?
What effect on Blood Pressure will you see with Norepi?
Increase in Systolic & Diastolic BP
Why might you see a fall in HR or no increase in HR with Norepi?
The brain senses an increase in BP so it activates the PSNS to stimulate Muscarinic receptors located in the heart - compensatory
Dosing of Norepinephrine?
Continuous IV - 4mcg/min and titrate
Usual dose = 8-12mcg/min
What is the RULE OF 6?
6 x weight(kg) x desired dose/desired IV rate = amount of med (mg) to add to 100ml fluid
Isoproterenol's affinity for alpha & Beta receptors?
Potent Beta agonist; Beta-1>Beta-2>>>>>>>>alpha
Response seen in blood vessels with Isoproterenol?
Response seen in the heart with Isoproterenol?
Increases inotropy & Chronotropy
Increased Cardiac Output
Fall in diastolic with slight increase or decrease in systolic
Why will you see a decreased Diastolic BP with Isoproterenol?
B/c Beta-2 effects
Dosing of Isoproterenol?
Arrhythmias = 5mcg/min IV infusion initially & titrate
Shock = 0.5-5mcg/min IV infusion & titrate
Dopamine's affinity for Alpha & Beta receptors?
Dosing for Dopamine?
LOW= 1-3mcg/kg/min (Dopa receptor activation)
INTERMEDIATE= 3-10mcg/kg/min (Dopa & Beta-1)
HIGH= >10mcg/kg/min (Dopa, Beta & Alpha)
Fenoldopam's affinity for Alpha & Beta receptors?
What effects in some vascular beds will you see with Fenoldopam?
Primary use for Fenoldopam?
Dobutamine's affinity for Alpha & Beta receptors?
Cardiac effects seen with Dobutamine?
Increased Inotropy & Chronotropy by activating selective beta-1 receptors
Dosing for Dobutamine?
Max = 40mcg/kg/min
MOA for Phenylephrine?
Pure alpha agonist
Is phenylephrine inactivated by COMT
3 Main uses for Phenylephrine?
1. Pupil dilation
3. Increased BP (minor)
MOA of Methoxamine?
Direct acting alpha-1 agonist
Effects of Methoxamine?
Prolonged increase in BP - Rarely used clinically
Why do you see bradycardia with Methoxamine?
Because it is a potent vasoconstrictor, the brain senses the increase in BP and activates the PSNS to stimulate muscarininc receptors in the heart to dec. HR
MOA of Midodrine?
Selective alpha-1 agonist - direct acting
What cardiac effects do you see with Midodrine?
Indication for Midodrine?
Why is Midodrine not used clinically?
Used to treat postural HYPOtension, but will see HYPERtension when pt. is supine
Where does Ephedrine come from?
Ma-huang plant from China
MOA of Ephedrine?
Orally active Direct acting sympathomimetic
Releases stored catecholamines
Mimics epinephrine (but doesn't increase BP as much)
Why have we been able to modify ephedrine and come up with new meds?
It has 2 points of chirality allowing for isomers to be derived.
Why do you see mild CNS stimulant effects with Ephedrine?
It crosses BBB
Main use for for ephedrine?
MOA of Xylometazoline & Oxymetazoline
Direct acting Alpha Agonist
Uses for Xylometazoline & Oxymetazoline
Constriction of Nasal Mucosa (Afrin)
Why do you not want to use Xylometazoline & Oxymetazoline long term?
Can cause rebound congestion b/c alpha receptors that are being stimulated get down regulated
Why may you see a Dec. in BP with increased used of Xylometazoline & Oxymetazoline?
You get good absorption systemically, it crosses BBB and can see effects of Alpha-2 stimulation in the brain leading to a dec. BP (like clonadine)
MOA of Amphetamines
Lipid soluble indirect sympathomimetic that Crosses BBB
Effects seen with Amphetamines
Marked stimulant effects on mood and alertness
Uses for Amphetamines
MOA of Methamphetamine
Indirect acting Sympathomimetic that has a higher ratio of central to peripheral actions
Uses for Methamphetamine
Phenmetrazine MOA and use?
Indirect Sympathomimetic, used as appetite suppressant
MOA for Methylphenidate & Pemoline and use?
Indirect Sympathomimetic - stimulant used in children for ADHD
MOA for Modafinil and use?
Alpha-1b receptor agonist in the brain
MOA of Cocaine?
Sympathomimetic that readily enters CNS and inhibits dopamine re-uptake into pre-synaptic neurons in the pleasure centers- Also alpha stimulation seen causing vasoconstriction
NOT a drug but rather a metabolite of tyrosine
Indirect sympathomimetic (similar to norepi)
Releases stored catecholamines
How is Tyramine metabolized?
Effects seen in blood vessels with Alpha receptor stimulation
Vasoconstriction, Inc. SVR & Inc. DBP
Effects seen in blood vessels with Beta receptor stimulation
Vasodialation, Dec. SVR
Effects seen in blood vessels with Dopamine receptor stimulation
D1 = Vasodilation in renal, coronary, visceral, & Cerebral vessels
Effects seen in the Heart with Beta Receptor Stimulation
Inc. Inotropy & Inc. Chronotropy
Beta 1 - is dominant
Effects seen in the Heart with Alpha receptor stimulation
Not many receptors present = no real effect
Effects seen in the eye with Alpha Stimulation
Pupil dilation via constriction of iris radial muscle & inc. in aqueous humor
Effects seen in the eye with Beta Stimulation
Pupil dilation via relaxing ciliary bodies & decreased in production of aqueous humor
Effects seen in the lungs with Alpha stimulation
Constriction of Bronchial blood vessels in upper airway = decongestants & dec mucus production
Effects seen in the lungs with Beta Stimulation
Bronchodilation via Beta -2
Effects seen in the GI tract with Alpha Receptor stimulation
Indirectly as heteroceptor - activates presynaptic alpha site on cholinergic nerve - leads to dec. ACh release and slowing of digestion
Also alpha 1 - contracts smooth muscle sphincters
Effects seen in GI tract with Beta Receptor stimulation
relaxes smooth muscle walls and slows down digestion - Beta -2
Effects seen in GU tract with Alpha Receptor stimulation
constriction of bladder base, urethral sphincter and prostate
Effects seen in GU tract with Beta Receptor stimulation
Relaxation of bladder walls - Beta 2
Uterine relaxation - Beta 2
Effects seen in sweat gland with alpha receptor stimulation
Apocrine - stimulation to release fatty oils
Eccrine - response to cool body off
Beta 2 receptor effects on metabolic functions
Glycogenolysis (breakdown glycogen for glucose)
Gluconeogenesis (protein breakdown for energy)
When do you want to use a direct acting alpha agonist?
- preserve cerebral blood flow
- Severe hemorrhage
- Spinal cord injury
- Anithypertensive OD
- CNS depressant OD
How do you initially want to treat shock?
Volume and treat underlying cause
What do you treat cardiogenic shock with?
CPR, possibly Beta agonists, but poor prognosis
What is an agent used in the OR to achieve Hemostasis?
Also reduces diffusion of local anesthetic away from desired site
Drug of Choice for Complete Heart Block & Cardiac Arrest
Epi & Isoproterenol
Drug used to treat Narcolepsy
2 alpha adrenoceptors used to treat ADHD
MOA for Clonidine in treating hypertension
UNIQUE alpha 2 agonist that can dec. BP by working on alpha receptors in the brain (presynaptic)
Other uses for Clonidine
Diarrhea, dec. appetite cravings, dec. hot flashes, treat hemodynamic instability in the OR
MOA for Desmedetomidine
Works on presynaptic inhibitory alpha 2 receptors in the brain to cause sedation
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