Lecture 14-16 - Scrogin - Adrenergics (Agonists) Flashcards
What are the direct-acting endogenous sympathomimetics?
NE, Epi, and dopamine
What is isoproterenol (ISO)
a synthetic catecholamine that is selective for beta receptors
Describe the efficacy of epi, NE, and ISO for alpha-1 receptors
Epi is greater than or equal to NE
Epi and NE are»_space; ISO
Describe the efficacy of epi, NE, and ISO for alpha-2 receptors
Epi is greater than or equal to NE
Epi and NE are»_space; ISO
*Note: this is the same for alpha 2
Describe the efficacy of epi, NE, and ISO for beta-2 receptors
Iso > Epi»_space; NE
NE is a partial agonist only
Describe the efficacy of epi, NE, and ISO for beta-1 receptors
Iso > Epi = NE
NE and Epi have equal potency and efficacy
Adrenomimetic agonists can be broken into what 2 classes?
Define them.
Direct acting = acts on receptors directly
Indirect acting = promotes increase in endogenous NT in synaptic cleft (releasers or reuptake inhibitors)
What receptors does epi bind?
alpha-1 and alpha-2
beta-1 and beta-1
*depends on concentrations
How is epi eliminated/degraded?
Degraded by COMT and eliminated in urine
Low doses/infusion rates of epi gives binding to which receptors?
Beta-1 and Beta-2
What are the indications for low doses of epi?
Anaphylaxis and bronchospasm (acute asthma attack)
High doses/infusion rates of epi gives binding to which receptors?
Alpha-1
Beta-1 and Beta-2
What are the indications for high doses of epi?
Cardiac arrest and heart block
What is the mechanism of action for low doses of epi (*at each receptor)?
Beta-1 = + chronotropy and inotropy (inc HR, CO, and systolic)
Beta-2 = peripheral vasodilation, dec diastolic, and bronchodilation
What is the mechanism of action for high doses of epi (*at each receptor)?
Alpha-1 = peripheral vasoconstriction (this is the predominant effect) and dec bronchial secretions
*a1/b1/b2 give inc CO and TPR
What is the side effect for epi?
arrhythmias
What are the contraindications for epi?
Late term pregnancy
*note: this was not underlined
What receptors does NE bind?
Alpha-1 and Alpha-2
Beta-1
*has little affinity for beta-2
How is NE eliminated/degraded?
Degraded by COMT and MAO
Eliminated in urine
Describe the relative half life for NE and route of administration?
short half life
give via controlled infusion
What is the indication for NE?
Vasodilatory shock (acute HYPOtension)
Describe the mechanism of action for NE in relation to the receptors it binds
Alpha-1 = vasoconstriction, inc TPR, inc diastolic
Beta-1 = inc CO, inc systolic
Baroreflex = dec HR (dominates over chronotropy)
*also gives + chronotropy and inotropy
Inc in MAP = overall
What is the side effect of NE?
ischemia
What are the contraindications for NE?
Ischemia and pre-existing vasoconstriction (*if NE were given, it could induce gangrene)
What receptor does dopamine bind?
Dopamine-1 (D1) at low concentrations
Beta-1 and Alpha-1/Alpha-2 at higher infusion rates
What is the indication for dopamine?
Cardiogenic shock (HYPOtension due to low CO)
What is the mechanism of action for Dopamine at low infusion rates?
Activates D1 receptors = dec TPR
What is the mechanism of action for Dopamine at medium infusion rates?
Activates Beta-1 receptors = inc contractility and inc HR (inc CO)
What is the mechanism of action for Dopamine at high infusion rates?
Beta-1/Alpha-1/Alpha-2 stimulation = inc BP and inc TPR
What are the side effects of dopamine at low infusion rates? high infusion rates?
Low infusion rates = HYPOtension
High infusion rates = Ischemia
What is the contraindication for dopamine?
Uncorrected Tachyarrhythmia
What are 6 direct-acting adrenergic agonists?
- Isoproterenol (ISO)
- Dobutamine
3/4. Terbutaline/Albuterol - Pheynlephrine
- Clonidine
What are the 6 indirect acting adrenergic agonists?
Amphetamine Methamphetamine Methylphenidate Ephedrine Pseudoephedrine Tyramine
What are the indications for ISO?
Bradycardia
Heart block when TPR is high
What receptor does ISO bind?
It is a NON-SELECTIVE Beta-agonist
How is ISO degraded?
By COMT
What is the mechanism of action for ISO, in relation to specific receptors?
Beta-2 = vasodilation!, bronchodilation!, dec TPR, dec diastolic/systolic
Beta-1 = + inotropy and chronotropy (inc CO)
What are the side effects for ISO?
Tachyarrhythmias
What is the contraindication for ISO?
Angina with ARRHYTHMIA
What receptor(s) does Dobutamine bind? with what affinity?
B1 > B2 > a
It’s a selective Beta-1 agonist
What are the indications for Dobutamine?
Short term Rx for CHF (cardiac insufficiency)
Cardiogenic shock (low cardiac contractility)
What is the mechanism of action for Dobutamine?
Inc CO
+ inotropy > + chronotropy (because of no/little beta-2 reflex tachy/vasodilation)
What is the mechanism of action for high doses of Dobutamine?
It’ll bind Beta-2 and cause HYPOtension with reflex tachycardia
What are the side effects for Dobutamine?
Hypotension (beta-2)
Arrhythmias (beta-1)
How is Dobutamine degraded?
Rapidly by COMT
What receptor(s) does Terbutaline/Albuterol bind? With what selectivity?
It is a Beta-2 agonist
What are the indications for Terbutaline/Albuterol?
Bronchospasm (asthma, bronchitis, and emphysema)
Obstructive Airway Disease
What does Terbutaline/Albuterol do?
Cause bronchodilation
Can give some Beta-1 agonist-like response (cardio effect)
What are the side effects for Terbutaline/Albuterol?
Beta-1 = tachy (@ high dose)
Beta-2 = tolerance, skeletal muscle tremor, and activation of pre-synaptic cholinergic beta-2 receptors
What receptor(s) does phenylephrine bind? Any selectivity?
Alpha-1 agonist
What are the indications for Phenylephrine?
Paroxysmal supraventricular tachy
Mydriatic agent
Nasal decongestant
Is Phenylephrine degraded by COMT?
No, because it’s not a catecholamine
Compare the duration of action for endogenous catecholamines and phenylephrine
Phenylephrine has a longer duration of action
What is the mechanism of action/effects of Phenylephrine?
Peripheral vasoconstriction, inc BP, activation of baroreflex, dec HR
Dilates pupil
Decreases bronchial secretions
What is the side effect of phenylephrine?
HTN
What receptoronidine does clonidine bind? Any selectivity?
Alpha-2 agonist
What is the indication for clonidine
HTN from excess symp drive
What is the mechanism of action for clonidine?
Peripheral effect = mild vasoconstriction, crosses BBB to dec symp outflow (reduce vasoconstriction an bp)
Central effect = dec BP
Overall: DEC BP
For clonidine, dec tonic excitatory input to sympathetic cells leads to a reduction in sympathetic output to ___
vascular smooth muscle
What are the side effects of Clonidine?
Dry mouth
Hypertensive crisis (after acute withdrawal)
How do indirect-acting sympathomimetics increase the concentration of endogenous catecholamines?
- release of cytoplasmic catecholamines
2. blockade of re-uptake transporters
Amphetamine-like drugs are taken up by ___ and cause ___
Taken up by re-uptake proteins
Cause reversal of transporter and lead to Ca2+ independent release of NT
Do amphetamines cross the BBB?
Yes, this leads to high abuse potential
What are indications of direct-acting adrenergic agonists?
ADD
Narcolepsy
Nasal Decongestion
Name 2 indirect acting agonists that are used for ADHD
Amphetamine, Methylphenidate,
Which indirect agonist is used for anesthesia?
Ephedrine
Which indirect agonist is used for nasal decongestion?
Pseudoephedrine
What is the therapeutic use of Tyramine?
There is none
It displaces NE
How is Tyramine degraded?
By MAO
What are the effects of indirect adrenergic agonists?
NE release gives peripheral vasoconstriction, + inotropy, inc conduction velocity
In the CNS it’s a stimulant and anorexic agent
What is the side effect for indirect adrenergic agonists?
Tachy (beta-1)
What is the contraindications for indirect acting adrenergic agonists?
Rx with MAOIs within the past 2 weeks
