Flashcards in Adrenergic System Deck (96):
What receptors does NE interact with?
What receptors does Epi interact with?
Alpha 1 Receptor Mediated EFFECTS (4)
2. Constricts arteries/veins
3. Constricts GI/GU sphincters
Beta 1 Receptor Mediated EFFECTS (5)
1. INC HR (heart)
2. INC Contraction (heart)
3. INC Conduction Velocity (heart)
4. INC Renin Secretion (Vasoconstricts/ INC BP)
5. INC Lipolysis (INC FFA)
Beta 2 Receptor Mediated EFFECTS (5)
2. Dilates arteriers in skeletal muscle
3. INC blood sugar
4. INC insulin secretion
5. Relaxes Uterus
Alpha 2 Recepter Mediated EFFECTS (3)
1. DEC Sympathetics from CNS (DEC BP -- vasodilation)
2. DEC NE Release
3. DEC Insulin Secretion
What is the most important factor for termination the action of neuronally released NE?
What is the most abundant urinary metabolite of NE and EPI? What usually acts on NE and EPI before it's excreted?
- BOTH MAO and COMT
Monoamine Oxidase (MAO) metabolizes what?
-Metabolizes many monoamines (non-specific)
-Protects against circulating and EXOGENOUS BIOLOGICALLY ACTIVE AMINES
Catechol-O-Methyl-Transferase (COMT) metabolizes what?
-Specifically metabolizes catechols
-Imp for metabolizing CIRCULATING CATECHOLAMINES
What is the rate limiting step in the synthesis of NE and EPI?
Tyrosine --> Dopa by Tyrosine Hydroxylase
What drug inhibits tyrosine hydroxylase? (Therefore decreasing formation of NE and EPI from Tyrosine)
When is Metyrosine used specifically?
What 2 drugs cause rapid release of NE from nerve terminal?
What is amphetamine (adderall) prescribed for?
What is a specific adverse effect of Amphetamine?
Marked CNS effects due to pronounced CNS stimulation
Why should you NOT combine Tyramine with MAOIs?
Enhanced action --> hypertensive crisis
What is the MOA for cocaine?
Inhibits NE reuptake
INC NE effects
What 2 drugs INHIBIT MAOs? (MAOIs)
MAOI's predispose patients toward what? How?
- Increase the levels of circulating dietary amines which leads to HYPERTENSION
What drug INHIBITS COMT?
What is Entacapone used for?
Adjunctive therapy with levodopa for PARKINSONISM
What are the 3 possible mechanisms of action for Adrenergic Receptor AGONISTS?
1. Direct interaction of drug with adrenergic receptor
2. Indirect action via drug induced release of NE/EPI (endogenously)
3. Mixed direct and indirect
What are the 5 catecholamines?
Are catecholamines effective if taken orally?
Short duration of action
Metabolized by COMT
OH on C3 and C4 of Benzene Ring
What are the 3 mentioned NON-Catecholamines?
Longer duration of action than catecholamines
What is the SELECTIVE Alpha 1 Receptor AGONIST?
What is the SELECTIVE Alpha 2 Receptor AGONIST?
What is the SELECTIVE Beta 2 Receptor AGONIST?
What is Phenylephrine used for? (3)
Myadritic (dilates eyes)
Decongestant (vasoconstrics nasal mucosa)
Prolong action of local anesthetics (local vasoconstrict)
What is Clonidine used for? (3)
Hypertension (reduces sympath from CNS)
What is Albuterol used for? (2)
Bronchial Asthma (bronchodilator)
What are 3 adverse effects of Clonidine?
1. Hypertensive crisis upon sudden withdrawl
3. Sexual Dysfunction
What are 2 adverse effects and 2 contraindications for Albuterol AND Isoproterenol?
1. Cardia Stimulation (LOST selectivity at high doses causing beta 1 activation) -- arrhythmias, engine
Isoproterenol is an AGONIST where?
Beta 1 AND Beta 2 Receptors
What is Isoproterenol used for?
1. Bronchospasm (when inhaled)
2. Cardia Arrest (+ chronotrope, +ionotrope)
3. Heart Block (INC AV conduction)
What are the overall effects of Isoproterenol?
2. DEC BP
3. INC HR
Epinephrine (Adrenaline, Epipen) is what type of drug?
AGONIST at alpha 1, alpha 2, beta 1, and beta 2 receptors
What are the cardiovascular effects of a LOW dose of Epinephrine? (similar to physiological levels during fight/flight response)
Vasodilation (DEC BP)
Tachycardia (INC HR)
What are the cardiovascular effects of HIGH dose of Epinephrine?
Vasoconstriction (INC BP)
Tachycardia (INC HR)
What are 5 uses for Epinephrine?
1. Anaphylaxis (dec mediator release, bronchodilates)
2. Bronchospasm (bronchodilation)
3. Cardiac Arrest (+chronotrope, +ionotrope)
4. Prolong local anesthetics (local vasoconstriction)
5. Glaucoma (INC aqueous outflow)
What are 4 adverse effects of Epinephrine?
1. MARKED HypERglycemia (DEC insulin, Inc glycogenolysis)
2. Cardiac Stimulation (arrythmia, angina)
3. Vasoconstriction (hypertension)
4. CNS Stimulation (Inc respiration, tremor)
What are the contraindications Epinephrine?
INC Toxicity with MAOIs
Norepinephrine (noradrenaline) is what type of drug?
AGONIST at alpha 1, alpha 2, and beta 1 receptors
What are the cardiac effects of Norepinephrine?
Vasoconstriction (INC BP)
+- HR (dose dependent)
What is Norepinephrine used for?
(vasoconstrics + ionotrope)
What are the adverse effects of Norepinephrine?
What are the contraindications for Norepinephrine?
INC toxicity with MAOIs
INC toxicity with cocaine (reuptake inhibitors)
What do we use Dobutamine for? Why?
Acute CHF (chronic heart failure)
It is a +ionotrope (INC CO)
What are the adverse effects of Dobutamine?
INC Myocardial O2 consumption
INC AV Nodal Conduction
Hypertension (in some pts.)
Dopamine has what type of actions?
-Direct AGONIST at Dopaminergic D1 Receptors (dilation of renal, splanchnic, cerebral, and coronary vessels)
-AGONIST at alpha 1, alpha 2, and beta 1 receptors
-Causes release of NE/EPI (adverse effects are similar to NE/EPI)
Effects of LOW doses of Dopamine
D1-receptor mediated selective vasodilation of renal and splanchnic vessels
Effects of MODERATE doses of Dopamine
D1-receptor mediated vasodilation (DEC TPR)
+ or - BP
Effects of HIGH doses of Dopamine
alpha receptor vasoconstriction (INC TPR)
beta 1 receptor (INC HR)
What is Dopamine used for? (low to moderate doses) (2)
Direct action at Adrenergic Receptors
Release of NE
Uses of Pseudoephedrine
Decongestant (vasoconstriction of nasal mucosa)
Adverse effects of Pseudoephedrine (2)
What are the actions of Adrenergic Receptor ANTAGONISTS? (2)
Inhibit actions of endogenous NE and EPI at receptor sites
Inhibit actions of exogenously administered drugs mediated by adrenergic receptors
Effects of Alpha 1 Receptor INHIBITION (3)
Vasodilation (DEC BP)
Relaxation of Bladder Sphincter
DEC Sexual Function
Effects of Alpha 2 Receptor INHIBITION
INC sympath from CNS
INC NE release
Phenozybenzamine is what type of drug?
NON-Competitive Block of alpha 1 and alpha 2 receptors
What do we use Phenoxybenzamine for?
-Preoperative or chronic therapy for PHEOCHROMOCYTOMA (along with Beta blockers)
- treatment of reversible vasospastic disease
What are the effects caused by taking Phenoxybenzamine?
Vasodilation (DEC TPR)
** LONG LASTING**
What are the contraindications/adverse effects of Phenoxybenzamine?
Tachycardia, arrhythmias, angina
What type of drug is Phentolamine?
Competitive inhibitor of alpha 1 and alpha 2 receptors
(similar to phenoxybenzamine)
What makes Phentolamine different from Phenoxybenzamine?
Shorter duration of action
MUST BE GIVE IV
What do we use Phentolamine for?
During surgical removal of pheochromocytoma
Reversible Vasospastic Disease (frostbite)
What are the 2 relatively specific alpha 1 receptor ANTAGONISTS?
1. Doxazosin (Prazosin)
What are the effects of Doxazosin?
Arteriolar Dilation (DEC BP)
Relaxation of Bladder Spincter
What do we use Doxazosin for?
1. Benign Prostatic Hypertrophy
What are the adverse effects of Doxazosin?
"First Dose Syncope" -- (DEC BP)
* only in volume depleted patients -- so begin it at night*
What do we use Tamsulosin for?
Relaxation of bladder sphincter in Benign Prostatic Hypertrophy.
*Selective inhibition of alpha 1a receptors my provide some SELECTIVITY for sphincter*
Effects of Beta 1 Receptor Inhibition (5)
DEC HR (heart)
DEC Contraction (heart)
DEC Conduction Velocity (heart)
DEC Renin Secretion
** more marked in states with high sympathetic tone like exercise, hyperthyroidism, anxiety**
Effects of Beta 2 Receptor Inhibition
If a drug has a lower lipid solubility, what side effects can this decrease?
CNS side effects
What receptor must I block to be "cardioselective"?
What are the 2 Non-Specific Beta Receptor Antagonists?
How does Propranolol work?
Competitively inhibits beta 1 and beta 2
What are the cardiovascular effects of Propranolol? (7)
DEC myocardial O2 consumption
DEC AV nodal conduction velocity
Long term = DEC BP
DEC Coronary Blood flow
What are the non-CV effects of Propranolol? (5)
Inhibits glycogenolysis in response to EPI (diabetics**)
DEC Intraocular Pressure in Glaucoma
DEC Lipolysis (INC Triglycerides)
What are the therapeutic uses of Propranolol?
Chronic Stable Angina
Idiopathic Hypertrophic Subaortic Stenosis (IHSS)
Adverse Effects of Propranolol?
DEC Myocardial Contractility
Cold Extremities (aggravates Raynaud's)
Dec Exercise Tolerance
Aggravates Variant Angina
INC Plasma Triglycerides
CNS (fatigue, lethargy, vivid dreams, insomnia, depression)
Sudden withdrawal = hypertension, angina, MI, sudden death
In what 2 populations should you avoid Propranolol?
1. Asthma/COPD Patients
2. Diabetics (causes hypoglycemia, inhibition of tachycardia in response to hypoglycemia)
Timolol is used for what?
What are the 2 CARDIOSELECTIVE Beta 1 Receptor Antagonists?
1. Metoprolol (atenolol)
Metoprolol has what MOA?
Inhibits Beta 1 receptors
Metoprolol is preferred over non-specific beta blockers in what patient populations? (3)
2. Raynaud's Syndrome
Metoprolol is used for what?
Similar uses as Propranolol
What is special about Esmolol? (3)
Very short acting
Metabolized by red cell ESTERASE
Used as Antiarrhythmic (IV ONLY)
How does Carvedilol work?
Non-specific beta blocker
Specific alpha 1 blocker
What are the effects of Carvedilol?
DEC TPR (DEC BP)
What is Carvedilol used for?