Adrenergic Agonists Flashcards
What are some of the effects of a1 activation?
- Vasoconstriction
- Pupil dilation
What are some of the effects of a2 activation?
- Inhibits NT release
- Vasoconstriciton
What are some of the effects of b1 activation?
-Stimulates increase in inotropy and chronotropy of the heart
What are some of the effects of b2 activation?
- Vasodilation
- Bronchodilation
What are some of the effects of D1 activation?
-Relaxes renal and splanchnic blood vessels
What are some of the effects of D2 activation?
-Inhibits adenylyl cyclase
What is the mechanism for a1?
Positive coupling of phospholipase C
What is the mechanism for a2?
Negative coupling of adenylyl cyclase
What is the mechanism for b1?
Positive coupling of adenylyl cyclase
What is the mechanism for b2?
Positive coupling of adenylyl cyclase
What is the catecholamine structure?
Catecholamines contain two hydroxyl groups on a phenyl ring.
What is the most effective agonist on the alpha receptors?
Epinephrine
What is the most effective agonist on the beta receptors?
Isoproterenol
What has the greatest effect on diastolic pressure?
TPR
What has the greatest effect on systolic pressure?
CO
What does EPI stimulate?
Stimulates α1, α2, β1 and β2 receptors
What are the effects of EPI at low doses?
β2 receptor activation causes peripheral vasodilation, thereby decreasing diastolic BP; β1 receptor activation has positive inotropic and chronotropic effects thereby increasing CO and systolic BP
What are the effects of EPI at high doses?
At higher doses (>0.2 μg/kg/min, solid lines) effects of α1 receptor activation predominate:
Producing peripheral vasoconstriction, elevated systolic pressure and elevated diastolic pressure due to increased TPR and increased CO.
What are the effects of EPI on the lung?
β2 receptor - bronchodilation
α1 receptor - decrease in bronchial secretions
EPI indication
- Anaphylaxis
- Cardiac arrest
- Bronchospasm
EPI Toxicity
Arrhythmia
EPI Contraindications
Late term pregnancy
What does NE stimulate?
α1, α2 and β1 receptors
What are the effects of NE?
β1: Increase CO
α1, α2: Increase TPR
Decrease in heart rate due to baroreceptor reflex
Increase in MAP
NE indication
Vasodilatory shock
What is the effect of NE on the lung?
NE has limited affinity for β2 receptors and so has limited effects on bronchiole smooth muscle.
NE Toxicity
Ischemia due to the increase in TPR
NE Contraindications
Pre-existing excessive vasoconstriction and ischemia
What does DOPA stimulate?
Stimulates D1,D2, β1, α1 and α2
What are the effects of DOPA at low dose?
D1: Decreased TPR
β1: Increased CO
What are the effects of DOPA at high dose?
Increased MAP
Increased TPR
β1, α1 and α2 are all activated too and lead to the increased BP
DOPA indication
Cardiogenic shock
What is an advantage of DOPA?
It has a vasodilatory effect in renal and mesenteric vascular beds
DOPA Toxicity at Low and High Doses
Low infusion rates – hypotension
High infusion rates – ischemia
DOPA Contraindications
Tachyarrhythmias and ventricular fibrillation
What does isoproterenol stimulate?
Stimulates β1 and β2
What are the effects of isoproterenol?
Decreased TPR
Increased CO
Small decrease in MAP
Isoproterenol indication
Bradycardia
Heart Block with high TPR
Isoproterenol Contraindications
Angina, particularly with arrhythmias
Isoproterenol Toxicity
Tachyarrhythmias
What happens to the baroreflex with isoproterenol?
It can lead to greatly increased HR due to the decreased MAP
What does dobutamine stimulate?
β1 > β2 > α
selective beta-1 agonist
What are the effects of dobutamine?
Increased CO
Dobutamine indication
Short-term treatment of cardiac insufficiency in CHF
Cardiogenic shock
Excess β-blockade
Dobutamine Toxicity
Hypotension
What is special about the β1 effects of dobutamine?
It has greater inotropy than chronotropy due to lack of β2 activation at low doses
What are the Direct Acting Sympathomimetics?
EPI
NE
DOPA
What is a Non-selective β-adrenergic Agonist?
Isoproterenol
What is a Selective β1-adrenergic receptor Agonist?
Dobutamine
What are Selective β2 adrenergic Agonists?
Terbutaline
Albuterol
What is a Selective α1-adrenergic Agonist?
Phenylephrine
What is a Selective α2-adrenergic Agonist?
Clonidine
What does terbutaline/albuterol stimulate?
Selectively activate β2 receptors
What are the effects of terbutaline/albuterol?
Bronchodilation
Uterine relaxation
Both via β2 receptor activation
Terbutaline and Albuterol indication
Bronchospasm
Obstructive Airway Disease
Terbutaline and Albuterol Toxicity
Tachycardia b1
Muscle Tremor b2
Tolerance b2
How can terbutaline and albuterol lead to muscle tremors?
Activation of β2- receptors expressed on pre-synaptic nerve terminals of cholinergic somatomotor neurons increases release of neurotransmitter. This can lead to muscle tremor, a side effect of β-agonist therapy.
What does phenylephrine stimulate?
Selective a1 receptor agonist
What are the effects of phenylephrine?
Increase TPR and MAP
Decrease HR (baroreflex)
Pupillary dilation
Decrease bronchiole and sinus secretions
All via a1 agonist
Phenylephrine indication
Paroxysmal supraventricular tachycardia
Mydriatic agent (dilation of eyes)
Nasal decongestant
Used for hypotension seen in anesthesia
Phenylephrine Toxicity
Hypertension
Phenylephrine Contraindications
Pre-existing hypertension
Ventricular tachycardia
What is the duration of phenylephrine action?
Phenylephrine is not a catecholamine and therefore is not subject to rapid degradation by COMT. It is metabolized more slowly; therefore it has a much longer duration of action than endogenous catecholamines.
What does clonidine stimulate?
Selective a2 adrenergic receptor agonist
What are the effects of clonidine?
Acute increase in BP (peripheral effect) Reduced BP (central effect)
Peripherally, clonidine causes mild vasoconstriction and slight increase in BP, also crosses BBB to cause reduced sympathetic outflow thereby reducing vasoconstriction and BP. The loss of sympathetic activity predominates over the direct vasoconstrictor effects of the drug leading to overall reduction in blood pressure.
Clonidine indication
Hypertension when cause is due to excess sympathetic drive
Clonidine Toxicity
Dry mouth Hypertensive crisis (after acute withdrawal)
How do indirectly acting sympathomimetics work?
Indirect acting sympathomimetic agents increase the concentration of endogenous catecholamines in the synapse and circulation leading to activation of adrenergic receptors. This occurs via either:
1) release of cytoplasmic catecholamines or
2) blockade of re-uptake transporters
What do the following stimulate: Amphetamine Methamphetamine Methylphenidate Ephedrine Pseduoephedrine Tyramine?
They stimulate the release of endogenous catecholamines. Amphetamine-like drugs are taken up
by re-uptake proteins and subsequently cause reversal of the re-uptake mechanism resulting in release of neurotransmitter in a calcium-independent manner.
What are the effects of the indirectly acting sympathomimetics?
Increased TPR and diastolic BP
Positive inotropic and chronotropic effects leading to an increased systolic pressure
CNS stimulant Probably increased NE
Anorexia Possibly increased DA
Indirectly acting sympathomimetics indication
Attention Deficit Disorder
Narcolepsy
Nasal congestion
Indirectly acting sympathomimetics Toxicity
Tachycardia
Indirectly acting sympathomimetics Contraindications
Rx with MAO inhibitors within previous 2 weeks
-This can cause exaggeration of the effect in cases like with tyramine
