Adrenergics Flashcards
What cardiovascular functions are parasympathetically innervated? Sympathetically?
Parasympathetic: HR
Sympathetic: PVR, HR, Contractile force, venous tone
What does stimulation of the sympathetic nervous system elicit?
Increase: HR, BP, blood flow to skeletal muscles, blood glucose
Decreased blood flow to skin and splanchnic region
Dilation of bronchioles and pupils
Piloerection
Where are adrenergic receptors found?
In the Sympathetic branch of the ANS:
Presynaptically- on postganglionic nerve terminals
(Alpha2 and Dopamine2 receptors)
Postsynaptically- on target tissues (cardiac and smooth muscles, gland cells, renal vasculature)
What are the three catecholamines that are naturally occurring and clinically useful? Where do they act/release?
Norepinephrine: primary neurotransmitter of adrenergic nerves
Epinephrine: released by the adrenal medulla
Dopamine: released by postganglionic sympathetic nerves of renal and splanchnic vascular smooth muscle
Catecholamine Biosynthesis
- What is the rate-limiting step?
- What controls rate of synthesis?
- Tyrosine –> DOPA by way of tyrosine hydroxylase; controlled by negative feedback inhibition
- Neuronal firing frequency: increased firing frequency = increased NT synthesis
What are the steps in adrenergic neurotransmission?
- Tyrosine enters nerve terminal as a precursor
- NE transported into vesicles via VMAT: vesicular monoamine transporter
- NE is released via exocytosis via Ca++
**NE is recycled via NET (NE transporter)
What two things metabolize catecholamines?
COMT (catechol-o-methyltransferase) or methylation: found in liver
MAO (monoamine oxidase) or deamination: found in adrenergic nerve terminals, liver, brain.
**methylation and/or deamination render NTs inactive and the metabolic products are excreted in the urine
Dopamine
- Mechanism of action
- What receptors are involved and what do they do?
- Dopamine agonist (D1=D2) (some small B and a agonism at high doses)
- D1 = Gs receptor, stimulating vasodilation
D2 = Gi receptor, provides negative feedback to decrease NT release
Fenoldopam
- Mechanism of action
- What receptors are involved and what do they do?
- Dopamine agonist (D1»D2)
- D1 = Gs receptor, stimulating vasodilation
D2 = Gi receptor, provides negative feedback to decrease NT release
- What is Norepinephrine Transporter (NET)?
- What happens when NET is inhibited?
- What drug groups specifically inhibit NET?
- Reuptake system for optimal adrenergic neurotransmission: >50% of NE released into synapse is transported back into the nerve terminal for reuse by NET
- NE levels rise in the synapse when transport is inhibited
- Cocaine, tricyclic antidepressants **causes vasoconstriction, tachycardia, mydriasis
- What is the response elicited by a2 and D2 antagonists?
2. What are drug examples of D2 antagonists?
- Eliminates feedback inhibition and facilitates continued release of NT
- Antipsychotic agents like haloperidol and chlorpromazine
- What types of drugs enter the nerve terminal via NET?
2. When used with MAOIs, what can these drugs elicit?
- Phenylethylamine derivatives (dopamine, tyramine, ephedrine, amphetamine)
- Since there is decreased NE metabolism from inhibition of MAO, and increased NE release from the tyramine, it elevates arterial pressure and brings on sympathetic crisis
How do amphetamines work in the nerve? What receptors can they stimulate?
They are taken in via NET, block NE reuptake, AND reverse transport, increasing intraneuronal NE.
They also stimulate a1 and B1 receptors.
Ephedrine
- Mechanism of action
- Use/effects
- Directly stimulates a1 and B1 receptors and acts as a releasing agent (mild B2 activity)
- Increase BP, CNS stimulation, bronchial smooth muscle dilation, nasal decongestant
What is elicited when these receptors are stimulated?
- a1
- B1
- B2
- Constriction of smooth muscle- vasoconstriction, mydriasis, increased cardiac output, **except it inhibits GI motility
- Increased HR and contractility, and increased lipolysis
- Stimulate relaxation of smooth muscle, vasodilation of bronchioles, intestines, uterus, arterioles of coronary and skeletal muscles
What is a pheochromocytoma? What are the signs and symptoms?
A tumor of the adrenal medulla causing increased release of epi and NE into circulation
S/sx: severe tachycardia, HTN, headache, increased sweating
Why is dopamine an effective therapy for shock?
It stimulates a1, B1, and D1 receptors causing vasoconstriction, increased cardiac rate/contractility, and increased blood flow.
Epinephrine
- What receptors does it stimulate?
- Use/effects
- a1=a2; B1=B2
- Potent vasoconstrictor and cardiac stimulant: systolic BP increased due to B1 effect on heart, a1 receptor on vascular beds.
* *B2 activity may cause decreased total peripheral resistance
Norepinephrine
- What receptors does it stimulate?
- Use/effects
- a1=a2; B1»B2
2. Increased peripheral resistance and BP
Isoproterenol
- What receptors does it stimulate?
- Use/effects
- B agonist
- Potent vasodilator: significant increase in CO due to B1 receptor activity; decreased MAP with vasodilation due to B2 receptor activity
What vasopressor is the most potent? Why?
Epinephrine; both a and B activity
**B activity predominates at low doses, a and B at high doses
What happens with a bolus injection of epinephrine?
The sharp rise in MAP elicits baroreceptor response and vagal reflex drop in MAP
What are the clinical uses for adrenergic agonists?
CV: increased blood flow or pressure with hypotension and shock; decreased blood flow for hemostasis; rescuing cardiac function due to heart block, failure, or arrest Pulmonary: asthma Anaphylaxis Ophthalmic: mydriasis, glaucoma GU: relax uterus and overactive bladder
a-methyldopa
- Use
- Mechanism
- Hypertension
- Partially replaces DOPA in the synthetic pathway for NE synthesis causing a weaker agonist response (False transmitter)
