Lec 5 Adrenergic Flashcards
What are two non-selective adrenergic agonists?
- epinephrine
- norepinephrine
What is one B-receptor agonist?
isoproterenol
What is one B2-selective agonist?
albuterol
What is one B-receptor blocker?
propanolol
What is one B1-selective blocker?
metoprolol
What is one a-receptor agonist?
phenylephrine
What is one a-receptor blocker?
phentolamine
Definition of an agonist
substance that binds protein receptor and causes response
Definition of antagonist
substance binds receptor and produces no effect but prevents binding of agonist to receptor – prevents agonist producing its effect
Kd of an agonist [equation]
Kd = [A][R]/[AR] where AR = concentration of agonist-receptor complex
What are the primary organs controlled by sympathetic [2 primary, 3 secondary]
primary: heart and vasculature
secondary: eye, lung, GI
What do adrenergic agonists do? What different mech?
act at end organ innervated by sympathetic neurons
- direct: mimic effect of norepinephrine or epinephrine by directly activating adrenergic receptors in organ
- indirect:
- —- cause release normal physiologic agonist from sympathetic nerve terminal
- —- inhibit termination of transmitter so prolong response
What are 4 receptor types found at cells of end organs innervated by sympathetic?
- alpha adrenergic receptors [a-receptors]
- beta adrenergic receptors [b-receptors]
- dopamine receptors [in renal + mesenteric vasculature]
- muscarinic ACh receptors [only in sweat glands]
What are two exceptions to the fact that most sympathetic postganglionic neurons release NE?
- in renal and mesenteric vasculature release dopamine
- in eccrine sweat glands release cholinergic
What is the only organ that secretes epinephrine?
adrenal gland
What are 2 names for the drugs that mimic NE/Epi?
- adrenergic
- sympathomimetic
What do you call drugs that interfere with adrenergic signal?
sympatholytic
Where are a1 receptors notably absent [2 places]?
- bronchioles
- heart
a1 receptors [what type of G protein do they activate, pathway, what function do they mediate]
- activate Gq which is couple to phospholipase C
- phospholipase C hydrolyzes PIP2 to DAG and IP3
- DAG activates protein kinase C [PKC]
- IP3 causes release of stored Ca
- mediated contraction of smooth muscle [splanchnic/cutaneous arterioles, apocrine sweat]
a2 receptors [pre or post synaptic, what type of G protein] * he said these are not very important for these lectures
presynaptic
coupled to Gi/o
What are two main subtypes of B receptors in ANS
B1 and B2
Mech of action of B receptors?
- coupled to Gs
- increase cAMP
- causes contraction of cardiac muscle and relaxation of smooth muscle
Which type of B receptor predominate in heart?
B1
Which type of B receptor predominate in vasculature of skeletal muscle?
B2
Which type of B receptor predominate in bronchioles?
B2
What tissues does a1 act in [2 types] and what action?
- most vascular smooth muscle –> contraction
- pupillary dilator muscle –> dilates pupil
What tissue does B1 act in and what action?
heart – increases force and contraction rate
What tissue does B2 act in and what action?
bronchioles and subset of blood vessels in skeletal muscle –> promotes smooth muscle relaxation
Effect of epinephrine [type of action/receptors, where is it released from, action on arterioles, BP, heart, bronchioles]
- non-selective adrenergic agonist
- direct acting
- acts on a1, B1, B2
- released as hormone from adrenal medulla
Functions
- increases systolic BP by interacting with B1 receptors on heart
- – get more contractile force [inotropic]
- – get higher HR/rate of contraction [chronotropic]
- vasoconstriction in most arterioles [via alpha] but dilation in skeletal vessels [via B2]
- dilates bronchioles
Where is epinephrine released from ?
adrenal medulla
Function of Epi on heart [via what receptor type?]?
Increases systolic BP by interacting with B1 receptors on heart
- – get more contractile force [inotropic]
- – get higher HR/rate of contraction [chronotropic]
Function of Epi on blood vessels [via what receptor types?]?
- vasoconstriction in most arterioles [via alpha]
- dilation in skeletal vessels [via B2] to get more blood to skeletal muscle for fight or flight
On what receptors does epi act?
All adrenergic receptors! its non-selective
On what receptors does NE act?
- direct agonist against a1 and B1
- no B2 activity
Where is NE released from?
adrenergic nerve terminals
Difference in EPI vs NE effect on skeletal vascular beds?
- NE not agonist against B2 so no effect
- EPI is agonist against B2 so causes vasodilation
Effect of NE on BP/HR
- causes largely increased BP [via B1]
- positive inotropic effect [increased contractile force]
- increased BP effect causes strong baroreceptor reflex that overwhelms direct effect of NE on heart [that would have increased HR] so end up with overall decreased HR
What receptors does Isoproterenol affect?
- B1 and B2 receptors only
- direct acting
Effect of isoproterenol on vasculature/BP/heart?
- dilates skeletal muscle arterioles
- decreases diastolic BP and mean arterial pressure
- increases cardiac output
- increases HR [chronotropic], contractile force [inotropic] via B1
Does isoproterenol causes vasoconstriction or vasodilation? Via which receptor?
Vasodilation via B2
What is pulse pressure? How does isoproterenol change it?
- pulse pressure = systolic - diastolic
- it is increased by isoproterenol
Effect of intravenous Epi on BP/HR/peripheral resistance
- decreased peripheral resistance [net vasodilation]
- increased HR [because want to increase sympathetic to heart]
- increased avg BP [increased systolic, decreased diastolic]
- increased pulse pressure [contractility of heart]
Effect of intravenous NE on BP/HR/peripheral resistance
A1 and B1 receptors
- increased BP [increased both sys and dia]
- pulse pressure may have increased
- decrease in HR [because reflex effect overwhelms direct effect of B1 receptors on heart]
- increased peripheral resistance [vasoconstriction, alpha mediated]
Effect of intravenous isoproterenol on BP/HR/peripheral resistance
just B receptors
- decreased BP [particularly diastolic]
- increased pulse pressure [difference sys - di]
- hugely increased HR [from combination reflex action and direct effect B1]
- decreased peripheral resistance [due to vasodilation in skeletal]
What is phenylephrine?
- a non-catecholamine
- non-selective a agonist [a1 and a2]
What receptors does phenylephrine act on?
a1 and a2
What is effect of phenylephrine on BP and vasodilation or constriction?
- interacts with a1 receptor in vascular smooth muscle –> vasoconstriction in custaneous and splanchnic arterioles + increased BP
What is effect of phenylephrine on HR?
baroreceptor senses increase in BP –> turns of parasympathetic and turns down sympathetic –> decreased HR
What is effect of phenylephrine on airway?
None – no a1 receptors in the bronchus!
What is phentolamine?
- alpha blocker
- competitive antagonist against a1 and a2
What receptors does phentolamine act on?
a1 and a2
How does phentolamine affect peripheral resistance?
decreased peripheral resistance by blocking a1
How does phentolamine affect diastolic pressure?
- decrease due to blocking of resting a1-mediated tone of vasculature
How does phentolamine affect HR
may get tachycardia via baroreceptor mediated reflex
What is bad negative side effect of phentolamine/a blockers?
orthostatic hypotension
What is propranolol?
- non-selective B blocker [B1, B2, B3]
- decrease HR
- lower BP
What is example where phentolamine is used clinically?
used in tumor of adrenal gland prior to surgery [pheochromocytoma] because in hypertensive crisis, more valuable in norepinephrine secreting receptor
Effect of propranolol on diastolic BP
- acutely get increased BP
- followed by long term decrease BP by other unclear mech
Effect of propanolol on vasculature?
constrict skeletal muscle vasculature because block B2
Effect of propanolol on HR?
decrease [because block B1]
Effect of propanolol on airway?
constrict [because block B2]
What is metoprolol?
- B1-selective blocker
- decreases BP but less likely to exacerbate asthma compared to non-selective [since B2 bronchodilates –> if you block you get bronchoconstriction]
- but still not specific: can have side effects of bronchospasm, wheezing, etc
What is albuterol?
- B2-selective agonist
- treatment for asthma
- dilates bronchioles
Why can albuterol cause tachycardia?
- because selective not specific –> can get vasodilation of vessels that express B2 [skeletal, atria] –> get tachycardia
