sympathomimetic drugs Flashcards
endogenous catecholamines
epi
norepi
dopamine
direct acting alpha receptor agonist (4 )
phenylephrine
methoxamine
clonidine
methyldopa
direct acting beta receptor agonist (6)
dobutamine isoproterenol albuterol metaproterenol salmeterol terbutaline
mixed acting sympathomimetics
ephedrine
pseudoephedrine
indirect acting sympathomimetics
amphetamine
tyramine
cocaine
sympathetic nervous system - whats released and receptors
postgang sympathetic fibers -> norepi acts on alpha and beta receptors
+ sweat glands -> ACh-> muscarinic
dopamine is also released from postgangl -> renal vasodilation at D1 receptors
alpha- 1 adrenergic receptors
tissue and action
radial muscle (eye) - increase Ca, contraction-> dilation
symp synapse in blood vessels -> increase Ca, contraction -> increase BP
GI / bladder: sphincters - increase Ca, contraction
GI wall : relaxation ( indirect via enteric)
salivary glands : increase Ca, increase secretion
alpha- 2 adrenergic receptors
tissue and action
presynaptic - decrease cAMP autoregulatory
pancreas - decrease cAMP, inhibit insulin release
Beta 1 adrenergic receptor
tissue and action
Heart -> increase HR , FOC and conduction
Kidney - increase renin release
eye - increase aqueous humor production
salivary- enhances amylase secretion
all increase cAMP
Beta 2 adrenergic receptor
tissue and action
bronchi - relax blood vessel wall - relax GI/bladder walls - relax liver, skeletal muscle- gluconeogenesis , glycogenolysis pancreas - slight insulin secretion
all increase cAMP
beta 3 adrenergic receptors
tissues and action
fat cells increase cAMP and lipolysis
signal transduction system alpha 1
7 transmembrane receptors coupled to guanine nucleotide binding proteins
- Gq-> increase in phospholipase C-> increase IP# and DG
- IP3 causes release of intracellular Ca++ and DG activates protein kinase C-> phosp and activate proteins
signal transduction system - alpha - 2
coupled to inhibitory G-protein termed Gi
-> inhibits adenylate cyclase -> decrease cAMP ( cAMP normally activates protein kinase-> phosp and regulates proteins)
signal transduction systems b adrenergic receptors
all coupled to stimulatory g-protein (Gs)
stimulates adenylate cyclase -> increase cAMP
receptor desensitization (4)
long term- occurs over days or hours and involves transcriptional or translational changes
short term: maybe due to phosphorylation of the receptor
homologous: receptor becomes unresponsive to own agonist-> when adrenergic receptors +agonist -> substrate for g-protein coupled receptor kinase phosphorylates receptor and increases affinity B arrestin and g protein interaction does not happen and it leads to endocytosis and degradation
heterologous: -> desensitization of 1 receptor also leads to desensitization of another receptor. REceptor activates kinase that phosphorylates another receptor
cardio - alpha -1 activation
increase intracellular Ca2+ within vascular smooth muscle cells -> activates myosin light chain kinases + phosphorylates myosin
- sensitize filaments to Ca2+ by inhibiting myosin phosphatase
- contraction of arterial resistance vessels and decrease in venous capacitance
- vasoconstriction in skin and splanchnic vessels
- increase in BP and reflec brady ( gang blockers or antimus block this)
over stimulation -> hemorrhage due to increase BP
ccardio - activation of alpha 2
occurs when norepi is released into synapse and will lead to a decrease in release
- decrease symp output leads to decrease bp
- direct stimulation on blood vessels -> vasoconstriction
cardio- activation of beta -1 receptors
thru cAMP - phosphorylation of alpha 1 subunit of Ca channels- > increase inward flow of Ca2+ cAMP phosphorylates troponin C which increase sensitivity of contractility
increase Ca2+ -> chronotropic , inotropic and dromotropic effects
overstimulation -> arrhythmias
cardio - activation of beta 2 receptors
vasculature relaxation/ vasodilation
- phosphorylation and inhibition of myosin light chain kinase
