Autonomics IV and V Flashcards
second messenger amplification
all adrenergic receptors have seven membrane spanning helixes and are amplified through various second messenger systems. G proteins increase or decrease cAMP or phosphotidyl inositol hydrolysis
termination of action as a transmitter
uptake 1: neuron specific (reuptake)
uptake 2: non-specific, high capacity, followed by metabolism (extra-neuronal)
diffusion
modification of chemical transmission by drugs
at each step, pharmacological intervention is possible. synthesis of transmitter, release of transmitter, combining with receptor, termination step.
B1 receptor prominent effector organ and effects
heart. increased rate and force of contraction. kidney: renin secretion
B2 receptor prominent effector organ and effects
arterioles: dilation. bronchial muscle, pregnant uterus: relaxation. several other sites see increased metabolic effects
B3 receptor prominent effector organ and effects
adipose tissue (lipocytes): increased lipolysis and thermogenesis
A1 receptor prominent effector organ and effects
arterioles in skin, mucosa, viscera, kidney. veins, uterus, and spleen are all constricted and contracted
A2 receptor prominent effector organ and effects
presynaptic nerve endings: inhibit NE release and ACh release in the gut. Postsynaptic in CNS: decreased peripheral sympathetic tone
D1 receptor prominent effector organ and effects
renal, mesenteric, and cerebral arterioles: dilation
autoreceptor
one neurotransmitter and receptor involved
heteroreceptor
more than one receptor/transmitter involved. for example, activation of A2 receptors by NE decreases release of ACh, resulting in relaxation of the gut
selectivity
we want to select for maximum desired effects with minimum side effects. we try to learn the specificities of the receptor involved and by designing chemical compounds that selectively activates or blocks that receptor
direct adrenergic agonist
“personal” interaction with postsynaptic receptor
indirect adrenergic agonist
tyramine and amphetamine. drug causes release of NE, which interacts with the postsynaptic receptor. NE is released from small cytoplasmic pool, not synaptic vesicles
mixed adrenergic agonists
partially indirect as well as direct
ephedrine and hydroxyamphetamine
dopamine low dose
direct action of DA on DA receptors causes vasodilation, resulting in lower blood pressure and increased urine output
dopamine medium dose
more of the same as low dose, but some direct action on B1 receptor in heart and some indirect action/NE release, so positive inotropic effect
dopamine high dose
more of medium dose, and some direct action on vascular A1 receptors and indirect action/NE release, thus vasoconstriction
fenoldopam
activates D1 receptors only! no A or B action, doesnt cause NE release. acts mainly to increase blood flow at renal, mesenteric, and cerebral arteries to lower blood pressure. short half life, used for hypertensive emergencies
Alpha 1 agonists uses
vasoconstrictor. Control hemorrhage (epinephrine), contain local anesthetic (epinephrine), nasal decongestion (ephedrine, phenylephrine), anaphylactic shock (epinephrine), ocular pharmacology, hypotension (dopamine), shock
some approaches in treating shock
treatment goal is to increase perfusion of organs. treat with volume, NE, isoproterenol, dopamine, alpha blockers
cautions with alpha agonists
localized ischemia may occur at infusion site. avoid extravasation. gradually decrease infusion
side effects of alpha adrenergic agonists
hypertension/headache, localized ischemia especially with extravasation, dramatic fall in BP on rapid withdrawal, nervousness, anxiety, and insomnia if they cross the blood brain barrier
alpha 2 agonists use
central control of blood pressure (nucleus tractus solitarus) decrease blood pressure by decreasing central sympathetic output
