Catecholamines and adrengergic pharm II Flashcards
What is the effect of NE on vasculature, heart, and bp?
vasoconstriction; incr. in bp
baroreceptor –> decr. HR
(pos ionotropic (contractility)/chronotropic (HR) effect in animals w/ot vagal nerve
What is the effect of isoproterenol on vasculature, hear, and bp?
visodilation, esp. of skeletal muscle
decr. bp
cardiac stimulant (Pos ionotropic/contractility and pos chronotropic (HR)
What is the effect of epi on vasculature, heart, and bp?
DOSE DEPENDENT.
low dose: vasodilator, cardiac stim. slight decr. in bp
high dose: vasoconstrictor, STRONG cardiac stim, DRAMATIC bp incr.
Alpha 1 adrenergic receptor (a-1 ARs). Where are these receptors? What do they do? what agents are most potent?
smooth muscle of vasculature (synapses)
vasoconstriction; decr. bronchial secretions
epi and NE are good stimulators
Where do we see alpha 2 receptors?
nonsynaptic regions of smooth muscle of vasculature
- presynaptic autoreceptors for NE regulation (ie. in the presynaptic cells of neurons that release NE)
- brain: parts the regulate bp.
What are some effects of stim of alpha 2 receptors?
- in smooth muscle vasculature, cause vasoconstriction.
BUT. - also present as presynaptic autoreceptors in cells that release NE. stim of these receptors acts as negative feedback and causes vasodilation by inhibiting release of NE.
- Brain, in centers that control bp. stime of these regions of the brain leads to decr sympathetic outflow and incr vagal outflow. leads to decr. bp and decr HR.
Pharm effects are complicated- in many pts effects 2 and 3 predominate and can be used as antihypertensives. in other cases, these drugs are less effective, probably due to result 1.
Where are beta-1 adrendergic receptors? Effects?
Present in the HEART.
stim is positive ionotropic (contractility) and chronotropic (HR) effects.
Where are Beta-2 adrendergic receptors?
smooth muscle and tissues other than the heart. esp. in smooth muscle of bronchials, gut, liver, and skeletal muscle.
What are the effects of stim of beta-2 adrenergic receptors? (4)
- dilation of bronchioles
- gut relaxation
- incr. glucose production by liver
- vasodilation of skeletal muscle vasculature
Where are beta 3 adrenergic receptors? What do they do?
present in adipocytes
stim leads to lipolysis
What are the key adrenergic receptors in the lungs?
beta-2: bronchiol dlation
alpha-1: decr. secretions
What are the key adrenergic receptors in the uterus?
beta-2. cause relaxation of uterus during pregnancy
alpha-1: causes constraction
What are the key adrenergic receptors in the eye?
alpha-1: contradtion of radial musles: opens the pupil (mydriasis)
What are the key adrenergic receptors in the liver?
beta 1, 2, maybe 3; alpha receptors: incr. glucose production.
What are the key adrenergic receptors in the kidney?
alpah 1: decr: renin release (neg feedback)
beta 1: incr. renin release.
What do all adrenergic receptors have in common?
All are membrane proteins that cross the membrane 7 times. activate intracellular signaling via membrane bound G proteins.
What are the key second messangers of beta adrenergic receptors?
Gs –> pos link w adenylate cyclase –> incr. in cyclic AMP
What are the key second messengers of alpha-1 receptors?
Gq –> pos link with phospholipase C –> incr. phosphatidylinositol turnover and incr. IP3 and DAG production –> incr.intracellular Ca and incr. protein kinase C
What are the key second messengers of alpha-2 receptors?
Gi protein –> neg link w adenylate cyclase –> decr. cAMP. also Gq pathways
What are the 3 classes of sympathomimetic drugs?
- direct-acting: bind directly to receptors and produce sympathetic effects.
- indirect-acting: diffuse into presynaptic neurons. displace NE from intraneuronal storage vesicals. NE escapes into synapse by reversal of NET transporter.
synaptic NE acts on post-synaptic receptors - mixed: both direct and indirect
How do you differentiate btw direct and indirect and mixed sympathomimetic drugs? Why?
dose response curves of these drugs before and after reserpine.
remember, reserpine prevents storage in vesicles leading to catecholamine degradation in the cytosol.
direct acting drugs’ dose response curve is the same after admin of reserpine.
indirect acting drugs don’t work after admin of reserpine (catecholamine stores are depleted, and these drugs depend on those stores to cause sympathetic effects)
mixed drugs still sort of work, but cause a right shift in the dose response curve.
What is the chronic effect of an indirect sympathomimetic drug? Why?
diminished sympathomimetic response (tachyphylaxis)
depletion of the releasable pool of NE in the nerve terminal
What is the beer, cheese, and red wine rxn?
beer, cheese, and red wine have lots of tyramine.
ppl who are taking an MAO inhibitor can’t metabolize tyramine well. so, tyramine builds up. tyramine can act as an indirect sympathomimetic: displaces NE from storage sites. too much acute NE release causes sympathetitc crisis: acute hypertension, cardiac arrhythmia, tachycardia, death (like cocaine OD).
What is the long term paradoxical hypotensive effect of tyramine? Who gets this, and what is the mechanism?
seen in pts on long term MAO inhibitor use.
as small amts of tyramine build up, we see production of octopamine by DBH enzyme in the vesicles. octopamine is a false transmitter: it looks like NE but doesn’t have NE functionality. if there is too much octopamine in the vesicles, octopomine will be released instead of NE, and we won’t get the desired NE effects on bp: paradoxical hypotension in these pts, esp. orthostatic hypotension.
