Sympathomimetics Flashcards
Sympathomimetics MOA
Activation of G-protein coupled receptor (D,B,a)
indirect: increased NE release from post-g SNS which activates receptor
Dicrect: drug binds to receptor and activates G-protein
*G-protein will active or inhibit cAMP, phospholipase C, or open close ion channel
-has eventual effect on intracellular Ca
the specific effect of a drug depends on…
thetypeofreceptor stimulated, receptor density in a given tissue, and what the second messengers activate at a molecular level in the cell.
- receptors wil up or down regulate based on plasma [ ] of sympathomimetic
- so if it has up regulated, than stoping drug suddenly is bad
Metabolism of Sympathomimetics
Catecholamines vs Non
*Catech: may options
-Reuptake I
–uptake I: neuronal reuptake
–uptake II: extraneuronal uptake
MAO
COMT
lungs
*Non-catech: can stick around
MAO
urinary excretion (unchanged)
-consider if pt on MAOI…hows it gonna metabolize?
postsynaptic adrenergic receptors
alpha 1, beta1, 2 can be activated by: NE from presynaptic Injected drugs Epi/NE from adrenal medulla (expect NE canNOT activate B2)
NE can activate
alpha 1, Beta2..both post synaptic
alpha 2 presysnaptic
-can also get reabsorbed and reused
Why would MAOI’s be a problem?
increase amount of Epi and NE bc not getting broken down
Selectivity of Adrenoreceptor
alpha-agonists
phenylephrine a1>a2»»b
clonidine a2>a1»»>b
Selectivity of Adrenoreceptor
mixed alpha and b-agonists
NE a1=a2 b1»»»>b2
*basically no effect on b2
Epi a1=a2 b1=b2
Selectivity of Adrenoreceptor
B agonists
Dobuamine b1>b2»»a
Isoproterenol B1=B2»»a
Terbutaline/albuterol B2»B1»»a
Selectivity of Adrenoreceptor Dopamine agonist
Dopamine D1=D2»B»a
Fenoldopam D1»D2
Epinephrine most potent on which receptor? routes lipid onset duration indications
Endogenous Catecholamines–prototype
Most potent activator ALPHA receptors
Routes: SQ or IV
Very poorly lipid soluble = little CNS effect
Onset: (SQ) 5-10 min (IV) 1-2 min
Duration: 5-10 min
Indications:
Bronchial asthma
Acute allergic reaction
Cardiac arrest, asystole Electromechanical dissociation
V.fib. unresponsive to initial defibrillation
Infusion to increase myocardial contractility
Epi dosing
Standard bolus dose for resuscitation is 10mcg/kg IV
Can start with 2-8mcg/kg (not in totally heart collapse)
Need infusion – with single bolus dose CV effects dissipate after 1-5min.
1-2mcg/minute IV = Beta-2
4-5mcg/min IV = Beta-1 (contractility)
10-20mcg/min IV = Alpha & Beta in Lg does get much more alpha effects
CV effects of epi
stimulates all adrenoreceptors
Major role-BP regulation
α1 - vasoconstriction - ↑ BP, ↑ CVP, ↑ Cardiac work
α2 - negative feedback - ↓ BP
β1 - increased contractility, HR, CO – ↑ BP (increase systolic)
β2 - peripheral vasodilation - ↓ BP (drop in diastolic)
–(balance, so afterload doesn’t get so high) With moderate epinephrine doses SBP tends to increase β1, α1 DBP tends to decrease β2, & MAP stays the same
α1 − skin, mucosa, hepatic, renal
β2 − skeletal muscle
Cerebral effects of Epi
At clinically relevant doses minimal vasoCONStriction of arterioles in: (flight/fight-want blood to flow)
Cerebral vasculature
-↑ cerebral blood flow in general (even with normal BP secondary to redistribution of blood flow)
Coronary vasculature
Pulmonary vasculature
Ocular effects of epi
Accommodation for far vision: α1 - mydriasis
Regulation of intraocular pressure:
α1, α2 - increase humoral outflow
β1 - increase production of aqueous humor
Resp effect of Epi
Dilate smooth muscles of bronchial tree: β2 tx: bronchospasm
Decreased release of vasoactive mediators (histamine) in bronchial vasculature: β2 tx: allergic reaction
Reduce mucosal secretion - decongestion: α1 tx: before nasa intubation
GI effects of Epi
Decreased digestive secretions: α2
Decreased peristalsis: α, β2 - direct smooth muscle relaxation
Decreased splanchnic blood flow: α1 –blood flow drastically reduced even if BP relatively normal
–concern is perfusion of gut
