Sympathomimetics Flashcards
(43 cards)
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
GU effects of epi
RenalVasculature– Important!!!!! α1 – renal blood flow drastically reduced even if BP relatively normal (constriction of renal tissue) β1 − in kidney increase renin release
Bladder:
α1 - contraction of urethral sphincter - urinary continence
β2 - relaxation - decreases urinary output (F/F don’t want to pee)
Erectile tissue: α1 - facilitates ejaculation
Uterus: β2 - relaxation - inhibits labor
Metabolic effects of Epi
Increased liver glycogenolysis and promotion of insulin release: β2 mobilizing glucose for use
Increased adipose tissue lipolysis: β3
Inhibition of insulin release (more minor effect because
opposed by β2 ): α2 inhibiting insulin release-for a well controlled/regulated
–will need to increased insulin therapy in per-op for IDDM pt
NE (levophed) dose, receptor effects, CV effects, Resp effects, Uses
Dose for hypotension: 4-16mcg/min
Peripheral IV administration dangerous if IV infiltrates-necrosis
Potent alpha and beta-1 effects, Minimal beta-2effects (no relaxation to balance)
Intense vasoconstriction skeletal muscles, liver, kidneys, cutaneous tissue
(at risk for metabolic acidosis)
-can lose finger and toes
Increased SBP, DBP, MAP (very strong response so see decreased HR)…
Baroreceptors activated, Decreased HR
Decreased respiration
Decreased HR (despite B1 effect)
**Use for: hemorrhage, massive fluid resizes, septic shock, NOT good for sick heart
Dopamine dosing
Endogenous precursor of NE
Stimulates all adrenergic receptors including dopamine receptors (low dose, mainly dopamine receptors)
Dosing guidelines
-1-3 mcg/kg/min – Dopamine 1 receptor stimulation dominate (“renal dose
dopamine” – misleading term)
-3-10 mcg/kg/min – Beta 1 receptor stimulation dominate
->10 mcg/kg/min – Alpha receptor stimulation dominate
*Just because one receptor is dominate at a dosage range does not mean other effects will not occur; dosage ranges are not reliable predictors of expected plasma concentration
Dopamine CV, Renal, CO, ocular
Peripheral IV administration dangerous if IV infiltrates
Concurrently ,increases myocardial contractility, renal blood flow, urine output, GFR
Also increases endogenous NE release=why dopamine not as useful with depleted catecholamine stores (nothing to increase)
Synergistic with dobutamine to reduce after load & improve CO (move vasodilation, mix helps with heart pt)
Inhibitory at carotid bodies–pt may have altered response to hypoxia
Increased IOP
Isoproterenol receptor, HR, CV, metabolism, dose
Selective B-1 and B-2 agonists, equal (no alpha)
Increases HR, contractility with decreased SVR (↑SBP, ↓DBP, ↓MAP)
The “chemical pacemaker”: 1-5mcg/min for heartblock & brady dysrhythmias
Rapid metabolism by COMT (need infusion)
Dobutamine dose, receptors, CO, CV
Dose is 2-10mcg/kg/min
B-1 selective at < 5mcg/kg/min (weak activity at the SA node)
Weak Alpha-1 stimulation at >5mcg/kg/min (2 stereo- isomers are antagonistic at alpha receptors) good for weak heart, bc can’t handle afterload (not much alpha)
Improves CO without increasing HR or BP substantially, increase contractility (good in CHF)
Is a coronary artery vasodilator
