Chapter 2 Peripheral nervous system drugs - direct sympathomimetics Flashcards
* target receptor: a, b
vascular effects –
1) vasoconstriction (a1) – counteracts local anesthetic (delays it) /// smooth muscles - including iris (dilation) via contraction of vessels, anal/uretheral sphinceter contraction, prostate contraction, pyloric sphincter contraction, and kidney vasoconstriction, decrease intestinal motility (more a1 receptors b/c not a vital organ, including skin) + decreased secretions
2) vasodilation (b2) // b2 - dilation of bronchial passages, vasodilation in muscle and liver, relaxation of uterine muscle, and release of insulin (pancreas). (don’t forget gut relaxation => other effects +++ bladder relaxation)
As a result, coronary arteries express more beta2 receptors compared to the peripheral vasculature to maintain some degree of vasodilation and blood flow to the heart.
Arterioles to skeletal muscles also express beta2 receptors, and alpha1 receptors are attenuated to allow for increased blood flow to skeletal muscles during a fight or flight response.
In summary, the number of alpha1 and beta2 receptors on blood vessels differ depending on the organ they are supplying.
cardiac effects –
* mainly b1 – inc HR, contractility, conduction
* automaticity of AV node, HIS-purkinje fibers, and ventricles
* renin release and lipolysis
pulmonary —
* bronchodilation (b2) — can be used therapeutically as bronchodilator
* vasoconstriction (NOT bronchial constriction) w/ decreased secretions (a)
metabolic —
* glyconeolysis (glycogen breakdown) and gluconeogenesis (generate glucose) + insulin release —- b2
* lipolysis —- b1 (renin release as well)
* inhibit insulin release —– a2 (more presynapthic mechanism – recycling // inhibit norepinephrine release, b islet cells of pancreas secrete less insulin, and decreased CNS postsynpatic terminals ==> dec sympathetic outflow from brain)
other effects —
gut relaxation — b2
bladder sphincter contraction + uterus contraction in non pregnant women (a1)
uterus relxation in near term women (b2)
norepinephrine (levophed)
catecholamine
**receptor targets — a > b1»_space;» b2
**
* Alpha1 receptor activation on the blood vessels supplying these less important structures will lead to vasoconstriction and decreased blood flow and perfusion to them and will divert blood flow to more vital structures.
* This is why patient’s skin can often appear pale during a sympathetic response.
* We can also see how this all comes together with the kidneys.
vascular effects:
a1 – intense vasoconstriction l/t inc’d mean arterial pressure (unopposed d/t drug failing to bind to b2 receptors [that can cause vasodilation] since they are present in lungs, bladder, uterus, GI tract, blood vessels and lead to smooth muscle relaxation
cardiac effects:
reflex slowing (parasympathetic-mediated) slowing of HR; this reflex bradycardia overhwhelms this weak b1 cardio effects
- not a viable bronchodilator
- weak glycogenolysis and gluconeogenesis (b2)
- USED only when intense vasoconstriction is needed — septic shock
Isoproterenol (isuprel)
catecholamine
target receptor — ONLY B
- intense vasodilation (b2) [no bind to a1]
- stimulates heart MORE than epinephrine [d/t direct effects]
- MOST potent brochodilator
- glyconeolysis (glycogen as energy – b2) and gluconeogenesis (b2) // insulin release (b2)
- increased lipids (b1)
- decreased gut motility + mast cell release (b2)
- metabolized by COMT
dobutamine (dobutrex)
catecholamine
b1 > b2 = a
- no vascular change d/t low affinity for b2 and a
- DRUG of choice to stimulate heart; preserve heart efficiency + keeps heart rate unchanged
SYNTHETIC derivative of dopamine – does not effect doapmine receptors
dopamine (intorpin)
catecholamine
- dopamine receptors and b1 adrenergic recptors
LOW DOSES–
* constrict arterioles (except brain and kidneys) ===> preserving flow to these vital organs
HIGHER doses – constricts all vessels
- inc contractility and systolic pressure (less effect on rate than isoproterenol)
- causes indirect release of norepinephrine and counteracted by inhibition of NE d/t presynaptic doapmine receptors
- KIDNEYS – increased GFR, blood flow, and Na+ excretion
- used to treat shock (underperfusion, reflex vasoconstriction) — think… vital organs
Phenylephrine (neosynephrine)
noncatecholamine
TARGET alpha receptor
- intense vasoconstriction
- decreased HR (reflex to increased mean arterial pressure) – can continue after drug removed
- clincally used to tx supraventricular tachycardia or SVT + paroxsymal atrial tachycardia (Paroxysmal means that the episode of arrhythmia begins and ends abruptly. Atrial means that arrhythmia starts in the upper chambers of the heart (atria). Tachycardia means that the heart is beating abnormally fast.)
- used in cold remedies (nasal decongestant d/t nasal vasoconstriction)
methoxamine (vasoxyl)
noncatecholamine
target ALPHA receptor
- intense vasoconstriction
- reflex bradycardia d/t inc MAP
- SVT and paroxysmal atrial tachycardia
- reflex hr maintained after drug removal
metaproterenol (alupent)
noncatecholamine
- b2 primarily
- vasodilation
- VERY few cardiac effects (no affinity to b1)
- bronchodilator
- other effects - CNS tremor
- relax uterus in near term pregnant women
- -enol
List of other brochodilators (6)
noncatecholamine
1) albuterol (ventolin)
2) bitolterol (tornalate)
3) terbuatline (brethine)
4) salmeterol (severevent)\
5) pirbuterol (maxair)
6) levalbuterol (xopenex)
NOTE —- look for -erol
target b2 receptor
- vasodilation
- little cardiac effect
- BRONCHODILATORS
- cns-tremor
- long acting salmeterol
noncatecholamine adrenergic agonists
- longer serum half-lives than catecholamines b/c not catabolized by COMT (Catechol-O-methyltransferase) or MAO (monoamine oxidase)
direct agonist
- bind straight to receptor after cleft, does not interact with presynpatic cleft
Catecholamines
- short duration of effects
- used to treat anaphylaxis, cardiac arrest, heart failure, and shock
