ANS: Sympathomimetics Flashcards
A1 actions
Vascular smooth muscle (and which)
Blood vessels, sphincters, bronchi
Contraction
A1 action
Iris
Pilomotor smooth muscle
Radial muscle contraction dilates pupils, mydriasis
Erects hair
A1 actions
Prostate and uterus
Heart
Contraction
Increases force of contraction but B1 more important
Tissues innervated by A1 6
Vascular smooth muscle, iris, pilomotor smooth muscle, prostate, uterus, heart
A2 actions
Platelets
GI tract
CNS
Aggregation
Relaxation (presynaptic)
Sedation and analgesia from decreased SNS outflow
A2 actions
Adrenergic and cholinergic presynaptic nerve terminals
Inhibits NT release, decreased BP and HR
A2 actions
Vascular smooth muscle
Contraction- post synaptic
Dilation- pre synaptic CNS
Tissues innervated by A2: 5
Plt, vascular smooth muscle, GI, CNS, adrenergic and cholinergic presynaptic nerve terminals
B1
Tissues innervated and action
Heart (inc force and rate of contraction)
Kidneys (stim renin release)
B2 action
Respiratory, uterine, vascular, GI, GU visceral smooth muscle
Smooth muscle relaxation
B2 action
Mast cells
Liver
Pancreas
Decreases histamine release
Glycogenolysis
Increases insulin secretion
B2 action
Adrenergic nerve terminals
Increases NE release
B2 Action
Skeletal muscle
K uptake, dilation of vascular beds, tremor, increased contraction speed
B3
Tissue innervated, action
Fat cells, lipolysis activation/thermogenesis
D1 tissue and action
Smooth muscle. Post synaptic: dilated renal, mesenteric, coronary, and cerebral blood vessels
D2 tissue and actions
Nerve endings. Pre synaptic: modulates NT release, Nausea and vomiting
Endogenous vs synthetic catecholamines
Endogenous: epi, NE, dopa
Synthetic: isoproterenol, dobutamine
Synthetic non catecholamines
Indirect
Direct
Indirect: ephedrine, mephentermine, amphetamines
Direct: phenylephrine, methoxamine
Selective A2 agonists
Selective B2 agonists
Clonidine, dexmedetomidine
Albuterol, terbutaline, ritodrine
SNS
Direct agonists have ___ affinities for: 4
Varied. A1/2, B1/2
SNS
Indirect agonists do what
Increase release of NTs
All sympathomimetics are __ __ ___
Beta phenylethylamine derivatives
All sympathomimetics have which side chain
What group on 3,4 carbons of benzene ring (what this is)
Amine NH2 side chain
Hydroxyl group, catechol (a and b receptor activity)
Why they are catecholamines
Sympathomimetic MOA
Activation of:
Indirect v direct
G protein coupled receptor
Indirect: drug inc NE release from post gang SNS nerves, activ receptor
Direct: drug binds to receptor and activ G protein itself
Termination of effect of sympathomimetics
Catecholamines
4
Reuptake: I (neuronal) II (extraneuronal)
MAO, COMT, lungs
Termination of effect
Non catecholamines: 2
MAO, urinary excretion (unchanged)
Alpha agonist selectivity
Phenylephrine
Clonidine
P: A1>A2»>B
C: A2>A1»>B
Both dont effect beta
Alpha and beta agonist selectivity
Norepi
Epi
A1=A2; B1»>B2
A1=A2; B1=B2
Beta agonist selectivity
Dobutamine
Isuprel
B1>B2»>A
B1=B2»>A
Bagonist selectivity
Terbutaline/albuterol
B2>B1»>A
Dopamine agonist selectivity
Dopamine
Fenoldopam
D1=D2»B»A
D1»D2
Epi
Most potent activator of what
Routes
Lipid solubility, implication
Alpha receptors
SQ or IV
Poorly lipid soluble= little CNS effect
Epi
Onset SQ vs IV
Duration
SQ 5-10 min, IV 1-2 min
5-10 min
Epi
Indications
6
Bronchial asthma, acute allergic rxn, cv arrest (asystole), electromechanical dissociation, vfib unresponsive to defibrillation, gtt to increase contractility
Epi dosing
Standard bolus for resuscitation
Can start w what for less severe hypotension
Need infusion when
10 mcg/kg IV
2-8 mcg/kg
Single bolus dose fx dissipate after 1-5 min
Epi dosing
For: beta 1, beta 2, alpha and beta
1-2 mcg/min beta 2
4-5 mcg/min beta 1
10-20 mcg/min alpha and beta
Epi stim all ___
Major role
Adrenoreceptors
BP regulation
Epi effects
A1
A2
A1- vasoconstriction, inc BP, inc CVP, inc cv work
A2- negative feedback, decreases BP
Epi cv effects
B1
B2
Increased contractility, HR, CO, inc BP
Peripheral vasodilation- decreases BP
Epi CV effects
A1 vs B2 targets
A1- skin, mucosa, hepatic, renal
B2- skeletal muscle
Epi
With moderate doses, ___ tends to increase, __, ___
DBP tends to ___ ___, __ stays the same
SBP, B1, A1
Decrease, B2, MAP
Epi effects in cerebral, coronary, and pulmonary vasculature
Minimal vasoconstriction of arterioles.
Inc cerebral BF even w/normal BP d/t redistribution of BF
Epi
Ocular effects
Actions of A1, A2, B1
A1- mydriasis to accommodate for distant vision
A1, A2- inc humoral outflow (reg intraocular P)
B1- Inc produc of aquous humor (reg intraocular P)
Respiratory fx epi
B2
A1
B2: dilate smooth muscles of bronchial tree, dec release of vasoactive mediators (histamine) in bronchial vessels
A1: decongestion, reduces secretions
GI fx epi
A, A1, A2, B
A, B2- decreased peristalsis from smooth muscle relaxation
A2- decreased gastric secretions
A1- decreased sphlanchnic BF (even if BP normal)
GU epi fx Renal vasculature (receptors and effects)
A1- renal bf reduced even if BP stable
B1- kidney inc renin release
GU fx epi
Bladder (receptors and effect)
A1- contracts urethral sphincter, continence
B2- Relaxation, decreases UOP
GU fx epi
Erectile tissue
Uterus
(Receptor/fx)
A1 facilitates ejaculation
B2- relaxes, inhib labor
Metabolic fx epi
A2
B2
B3
A2- inhib insulin release (opposed by B2)
B2- increased liver glycogenolysis and promotes insulin release
B3- Increased adipose tissue lipolysis
NE
Hypotension dose
Potent effects where
4-16 mcg/min
Alpha and beta 1
NE
Beta 2 effects
Minimal. Vasoconstriction skel musc, liver, kidneys, cutaneous tissue. Inc SBP, DBP, MAP. Baroreceptors activ (dec HR and RR) Dec venous return, CO, HR (despite B1)
Dopamine
Precursor of
Stim what
NE
All adrenergic receptors inc dopamine
Dopamine
Dosing guidelines
1-3 mcg/kg/min D1
3-10 mcg/kg/min B1
>10 mcg/kg/min alpha
Dopamine
Increases 4
Also inc ___ why its not as useful when
Contractility, GFR, renal BF, UOP
NE, depleted catecholamine stores
Dopamine
Synergistic w/___ to reduce ___ and improve __ __
Inhibitory at __ __, pts may have alt response to ___
Inc __ pressure
Dobutamine, afterload, CO
Carotid bodies, hypoxia
Intraocular
Isoproterenol \_\_ \_\_ and \_\_ agonists Chemical \_\_\_ Rapid metab by \_\_\_ (need \_\_) Pt at risk:
Selective B1 and B2
Pacemaker
COMT (gtt)
CAD
Isoproterenol
CV effects
Dose for heart block and bradydysrhythmias
Inc hr, contractility, SBP
Dec SVR, DBP, MAP
1-5 mcg/min
Dobutamine
Dose gtt
CV effects
2-10 mcg/kg/min
Improves CO w/o inc HR or BP (good CHF drug)
Coronary artery vasodilator
Dobutamine
Effects when:
<5 mcg/kg/min
>5 mcg/kg/min
<5: b1 selective, weak activity at SA node
>5: weak alpha 1 stim
Ephedrine
Agonist where
Routes
Indirect and direct at alpha and beta
PO, IM, IV
Ephedrine
Use in anesthesia
Dose
Correct hypotension, inc HR also
10-25 mg IV, 10-50 mg IM
Ephedrine
Why it isn’t truly a weak epi
Lasts 10x longer
Ephedrine
___ with repeat dosing and implic
Tachyphylaxis (NE depletion). Occupies receptor long 1/2 life, cv compensation
Ephedrine
Excretion, metabolism, E 1/2
Unchanged in urine (40%)
Slow metab by MAO and conjugated in liver
3 hrs
Phenylephrine
Stim what receptor, acting
Constriction
A1 primarily, mostly direct acting
Venous more than arterial
Phenylephrine
Comparison to NE
Use in anesthesia
Less potent, lasts longer
Correct BP, decreases HR
Phenylephrine
Dose
CV effects
50-200 mcg IV, 20-50 mcg./min gtt
Inc MAP, SBP, DBP, SVR. Decreases HR and CO
What you give if OD of:
Phenylephrine
Epi
Phenylephrine- vasodilator. NOT BB (A1 issue)
Epi- vasodilator/nipride, then BB after (NOT BB first)
B2 agonist overview
Relaxes: 2
Duration of action, why
Bronchioles smooth muscle, uterine smooth muscle
Long bc different placement of hydroxyl groups on benzene ring
B2 agonist
Routes
Useful in which popn
PO, inhalation, SQ, IV
Premature labor, asthma, COPD
B2 agonist
SE
Tremor (B2 skel muscle) Reflex tachycardia (vasodilation and B2 in heart)
Albuterol
Prototype for:
Preferred for what
Selective B2 agonist
Bronchospasm d/t asthma
Albuterol
MDI dosing
Neb dose for life threat
Can cause what
100 mcg/puff. 2 puffs q4-6h, max 16-20 puffs
15 mg/hr for 2 hrs
Tachycardia and hypokalemia in large doses
Terbutaline
Agonist where
Routes, dose
Indic
B2
Oral, SC (0.25 mg), IV or puffs
Asthma or premature labor
Salmetrol Route Duration Sim to Receptor
MDI, >12h, albuterol
B2 agonist
Ritordine
Receptors, fx
Tx of
Can cause what
B2, some B1 (inc hr and CO), for premature labor
Pulm edema d/t dec excretion of Na/K/water
What midodrine is, tx for what
Direct acting, non catecholamine, A1 agonist
For postural hypotension
3 drugs direct sympatho, non catechol, A1 agonist, indic
Oxymetazoline, tetrahyudrozaline, xylometazoline
Nasal and ocular decongestants
What clonidine is
What dexmedetomidine is
What methyldopa is
Colon- partial A2 selective agonist
D- full A2 selective agonist
M- A2 selective agonist
A2 selective agonists
Effects
Decreased SNS output from CNS. Decreases bp. Sedation and analgesia
Amphetamine
Classification
Effects
Indirect acting sympathomimetic
Inc release of NE, 5HT, and dopamine
Blocks reuptake and vesicular transport, inhib MAO
Methamphetamine
Classification
Comparison to amphetamine
Indirect acting sympathomimetic
Higher CNS effects
Ritalin, cylert, and amphetamine variants classification
Indirect acting sympathomimetic
Reserpine
Classification
Effects
Inhib catecholamine storage/reuptake
Vesicles lose ability to store NE, 5HT, and dopamine
MAO breaks down excess exc high doses.
Hypotension and depression
Cocaine
Classification
Action
Inhib catecholamine storage and reuptake (NE, DA, 5HT)
Interferes w catecholamine transport
