CV Stimulants Flashcards
What are some CV stimulants?
-Epi-Nor-Dopamine-Dobutamine-Isoproterenol-Phenylephine-Ephedrine
What does stimulation of beta receptors in the heart (B1) lead to?
-accelerated SA/AV node (HR up)-accelerated ectopic pacemakers-increased contractility
What does stimulation of beta receptors in skeletal muscle vasculature lead to?
relaxation via preventing the entry of calcium that is critical to the contraction of vascular smooth muscle.
What does binding of epinephrine or NE to β adrenoceptors result in?
Stimulates adenylyl cyclase by activating the stimulatory Gprotein, Gs, which leads to the dissociation of its alpha subunit charged with GTP. This activated αs subunit directly activates adenylyl cyclase, resulting in an increased rate of synthesis of cAMP.
What does binding of epinephrine or NE to a2 adrenoceptors result in?
Binding of presynaptic alpha2-adrenoceptor ligands inhibits adenylyl cyclase by causing dissociation of the inhibitory G protein, Gi, into its subunits; ie, an activated αi subunit charged with GTP and a β-γ unit. The mechanism by which these subunits inhibit adenylyl cyclase is uncertain. cAMP binds to the regulatory subunit (R) of cAMP-dependent protein kinase, leading to the liberation ofactive catalytic subunits (C) that phosphorylate specific protein substrates and modify their activity.
Which receptors are linked to the Gq protein?
a1M1M3
Which receptors are linked to the Gi protein?
a2D2M2
Which receptors are linked to the Gs protein?
B1/B2D1
Which sympathomimetic agents act on a-receptors?
-Epi (locally vasoconstrict)-NE-DA (at higher dose)-Dobutamine-Phenylephrine-Ephedrine
Which sympathomimetic agents act on B-receptors?
-Epi-DA (at higher dose)-Dobutamine-Isoproterenol-Ephedrine
Sympathomimetic drugs are classified based upon their mechanism of action either in the pre-synaptic terminal or on the post-synaptic membrane. What do direct acting drugs do?
stimulate postsynaptic receptors
What do indirect acting drugs do?
Indirectly-acting drugs cause an increase of E or NE via:- causing release from pre-synaptic terminals- blocking transport into sympathetic neurons (cocaine)- blocking metabolizing enzymes
What are some stimulant metabolizing enzymes?
-monoamine oxidase (MAO)-catechol-O-methyltransferase (COMT)
Drugs that cause a release of neurotransmitter, but they also themselves stimulate the receptors are called what?
mixed-acting drugs
What are some direct acting selective adrenergic agonists?
a1-phenylephrinea2-clonidineB1-dobutamineB2-terbutalineplease call dad tomorrow
What are some direct acting non-selective adrenergic agonists?
a1/2 oxymetazolineB1/2 isoproterenola1/2, B1/2 Epia1/2, B1- Nor
T or F. Both selective and non-selective direct acting adrenergic agnostic are not reduced by reserpine pretreatment
T. May actually increase because NE induces changes that up-regulate receptors or enhance signaling pathway
What are some mixed acting adrenergic agnostic?
Ephredrine
Is Ephredrine reduced by prior treatment with reserpine?
Effects are blunted, but not abolished
What are some indirect acting adrenergic agonists?
-Cocaine-MOAI/COMTI-Tyramine-Amphetamine
How do MAOIs or COMTIs cause indirect effects?
By preventing the breakdown of releasedneurotransmitter
How doe Tyramine and Amphetamine cause indirect effects?
cause the release of preformed transmitter that is normally stored successfully in the presynaptic vesicles
What does reserpine do?
depletes NE from sympathetic neurons
Does pretreatment with reserpine affect the effects of indirect adrenergic agonists?
Yes, abolishes them
What is the receptor specificity for Dobutamine?
B1 more than B2, alpha
What are the uses of Dobutamine?
HF (ino over chrontropic), stress tests
What is the receptor specificity for DA?
D1=D2 more than B more than alpha
What are the uses of DA?
-unstable bradycardia-HF-shock-inotropic and chronotropic effects predominate at high doses
What is the receptor specificity for Epi?
a1=a2; B1=B2
What are the uses of Epi?
-anaphylaxis-cardiac arrest-hypotension
What is the receptor specificity for Isoproterenol?
B1=B2
What are the uses of Isoproterenol? Side-effect?
-electrophysiologic evaluation of tachyarryhthmiacan worsen ischemia
What is the receptor specificity for Nor?
a1 over a2 over B1
What are the uses of Nor? But?
hypotension, but decreases renal perfusion
What is the receptor specificity for Phenylephrine?
a1 over a2
What are the uses of Phenylephrine?
hypotension (vasoconstrictor)
What is the receptor specificity for Ephedrine?
a1 over a2 over B1
What are the uses of Ephedrine?
-hypotension of anesthesia-narcolepsy-nasal congestion-asthma-bronchospasm NoBody asks henry nelson
At low doses, which receptors dominate for DA?
D1/D2 receptors
At intermediate doses, which receptors dominate for DA?
b-receptors
At high doses, which receptors dominate for DA?
a-receptors
What does Epi cause at low dose?
produces a widening of pulse pressure (difference between systolic and diastolic) though effects upon beta-2 receptors
What does Epi cause at high dose?
produce overall vasoconstriction via a strong alpha-1mediated action.
What does NE do to BP?
NE produces a strong vasoconstrictive action via alpha-1 receptors, leading to a rise in SBP and DBP and in MAP
What does NE do to pulse?
Pulse rate is reduced via a baroreceptor mediatedreflexive action.
What does Epi do to BP?
By contrast, E, with its beta-2 mediated relaxation ofskeletal muscle vasculature, produces a widening of pulse pressure, but no significant change in MAP
What does Epi do to pulse?
increase in pulse rate mediated by beta-1 stimulation that is unopposed by the baroreceptor reflexive mechanism.
What does Iso do to BP?
This drug also stimulates beta-2 receptors leading to a fall in DBP, but the small rise in SBP is attributable to the beta-1 mediated increase in cardiac output, rather than to nonexistent alpha-1 effects.
What does Iso do to pulse?
In comparison with Epi, isoproterenol tends to increase pulse rate more and reduce peripheral resistance more for the same reason, a lack of alpha-1 mediated effect.
An important “take home” message is that the net effect of any drug depends not only on its relative receptor selectivity, but also by compensatory baroreflex mechanisms aimed at restoring BP homeostasis
An important “take home” message is that the net effect of any drug depends not only on its relative receptor selectivity, but also by compensatory baroreflex mechanisms aimed at restoring BP homeostasis
How is Epi given?
IV, inhaled, IM, or SC (which has the most potent vasoconstrictive effects)
Adverse effects of Epi?
-cerebral hemorrhage -angina-ventricular arrhythmias
Uses of Epi?
-hypersensitivity rxns-vasoconstrictor with local anesthetics-restoring cardiac rhythm in patients with cardiac arrest
How does Epi affect the heart?
-powerful direct cardiac stimulant-increases HR, CO, and O2 consumption and shortens systole-increases relaxation rate of ventricular muscle-accelerates SA node action-shortens AV refractory period-activates latent pacemaker cells in the SA node
T or F. Premature ventricular contractions can occur via Epi
T.
Epi primarily acts on what kinds of vessels?
-smaller arterioles-precapillary sphincters
What are the main effects on blood distribution of Epi?
-decreased cutaneous BF and renal BF -increased B2 mediated skeletal muscle BF, coronary BF, and pulmonary BF
How does Epi affect the kidneys?
increases renal vascular resistance; decreases renal BFdoes not affect GFR, but causes decreased excretion of Na+, K+, and Cl- and increased renin secretion (B1 receptors in JGA)
What lung conditions would be contraindicated with Epi?
pulmonary edema can be precipitated by high concentrations of Epi
What does the increase in coronary BF caused by Epi cause?
-increased aortic pressure-increased O2 myocardium consumption
What are the main effects of Nor?
-decrease CO-increase total peripheral resistance and stroke volume-predisposes to arryhthmias-does not play a major role in stimulating HR
How does Nor affect blood distribution?
-increase coronary BF
How is Nor given?
IV
What are the side effects of Nor?
same as Epi but increase in BP are more prominent- careful monitoring needed-necrosis at infusion site
Where are dopamine receptors found?
most notably in the renal vasculature where activation of D1 receptors leads to vasodilation
Indications for dopamine?
-CHD-RFHaving a shortduration of action the drug is only suitable for inpatient treatment.
How is dopamine given?
IV infusion (monitor urine output as a 2ndary marker of drug effect)
What does low dose DA cause?
-mainly D1 action-vasodilation of renal, mesenteric, coronary, and intracerebral vasculature-improves GFR
What does moderate dose DA cause?
-mainly D1 + B1- increase CO (contractility over HR) and vasodilation- release of NE
What does high dose DA cause?
-a-agonism dominate- increased peripheral vascular resistance and renal vasoconstriction
What are the effects of dobutamine?
-increased CO, stroke volume-does not affect HR-increased myocardial contractility with decreased left ventricular filing pressure- increased urinary output 2ndary to increased CO
What is dobutamine indicated for?
short term treatment of cardiac decompensation after cardiac surgery, CHF, or acute MI
How is dobutamine given?
infusion: T1/2= 2min (very short)
What are the effects of isoproterenol?
-mainly B receptors-increased CO (into and chronotropic)-decreased diastolic BP
Side effects of isoproterenol?
-palpitations common-sinus tachycardia-arrhythmias -headache-flushing
How is iso given?
parenterol or aerosol
What is iso used for?
not commonly used today but used in emergency to stimulate HR in patients with bradycardia or heart block, particularly in anticipation of inserting an artificial cardiac pacemaker or in patients with the ventricular arrhythmia tornadoes de pointes
What does phenylephrine cause?
- a1 agonist with systemic vasoconstrictor- increased SBP and DBP
How is phenylephrine given?
SC, IM, IV
What is phenylephrine used for?
control of hypotension, including hypotension associated with regional or spinal anesthesia Phenylephrine is also mixed with some local anesthetics as a vasoconstrictive agent and is employed to produce mydriasis prior to ophthalmologic examination
Adverse effects of phenylephrine?
-angina-anxiety-hallucinations-HTN-dizziness-insomnia/ restlessness/excitability-pallor
What does ephedrine cause?
direct agonist at both a- and b-receptors that enhances release of NE from neurons that causes:-increased HR, CO, and BP-increased cardiac workload=possible angina
Side effects of ephedrine?
- angina- stimulates myocardium and may cause ventricular dysfunction, palpitations, and s-TACH- fatal arrhtyhmias
Uses of ephedrine.
-hypotensions-treatment of asthma and bronchospam (stimulates beta-receptors directly, particularly in bronchiolar smooth muscle.)-cooking that crystal
Ephedra or Ma Huang (a family of botanicals) contains primarily ephedrine, with some pseudoephedrine and lesser levels of ephedra alkaloids. Ma Huang was once promoted as a dietary supplement for several conditions, including weight loss. In the early 2000s the FDA took action under the 1994 Dietary Supplement Health and Education Act (DSHEA) provisions for banning a dietary supplement that presents a significant and unreasonable human health risk.
The FDA reviewed an extensive amount of data, which confirmed CV risks, including HTN, heart problems and stroke from the use of the herb; conversely, there was little evidence of effectiveness except for use for short-term weight loss. Given its bronchodilatory effects, ephedrine continues to be available in many OTC cold and sinusproducts.
