9-14 Adrenergic Receptor Agonists & Antagonists - Martin Flashcards Preview

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Flashcards in 9-14 Adrenergic Receptor Agonists & Antagonists - Martin Deck (80):

What are some important adrenergic agonists that we should know? What receptors do they work on?

(a1, a2, b1, b2, b3)

(a1, a2, b1, b3)

Isoproterenol (b1, b2, b3)

Dobutamine (b1)


Dopamine (D1 > b1 > a1)

Fenoldopam (D1)


Clonidine (a2)

Methyldopa (a2)


What are 2 important alpha receptor antagonists? What receptors do they work on?

Prazosin (a1)

Phentolamine (a1, a2)


What are is an important alpha receptor agonist? What other class of drugs are alpha receptor agonists?


Other Pressor Agents


What are some non-selective beta blockers?







*= Intrinsic Sympathomimetic Activity (ISA)


What are some important cardioselective beta receptor antagonists?






What are some third generation beta receptor antagonists?






What is an important effect of dopamine that is outside of the nervous system? What receptor is this effect mediated by?

Renal Afferent Blood Vessels

D1 – Dilation

Increase blood flow to kidney


What is the role of dopamine in the nervous system? What receptors does it work on?


D1, D2, D3, D4, D5

Essential neurotransmitter in many different neural circuits


Nerve Endings

D2 – Modulate neurotransmitter release


What is the effect of the following receptors after stimulation:

beta 1


beta 1: stimulation of heart rate & force

muscarinic: decrease in heart rate


What receptors are the afferent arms of the baroreceptor reflex pathway? What does stimulating these receptors cause?

Stretch receptors in aortic arch (via X) or in carotid sinus (via IX) respond to changes in blood pressure


increased BP will cause PNS to be stimulated

SNS tone will be reduced/inhibited


decreased BP will reduce stimulation of PNS

SNS tone will be un-inhibited


What is the effect of NE on pulse rate, BP and peripheral resistance?

decreased pulse rate

increased BP - systolic & diastolic

INCREASED peripheral resistance

(at low doses)


What is the effect of Epi on pulse rate, BP and peripheral resistance?

increased pulse rate

similar BP - increased systolic, decreased diastolic

decreased peripheral resistance


What is the effect of isoproterenol on pulse rate, BP and peripheral resistance?

INCREASED pulse rate

decreased BP - increased systolic and more decreased diastolic

DECREASED peripheral resistance


What is another name for alpha 1 adrenergic agents?

pressor agents


What is the prototypical pressor?

Phenylephrine (neosynephrine)

an OTC nasal decongestant


What is midodrine indicated for? What receptors does it work on?


Midodrine (Pro Amatine)

oral – pts w/ autonomic insufficiency

alpha 1 adrenergic agonist


What is a mixed acting alpha agonist?

metaraminol (Aramine)


What are the effects of phenylephrine? What is it blocked by?


increase peripheral resistance; increase BP

increased blood pressure causes reflex bradycardia (blocked by atropine)


Other than a nasal decongestant, what is phenylephrine used for?

maintain BP in hypotensive states

 - spinal anesthesia


paroxysmal atrial tachycardia

 - induces baroreceptor reflex slowing of rate


What vascular beds does dopamine dilate? Via what receptors?

vasodilates renal, coronary, & mesenteric vascular beds (D1 receptors)


In addition to increasing blood flow to the kidney, what is the effect of dopamine in the periphery?

increase blood flow to kidney

heart: mild increase in rate & force (partial agonist b1 and increases release of NE)

blood vessels: high doses cause vasoconstriction & increased BP (a1)-in the situation of “shock”, this is an undesirable effect bec. Decrease tissue perfusion


What are the clinical uses for dopamine? What are the ultimate effects?

Shock; cardiogenic shock, unstable CHF

Sometimes used in manage acute crisis in chronic CHF

Increases cardiac output and enhances perfusion of kidney


What should you do when giving dopamine?

Must monitor BP carefully because higher infusion rate or dose causes vasoconstriction and decreased tissue perfusion


What are the pharmacological effects of dobutamine?

b1-selective agonist

actually complicated b1 agonist,
a1 agonist/antagonist


What are the clinical effects of dobutamine?

Clinically mostly b1-effects

positive inotropic & some increase in rate

Cardiac output increases

little vascular effect


What are the clinical uses of dobutamine?


Clinical Use: cardiogenic shock, MI, CHF


What are the adverse effects associated with dobutamine?

Adverse effects:  may increase size of infarct

potential arrhythmias

Increases the work/O2 requirement


What are the clinical uses for alpha-1 selective receptor blockers?

Clinical use = 2nd or 3rd line treatment of essential hypertension; added to other agents from different class



What are the effects of a1-selective receptor blockers?

↓PVR, ↓venous return, ↓ preload

Usually do not ↑ heart rate or cardiac output

Do not ↑ NE release (no a2 block)

Favorable effects on lipids

 - ↓LDL & triglycerides; ↑HDL


What are the adverse effects associated with a1-seletive receptor blockers? How are these effects minimized?

Can cause marked postural hypotension & syncope, orthostatic hypotension, especially with initial doses

Usually given at bedtime to minimize hypotensive effects


What are some important a1-selective receptor blockers, and what are some pharmacological differences between them?

Prazosin (Minipress)

 - 100x a1 selective

 - Short t1/2, BID or TID dosing, titrate upward


Terazosin (Hytrin)

 - Like prazosin but long t1/2 & high bioavailability allows QD dosing


Doxazosin (Cardura)

 - Like prazosin but long t1/2 & high bioavailability allows QD dosing


What are some mechanisms of vasodilation activated by 3rd generation beta blockers?

blockade of L-type VGCC

 - reduced smooth mm contraction


agonist at beta 2 receptors

 - increased cAMP, cGMP causes vasodilation


antioxidant effects

 - reduced LDL oxidation, lipid peroxidation, endothelial dysfxn, apoptosis


What are the clinical uses of beta blockers in heart patients?

Hypertension. Decreases CO and produces slow decrease in peripheral resistance.


Ischemic Heart Disease: Angina, myocardial infarction, acute coronary syndromes. Reduces cardiac work and O2 consumption.


MI & Post-MI prophylaxis

 - protects against arrhythmias & limits infarct size

 - Acute MI:  assess LV function

 - 5-12 days after MI, reduces O2 demand & spread of infarct zone


Congestive Heart Failure

 - Improves morbidity and mortality


Arrhythmias: sinus tachycardia and supraventricular ectopic beat

 - Recurrent VT, VF - especially when due to ischemia


In addition to heart problems, beta blockers are also useful in helping to treate what conditions?


- hyperthyroid patients have increased­ b receptor sensitivity

 - Beta  blockers reduces sensitivity of myocardium to adrenergic stimulation in hyperthyroid patients.


Adjunctive treatment for anxiety (panic) attacks

 - reduces peripheral sympathetic signs and symptoms, e.g., palpitations


Migraine headache (Prophylactic treatment)



What is the mechanism of beta adrenergic receptor blockers? What is the prototypical beta blocker?

Mechanism: competitive antagonists at b-1, b-2, & b-3 receptors.
b blockers differ in their degree of receptor selectivity


Propranolol (Inderal) is the prototype


What is the effect that some beta blockers have on membranes?

Some b blockers have intrinsic sympathomimetic activity (ISA), i.e., partial agonist activity


Some b blockers at high therapeutic doses may also have a non-receptor related quinidine-like or membrane-stabilizing effects.


When would beta blockers have a greater pharmacological effect? Would the effects be the same for everyone?

The effect of  antagonists are due to blocking existing sympathetic tone.

Effects are greater if sympathetic tone is high, e.g., during stress (MI) or exercise.


Effects are different in normal subjects compared to patients with hypertension or myocardial ischemia.


What are the effects that beta blockers have on the heart?

Pharmacological Effects - depend on existing sympathetic tone


Decreases in the heart:

¯ heart rate and cardiac output

¯ exercise tolerance

¯ rate of depolarization of ectopic pacemakers

¯ O2 demand

¯ AV nodal conduction (can produce AV block)

¯ infarct size & re-infarction- prevent sudden death


What are the short and long-term cardiovascular effects of beta blockers?

Cardiovascular Effects


Short term - ↓CO, ↓HR

 - PVR ↑ to maintain BP as a result of blockade of b2 receptors & compensatory reflexes


Long term – PVR returns to initial values or ↓ in patients with hypertension (HTN)

 - a/b blockers – CO is maintained with greater ↓ in PVR


What are the effects of beta blockers on rhythm and automaticity of the heart?


↓sinus rate

↓spontaneous rate of depolarization of ectopic pacemakers

Slow conduction velocity in the atria and AV node

↑ functional refractory period of AV node


What are the effects of beta blockers on exercise tolerance?

b blockers blunt the increase in HR and contractility that normally occurs with exercise

Cardiac output (CO) is less affected because stroke volume is increased

b blockers decrease work capacity

b1-selective agents have lesser effects on exercise tolerance than nonselective agents


Beta blockers will generally decrease myocardial O2 demands, but what paradoxical effect can happen? What is the net effect?

However, b blockers may tend to ↑ oxygen demand by increasing end-diastolic pressures and systolic ejection time period

Usually, the net effect is to improve the relationship between cardiac supply and demand; exercise tolerance is improved in patients with angina, whose capacity to exercise is limited by chest pain


Do beta blockers lower BP in normotensive people?

b blockers do not usually lower BP in patients with normal BP but are effective treatment for patients with HTN

Mechanisms for this effect are not well understood


What is the effect of gradually increasing propranolol over weeks on:

max exercise heart rate


plasma renin concentration

HR - decreases

BP - decreases systolic more, and some diastolic

renin - gradual but significant decrease


How do beta blockers cause a decrease in renin?

Catecholamines stimulate b1 receptors in kidney juxtoglomerular apparatus to increase release of renin; b blockers block this increase in renin


Beta blockers will decrease renin release from JG cells in the kidney. What is the relevance of this effect on BP? Why?

Relevance of this effect to BP lowering is not clear. 

However, BP is decreased the most in pts with elevated renin

b blockers are effective in lowering BP in patients with low or normal renin levels

Pindolol is an effective antihypertensive agent even though it has little effect on renin levels


Do beta blockers have an effect on vascular smooth mm?

Although b blockade would not be expected to decrease contractility of vascular smooth muscle, long term administration of these drugs to hypertensive pts ultimately leads to ↓ PVR

The mechanism for this effect is not known, but ↓ PVR in the face of persistent reduction in CO appears to account for much of the antihypertensive effect.


A CNS effect has been hypothesized – but there is little evidence to support this idea and drugs that penetrate into the CNS poorly are still effective.


What are some non-selective vasodilating beta blockers?

Carteolol, carvedilol, bucindolol, labetolol


What are some beta-1 selective vasodilating beta blockers?

Betaxolol, celiprolol, nebivolol


How do non-selective and b1 selective vasodilating beta blockers produce peripheral vasodilation?


2.Activate b2 receptors

3.Block of a1 receptors

4.Block Ca++ entry

5.Open K+ channels

6.Antioxidant activity

7.Antiproliferative effects


Vasodilating beta blockers are also associated with a decreased incidence of:

Bronchospasm, impaired lipid metabolism, impotence, reduced regional blood flow, increased vascular resistance, and withdrawal symptoms.


What patients and conditions would vasodilating beta blockers be helpful for?

particularly beneficial in patients with insulin resistance, diabetes mellitus, and metabolic syndrome.

These effects are also being intensively investigated in relation to treatment of patients with congestive heart failure and peripheral arterial disease.


What drugs are helpful in treating chronic coronary aa disease/stable angina?


beta blockers


Ca++ channel blockers

ACE inhibitors



What drugs are helpful in treating unstable angina or non-ST elevation MI?


beta blockers





GPIIb-IIIa antagonist

 - or - 


ADP receptor antagonist


What drugs are helpful in treating a STEMI in addition to a thrombolytic agent?


beta blockers




(thrombolytic agent)


ADP receptor agonist


What drugs are helpful in treating a STEMI in addition to angioplasty?


beta blockers 





GIIb-IIIa antagonist

ADP receptor antagonist

 - or - 


ADP receptor antagonist


What drugs are useful for post-MI infarction management?

beta blockers


ACE inhibitor

Aldosterone receptor antagonist


ADP receptor antagonist

(lots of conflicting messages about this subject, check UpToDate and edit as needed - 9/18 KMS)


Why are beta blockers so beneficial in treating patients with MI or ischemic heart disease?

b blockers are effective in reducing the severity and frequency of attacks of exertional angina & in improving survival in patients who have had an MI.

 - Not useful for vasospastic angina –may worsen


Which beta blockers are cardioprotective?

Timolol, metoprolol, atenolol, and propranolol


The beneficial effects of beta blockers for MI or angina are due to what?

Fall in myocardial oxygen demand & increased flow to ischemic areas

↓HR, ↓contractility, ↓arterial BP (especially during exercise or stress


What types of heart patients are beta blockers not good for?

In patients with limited cardiac reserve who are critically dependent on sympathetic stimulation, b blockade can result in profound decreases in left ventricular function.

Can also worsen vasospasm-mediated angina


In addition to reduced mortality, what other effects of beta blockers are beneficial to MI patients?

Antiarrhythmic effects are also beneficial in MI patients

Despite this clear evidence many patients who experience an MI do not receive b blockers


What are the results of beta blockers in CHF treatment?

Beta blockers prevent HF in >50%, strokes reduced by >38%, occurrence of CAD and other CV events significantly decreased, improve ventricular remodeling


Mortality rate reduced 65% by carvedilol, 34% by metoprolol, 33% by bisoprolol – hospitalization reduced


How do beta blockers help treat CHF?

increase LVEF, cause beneficial remodeling of heart


What types of CHF should you use beta blockers with? What other drugs should you use in addition?

Use only in stable CHF (class II & III), gradually titrate dose


Patients also treated with diuretic, ACE inhibitors, & digoxin


What are some relative contraindications of beta blockers? Why?

Bronchial Smooth Muscle

 - Block sympathomimetic bronchodilation

 - precaution or contraindication in asthma & COPD



 - Blocks beta receptor effects on lipolysis and glycogenolysis.

 - May mask signs of hypoglycemia, e.g., tachycardia, BP changes, tremor.  Delays recovery from insulin-induced hypoglycemia.


What are some common side effects of beta blockers?

dizziness, fatigue, diarrhea, constipation, nausea, depression, sexual dysfunction, bizarre dreams


What are some rare but severe side effects of beta blockers?

purpura, rash, fever


What metabolic effects can result from chronic use of beta blockers?

May Interfere with SGOT and BUN tests


Chronic use ­VLDL & ↓HDL

 - effects vary among agents


Sudden withdrawal of beta blockers can result in what?

Sudden Withdrawal: rebound hypertension, anginal attack & possibly MI if drug suddenly withdrawn after chronic therapy.

Beta receptor synthesis is increased by beta blocker use. Example of receptor up-regulation, supersensitivity.


In addition to asthma, DM, and COPD what are some more contraindications for beta blockers?

Acute treatment of decompensated heart failure; 2nd and 3rd degree heart block, and cardiogenic shock.


What are some interactions between beta blockers and other medications?

Other hypotensive medications

 - reserpine, guanethidine, methyldopa


Other antiarrhythmic agents

 - calcium channels blockers

 - lidocaine


Insulin and oral hypoglycemic drugs

 - prolongs hypoglycemia and masks signs


Masks symptoms of hyperthyroidism


Beta1 selective blockers are more potent at what receptor?  How is this beneficial for relative contraindicatoins?

at higher doses, block b2 as well

lessen risk of bronchospasm -still contraindicated in asthmatic

do not usually prolong hypoglycemia


What is important about the pharmacokinetics of esmolol? What receptors does it work on? What is it used for?

Very rapid onset & short duration of action


Used as IV infusion for peri-operative tachycardia and hypertension, arrhythmias

Used in electroconvulsive therapy


What receptors does labetolol work on? What are the clinical uses?

Normodyne, Trandate

Selective a 1 blocker

Nonselective b1 & b2 blocker

Partial agonist at b2


Clinical Uses:




What receptors does carvedilol work on? What are some of the chemical and pharmacodynamic properties of the drug? What condition does it help?



Nonselective b-blocker + a-blocker


Very lipid soluble

Also has antioxidant properties


Very dramatic results in CHF clinical trials

Decreased mortality by 65%


What receptors does clonidine work on?

alpha2 adrenergic receptor agonist


What are the effects of clonidine with the different routes of administration?

IV- increase BP (peripheral a2B) followed by decreased BP (central a2A)

Oral - decreased BP (decreased C.O., preload)

Patch - same as oral


What are the clinical uses for clonidine?

Essential  hypertension (very little use now)

adjunct for narcotic, alcohol, & tobacco withdrawal and many other “off label” uses


What are the side effects associated with clonidine?

dry mouth, sedation, impotence - same as methyldopa

sudden withdrawal causes hypertensive crisis