adrenergic agonists and antagonists (Martin)

Question 1

epinephrine

Answer 1

agonist at alpha 1 and 2, beta 1 and 2

increase inotropy (b1)
increase heart rate (b1)
work of heart and its O2 consumption are markedly increased

Question 2

vascular effects of epi

Answer 2

vasoconstriction via alpha 1 at higher doses

lower doses b2 vasodilation

Question 3

what type of receptor is on the juxtaglomerular apparatus

Answer 3

B1 receptors

Question 4

what are the therapeutic uses of epinephrine

Answer 4

restoration of cardiac rhythm in patients with cardiac arrest

anaphylaxis

local or topical hemostat - mouth and bleeding peptic ulcers during endoscopy of the stomach and duodenum

hemodynamic support after CABG surgery

used in anesthetic to cause local vasoconstriction so the anesthetic lasts longer

Question 5

NE

Answer 5

is a full agonist at all adrenergic receptors BUT has a very low affinity for B2’s

increases TPR by acting on alpha 1

reduces renal blood flow ***

constricts mesenteric and splanchnic and hepatic blood flow

Question 6

what is the clinical use of NE ?

Answer 6

NE is the pressor agent of choice for the treatment of septic shock and may be more appropriate than dopamine as first-line treatment for other types of shock as well, especially cardiogenic shock.

NE can be used as a pressor agent to support blood pressure in surgical or intensive care settings.

Unlike dopamine, NE decreases renal blood flow.

Question 7

dopamine

Answer 7

full agonist at all dopaminergic receptors (D1-D5)

at high concentrations it can activate B1 on the heart

even higher conc can activate alpha 1

***Mediate vasodilation in the renal and mesenteric vascular beds–> increases blood flow to the kidney

Vasodilates coronary beds (D1 receptors)

Question 8

what is the effect of dopamine on the heart?

on blood vessels?

Answer 8

heart–> increase in rate and force (partial agonist at B1 and increases release of NE)
-improves cardiac output in the scenario of shock

blood vessels: high doses–> vasoconstrict and increase BP (in the situation of shock) which is undesirable cause for decreased tissue perfusion

Question 9

what are the clinical uses of dopamine

Answer 9

shock, cardiogenic shock (B1 on heart), unstable CHF

increases CO and enhances tissue perfusion of kidney (increase GFR- natriuresis)

sometimes used in manage acute crisis in chronic CHF

TPR is usually unchanged when low or intermediate doses of DA are given probably b/c of the ability of DA to reduce regional arterial resistance in some vascular beds

Question 10

Dobutamine

Answer 10

B1 -selective agonist

Clinically mostly Beta1-effects
positive inotropic & some increase in rate
Cardiac output increases
little vascular effect

Question 11

what are the clinical uses of dobutamine?

Answer 11

Cardiogenic shock

MI

CHF

Question 12

adverse effects of dobutamine

Answer 12

may increase the size of the infarct

potential arrhythmias

increase the work/O2 requirement

Question 13

what are the centrally acting anti-hypertensive agents

Answer 13

Methyldopa
Clonidine

act as agonists at alpha 2

control (inhibit) sympathetic outflow to periphery

decrease sympathetic tone

Question 14

clonidine

Answer 14

Clinical use –> Essential HTN
adjunct for narcotic, alcohol, and tobacco withdrawal

IV –> increase BP (peripheral alpha 2 receptors) followed by decreased BP (central alpha 2)

oral- decreased BP (decreased CO and preload)

patch- same as oral

Question 15

what re the side effects of clonidine

Answer 15

dry mouth, sedation, impotence

sudden withdrawal causes hypertensive crisis

Question 16

methyldopa

Answer 16

preferred drug to treat HTN in pregnancy- b/c of its safety

side effects - sedation, dry mouth, sexual dysfunction

Question 17

phenylephrine

Answer 17

selective alpha 1 agonist–> vasoconstriction, increased TPR, increased BP–> causes reflex bradycardia (blocked by atropine)

IV vasopressor agent

OTC nasal decongestant

Question 18

what are the clinical uses of phenylephrine

Answer 18

to maintain BP in hypotensive states (spinal anesthesia)

paroxysmal atrial tachy –> give a pressor agent to elevated TPR which induces baroreceptor reflex slowing of rate

Question 19

what are the clinical uses of alpha 1 selective receptor blockers

Answer 19

2nd or 3rd line treatment of essential HTN

added to other agents from different class

EFFECTS:
↓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

Question 20

what are the adverse effects of alpha 1 selective receptor blockers

Answer 20

Can cause marked postural hypotension & syncope, orthostatic hypotension, especially with initial doses
Usually given at bedtime to minimize hypotensive effects

Question 21

phenoxybenzame

Answer 21

alpha 1 and 2 blocker

Question 22

phentolamine

Answer 22

alpha 1 and 2 blocker (reversible)

Question 23

propranolol

Answer 23

nonselective B blocker

high first pass metabolism

Question 24

Atenolol

Answer 24

b1 selective

used for HTN

Question 25

metoprolol

Answer 25

b1 selective used for HTN, CHF

Question 26

esmolol

Answer 26

b1 selective very short acting used during surgery to control HR 1/2 life of min used as IV infusion for peri-operative tachy, HTN and arrhythmias

Question 27

Labetolol

Answer 27

alpha 1 and nonselective beta blocker partial agonist at B2 vasodilating used in HTN, pheochromocytoma

Question 28

carvedilol

Answer 28

alpha and nonselective beta blocker vasodilating has antioxidant and anti-inflammatory effects very lipid soluble ***improves ventricular function and reduces mortality and morbidity in patients with mild to severe CHF

Question 29

what are the adverse effects of b-blockers on the cardiovascular system?

Answer 29

blockade of beta receptors may cause or exacerbate heart failure in patients with compensated heart failure, acute MI, cardiomegaly bradycardia don't use together with CCB's b/c these can lead to heart block decreased exercise tolerance make sure to slowly come off chronic use of these b/c there is increased risk of sudden death or exacerbation of angina exacerbation of asthma (b2) masks hypoglycemia

Question 30

what are the benefits of b-blockers

Answer 30

effective in prolonging life in the therapy of heart failure in selected patient's

Question 31

what are the clinical uses of B-blockers?

Answer 31

HTN- decreases CO and SLOW decrease in peripheral resistance Ischemic heart disease (angina, MI, acute coronary syndrome) --> decreases work of heart by reduces cardiac work and O2 consumption MI and post-MI prophylaxis- 5-12 days after --> reduces O2 demand and spread of infarct Also by blocking B2 - there is less "negative" remodeling COngestive heart failure Arrhythmias - sinus tachy and supraventricular ectopic beat

Question 32

how are b-blockers used in thyrotoxicosis.....

Answer 32

hyperthyroid patients have increased beta receptor sensitivity Beta blockers reduces sensitivity of myocardium to adrenergic stimulation in hyperthyroid patients.

Question 33

when are the effects of beta blockers greater?

Answer 33

if the sympathetic tone is high (during stress (MI) or exercise)

Question 34

what are the effects of beta blockers on the heart

Answer 34

decrease heart rate and cardiac output decrease exercise tolerance decrease rate of depolarization of ectopic pacemakers decrease O2 demand decrease AV nodal conduction (can produce AV block) decrease infarct size & re-infarction- prevent sudden death decrease phase 4 of the pacemaker AP

Question 35

what are the short term cardiovascular effects of b-blockers? long term?

Answer 35

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

Question 36

beta blockers effects on rhythm and automaticity

Answer 36

decrease sinus rate decrease spontaneous rate of depolarization of ectopic pacemakers slow conduction velocity in the atria and AV node increase functional refractory period of AV node

Question 37

betaxolol

Answer 37

b1 selective vasodilating beta blocker

Question 38

why are b-blockers beneficial in the treatment of ischemic heart disease, angina and MI

Answer 38

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 Timolol, metoprolol, atenolol, and propranolol have been shown to exert cardioprotective effects Beneficial effects due to: Fall in myocardial oxygen demand & increased flow to ischemic areas ↓HR, ↓contractility, ↓arterial BP (especially during exercise or stress Both acute and long-term treatment with b blockers has been repeatedly shown to decrease mortality from MI by as much as 25% or more.

Question 39

should you use b-blocker in CHF?

Answer 39

YES prevent HF in >50% improve ventricular remodeling and reduce mortality increase LVEF use only in stable CHF

Question 40

contraindications for beta blockers

Answer 40

Asthma/COPD mask signs of hypoglycemia (tachy, BP changes, tremor, delays recovery from insulin-induced hypoglycemia) acute treatment of decompensated heart failure 2nd and 3rd degree heart block cardiogenic shock

Question 41

what are side effects of beta blockers

Answer 41

``` Common: dizziness, fatigue, diarrhea, constipation, nausea, depression, sexual dysfunction, bizarre dreams Severe but rare purpura, rash, fever May Interfere with SGOT and BUN tests Chronic use VLDL & ↓HDL effects vary among agents ```