Adrenergic Receptor Agonists and Antagonists Used to Treat Cardiovascular Disease Flashcards

Question

Mixed Acting Alpha agonists

Answer 1

Metaraminol (Aramine) have direct alpha receptor agonist properties and release norepi from nerve ending

Answer 2

increase BP

Answer 3

Effects: vasoconstriction increase peripheral resistance; increase BP increased blood pressure causes reflex bradycardia (blocked by atropine)

Answer 4

to maintain BP in hypotensive states spinal anesthesia paroxysmal atrial tachycardia induces baroreceptor reflex slowing of rate Nasal decongestant –over the counter cough and cold medications

Answer 5

for pressor agent bc of its alpha effects

Answer 6

Important neurotransmitter in CNS CNS receptors: D1, D2, D3, D4, D5 Peripheral receptors: D1, b1, a1

Answer 7

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

Answer 8

at low levels d1 is kicked in for renal hihger levels with b1 receptor in heart at really ighg it will cause vaso from alpha 1

Answer 9

Shock; cardiogenic shock, unstable CHF Increases cardiac output and enhances perfusion of kidney Must monitor BP carefully because higher infusion rate or dose causes vasoconstriction and decreased tissue perfusion Sometimes used in manage acute crisis in chronic CHF

Answer 10

b1-selective agonist actually complicated b1 agonist, a1 agonist/antagonist inotropic agent to increase co

Answer 11

positive inotropic & some increase in rate Cardiac output increases little vascular effect

Answer 12

Clinical Use: cardiogenic shock, MI, CHF short term treatemnt to give th heart a boost

Answer 13

may increase size of infarct potential arrhythmias Increases the work/O2 requirement after crisis it can exacerbate the ischemia

Answer 14

2ndor 3rdline treatment of essential hypertension; added to other agents from different class

Answer 15

Effects ↓PVR, ↓venous return, ↓ preload Usually do not ↑ heart rate or cardiac output Do not ↑ NE release (no a2 block) (good bc you arent limiting ne release) Favorable effects on lipids ↓LDL & triglycerides; ↑HDL

Answer 16

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

Answer 17

Prazosin(Minipress) Terazosin(Hytrin) Doxazosin(Cardura)

Answer 18

100x a1 selective Short t1/2, BID or TID dosing, titrate upward Prototype?

Answer 19

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

Answer 20

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

Answer 21

Nonselective = both b1and b2blocked Propranolol(prototype)(inderol) Nadolol Timolol *Pindolol partial agonist *Carteolol partial agonist Sotalol ``` *ISA =intrinsic sympathomimetic activity (or partial agonist) ```

Answer 22

b1-selective = Cardioselective Atenolol (prototype) Metoprolol (prototype) Bisoprolol (used for CHF) Esmolol -very short acting (surgery to control tachycardia) Others Acebutolol partial agonist, ISA

Answer 23

Alpha and Beta Blockers Labetolol Carvedilol Vasodilating Carteolol Bucindolol (not available in USA)

Answer 24

Betaxolol Carteolol ``` Others not yet available in USA Celiprolol Nebivolol Bopindolol Nipradilol Bevantolol Tilisolol ```

Answer 25

Block Ca - block contraction increase camp and cgmp - vasodilation block ROS - antioxidant

Answer 26

Hypertension Congestive Heart Failure Arrhythmias Thyrotoxicosis: dotn work as well in black people

Answer 27

Decreases CO and produces slowdecrease in peripheral resistance. Ischemic Heart Disease: Angina, myocardial infarction, acute coronary syndromes(give aspirin and beta blocker). Reduces cardiac work and O2consumption. MI & Post-MI prophylaxis  protects against arrhythmias & limits infarct size  Acute MI: assess LV function  5-12 days after MI, reduces O2demand & spread of infarct zone

Answer 28

Improves morbidity and mortality

Answer 29

sinus tachycardia and supraventricular ectopic beat  Recurrent VT, VF -especially when due to ischemia

Answer 30

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) Pheochromocytoma

Answer 31

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

Answer 32

bblockers differ in relatively lipid solubility; this effects their relative distribution to the CNS These drugs differ in their bioavailability, biotransformation, and thus their pharmacokinetic properties Somebblockers have intrinsic sympathomimetic activity (ISA), i.e., partial agonist activity Some bblockers at high therapeutic doses may also have a non-receptor related quinidine-like or membrane-stabilizing effects.

Answer 33

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.

Answer 34

Decreases: heart rate and cardiac output exercise tolerance rate of depolarization of ectopic pacemakers O2demand AV nodal conduction (can produce AV block) infarct size & re-infarction-prevent sudden death

Answer 35

-↓CO, ↓HR  PVR ↑ to maintain BP as a result of blockade of b2 receptors & compensatory reflexes

Answer 36

PVR returns to initial values or ↓ in patients with hypertension (HTN)  a/bblockers –CO is maintained with greater ↓ in PVR

Answer 37

↓sinus rate ↓spontaneous rate of depolarization of ectopic pacemakers Slow conduction velocity in the atria and AV node ↑ functional refractory period of AV node

Answer 38

bblockers blunt the increase in HR and contractility that normally occurs with exercise Cardiac output (CO) is less affected because stroke volume is increased bblockers decrease work capacity b1-selective agents have lesser effects on exercise tolerance than nonselective agents Coronary blood flow increases during exercise to meet the demands of the heart Increased catecholamines during exercise or stress (MI) increase the work of the heart and myocardial oxygen demand Patients with coronary artery disease have fixed narrowing of these vessels which attenuates the expected increase in flow, leading to myocardial ischemia. why beta selective agents are good they dont cause this

Answer 39

bblockers decrease myocardial oxygen demand 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

Answer 40

bblockers 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

Answer 41

Catecholamines stimulate b1 receptors in kidney juxtoglomerular apparatus to increase release of renin; bblockers block this increase in renin Relevance of this effect to BP lowering is not clear. However, BP is decreased the most in pts with elevated renin bblockers 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

Answer 42

Although bblockade 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.

Answer 43

1. ↑NO 2. Activate b2 receptors 3. Block of a1 receptors 4. Block Ca++entry 5. Open K+ channels 6. Antioxidant activity 7. Antiproliferative effects

Answer 44

Bronchospasm, impaired lipid metabolism, impotence, reduced regional blood flow, increased vascular resistance, and withdrawal symptoms. A lower incidence of these adverse effects is 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.

Answer 45

Carteolol, carvedilol, bucindolol, labetolol

Answer 46

Betaxolol, celiprolol, nebivolol

Answer 47

exertional angina & in improving survival in patients who have had an MI. Not useful for vasospastic angina –may worsen

Answer 48

cardioprotective effects

Answer 49

Fall in myocardial oxygen demand& increased flow to ischemic areas ↓HR, ↓contractility, ↓arterial BP (especially during exercise or stress

Answer 50

In patients with limited cardiac reserve who are critically dependent on sympathetic stimulation

Answer 51

decrease mortality from MI by as much as 25% or more.

Answer 52

are also beneficial in MI patients

Answer 53

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

Answer 54

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

Answer 55

LVEF, cause beneficial remodeling of heart

Answer 56

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

Answer 57

diuretic, ACE inhibitors, & digoxin

Answer 58

Bronchial Smooth Muscle Block sympathomimetic bronchodilation precaution or contraindication in asthma & COPD Metabolic 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.

Answer 59

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

Answer 60

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.

Answer 61

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

Answer 62

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

Answer 63

Nadolol (Corgard) Timolol (Blocadren) Pindolol (Visken) Carteolol

Answer 64

longer acting; once-per-day dosing

Answer 65

more potent than propranolol

Answer 66

partial agonist; partial blockade less incidence of rebound hypertension less bradycardia

Answer 67

has vasodilating properties

Answer 68

All are more potent at b1 than b2 receptors at higher doses, block b2 as well lessen risk of bronchospasm -still contraindicated in asthmatic do not usually prolong hypoglycemia Atenolol(Tenormin) Metoprolol(Lopressor, Topral XL) Acebutolol (Sectral) Bisoprolol(Zebeta)

Answer 69

hypertension

Answer 70

hypertension, CHF

Answer 71

partial agonist, hypertension, arrhythmias

Answer 72

clinical trials show dramatic benefits in CHF

Answer 73

Very rapid onset & short duration of action b1-selective Used as IV infusion for peri-operative tachycardia and hypertension, arrhythmias Used in electroconvulsive therapy

Answer 74

Selective a 1blocker Nonselective b1 & b2 blocker Partial agonist at b2 Clinical Uses: hypertension pheochromocytoma

Answer 75

Nonselective b-blocker + a-blocker Very lipid soluble Also has antioxidant properties Very dramatic results in CHF clinical trials Decreased mortality by 65%

Answer 76

Brain stem a2-receptors Control (inhibit) sympathetic outflow to periphery Decrease sympathetic tone sympatholytic agents

Answer 77

False neurotransmitter concept Converted to methyl-NE stored in vesicles instead of NE released & acts as a centrally acting a2-agonist Decreases central sympathetic outflow & decreases blood pressure A preferred drug to treat hypertension in pregnancybecause of its safety

Answer 78

Many side effects –sedation, dry mouth, sexual dysfunction

Answer 79

An a2-adrenergic receptor agonist IV-increase BP (peripheral a2B) followed by decreased BP (central a2A) Oral -decreased BP (decreased C.O., preload) Patch -same as oral

Answer 80

Essential hypertension (very little use now) adjunct for narcotic, alcohol, & tobacco withdrawal and many other “off label” uses

Answer 81

dry mouth, sedation, impotence  sudden withdrawal causes hypertensive crisis