anti-HTNs: sympathoplegic agents

Question 1

general points about beta blocker function, potential hazard, and when they are most effective, the classes of drugs

Answer 1

1) alter sympathetic ns function
2) efficacy may be limited due to a compensatory mechanism of sodium and fluid retention
3) most optimal when used with a diuretic
4) beta blockers (non selective and selective)
5) alpha blockers, alpha agonists

Question 2

beta adrenoreceptor antagonists classification

Answer 2

1. nonselective: non-ISA and ISA
2. selective: non-ISA and ISA

isa = sympathomimetic activity

Question 3

beta antagonist non-selective and selective drugs

Answer 3

non-selective:

1. non-ISA: propanaolol and carvediol
2. ISA: labetolol

beta-1 selective

1. non-ISA: metoprolol, atenolol
2. ISA: acebutolol and nebivolol

Question 4

beta blockers with alpha1 receptor blocking activity

Answer 4

carvedilol, labetalol

Question 5

beta blockers with vasodilating activity

Answer 5

carvedilol, labetalol, nebivolol

Question 7

beta blockers: when are they useful?

Answer 7

1. preventing reflex tachycardia that results from use of other vasodilators in severe HTN
2. reduces mortality after MI
3. prototype: propanolol

Question 8

the MOA of non-selective beta blockers

Answer 8

act primarily by decreasing blood pressure via decreasing cardiac output

Question 9

Blockade of β1 receptors in the kidney

Answer 9

1. inhibits renin release (see notes on ACE inhibitors and ARBs)

Question 10

Form of administration of beta blockers, lipid solubility

Answer 10

1. all are available as oral preparations except esmolol
2. carvedilol, metoprolol, propranolol available as extended-release tablets
3. atenolol, esmolol, labetalol, metoprolol, propranolol: available as parenteral preparations
4. Most exhibit low-to-moderate lipid solubility: exceptions are propranolol and penbutolol
5. propranolol and penbutolol: lipophilic and readily cross the blood-brain barrier

Question 11

beta blocker AE/CI

Answer 11

1. blockade of beta 2 Rs in bronchial SM–> exacerbation of COPD (asthma etc)
2. glycogenolysis: partly inhibited by beta 2 blockage, may mask insulin induced hypoglycemia
3. most common:

• bradycardia
• fatigue
• sexual dysfunction
• depression (sometimes)

4. Chronic use: increased VLDL and reduced HDL
5. rebound hypertension, angina, possibly MI

Question 12

if combined with the CCBs verapamil or diltiazem,

Answer 12

beta blockers can cause heart block, especially if combined with the CCBs verapamil or diltiazem, which also slow conduction

Question 13

Clinical Uses of beta blockers:

Answer 13

1) HTN (metoprolol and atenolol most widely used) but not for monotherapy
2. HF: may worsen acute CHF. as well, and specifically, carvedilol, bisoprolol, and metoprolol reduce mortality (“MBC reduce mortality”)
3. Ischemic HD: reduce frequency of agina episodes, improve exercise tolerance: timolol, metoprolol, and propranolol prolong survival after MI
4. cardiac arrhythmias
5. glacuoma
6. beta 1 blockers- asthma, diabetes, decreasing peripheral vascular resistance
7. beta 2 blockers- bradyarrhtymias, peripheral vascular disease

Question 14

_______ prolong survival after MI

carvedilol, bisoprolol, and metoprolol _________

Answer 14

1. timolol, metoprolol, and propranolol: prolong survival after MI
2. carvedilol, bisoprolol, and metoprolol: reduce mortality in acute congestive heart failure, decompensated heart failure, cardiac decompensation

Question 16

alpha 1 antagonist prototype

Answer 16

prazosin, reversible antagonist

Question 17

prazosin

Answer 17

alpha 1 antagonist that prevents vasoconstriction of arteries and veins

relaxes smooth m. in prostate

causes rention of salt water when used without a diuretic

causes no change in lipid profile

Question 18

prazosin: AE and contraindications

Answer 18

1. Orthostatic hypotension, dizziness (especially “first-dose” syncope), palpitations, headache, lassitude
2. Less incidence of reflex tachycardia than non-selective alpha adrenergic blockers because
3. α2 receptor inhibition of NE release from nerve endings is unaffected

Question 19

alpha 1 antagonist: when are they most effective?

Answer 19

when used in combo with other agents like a beta blocker or a diuretic

used mostly by men for BPH and concurrent HTN

Question 20

CENTRALLY ACTING AGENTS (α2-AGONISTS): MOA

Answer 20

1. General MOA:
   
   1. reduce sympathetic outflow from vasomotor centers in the brainstem but allow these centers to retain or even increase their sensitivity to baroreceptor control
2. Agonists at central α2 receptors
   
   1. Slight variations in hemodynamic effects of clonidine and methyldopa suggest that these two drugs may act at different populations of central neurons
3. Clinical Use
   
   1. With the exception of clonidine, these agents are rarely used today
   2. methyldopa is used for hypertension during pregnancy

Question 21

clonidine

Answer 21

1. Pharmacodynamics: lowers blood pressure by reducing cardiac output (decreased heart rate and relaxation of capacitance vessels) and reducing peripheral vascular resistance
2. Adverse Effects:
   
   1. sedation, dry mouth, depression, sexual dysfunction
   2. Transdermal preparation is associated with less sedation than oral, but may cause skin reaction
   3. Abrupt withdrawal can lead to life-threatening hypertensive crisis

Question 22

Methyldopa

Answer 22

Methyldopa

i) Pharmacodynamics: lowers blood pressure by reducing peripheral vascular resistance; variable reduction in heart rate and cardiac output
ii) Pharmacokinetics: Methyldopa is an analog of L-dopa; it is converted to α- methylnorepinephrine by an enzymatic pathway that directly parallels synthesis of norepinephrine from L-dopa
iii) Adverse Effects: sedation, dry mouth, lack of concentration, sexual dysfunction

Question 23

timolol, betaxolol, carteolol

Answer 23

used for glaucoma (droplet form) to reduce intraocular pressure

Question 24

____ useful in treating patients with comorbid asthma, diabetes, or peripheral vascular disease

Answer 24

beta 1 selective agents

Question 25

_______may be advantageous in patients with bradyarrhythmias or peripheral vascular disease

Answer 25

beta 2 selective