anti-HTNs: sympathoplegic agents Flashcards
general points about beta blocker function, potential hazard, and when they are most effective, the classes of drugs
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
beta adrenoreceptor antagonists classification
- nonselective: non-ISA and ISA
- selective: non-ISA and ISA
isa = sympathomimetic activity
beta antagonist non-selective and selective drugs
non-selective:
- non-ISA: propanaolol and carvediol
- ISA: labetolol
beta-1 selective
- non-ISA: metoprolol, atenolol
- ISA: acebutolol and nebivolol
beta blockers with alpha1 receptor blocking activity
carvedilol, labetalol
beta blockers with vasodilating activity
carvedilol, labetalol, nebivolol
beta blockers: when are they useful?
- preventing reflex tachycardia that results from use of other vasodilators in severe HTN
- reduces mortality after MI
- prototype: propanolol
the MOA of non-selective beta blockers
act primarily by decreasing blood pressure via decreasing cardiac output
Blockade of β1 receptors in the kidney
- inhibits renin release (see notes on ACE inhibitors and ARBs)
Form of administration of beta blockers, lipid solubility
- all are available as oral preparations except esmolol
- carvedilol, metoprolol, propranolol available as extended-release tablets
- atenolol, esmolol, labetalol, metoprolol, propranolol: available as parenteral preparations
- Most exhibit low-to-moderate lipid solubility: exceptions are propranolol and penbutolol
- propranolol and penbutolol: lipophilic and readily cross the blood-brain barrier
beta blocker AE/CI
- blockade of beta 2 Rs in bronchial SM–> exacerbation of COPD (asthma etc)
- glycogenolysis: partly inhibited by beta 2 blockage, may mask insulin induced hypoglycemia
- most common:
- bradycardia
- fatigue
- sexual dysfunction
- depression (sometimes)
- Chronic use: increased VLDL and reduced HDL
- rebound hypertension, angina, possibly MI
if combined with the CCBs verapamil or diltiazem,
beta blockers can cause heart block, especially if combined with the CCBs verapamil or diltiazem, which also slow conduction
Clinical Uses of beta blockers:
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
_______ prolong survival after MI
carvedilol, bisoprolol, and metoprolol _________
- timolol, metoprolol, and propranolol: prolong survival after MI
- carvedilol, bisoprolol, and metoprolol: reduce mortality in acute congestive heart failure, decompensated heart failure, cardiac decompensation
alpha 1 antagonist prototype
prazosin, reversible antagonist
prazosin
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
prazosin: AE and contraindications
- Orthostatic hypotension, dizziness (especially “first-dose” syncope), palpitations, headache, lassitude
- Less incidence of reflex tachycardia than non-selective alpha adrenergic blockers because
- α2 receptor inhibition of NE release from nerve endings is unaffected
alpha 1 antagonist: when are they most effective?
when used in combo with other agents like a beta blocker or a diuretic
used mostly by men for BPH and concurrent HTN
CENTRALLY ACTING AGENTS (α2-AGONISTS): MOA
- General MOA:
- reduce sympathetic outflow from vasomotor centers in the brainstem but allow these centers to retain or even increase their sensitivity to baroreceptor control
- Agonists at central α2 receptors
- Slight variations in hemodynamic effects of clonidine and methyldopa suggest that these two drugs may act at different populations of central neurons
- Clinical Use
- With the exception of clonidine, these agents are rarely used today
- methyldopa is used for hypertension during pregnancy
clonidine
- Pharmacodynamics: lowers blood pressure by reducing cardiac output (decreased heart rate and relaxation of capacitance vessels) and reducing peripheral vascular resistance
- Adverse Effects:
- sedation, dry mouth, depression, sexual dysfunction
- Transdermal preparation is associated with less sedation than oral, but may cause skin reaction
- Abrupt withdrawal can lead to life-threatening hypertensive crisis
Methyldopa
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
timolol, betaxolol, carteolol
used for glaucoma (droplet form) to reduce intraocular pressure
____ useful in treating patients with comorbid asthma, diabetes, or peripheral vascular disease
beta 1 selective agents
_______may be advantageous in patients with bradyarrhythmias or peripheral vascular disease
beta 2 selective
