beta receptor antagonist Flashcards
major consequences of Beta receptor blockade
• negative chronotropic and inotropic actions on the
heart (β1)
• decreased blood pressure (in part due to the inhibition of renin release - β1)
• bronchoconstriction (β2)
• local vasoconstriction – end-arteries, and diseased peripheral vessels (β2)
• decreased aqueous humor production in the eye
• impaired recovery from hypoglycemia (β2)
• increased plasma concentrations of VLDL and
decreased concentrations of HDL
Potential indications of β blockers
• hypertension
• angina pectoris (exc.: vasospastic)
• tachyarrhythmias (supraventricular)
• congestive heart failure (long-term use prolongs
survival – acutely they may worsen heart failure!)
• after myocardial infarction (secondary prophylaxis)
• hypertrophic obstructive cardiomyopathy
• hyperthyreoidism, pheochromocytom
• portal hypertension, esophagus varices (reduce risk of bleeding)
• glaucoma (eye drop)
• somatic manifestations of anxiety (performance anxiety)
• migraine headache (prevention: propranolol, pindolol – as 5-HT2-antagonists?)
• essential tremor, proliferating hemangiomas in newborns (propranolol)
Adverse effects of β blockers
Adverse effects of β blockers
• bronchoconstriction (worsening of bronchial asthma)
• cardiac decompensation - if cardiac output is critically dependent on
increased sympathetic drive (interaction with other negative inotropic drugs is
dangerous, combination is contraindicated)
• bradycardia, decreased AV-conduction
• cold extremities, worsening of peripheral vascular diseases
• uterus contractions in pregnancy
• hypoglycaemia
• hyperlipidemia
• contribution to increased potassium level
• sleep disturbances (nightmares), mental depression
• abrupt discontinuation of therapy after chronic use –
increased risk of ischemic heart disease- MOST IMPORTANT!!!
Major differences among the
β blockers
similar: all clinical available beta blockers are competitive antagonists.
divided into 2 major groups: non selective and cardioselective (block beta 1 receptors).
differ: • selectivity • intrinsic avtivity (partial agonistic activity - ISA) • lipid solubility • additional actions on ion channels • additional vasodilatory action • half-life
advantage of beta 1 receptor blockers
less bronchoconstriction, hypoglycemia and peripheral circulatory problems.
All beta blockers will lower BP but will not cause postrual hypotension because the alpha adrenoreceptors remain functional.
mention all selective Beta 1 antagonists!
β1 selective (cardioselective) blockers (2nd generation) 1. atenolol 2. metoprolol 3. bisoprolol 4. esmolol 5. celiprolol 6. betaxolol 7. nebivolol (+ NO) 8. acebutolol
nmemonic for 5: AMEBA+ CBN β1 selective blockers cause less bronchoconstriction, hypoglycaemia and peripheral circulatory problems. CAUTION: β1 selectivity is never absolute!
non selective-
Nonselective β blockers • propranolol- important • pindolol - important • oxprenolol • alprenolol • nadolol • carteolol • levobunolol • penbutolol • timolol - important • sotalol (+K-ch-bl.) - important • carvedilol (+α1 -bl.) - important • labetalol (+α1 -bl.)- important
pro-car-lab- so timpin
which are not beta blockers?
labetalol, sotalol, carvedilol
Partial agonistic (ISA) activity of the β blockers β blockers with ISA (intrinsic sympathomimetic activity)
the beta blockers exert partial agonism at the adrenergic receptors while simultaneously blocking the endogenous catecholamines from binding to the receptor; meaning they are less potent than other beta agonists or the endogenous catecholamines- baiscly partial agonist. • pindolol • acebutolol • oxprenolol • alprenolol • celiprolol
so in effect this causes:
Less bradycardia (B1).
Slight vasodialation or bronchodialation (B2)
Minimal change in plasma lipids.
Lipid solubility of the β blockers
β blockers with the highest lipid solubility • propranolol • nebivolol lowest lipid solubility • atenolol • sotalol • acebutolol • Pharmacokinetics
lipophilic drugs – must be metabolized in the liver
hydrophilic drugs – can be excreted unchaged
(importance of kidney/liver diseases in elimination)
• Only lipid soluble β blockers can be used for CNS
indications (e.g. tremor)
• Drugs with low lipid solubility cause less CNS adverse
effects (e.g. nightmares, mental depression)
Action of the β blockers on ion channels
• Some β blockers possess weak local anesthetic (Na+ channel blocking) effect • propranolol metoprolol • acebutolol • pindolol
It is unlikely that this effect is important in case of systemic use.
Eye drops mustn’t possess this action - timolol doesn’t block
Na channels - that is one reason why it is used for glaucoma.
• Sotalol blocks K+ channels – a class II + III. antiarrhythmic drug
β blockers with additional vasodilatory action (3rd generation)
β blockers with additional vasodilatory action (3rd generation)
• additional blockade of α1 receptors
• labetalol, carvedilol
• racemic mixtures: one isomer is a selective α1 blocker,
another isomer is a β blocker
- indications: hypertension, congestive heart failure, stable angina
- synergistic antihypertensive actions without tachycardia
• less (no) changes in lipid profile
• NO-mediated vasodilation
• nebivolol • antihypertensive indication
• racemic mixture: one isomer is a selective β1 blocker,
another isomer induces NO release
Half-life of the β blockers
Half-life of the β blockers
• Ultrashort-acting
• esmolol
• β1 selective blocker, 10 min. half-life
• It is much safer in critically ill patients who require β
blocker therapy (e.g. supraventricular arrhythmias,
perioperative hypertension)
- β blockers with long half-life (more than 10 hours)
- nadolol (16-20 h)
- betaxolol (14-20 h)
- bisoprolol (10-12 h)
- nebivolol (~10 h)
propanolol
non-selective beta blocker.
action:
1. Diminishes CO and reduce workload on the heart (oxygen consumption decreases).
2. Peripheral vasoconstriction: nonselective beta2 blockade- vasodialation- reduction of diaastolic blood pressure.
3. Bronchoconstriction- contraindicated in COPD and asthmatics.
4. Hypoglycemia may ensue after insulin treatment in diabetics (beta blockade reduces glucose production and insulin release).
Theraputic use:
- Hypertension- decreased cardiac output and inhibition of renin release and decrease of TPR with long term use.
- Angina pectoris- decrease of oxygen requirement.
- prophylatic MI-> reduction of MI size and hastens recovery.
- Migraine- reduced migrane episodes and also lipophilic so it can enter brain.
- Hyperthyroidism- lifesaving in protection against arrhythmias which may be induced by thyroid hormone storm.
pharmacokinetics- oral administration, almost completely absored.
25% bioavailability (subject to first pass effect).
volume of distribution is quite large- 4L per Kg.
excreted in urine.
Adverse effects:
Bronchoconstriction- contra-indicated in asthmatics and COPD.
arrhythmias- should never be stopped abruptly and can worsen angina.
Sexual impairment.
Metabolic disturbances- glycogenolsysis and glucagon secretion decreased.
Fasting hypoglycemia.
increase of LDL and reduced HDL.
CNS effects- depression, dizziness, lethargy, fatigue and weakness, and more.
d
what is the advantage of b1 selectve drugs
β1 selective blockers cause less bronchoconstriction, hypoglycaemia peripheral circulatory problems. CAUTION: β1 selectivity is never absolute!
