| What are beta blockers? | Block binding of NE and Epi on beta adrenergic receptors, inhibit sympathetic effects , they are the treatment option of HTA w/ or w/out HF, do not induce postural hypotension since a receptors still are functional, effective in tx of other diseases. |
| How is classification of beta blockers? | 1st gen (nonselective for b1 and b2 [propranolol, nadolol, Pindolol, Sotalol, Timolol)
2nd gen (b1 selective or cardio selective [atenolol, acebutolol, bisoprolol, metoprolol, esmolol])
3rd gen (block a receptors selective nebivolol and nonselective carveilil and labetalol |
| How is another way of classification of beta blockers according to intrinsic sympathomimetic activity (ISA - partial agonist)? | . |
| How is membrane stabilizing effect of beta blockers? | Some beta blockers increase AP duration and refractory period thus exert Na+ channel blocking effect at high doses, decrease automaticity and conduction velocity and increase refractoriness thus membrane stabilizing effect.
They diminish phase IV depolarization, depress automaticity prolong AV conduction and decrease HR and contractility |
| How is mechanism of action of beta blockers? | Cardiac effects (b1) [decrease SA HR, decrease CO thus lowering BP, decreased myocardial contractility decreased cardiac work and O2 consumption, slow down AV conduction, membrane stabilizing (MSA)]
Renal effect (inhibit secretion of renin (b1))
Bronchial effect (Bronchoconstriction (b2))
Metabolic effect (block glycogenesis and prevent glucose mobilization in response to hypoglycemia [B2], reduce HDL and increase LDL and TGs [b1])
Note that selective b1 blockers improve lipid profile unlike nonselective since b2 action causes vasorelaxation thus better action of endothelial lipoprotein lipase action |
| What are the therapeutic uses of propanolol prototype of beta blockers? | HTA (reduce CO, inhibit renin secretion enhancing renal loss of sodium and water)
Arrythmias (inhibit cardiac electrical activity, decrease sinus rate, conduction velocity imp especially in SVT [AF use atenolol/bisprolol/metoprolol])
Angina and MI (reduce cardiac work and O2 consumption and demand reduce CAD)
Glaucoma (decrease aqueous humor Timolol opthalmic solution)
Hyperthyroidism (decrease symptoms of increased HR, anxiety, heat intolerance best one is propanolol)
Migraine Prophylaxis (Ones that cross BBB stabilize blood vessels prevent dilation associated with headaches)
Acute Panic Syndrome (reduce symptoms, usually propanolol and atenolol) |
| How are pharmacokinetics of beta blockers? | Fat soluble/Water soluble
Fat soluble (absorbed 80%, high protein binding and passage through membrane, high hepatic metabolism, elimination in bile [Labetalol, Metoprolol, Propanolol])
Water soluble (incomplete intestinal absorption, low passage, very low hepatic metabolism, renal elimination [atenolol, nadolol, sotalol])
Imp to know ISA in acebutolol, pindolol and not propanolol. |
| What are side effects of beta blockers? | CV (bradycardia, hypotension, AV block)
Bronchoconstriction (b2 receptors inducing bronchodilations are blocked)
Asthma and COPD (nonselective blockers)
CNS (fatigue, sleep disturbance, depression)
Mask symptoms of insulin dependent diabetes [tachycardia]
Abrupt discontinuation may lead to angina and CSD
Leads to upregulation of receptors sensitive to agonists |
| How are drug interactions with beta blockers? | 1- Aluminum salts, Cholestyramine: decrease the absorption of β blockers.
2-Drugs such as phenytoin, rifampin, and phenobarbital, as well as smoking (enzymatic inducer) : Induce hepatic biotransformation enzymes and may decrease plasma concentrations of β receptor antagonists that are metabolized extensively (e.g., propranolol).
3-Cimetidine (enzymatic inhibitor) may increase the bioavailability of agents such as propranolol and metoprolol |
| What are the main b1 selective beta blockers? | They eliminate unwanted bronchoconstriction effect of propanolol given for asthmatic pt, dose 50-100 times less than non-selective one but selectivity is lost in high doses.
Therapeutic use in HTA, useful in pt w/impaired pulmonary function/diabetic...Improve lipid profile as well
Include Acebutolol, Atenolol, Metoprolol, Esmolol (only IV short half life) Rapidly metabolized by esterases in RBCs. |
| What are beta blockers with partial agonist activity? | Acebutolol and Pindolol, have ISA, stimulate beta receptors and inhibit stimulation by more potent catecholamines, much diminished effect than beta blockers w/out ISA, decrease metabolic effect minimize disturbances
Therapeutic uses (HTA w/bradycardia, HTA in diabetic) |
| What are all beta blockers therapeutic uses? | Propanolol (Inderal, lacks ISA, non selective, for HTA, angina, SVT, MI, and migraine prophyalxis)
Acebutolol (selective B1, w/ ISA, for HTA and V arrythmia)
Bisprolol (highly selective B1, no ISA, for HTA)
Nebivolol (most selective B1 and a1 blocking antioxidant action, tx of HTA reduce resistance)
Carvedilol (non selective, MSA no ISA, lower BP by a1 antagonism tx congestive HF |
| Table of actions of beta blockers. | . |
