Adrenergic Antagonists Flashcards
Adrenergic Antagonists
- Two major groups:
* Alpha-adrenergic blocking agents • Beta-adrenergic blocking agents
Therapeutic Applications of Alpha Blockade
- Inresponsetovenousdilation:
- Returnofbloodtotheheartdecreases
- Cardiac output decreases
- Arterial pressure is reduced
Adverse Effects of Alpha1 Blockade
- Detrimental effects result from the blockade of alpha1 receptors
- Effects from alpha2 receptors are minor • Orthostatichypotension
- Blockade of alpha receptors on veins
- Reduced muscle tone in the venous wall
- Upon standing, blood pools in the veins
- Returnofbloodtotheheartisreduced
- Cardiac output decreased: Blood pressure drops
- Reflextachycardia
- Reflextoincreaseheartrateviatheautonomicnervoussystem(ANS)
- Nasal congestion
- Dilatesthebloodvesselsofthenasalmucosa
- Inhibitionofejaculation
- Alpha1activationrequiredforejaculation
- Impotence is reversible; resolves when drug is discontinued
- Sodium retention and increased blood volume
- Reducedbloodpressurepromotesrenalretentionofsodiumandwater • Usuallycombinedwithdiureticwhenusedforhypertension
Adverse Effects of Alpha2 Blockade
Most significant adverse effect associated with alpha2 blockade: Potentiation of reflex tachycardia
• Alpha2 receptors are located presynaptically
• Blockade of alpha2 results in increased norepinephrine
release
Beta-Adrenergic Antagonists I
Adverse effects of beta blockade
• Therapeuticresponsestobetablockersareduealmost
entirely to the blockade of beta1 receptors
• Adverse effects involve both beta1 and beta2 blockade
• Nonselective beta-adrenergic blocking agents (i.e., drugs that block beta1 and beta2 receptors) produce a broader spectrum of adverse effects than do the “cardioselective” beta-adrenergic antagonists (i.e., drugs that block beta1 receptors only at therapeutic doses)
Adverse effects of beta1 blockade • Bradycardia
• The blockade of cardiac beta1 receptors can produce bradycardia (excessively slow heart rate)
• Theheartratecanbeincreasedwiththeuseofabeta- adrenergic agonist (e.g., isoproterenol) and atropine, which is a muscarinic antagonist
- Adverse effects of beta1 blockade • Reducedcardiacoutput
- Beta1 blockade can reduce cardiac output by decreasing the heart rate and the force of myocardial contraction
- Beta blockers must be used with great caution in patients with heart failure or reduced cardiac reserve
- Further decrease in cardiac output could result in insufficient tissue perfusion
- Adverse effects of beta1 blockade • Precipitation of heart failure
- Suppressionofcardiacfunctionwithabetablockercan cause heart failure
- Patients should be informed about the early signs of heart failure (e.g., shortness of breath, night coughs, swelling of the extremities) and instructed to notify the prescriber if these occur
- Althoughbetablockerscanprecipitateheartfailure,theyare also used to treat heart failure
- Adverse effects of beta1 blockade • AVheartblock
- AV heart block is defined as a delay in the conduction of electrical impulses through the AV node
- The blockade of cardiac beta1 receptors can suppress AV conduction, so the production of AV block is a potential complication of beta blocker therapy
- Betablockersarecontraindicatedforpatientswith preexisting AV block
- Adverse effects of beta1 blockade • Reboundcardiacexcitation
- The long-term use of beta blockers can sensitize the heart to catecholamines
- If a beta blocker is withdrawn abruptly, anginal pain or ventricular dysrhythmias may develop
- Theriskofreboundexcitationcanbeminimizedby withdrawing these drugs gradually (e.g., by tapering the dosage over a period of 1 to 2 wk)
- Adverse effects of beta2 blockade • Bronchoconstriction
- Theblockadeofbeta2receptorsinthelungcancause constriction of the bronchi
- In patients with asthma, the resulting increase in airway resistance can be life threatening
- Drugs that block beta2 receptors are contraindicated for people with asthma
- These patients should be given an agent that is beta1 selective (e.g., metoprolol)
Adverse effects of beta2 blockade
• Hypoglycemia from inhibition of glycogenolysis
• Epinephrine, acting at beta2 receptors in skeletal muscle and the liver, can stimulate glycogenolysis
• Beta2 blockade will inhibit this process, posing a risk of hypoglycemia in susceptible individuals
• Patients with diabetes are especially dependent on beta2- mediated glycogenolysis as a way to overcome insulin-induced hypoglycemia
• Ifapatientwithdiabetesrequiresabetablocker,abeta1- selective agent should be chosen
Adverse effects in neonates from beta1 and beta2 blockade
• Theuseofbetablockersduringpregnancycanhave residual effects on the newborn infant
• Betablockerscanremaininthecirculationforseveraldays after birth, so neonates may be at risk for bradycardia (from beta1 blockade), respiratory distress (from beta2 blockade), and hypoglycemia (from beta2 blockade)
Propranolol
Blockingcardiacbeta1receptors:Reducedheartrate,decreasedforceof ventricular contraction, and suppressed impulse conduction through the AV node
• Neteffectisareductionincardiacoutput
• By blocking renal beta1 receptors, propranolol can suppress the secretion of
renin
• Blocking beta2 receptors
• Bronchoconstriction (through beta2 blockade in the lung)
• Vasoconstriction (through beta2 blockade on certain blood vessels)
• Reduced glycogenolysis (through beta2 blockade in skeletal muscle and liver)
- Therapeutic uses • Hypertension
- Anginapectoris
- Myocardialinfarction
- Prevention of migraine • “Stagefright”
- Adverseeffects
- Bradycardia:Atropineandisoproterenol
- AVheartblock:Drugiscontraindicatedforpatientswith preexisting AV block (if block is greater than first degree)
- Heartfailure:Inpatientswithheartdisease,suppressionof myocardial contractility by propranolol can result in heart failure
- Reboundcardiacexcitation:Abruptwithdrawalof propranolol can cause rebound excitation of the heart, resulting in tachycardia and ventricular dysrhythmias
• Bronchoconstriction: Blockade of beta2 receptors in the
lung can cause bronchoconstriction
• Inhibition of glycogenolysis: Blockade of beta2 receptors in skeletal muscle and liver can inhibit glycogenolysis
• Central nervous system effects: Crosses blood-brain barrier, can result in depression
- Drug interactions
- Calcium channel blockers • Insulin
- Precautions, warnings, and contraindications • Severe allergy
- Diabetes
- Cardiac, respiratory, and psychiatric disorders • Neonates
