Adrenergic Antagonists Flashcards
(36 cards)
This set of cards will discuss the adrenergic antagonists, what is the action of these drugs?
Bind to adrenoreceptors but do not trigger receptor mediated intracellular effects
–act by either reversibly or irreversibly binding to the receptor, thus preventing its activation by endogenous catecholamines
The first drugs are the alpha adrenergic blockers, what is the action of these drugs?
Affect blood pressure
–reduces the sympathetic tone of the blood vessels , resulting in decreased peripheral vascular resistance
First are the non selective alpha adrenergic blockers, phenoxybenzamine, what is the action of this drug?
Alkylates and thus irreversibly blocks alpha adrenergic receptors
- -also blocks H1, muscarinic and serotonin receptors
- -inhibits reuptake of norepinephrine by presynaptic adrenergic nerve terminals
What are the cardiovascular effects of phenoxybenzamine?
By blocking alpha receptors, phenoxybenzamine prevents vasoconstriction of peripheral vessels by endogenous catecholamines
- -this provokes reflex tachycardia
- -blocking alpha 2 receptors in the heart leads to increased cardiac output
- -not used for maintaining blood pressure in hypertension
What is the main use of phenoxybenzamine?
Management of Pheochromocytoma (a catecholamine secreting tumor of cells derived from the adrenal medulla)
- -administered in the preoperative period to help control hypertension and sweating
- -useful in the chronic treatment of inoperable or metastatic pheo
A beta blocker may be required after alpha receptor blocker has been instituted why?
In order to control tachycardia
Why should a beta blocker not be given before establishing effective alpha blockage?
Unopposed beta blockage could cause blood pressure elevation due to increased vasoconstriction
What are the adverse effects of phenoxybenzamine?
Postural hypotension, nasal stiffness, n/v
It can inhibit ejaculation
May induce tachycardia, mediated by baroreceptor reflex, and its contraindicated in patients with decreased coronary perfusion
The next non selective alpha adrenergic blocker is phentolamine, what are some features?
- -reversibly blocks alpha 1 and alpha 2 receptors
- causes postural hypotension
- -contraindicated in patients with decreased coronary perfusion
- can trigger arrhythmias and anginal pain
- blocks serotonin receptors, and is an agonist at muscarinic H1 and H2 receptors
- -induces reflex cardiac stimulation and tachycardia are mediated by the baroreceptor reflex
What are the uses of phentolamine?
- Prevention/Control of HTN episodes that may occur as a result of stress or manipulation during preoperative preparation and surgical excision (in pheo)
- dx of pheochromocytoma by the phentolamine blocking test
- prevention of dermal necrosis after the inadvertent extravasation of norepinephrine
- use in HTN crisis associated with stimulant drug overdose
- Used in adjunct for cocaine induced acute coronary syndrome to reverse coronary artery vasoconstriction
- used in HTN crisis associated with withdrawal of sympatholytic antihypertensive meds (Clonidine)
- used in HTN crisis resulting from interaction between monoamine oxidase inhibitors and tyramine or other sympathomimetic amines
All alpha adrenergic blockers reverse the alpha agonist of epinephrine. Give an example of this
Vasoconstrictive action of epinephrine is blocked
- -but vasodilation of other vascular beds caused by stimulation of beta receptors is not blocked
- -therefore the systemic blood pressure decreases in response to epinephrine given in the presence of phenoxybenzamine
Are the actions of norepinephrine reversed when giving a patient an alpha adrenergic blocker?
Not reversed but diminished
–since norepinephrine lacks significant beta agonist action on the vasculature
The next set of drugs to discuss are the alpha 1 selective adrenergic blockers, in general what is their role?
Tx of hypertension
The prototype for alpha 1 selective adrenergic blockers is prazosin, what is the use of this drug?
- -decrease peripheral vascular resistance and lowers arterial blood pressure by causing relaxation of both arterial and venous smooth muscle
- -tachycardia reflex does not typically occur
- -also acts on the CNS to suppress sympathetic outflow
- -decrease LDL and TAGs, while increasing HDL
- -approved for HTN
The next two drugs are alpha1 selective adrenergic blockers, Terazosin and Doxazosin, what is their use?
longer half life than prazosin, allowing less frequent dosing
–approved for HTN and BPH
The last alpha1 selective adrenergic blocker is tamsulosin what is the use of this drug?
Alpha 1 adrenoceptors mediate contraction of GI as well as vascular smooth muscle
–therefore they treat BPH
There are three subtypes of alpha receptors: alpha 1a, alpha1b and alpha1d. which subtype does tamsulosin fall under?
Selective antagonist at alpha 1a receptors
- -alpha1a predominates in GI smooth muscle
- -selectivity for this receptor decreases the incidence of orthostatic hypotension
- -very little effect on blood pressure
Therefore alpha 1 selective adrenergic blockers are used for HTN and BPH. explain the effects on HTN
- -Prazosin and congeners are used in tx of HTN
- -they are not drugs of choice for HTN
- -the first dose produces an exaggerated hypotensive response that can result in syncope – called the first dose effect
Explain the effects on BPH for alpha 1 selective adrenergic blockers
Alpha1 receptors in the trigone muscle of the bladder and urethra contribute to resistance to outflow of urine
- -alpha1 adrenergic antagonists relax smooth muscle in the bladder neck, prostate capsule and prostatic urethra improving urinary flow
- -alpha 1 adrenergic blockers are the drug of choice for BPH
What are the adverse effects of alpha one blockers?
May cause dizziness, lack of energy, nasal congestion, headache, drowsiness, orthostatic hypotension
- –retain sodium and fluid so frequently are given with a diuretic
- –male sexual function is not as severely affected by these drugs as it is by phenoxybenzamine or phentolamine
Lastly in regards to alpha blockers is the alpha 2 selective adrenergic blocker, yohimbine, what is the use?
- -Tx erectile dysfunction but phosphodiesterase type 5 inhibitors have replaced it
- -can reverse the antihypertensive effects of an alpha 2 adrenoreceptor agonist such as clonidine
Next we will discuss beta adrenergic blockers, why are these drugs clinically important?
–Efficacy in the treatment of HTN, ischemic heart disease, CHF and arrhythmias
Beta adrenergic blockers are classified on the basis of receptor subtype selectivity and partial agonist activity:
- Non selective beta blockers: block both beta1 and beta2
- Cardioselective beta blockers: primarily block B1
- alpha 1 and beta blockers
- partial agonists
The first non-selective beta adrenergic antagonist is propranolol, which blocks beta 1 and beta 2, what are the cardiovascular effects?
–Slows heart rate and decreases myocardial contractility
when sympathetic nervous system is activated, during exercise or stress, beta blockers attenuate (Reduce) the expected rise on heart rate
–Short term administration of beta blockers decreases cardiac output
–peripheral resistance increases due to blockage of vascular beta2 receptors and compensatory sympathetic reflexes activate vascular alpha adrenergic receptors
