adrenergic antagonists Flashcards
physiological effects of alpha adrenergic antagonists - reversible
competitively inhibits the binding of the physiological agonist to the receptor. the effect can be overcome by increasing the concentration of the agonist. MAx response is not affected.duration of action is dependent on the half life of the drug and the dissociation from the receptor.
physiological effects of alpha adrenergic antagonists - irreversible
covalently binds to the receptor. the effect of this antagonist cannot be overcome by increasing the concentration of the agonist. the max response is decreased. the effect of this antagonist will persist long after the drug concentration in the plasma reaches zero. new receptors need to be produced to restore the response.
physiological effects of alpha adrenergic antagonists- cardio
alpha adrenergic receptor stimulation on the vasculature plays a major role inperipheral vascular resistane. antagonist -> orthostatic hypotension and may cause reflex tachy. nonspecific agents are more likely to cause tachy bc they block the inhibition of alpha 2 receptors-> leads to more norepi release at the heart
physiological effects of alpha adrenergic antagonists- epinephrine
if epi is given alone at high concentrations the alpha receptor response will predominate and result in increased bp . if and alpha antagonist is given before epi the effect of the beta-2 receptors will predominate and the bp will fall. “ epinephrine reversal” HR will increase due to reflex tachy and beta-1 receptor stimulation
side effects of long term administration
abrupt withdrawal will cause rebound hypertension
effects of alpha adrenergic antagonist on bladder and prostate
alpha -1 receptors cause contraction of the urethral and prostate sphincters - so blocking the alpha -1 receptors can facilitate flow in pts with urinary retention
effects of alpha adrenergic antagonist on eye
blockade of the alpha-1 receptor on the radial muscle allows the parasym to predominate -> miosis
effects of alpha adrenergic antagonist on the nasal mucosa
nasal stuffiness occurs ( opposite of the alpha agonist)
effects of alpha adrenergic antagonist on the GI
GI hypermotility due to removal of the relaxing influence of alpha adrenergic receptor stimulation
effects of alpha adrenergic antagonist other random effects
sexual dysfunction, dry mouth, dizziness, somnolence and headache
phenoxybenzamine
alpha adrenergic antagonist
irreversible non-selective antagonist
-reduce BP when sympathetic tone is high-> pt with pheochromocytoma
-adverse effect -> tachy, due to blockade of alpha 2 and reflex mechanisms
phentolamine
competitive alpha adrenergic antagonist at both alpha 1 and 2.
-adverse effect -> tachy, due to blockade of alpha 2 and reflex mechanisms
prazosin
selective alpha-1 adrenergic antagonist
less likely to cause tachy
terazosin and doxazosin
alpha-1 selective adrenergic antagonist
tamsulosin
alpha-1A and 1D adrenergic antagonist
receptors are thought to predominate in the prostate
yohimbine
alpha-2 adrenergic antagonist
clinical uses of alpha adrenergic antagonist
treatment of
- pheochromocytoma
- chronic htn
- peripheral vascular disease
- urinary obstruction
- erectile dysfunction
treatment of pheochromocytoma
tumor of adrenal medulla that release large amounts of norepi and epi -> hypertension, headaches, tachy and sweating
- alpha 1 antagonist used for preop management of tumor.
phenoxybenzamine -given several weeks before surgery and also for inoperable tumors.
might need to give beta blockers but should be given after alpha 1 blockade to avoid unopposed alpha 1 mediated vasoconstriction
treatment of chronic hypertension
alpha 1 antagonist such as prazosin are used with other drugs.
side effects: orthostatic hypotension
and sometimes palpitations
treatment of peripheral vascular disease
occasionally prazosin or phenoxybenzamine are used to treat vasospasm in the peripheral circulation ( raynaud’s phenomenon) but ca 2+ blockers are preferred
treatment of urinary obstruction
benign prostatic hyperplasia is common in older men and can be treated with alpha-1 antagonist such as prazosin, doxazosin and terazosin.
tamsulosin is more selective for prostate and can be used with pt with problems with orthostatic hypo since it have little effect on bp
treatment of erectile dysfunction
phentolamine is used as part of a mixture that is injected into the penis, that facilitates erection in patients that have dysfunction.
Pharmacokinetics of beta adrenergic antagonists
bioavailability: low bioavailability bc they undergo significant first pass metabolism - first dose should be titrated based on individual response
clearance: several drugs in this class are extensively metabolized by the liver via cytochrome p450 enzymes - propranolol and metoprolol. there are polymorphisms that cause some patients to be poor metabolizers leading to elevated concentrations of the drug
physiological effects of beta adrenergic antagonist on - cardio
beta -blockers cause bradycardia
- this is the main problem with beta blocker toxicity-> can be treated with glucagon that acts to increase cAMP in the heart independent to beta receptors.
- depress contractility and excitability
- can precipitate heart failure if the pt have an abnormal cardiac function and is dependant on sympathetic drive
- should be tapered when coming off of them - rebound htn
- lower bp in pt with htn - mech unknown
- angina and CHF only moderate - carvedilol - contraindication for severe CHF
- non-specific beta blockers can cause cold extremities bc of the unopposed alpha-1 mediated vasoconstriction - may also give rise to early rise in bp
physiological effects of beta adrenergic antagonist on - respiratory tract
beta-2 receptor blockade can lead to bronchoconstriction particulary in pts with ashtma.
avoid non-specific beta blockers that block beta 1 and beta 2 receptors.
beta-1 specific receptors antagonist should not cause bronchoconstriction but the specificity is not that great so it shouldn’t be used in asthmatics either
physiological effects of beta adrenergic antagonist on - eye
beta blockers -> used to treat glaucoma bc the decrease the production of aqueous humor
physiological effects of beta adrenergic antagonist on - carbohydrate metabolism
beta 2 blockade -> inhibits epi mediated stimulation on glycogenolysis. ( role of beta 2 is unclear in the capacity of response to hypoglycemia)
beta blockade will mask the symptoms of hypoglycemia by blocking tachy and inhibiting tremors-> dont use in diabetics
physiological effects of beta adrenergic antagonist on - lipids
non-specific beta antagonists will increase VLDL, TG and decrease HDL. LDL doesnt change but lowering the HFL, alters the HDL/LDL ratio.
- thought to be due to an inhibition of the hormone sensitive lipase
- less likely to occur with beta antagonists that have intrinsic sympathomimetic activity and with beta -1 selective antagonists
physiological effects of beta adrenergic antagonist on - membrane stabilization
propranolol, pindolol, metoprolol can have membrane -stabilizing activity.
- local anesthetic action, thru the blockade of sodium channels
- can affect myocyte sodium channels
- usually not a problem but can contribute to toxicity by prolonging the QRS duration and impairing cardiac conduction
- bb with local anesthetic action would not be used on the eye in pts with glaucoma
physiological effects of beta adrenergic antagonist on - intrinsic sympathomimetic activity
pindolol and acebutolol also have beta-agonist properties. considered to be partial agonists.
their agonist property is weaker than that of catecholamines they are capable of stimulating beta receptors, especially when catecholamine levels are low
cause less bradycardia and slight vasodilation and minimal change in lipds
physiological effects of beta adrenergic antagonist on -CNS
if beta blockers enter the cns they could cause dizziness, fatigue, depression and sexual dysfunction. hydrophilic drugs such as atenolol have fewer CNS effects
propranolol
nonselective beta adrenergic antagonist
used for : HTN, angina, arrhythmias, migraine, thyrotoxicosis, and essential tremor
- lipid soluble and enter CNS -> some pts may have excessive somnolence and impaired cognition.
standard agent which the other beta blockers are assessed
timolol
nonselective beta adrenergic antagonist
has no membrane stabilizing activity. widley used to treat glaucoma
Nadaolol
nonselective beta adrenergic antagonist
same indications as propranolol, but has a really long half life
atenolol, metoprolol
beta-1 selective antagonist ( cardioselective)
prefered in pts who experience bronchoconstriction after propranolol, also pts with copd, diabetes or peripheral vascular disease.
selectivity for beta-1 is no absolute so should be used with caution with these patients
atenolol has a very low lipid solubility so its CNS effects are diminished. -> used to treat HTN
metoprolol is more lipid soluble but is still used to treat htn and other cardiac effects
esmolol
beta-1 selective antagonist ( cardioselective)
very short acting antagonist due to the fact that it has an ester linkage which is cleaved by esterases in the rbcs.
- half life of 10 min - steady state concentrations can be achieved rapidly and therapeutic actions can be terminated rapidly
- good for the critically ill
- intraoperative and postop htn
betaxolol
beta-1 selective antagonist
used for glaucoma, less likely to cause bronchoconstriction
acebutolol
is beta-1 selective but also a partial agonist
labetalol
beta blockers with alpha-1 blocking activity
blocks beta receptors a little less than propranolol and alpha-1 receptors less than phentolamine, used for htn and severe htn. same adverse effects of alpha and beta blockers
carvedilol
beta blockers with alpha-1 blocking activity
blocks beta receptors more effectively than alpha 1 receptors. this is one of the beta blockers that are used to treat CHF. the effectiveness in CHF may attributable , in part, to other effects of carvedilol, such as attenuation of oxygen free radical action and inhibition vascular smooth muscle mitogenesis.
pindolol
non selective beta blocker with intrinsic sympathomimetic activity . these agents are less likely to cause bradycardia and changes in lipids but clinical advantage is unclear
acebutolol
beta-1 selective blocker with intrinsic sympathomimetic activity like pindolol
guanethidine
indirect acting adrenergic antagonist
rarely used. enters the synapse thru the norepi reuptake system and slowly displaces the norepi causing a chemical sympathectomy, used for severe htn. agents that block reuptake will inhibit its action
reserpine
indirect acting adrenergic antagonist
rarely used- inhibits the vesicular transport system, so the norepi cannot be taken up into the vesicles.
the norepi is degraded by the monoamine oxidase that is present in the cytoplasm. this agents causes depletion of dopamine and serotonin both peripherally and centrally. -> can cause severe adverse effects like depression
clinical uses of beta adrenergic antagonists
htn ischemic heart disease arrhythmias heart failure glaucoma hyperthyroidism migraine tremors, performance anxiety
clinical uses of beta adrenergic antagonists- HTN
beta receptor antagonists are used to treat htn. but usually in combo with other agents such as diuretics or ace inhibitors.
clinical uses of beta adrenergic antagonists- ischemic heart disease
if a pt has angina, beta antagonist will reduce the frequency of angina episodes and improve exercise tolerance. only some are effective: timolol, propranolol, metoprolol - dont use in pts with brady or hypotension
clinical uses of beta adrenergic antagonists- arrhythmias
they slow AV nodal conduction so that can be used for atrial flutter and fibrillation. used to treat ventricular arrhythmias due to ectopic beats if they are due to excessive norpi or epi stim
clinical uses of beta adrenergic antagonists- heart failure
selected beta antagonists are used to treat heart failure, among them carvedilol. no used in acute heart failure. in pts with moderate heart failure the dose is titrated up slowly
clinical uses of beta adrenergic antagonists - glaucoma
beta blockers are most used to treat glaucoma, they are better tolerated than pilocarpine. applied directly to the eye, there is some systemic absorption. may have effect on the heart or bronchoconstriction. may also by combine with other drugs like ca2+ channel blockers to slow av nodal conduction
clinical uses of beta adrenergic antagonists- hyperthyroidism
beta-blockers are ideal for this condition. the effect is thought to be due to blockade of beta receptors and conversion of thyroxine to triiodothyronine
clinical uses of beta adrenergic antagonists- migraine
beta blockers are used for prophylaxis of migraine headaches
clinical uses of beta adrenergic antagonists- tremors, performance anxiety
beta-antagonists reduce certain tremors and low doses are used for performance anxiety
