Sympatholytics: The alpha and beta receptor antagonist Flashcards
What is phetolamine?
its an alpha receptor antagonist
What is phetolamine called commerically?
regitine
What is phentolamine exactly?
an imidazole that a competitive nonselective alpha receptor antagonist
What is the use of phentolamine?
used systemically for the treatment and prophylaxis of pheochromocytoma hypertension and tachycardia
What can phentolamine be used to prevent after using IV NE?
dermal necrosis
What drug can be combined with phentolamine to prevent impotence?
papaverine
How long does phentolamine last if it is injected by IV or intracavernosally?
duration of action is 1-6 hours
What effect does phentolamine have on the heart?
cardiac stimulation due to blockade of presynaptic alpha-2 receptors which allows more NE to be released; this mean beta-1 receptors on the heart will become activated causing tachycardia
The increase in heart rate my also be due to reflex tachycarida b/c of a decrease in blood pressure
What is the effect of phentolamine on the vasculature?
blockade of bother presynaptic alpha-2 receptors and postsynaptic alpha 1 receptors; when NE is release, an overall decrease in vasocontriction occurs because of the alpha-1 blockade
What is the overall effect on phentolamine on the vasculature?
a decrease in total peripheral resistance; the strength of effect is based on the level of sympathetic tone, so you will see a greater change in pressure in someone who is standing up than someone lying down
What is the impact of phentolamine on GI system?
blockade of alpha-2 receptors (which causes relaxation in the gut and increase in gastric secretions
What is the impact of phentolamine on the urinary tract?
remember alpha-1 receptor activation contracts the trigone and the sphincter muscles of the bladder resulting in urinary retention; blockade of these alpha-1 receptors would lead to relaxation and decrease the resistance to urinary flow
What is the effect of phentolamine on the penis
Injection causes relaxation of the penile arteries allowing increased blood flow and relaxation of the trabecular intracavernosal muscles. The papaverine which is used in conjunction with phentolamine selectively decreases venous outflow.
Injection causes relaxation of the penile arteries allowing increased blood flow and relaxation of the trabecular intracavernosal muscles. The papaverine which is used in conjunction with phentolamine selectively decreases venous outflow.
what are the side effects of phenotolamine?
Severe tachycardia Angina Arrhythmia Diarrhea and abdominal pain Orthostatic hypotension, fainting Stuffy nose Priapism Fibrosis
When is phentolamine contraindicated?
Angina
Coronary artery insufficiency
Myocardial infarction
What are the drug interactions of phentolamine
- Sympathomimetics (a-agonists)
- Guanadrel and guanethidine
When phentolamine interacts with sympathomimetics (alpha agonist) what happens?
blockade of the therapeutic effect of a-agonist and vice-versa.
When phentolamine interacts with guanadrel and guanethidine what happens?
increased incidence of orthostatic hypotension
What is phenoxybenzamine?
alpha-receptor
What is phenoxybenzamine?
dibenzyline
what is phenoxybenzamine used for?
the treatment of hypertension and sweating in patients with pheochromocytoma. It is not used for the treatment of essential
hypertension due to its side effects.
What is the duration of action when phenoxybenzamine is given orally?
The duration of action is 3-4 days but it is dosed daily.
Enters the CNS.
Which receptors does phenoxybenxzamine impact?
irreversible antagonist at a1 and a2-receptors.
What impact does phenoxybenzamine have on the vasculature?
blockade of a1-receptors on the smooth muscle results in vasodilation, thereby decreasing total peripheral resistance. The decrease in blood pressure is most noticeable in upright individuals
due to increased sympathetic tone
How does phenoxybenzamine impact the heart?
Rate and cardiac output is increased due to reflex tachycardia and increased NE release produced by the blockade of pre-synaptic a2-receptors and by the blockade of NE transporters leading to increased b1-receptor stimulation.
What are the other effects of phenoxybenzamine?
effects of phenoxybenzamine on other organ systems are the
same as phentolamine but they last longer
What are the side effects of phenoxybenzamine?
Orthostatic hypotension Fainting Tachycardia Stuffy nose Miosis Inhibition of ejaculation Fatigue and sedation
What are the drug interactions of phenoxybenzamine?
Same as phentolamine
When is phenoxybenzamine contraindicated?
Coronary artery disease
CHF
Respiratory infection
(aggravates stuffy nose).
What is prazosin?
its an alpha one antagonist
what is the commercial name for minipress?
prazosin
What is the use of parzosin?
Useful in the treatment of hypertension usually as a second alternative, a second add-on or as a third add-on. Also used for CHF
and pheochromocytoma.
When is parazosin given orally?
Given orally and is readily absorbed. Highly protein bound. Durationof action is -10 hrs. Can enter the CNS
What is the mechanism of action of alpha-1 receptors?
Selective competitive a1-receptor antagonist;
What is the mechanism of action of prazosin on the vasculature?
blockade of post-synaptic a1-receptors on the smooth muscle of both veins and arteries, producing vasodilation. Causes a decrease in peripheral resistance and decreases venous return to the heart.
What is the mechanism of action of the hypertensive heart?
Tachycardia is absent likely due to a lack
of a2-receptor blockade and a depression of sympathetic outflow in the CNS. The decrease in peripheral resistance decreases cardiac
preload (filling pressure) thus having little effect on cardiac output and rate.
What is the mechanism of action of the congestive heart failure?
Vasodilation produces a decrease in pre-load
(filling pressure) and afterload (resistance against which the heart pumps) which increases cardiac output and decreases pulmonary congestion.
What is the mechanism of action of the genitourinary?
reduces the tone of the trigone and sphincter to
decrease the resistance to urinary outflow. May be useful in patients with impaired emptying
What are the side effects of prazosin?
First dose can result in orthostatic hypotension - 0.5-2 hrs after initial dose. More likely to occur in geriatric patients and those who are volume depleted. Begin with an initial 1 mg dose increase gradually.
Angina
Fainting due to orthostatic hypotension
Irregular heartbeat
Tolerance to the CHF effects after long-term use.
What is the result of drug interaction of prazosin with NSAIDS?
may block the anti-hypertensive effect by inhibition of renal prostaglandin synthesis, thus causing Na+ and fluid retention.
What is the effect of prazosin with other hypotension producers?
potentiated effects
What is prazosin contraindicated with?
mutual inhibition of effects
What is tamsulosin ?
A selective antagonist of alpha1A (a1A) adrenoceptors in prostrate.
What is the commerical name for tamsulosin?
flomax
What is tamsulosin used to treat?
treatment of benign prostatic hyperplasia (BPH).
Who should use tamsulosin?
use by men only
what are effects of tamsulosin?
Highly selective for alpha 1 receptors in the human prostate.
Relaxes the muscles in the prostate and bladder neck at the site of obstruction, resulting in improved urine flow and reduced
BPH symptoms.
Not used as an antihypertensive
What are the side effects of tamsulosin?
Fainting due to orthostatic hypotension
Priapism (very rarely)
What are the drug interactions of tamulosin?
Other hypotension producers- Potentiate effects
What is yohimbine?
sympatholytics
What is a commerical name for yohimbine?
Actidine, Aphrodyse, Yocan,
What is the use of yohimbine?
Used for the treatment of erectile impotence- herbal viagra. Improve
symptoms in patients with painful diabetic neuropathy or Raynaud’s
syndrome.(abnormal vasoconstriction of the extremities upon exposure
to cold or emotional distress).
How is yohimbine aborbed and what is its onset of action?
Rapidly absorbed. The onset of action is 2-3 weeks. Enters the CNS
What is the mechanism of action of yohimbine?
Selective, competitive a2-receptor antagonist
What are the side effects of yohimbine?
Increase in blood pressure and heart rate.
Dizziness, headache and nervousness.
Nausea or vomiting (rare)
What are the drug interactions of yohimbine?
- Antidepressants and mood modifiers- antagonize their effects.
- Anti-hypertensives- may block their effect.
What are the contraindications of yohimbine?
- Angina
- Cardiac disease
- Hypertension
- Renal impairment
Why have sympatholytics received enormous clinical attention?
due to their efficacy in treating hypertension, ischemic heart disease, congestive heart failure and certain arrhythmias.
How can the pharmacological properties of yohimbine be explained? given an example.
The pharmacological properties can be largely explained based on the responses elicited by the receptors in the various tissues and the activity of the sympathetic nerves that innervate these tissues. For eg. b-receptor blockade has relatively little effect on the normal heart of an individual at rest but has profound effects when sympathetic control of the heart is dominant as during exercise or stress. The major therapeutic effects are on the cardiovascular system in individuals.
What is propranolol?
sympatholytic-beta blocker
What is the clinical use of propranolol?
Used for treatment of chronic angina, cardiac arrhythmia,hypertension as a first line agent, cardiomyopathy, myocardial re-infarction (prophylaxis), pheochromocytoma (adjunct), vascular headache, tremors, physical symptoms of anxiety, mitral valve prolapse and thyrotoxicosis.
What is the commerical name from propranolol?
inderal
What is the mechanism of action of propranolol?
Non-selective b-blocker- prototypical agent
How is propranolol administered?
Given orally or as an IV solution. When administered orally, multiple, increasing does may be required.
Can propranolol the CNS?
well absorbed and highly lipophilic it enters the CN
What is propranolol impact on the heart?
- Blocks the action of NE and EPI at the b1-receptors on the heart. At rest there is little sympathetic activity thus, the effect on
heart rate and force of contraction is small. When the sympathetic system is activated, the effect of b-blockers is more pronounced and the increase in heart rate and contractility is reduced.
What is propranolol’s impact on the vasculature?
short term b-blocker use decreases cardiac output
resulting in reflex vascular constriction via a1-receptor activation and blockade of b2-receptors in the vasculature of the skeletal muscles. The result is an increase in total peripheral resistance.
After long-term use the total peripheral resistance decreases but the reason is unclear.
What is proprnolol impact on oxygen use?
Improves the relationship between O2 supply and
demand.
How does propranolol impact heart rhythm and automaticity?
Reduction in sinus rate, a decrease in
the spontaneous rate of depolarization of the pacemaker cells, a slowing of the conduction in the atria and the AV node and an increase in the refractory period of the AV node.
How does propranolol impact heart cardiovascular function?
Does not reduce blood pressure in patients
with normal B.P. B.P. lowering mechanism(s) are not well understood.
How does propranolol impact pulmonary?
Blocks the b2-receptors on the smooth muscle of
the lung. In normal individuals it is of little consequence. In someone with chronic pulmonary obstructive disease it can lead to dangerous bronchoconstriction.
What are the metabolic effects of propranolol?
Modifies the metabolism of glycogen and
glucose (carbohydrates). May slow the recovery from hypoglycemia. No real effect on insulin release.
What are ocular effects of propranolol?
Although propranolol is not used ophthalamically, other nonselective b-blockers are (i.e. timolol). Blockade of b-receptors in the ciliary body (not muscle) reduces the production of aqueous
humor thereby reducing fluid input and thus the pressure. Many of these compounds can enter the systemic circulation.
What is hyperthyrodism and pheochromocytocoma?
characterized by elevated catecholamines, which may adversely affect the cardiovascular system. The b-blockers antagonize the effects of the
elevated catecholamine levels on the heart. .
What are the side effects of propranolol?
Mental depression - due to CNS effects. Wheezing - greater risk in obstructive pulmonary disease. Slow heartbeat Decreased sexual ability Diarrhea Dizziness Drowsiness Nausea and vomiting Numbness and tingling Trouble sleeping
What happens is propranolol is abruptly discontinued?
Abrupt discontinuation of b-blockers is very dangerous possibly due to upregulation of the b-receptors.
What are the side effects of abruptly discontinuing propranolol?
Fast or irregular heartbeat- dangerous in those with heart disease. Chest Pain Headache Shortness of Breath Sweating Trembling
What are the drug interactions of insulin with propranolol?
increased risk of hypoglycemia
What are the drug interaction of propranolol with calcium channel blockers?
potentiated hypotensive effects. Never discontinue two agents at once,
may lead to hypertensive crisis
What are the drug interactions of sympathomimetics with sympatholytics ?
Mutual inhibition of effects. Unopposed a
receptor stimulation results in hypertension and bradycardia.
What are the drug interactions of sympatholytics and xanthines?
(theophylline)- mutual inhibition of pulmonary effects
What are the contraindications for propranolol?
cardiac failure, heart block and sinus bradycardia
When should you be careful when using sympatholytics?
Allergy, asthma and emphysema
Diabetes
Hyperthyroidism - may mask symptoms
Mental depression
What is butoxamine?
It is b2-receptor selective but has no therapeutic value. You should
be able to figure out why
What is nadolol?
Corgard
What is the commerical name of nadolol?
Antagonizes both b1 and b2 receptors and it is devoid of membrane stabilizing and intrinsic sympathomimetic activity.
Distinguishing character is its relatively long half-life.
What is Timolol?
Non-selective b adrenergic antagonist with no membrane stabilizing activity. Used for the treatment of glaucoma.
When given in the eye may be absorbed systemically.
What is the commerical name of Timolol?
Blocardren
What is pindolol?
Visken
What is the commerical name for pindolol?
Non-subtype selective b adrenergic antagonist with intrinsic sympathomimetic activity. May produce smaller reductions in resting
heart rate and blood pressure.
Preferred antihypertensive in individuals with diminished cardiac reserves or a propensity for
bradycardia.
What is the commerical name for metoprolol?
Lopressor, Toprol
What is metoprolol?
1
What is metorprolol used to treat?
for the treatment of angina, hypertension (initial therapy), arrhythmia, cardiomyopathy, prophylaxis for myocardial reinfarction, pheochromocytoma, vascular headache, tremors and anxiety.
How is metoprolol administered?
Can be given orally or IV
What is the mechanism of action for metoprolol?
selective antagonist of b1-receptors
How is metoprolol cardioselective?
At higher doses increased increased b2-blockade occurs.
Since there is little b2-receptor blockade, theoretically the risk of bronchospasm, hyperglycemia and peripheral vasoconstriction
(at the skeletal muscle) is reduced.
What are side effects, drug interactions and contraindications?
The side effects, drug interactions and contraindications are the
same as propranolol.
What is atenolol?
b1 Selective
What is the commerical name for atenolol?
Tenormin
What is atenolol used for?
Devoid of intrinsic sympathomimetic activity
What does it penetrate?
Highly hydrophilic and will penetrate the brain to a limited extent
What is the commerical name for esmolol?
Brevibloc
What is the duration of action of esmolol?
Very short duration of action with a half life of about 10 minutes
When is esmolol used?
Used when b blockade of short duration is needed in critically ill patients in whom adverse effects of bradycardia, heart failure, or hypotension may necessitate rapid withdrawal of the drug.
What is the commerical name of acebutolol?
Sectral
what is acebutolol?
In addition to b1 blockade agent possesses some intrinsic sympathomimetic activity.
What is acebutolol used to treat?
Used for the treatment of hypertension and ventricular arrhythmias
