Alpha Blockers Flashcards
Where do Alpha Blockers Typically act?
• Location?
Act on Alpha-Receptors found in VASCULATURE
Which of the Alpha blockers act primarily on the Alpha 1 receptor?
- Doxazosin
- Terzosin
- Prazosin
Which of the Alpha Blockers act almost equally on alpha 1 and alpha 2 receptors?
- Phenoxybenzamine
* Phentolamine
What are the subtypes of alpha-1 receptor?
• Where are they found?
- Alpha 1 b and d are found primarily in VASCULATURE
* Alpha 1 a (prostate)
What does Alfuzosin used to treat?
• why does this work?
Alfuzosin - used to treat benign prostatic hypertrophy (BPH)
• Works because its an alpha-1a blocker and alpha-1a makes up 70% of the alpha receptors in the prostate
In what areas of vasculature are alpha receptors found?
• what happens when these receptors are stimulated?
Where:
• Found in Skin, and Splanchnic Vessels
• Skeletal Muscle Vessels
What happens…
These Trigger Vascular Contraction
***Note these are not found in the endothelium of vessels in the heart, brain, or viscera
Alpha 2 Receptors:
• Where are they found?
• How do they work?
• What do they do?
Where:
• Pre-synaptic terminal
• Allows them to function as a feedback sensor that norepinephrine has been released and is still in the cleft
How do they work:
• Receptor Blocks conversion of ATP –> cAMP inside the neuron
What do they do:
• cAMP is needed for release of the vesicle containing Norepinephrine
• No norepinephrine getting released means lack of sympathetic effects
• BRADYCARDIA and HYPOTENSION are adverse effects of too much agonism
What is the effect of Alpha 2 blockers?
• Name drugs that have the most alpha 2 activity.
Phenoxybenzamine
Phentolamine
What does it mean that alpha receptors are autoreceptors and heteroreceptors?
Autoreceptor:
• Norepinephrine cells that expresses Norepinephrine (alpha 2) receptor
Heteroreceptor:
• Acetylcholine neuron that expresses Norepinephrine (alpha 2) receptor
***Heteroreceptors prevent simultaneous sympathetic-parasympathetic stimulation
Alpha 1 Receptors:
• Where are they found?
• How do they work?
• What do they do?
Where:
• POST-synaptic membrane
How do they work:
•Norepinephrine binding to Alpha 1 receptor stimulates PLC to cleave PIP2 to DAG and IP3 ultimately leading to CALCIUM RELEASE from ER.
• Ca2+ binds to proteins and upregulates cell activity
What do they do:
• Cell Stimulation Increases BP etc.
Why is activation of alpha-2 though to cause Bradycardia and hypotension?
• Stimulation of Vagal Activity
What is the effect of blocking:
• Alpha 1 receptor
• Alpha 2 receptor
Alpha 1 blockade:
• Hypotension
Alpha 2 blockade:
• HypERtension - would be overstimulation of sympathetic effects from cell not sensing that there is norepinephrine in the cleft
What receptors does Norepinephrine work on?
Alpha 1
Alpha 2
Beta 1
What receptors does epinephrine work on?
Alpha 1
Alpha 2
Beta 1
Beta 2
What receptors does Isoproterenol work on?
Beta 1
Beta 2
What endogenous agonists are there for the alpha 1 receptor?
Epinephrine
Norepinephrine
What endogenous agonists are there for the alpha 2 receptor?
Epinephrine
Norepinephrine
What endogenous agonists are there for beta 1 receptor?
Epinephrine
Norepinephrine
Isoproterenol
What endogenous agonists are there for the beta 2 receptor?
Epinerhrine
Isoproterenol
What are the effects of Epinephrine on blood pressure when administered with a Beta Blocker?
Epinephrine causes a sharper than usual spike in blood pressure when given with a beta blocker because epinephrine stimulation of BETA receptors acts to decrease blood pressure
What are the effects of Epinephrine on blood pressure when administered with an alpha Blocker?
Epinephrine causes a dip in blood pressure as opposed to the normal spike when given with an alpha blocker because the effects of alpha stimulation result in increased blood pressure and effects of beta stimulation are to decrease blood pressure
NOTE: beta action of epinephrine in a person NOT treated with blockers can be seen as a dip in BP after the initial spike
What are the effects of Norepinephrine on blood pressure when administered with a Beta Blocker?
Norepinephrine causes only a slightly stronger spike in blood pressure when given with a beta blocker
NOTE: Norepinephrine doesn’t work on both classes of beta receptors so you don’t see the same dip following the intial spike that you typically see in a person who is given epinephrine
What are the effects of Norepinephrine on blood pressure when administered with an Alpha Blocker?
Norepinephrine causes a much slighter spike in blood pressure when given with an alpha blocker
What are the effects of Isoproterenol on blood pressure when administered with a Alpha Blocker?
Nearly no change in effect of depressing the blood pressure because it doesn’t act on alpha receptors very much (or at all) so giving an alpha blocker doesn’t change how it binds beta receptors
What are the effects of Isoproterenol on blood pressure when administered with a beta blocker?
Only a very slight dip in blood pressure occurs because the only receptor type that isoproterenol works on is blocked
Rank the alpha-1 blockers by length of half life.
• which has the most severe adverse side effects?
- Doxazosin - 22hr (daily dosing)
- Terazosin - 12 hr (daily dosing)
- Prazosin - 4 hr (every 8 hr)**
Prazosin has most risk of FIRST DOSE ORTHOSTATIC HYPOTENSION - no correlation with blood level.
What are some things you can do to attenuate the adverse effects of Prazosin?
- Reduce Dose and take with food
* Take first dose before bed
**What the side effects of ALL alpha blockers?
• What is the root cause of these effects?
• Which of the alpha blockers are more likely to do this?
Side Effects:
• Tachycardia, Angina, Palpitations
• Syncope
• Vertigo
Root Cause:
• small amount of Beta-1 activity of epinephrine causes Tachycardia in LOW doses and Vasocontriction in HIGH doses
• Blocking alpha-2 prevents the pre-synaptic terminal from knowing that it released norepinephrine
Drugs:
• Phentolamine
• Phenoxybenzamine
What are the two non-specific alpha blockers?
• which is longer acting and why?
Phenoxybenzamine and Phentolamine
• Phenoxybenzamine is VERY LONG ACTING because it COVALENTLY binds to BOTH alpha-1 and alpha-2 receptors
Phenoxybenzamine
• Use to Treat?
• Onset, Duration?
Treats:
• Pheochromocytoma
• OFF LABEL use for Raynaud’s
Onset/Duration:
• Slow onset (hours) LONG duration (3-4 days)
What are the side effects of the longest acting non-specific alpha inhibitor?
Side Effects: • Nasal Congestion, Dry Mouth • Sinus Tachycardia • Laziness • Ejaculation Dysfunction
What drug has the most balanced action on both alpha 1 and alpha 2 receptors?
•**when is is used to treat?
Phentolamine
Treats:
• Pheochromocytoma
• Hypertensive emergency
Explain the different effects of Phentolamine at low doses and at high doses.
Low Dose:
• INCREASES blood pressure, this is because its blocking alpha-1 and alpha-2 receptors so more Norepinephrine is secreted and makes it to beta-1 receptors
• Beta-1 receptors are found in large on the Heart and lead to cardiact stimulation
High Doses:
• Vasodilation occurs because so much Norepinephrine is being released that it makes it to Beta-2 receptors in the periphery??
What are the side effects of phentolamine?
- Postural Hypotension, which can lead to…
- Tachycardia (once baroreceptors realize BP is dropping) leading to Arrhythmia
Negative effects here really limits the use of this drug to use in Essential Hypertension
T or F: alpha blockers are still widely used for hypertension
False, they have been replaced by better drugs
