Flashcards in Adrenergic Receptor Antagonists Deck (33)
Name some cardiovascular effects of antagonizing the alpha1 receptor.
1. Decreased PVR
2. Lowered BP
3. Postural hypotension due to failure of venous vasoconstriction upon standing
(Remember alpha 1 is really important for venoconstriction and vascular tone for maintaining changes in tone with position changes etc. If we block it we are blocking compensation for these types of changes)
Name some cardiovascular effects of antagonizing the alpha 2 receptor.
1. Increases NE release from nerve terminals (we are blocking that negative feedback mechanism).
Remember: you can end up with increased circulating NE so if we block the alpha receptor and not the beta NE could end up stimulating the B1 receptor and cause tachycardia.
What kind of effects does antagonizing the alpha receptors have the GU system, eyes and nose?
1. GU- blockade in the prostate and bladder cause MUSCLE RELAXATION and EASE micturation (used in BPH for this effect)
2. Eyes: Miosis: contracted pupil
3. Nose: increased nasal congestion (side effect).
What kind of antagonism is possible with alpha antagonists?
Either competitive antagonism or covalent antagonism.
At what receptor does Phentolamine work? What does it result in?
1. It is NON-selective alpha blocker.
2. Vasodilation, decreased BP, increased HR and increased CO.
*Increased HR is because of the blocked negative feedback and baroreceptors which make this reflexive tachycardia a bit more dramatic.
When is Phentolamine used? Dose? Onset? DOA? Elimination 1/2 time?
1. Used in hypertensive emergencies (pheocromocytoma or autonomic dysreflexia) where the dose is 30-70 mcg/kg IV with an onset of 2 minutes and a DOA of 10-15 minutes. Elimination half time is 19 minutes which makes this drug EXCELLENT to control on a short term basis.
2. Used in local infiltration for accidental extravascular administration of sympathomimetics, 2.5-5.0MG in 10ml (infiltrate in the area to combat constriction).
Why must we pay special attention to phenoxybenzamine? What kind of selectivity does it have?
1. Because it binds covalently so you are STUCK with it.
2. A little more selective for alpha one than alpha 2
What kind of action does phenoxybenazmine have?
It decreases SVR, vasodilation.
*Some HR increases but not as much as phentolamine but we do still have the baroreceptors contributing and a little hit on alpha 2.
What kind of drug is phenoxybenzamine? Onest? Half-time? When is it used?
1. Pro-drug (liver metabolizes)
2. 1 hour onset time
3. Long acting E1/2t : 24 hours
4. Pre-op pheoxchromocytoma and Raynaud's
What kind of effect do beta-adrenergic receptor antagonists have on the heart?
1. Improve O2 supply and demand balance (decrease HR)
What kind of effect can beta-adrenergic receptors antagonists have on the airway?
1. Can provoke bronchospasm.
What kind of effect do the beta-adrenergic receptor antagonists have on the juxtaglomerular cells?
1. Decrease renin release (an indirect way of decreasing BP)
What kind of effect do the beta-adrenergic receptor antagonists have on the pancreas?
1. Decreased stimulation of insulin release by epi at B2
2. Masked symptoms of hypoglycemia at B1
What kind of effect do the beta-adrenergic receptor antagonists have on the blood vessels?
1. Vasoconstriction in skeletal muscles, PVD symptoms increased (SE = decreased excercise tolerance).
Name the three MOAs of the beta-adrenergic receptor antagonists.
1. Selective binding to beta receptors
2. Competitive and reversible inhibition
3. Chronic use is associated with increase in the number of receptors.
Beta-adrenergic receptor antagonists are derivatives of what drug?
Large doses of cardioselective beta blockers....?
Lose their selectivity.
What kind of agonist is Metoprolol? What is it's selectivity related to? What two things does it decrease?
1. Selective B1 blocker
2. Selectivity is dose related
3. Decreases inotropy and chronotropy
How much of Metoprolol goes through the first pass effect? Dose PO? Dose IV? E1/2T?
2. PO 50-400mg
4. 3-4 hours.
Which drug is the most selective beta-1 antagonist? When is it very useful
Atenolol, in cardiac patients with CAD.
What is the E1/2t of atenolol? When is it increased?
1. 6-7 hours
2. renal disease
Esmolol works at which receptor? Onset? DOA? Typical Dose? E1/2t?
1. Selective B1 antagonist
2. Rapid onset
3. Short acting DOA under 15 minutes
4. Typical dose of 0.5mg/kg IV or (10-180mgIV) can start an infusion of 50-200mcg/kg.min
5. 9 minutes
Esmolol affects heart rate without affecting what?
without decreasing blood pressure significantly. In doses uses, it does not occupy sufficient beta receptors to cause negative inotropy.
What is esmolol rapidly hydrolyzed by?
Plasma esterases, but not the same ones responsible for the metabolism of succhs.
What kind of side effects do we see with B blockers?
1. CV system (b1) decrease Hr, Contractility and BP
2. Exacerbation of PVD (block of beta 2 vasodilation)
3. Airway resistance bronchospasm
4. Metabolism- alter carb and fat metabolism, mask hypoglycemic increase in HR
5. Distribution of extracellular potassium- inhibit uptake of potassium into skeletal muscles (B2)
6. Interaction with anesthetics- may have decreased BP with IAs
6. Nervous system- fatigue, lethergy
What are four relative contraindications of beta blockers?
1. Pre-existing AV heart block or acute cardiac failure.
2. Reactive airway disease
3. DM (need to be really really really advised about hypoglycemia and strict BS monitoring)
Name 6 clinical uses of B-blockers.
HTN, Management of Angina, Decrease mortality in treatment of post MI patients, used periop and preop for patients at risk for MI, suppression of tachyarrythmias, prevention of excessive SNS activity.
Which drug is a combined alpha and beta blocker? Which receptors?
2. Selective at alpha one, beta 1 and 2 receptors. The IV Beta : Alpha blockade is 7:1.
How is labetalol metabolized? What is its' E1/2t? When is it prolonged?
1. Conjugation of glucuronic acid <5% in the urine.
2. 5-8 hours.
3. Liver disease