Beta Blockers Flashcards
Where can Beta-1 receptors be found?
• Are there Beta-2 receptors located here as well?
• What is their action at these sites?
Beta-1 and Beta-2 are found Together in the following sites:
• SA node - Accelerates
• Ectopic Pacemakers - Accelerates
• Contractability - Increases
B1 increases these effects, B2 decreases them
Beta-2 only:
• Skeletal Muscle Vessels - Dilates
What is the difference between Beta-1 and Beta-2 stimulation on the heart?
B1 stimulation Increases cardiac output
B2 stimulation decreases cardiac output
What type of Beta receptors are found on the kidney?
• what is their role?
• What role do NSAIDs play?
Beta-1 receptors are stimulated tipping of the renin –> angiotensin I —> angiotensin II pathway.
• Overall effect is potent vasocontriction and perfusion of kidney because of increased blood pressure
NSAIDs:
• prevents PG receptors from triggering the same path and can lead to deficient renal perfusion, especially in the elderly
What does it mean if a drug has intrinsic sympathomimetic activity?
- Drugs are weak partial agonists that bind the Beta receptor causes partial stimulation
- At the same time this drug is blocking Epinephrine and Norepinephrine from binding so full stimulation cannot occur
Result is a more regulated effect like a Dimmer instead of an on off switch
What is the characteristic action of 3rd generation beta blockers?
• Agents that have effects on alpha receptors or activate other signal pathways to prevent reflexive vasocontriction that results from blocking Beta stimulation
**Without this baroreceptors just sense low BP and trigger alpha-1 vasocontriction
Why would you want to make Beta blockers more or less lipid soluble?
More Lipid Soluble drugs can cross the BBB
Crossing the BBB can cause CNS effects like bad dreams, this is reduced in less lipid soluble drugs
What membrane depressant effects can beta blockers have on cardiac activity?
Membrane depressant effects means that the drug depresses myocardial contractility and conduction
What Beta Blockers have membrane depressant effects?
Propanolol
Acebutolol
Carvedilol
mem(ber)-PrACticE
What Beta Blockers have intrinsic agonist activity?
Pindolol
Acebutolol
Beta-Activating Ace-Pin
Which of the Beta Blockers are the most Lipid Soluble?
• consequences?
*CNS problems will be a likely side effect
Propranolol (high) Carvedilol (moderate) Metoprolol (moderate) Betaxolol (moderate) Timolol (low to moderate)
Fat loving PCM BiTes
What are the First Generation Beta Blockers?
• What makes them 1st generation
• which has the longest half-life?
Non-selective = First Generation (N–>T):
- Nadolol (Longest 20-24 hours)
- Pindolol
- Propranolol
- Timolol
**rest are around 4 hours
Nadolol NEVER ends
What are the 2nd generation beta blocker?
• What makes them 2nd generation?
• Which has the shortest half-life?
Beta 1 selective = Second Generation:
- Acebutolol
- Atenolol
- Esmolol (Shortest half-life - 15 minutes)
- Metoprolol
Others have a half-life between 3-7 hours
What are the 3rd generation Beta blockers?
• what makes them 3rd generation?
all 3rd generation drugs try to prevent to reflexive vasoconstriction that follows drug administration
Non-selective but have additional actions = 3rd Generation
• Carvedilol
• Labetalol
Selective Beta 1 blockers with additional actions = 3rd Gen
• Betaxolol
• Nebivolol
What are the additional actions of Nebivolol?
Works to inhibit Beta1 while stimulating Beta3 which leads to synthesis of NO and Vasodilation
What are the beta blockers that also act as membrane stabilizing drugs?
• What is membrane stabilization?
• What are the effects on the heart?
Propranolol, Acebutolol, Carvedilol
• Stabilize Membrane by Binding to Fast Na+ receptors in addition to the beta receptor
Effect on Heart:
• Decreased depolarization in phase 0, so there is less of an action potential and smaller contractions
What is the significance of the membrane stabilizing drugs?
• Name them.
Significance:
• They can be used as anti-arrhythmics
Drugs:
Propanolol
Acebutolol
Carvediol
What kind of patients might benefit from drugs that have intrinsic Sympathomimetic Activity?
• Why?
• Name these drugs.
These drugs Partially activate the beta receptor as they block binding of Catecholamines
This is good for patients who can’t handle the extreme bradycardia or diminished cardiac contraction of pure agonists
Drugs:
• Pindolol
• Acebutolol
What is inverse agonism?
The drug binds the inactive form of a receptor and locks it into that form preventing the drugs from binding
What drugs have extended actions?
• Name the action and the drug doing it.
Nebivolol
• NO production
• Acts as Antioxidant (by making NO)
Carvedilol
• Alpha-1 antagonism
• Ca2+ entry blockade
• Antioxidant activity
Labetalol
• Alpha-1 antagonism
Betaxolol
• Ca2+ blockade entry
What drugs have the following extended actions: • Nitric Oxide Production •Alpha-1 antagonism • Ca2+ entry blockade • Antioxidant Activity
NO production:
• Nebivolol
Alpha-1 antagonism:
• Carvedilol
• Labetalol
Ca2+ entry blockade:
• Carvedilol
• Betaxolol
Antioxidant activity:
• Carvedilol
• Nebivolol
What are the four major conditions that beta-blockers are used to treat?
- Hypertension
- Ischemic Heart Disease
- Supraventricular and Ventricular Arrhythmias
- Congestive Heart Failure (CHF)
How can a beta blocker that has no alpha receptor activity act to decrease blood pressure?
- Beta 1 receptors in the Kidney trigger Renin, angiotensin I, angiotensin II cascade which means blocking them may help prevent rises in blood pressure
- ALSO, presynaptic ß-adrenoreceptors may bind these drugs augmenting Norepinephrine release
In the case of a Myocardial infarction do you think it would be more beneficial to use a pure antagonist or a partial agonist”
Pure Antagonists are thought to be better for this
T or F: its okay to abruptly stop taking beta blockers.
False, after taking it your body will have upregulated beta receptors stopping therapy immediately could cause rebound (intense beta stimulation, pt. would probably be very tachycardic)
How would a patient that have overdosed on beta blockers present to the ED?
• Bradycardia and Bradyarrhythmia would be observed
With what Beta blockers might you observe a tachyarryhthmia instead of a slow one on overdose?
• Why?
Membrane Stabilizing Drugs:
• Propranolol
• Acebutolol
• Carvedilol
With less powerful contractions from reduced phase 0 depolarization the heart will have to work harder to pump blood to prevent hypoxia in drug toxicity
Someone comes in the ED experiencing siezure and coma.
• Drug Responsible?
• Propranolol is VERY lipid soluble so will cause CNS effects like this
Adverse effects common to:
• Acebutolol
• Pindolol
*why these drugs?
Tachycardia and Hypertension = common adverse effect
Intrinsic Sympathomimetic drugs - act as partial agonists
Why might it be easier to overdose on a third generation drug that the others?
• Name drugs.
These drugs have off target effects such as NO production, antioxidant activity, Ca2+ channel blocking and alpha 1 antagonism all cause intensified hypotension (due to vasodilation)
Drugs: • Betaxolol • Carvedilol • Nebivolol • Labetalol
What patients are at the highest risk of experiencing adverse effects of beta blockers?
• People with underlying Cardiovascular or Pulmonary Disease
What beta blockers would definitely be contraindicated in a patient with asthma and why?
Beta-2 signaling is important in BRONCHODILATION thus if that pathway is blocked ppl. with asthma will have severe bronchospasm
Contraindicated = NON-specific Beta Blockers (1st generation) • Nadolol • Pindolol • Propanolol • Timolol
*Remember Receptor Specificity isn’t 100% so Beta 1 specific drugs still may block beta-2 to a lesser extent
What off target CNS effects do you see with Beta Blockers?
• Beta Blockers most commonly implicated
Mental Disorders or Fatigue
Intense Dreams
Lipophilic Drugs implicated: • Propanolol (most likely = most lipophilic) • Carvedilol • Metoprolol • Betaxolol • Timolol
What problems might diabetics have with Beta Blockers?
B-1 blockers mask tachycardia which tells them that they may be HYPOGLYCEMIC FROM TOO MUCH INSULIN
T or F: Beta blockers can cause hypoglycemia
True.
Beta 2 blockers (1st gen)
• Beta-2 adrenoreceptors stimulated glycogen breakdown (in liver)
• Beta-2 adrenoreceptors in pancreas stimulate GLUCAGON release
What off target effects do beta blockers have on lipid profile?
• what patient would this be hard on?
- Little effect on TOTAL cholesterol and Plasma LDLs
- INCREASE triglycerides and DECREASE HDLs (BAD)
Patients with Congestive Heart Failure DO NOT need their triglycerides to get any higher
What beta blockers would be most likely to trigger hypoglycemia?
1st generation • Nadolol • Propranolol • Pindolol • Timolol
Of the Beta Blockers which are better about not having such a bad effect on the lipid profile (i.e. raising TGs and depressing HDLs)?
Intrinsic Sympthomimetic Activity or Cardioselectivity = Better
• B/c these are acting as partial agonists
Those with both ISA and Cardioselectivity LOWERED LDL and total cholesterol
What are some used for beta-blockers other than in cardiovascular health?
- Essential Tremor
- Thyrotoxicosis
- Anxiety
- Prophylaxis of Migraine Headache
- Treatment of Glaucoma
- Prophylaxis (secondary) with esophageal Varicies
