CV Pharm-Anti Hypertensives Flashcards
What are the effects of the sympathetic nervous system in HTN?
- Via Barometric reflex
- increases HR
- Vasoconstriction
Where does AT act to produce hypervolemia via retention of Na and H2O?
Proximal tubule
What is the neurotransmitter of the sympathetic nervous system?
Norepi
Which receptors does Norepinephrine act on?
Alpha adrenergic & Beta Adrenergic
What type of receptors are the Angiotensin receptors and Alpha adrenergic receptors?
These are GQ coupled receptors, whose activation results in the release of Phospholipase C which acts on PIP2 to create DAG & IP3 which results in release of Calcium from the SR
Where are the Alpha Adrenergic and ATII receptors primarily?
In Smooth muscle (VSM) cells
What kind of receptors are in the heart cells?
Beta Adrenergic receptors
What are the Beta Adrenergic receptors coupled to?
GS coupled
What does activation of the Beta Adrenergic receptors result in?
Activation of Adenylate cyclase which converts ATP to cAMP which the activates the L-Type Calcium channels via PK-A
Where is Epinephrine made?
Adrenal Medulla
What are the predominant receptors in the heart and Lung?
B1 in the Heart
B2 in the Lung
What are the effects of NorEpi after binding with Beta1 receptors in the heart?
- Increase of force of myocardial contraction
- Increase in HR
- Increase in the rate of myocardial relaxation
What is the major receptor upon which norepi acts in peripheral blood vessels?
Alpha 1 receptors (including in the kidney)
What is the effect of norepi action on PBV?
Increase in systolic and diastolic Pressures
Which causes the greater vasoconstriction Norepi or Epi and why?
Norepinephrine because it does not induce compensatory vasodilation via Beta2 receptors on blood vessels supplying skeletal muscle
What are the peripheral vessels most acted on by the sympathetic nervous system?
- Precapillary arterioles
2. Venules
What is the function of the Alpha2 receptors in the presynaptic cleft?
To feedback inhibit the release of norepi
How is adrenergic receptor signalling terminated?
By Uptake 1 of the transmitter usually by the presynaptic neuron
How does Reserpine work?
Inhibits (uptake 2) VMAT the transporter of Dopamine and Norepi into transmitter vesicles of adrenergic nerves
What is the effect of reserpine?
TPR is reduced due to the highly reduced amount of norepi to act on Alpha receptors
How is reserpine administered?
.5mg Orally
What are the side effects of Reserpine?
Sedation and mental depression
When is reserpine contraindicated?
- In patients with a history of mental depression (increases suicidal tendencies)
- In patients with a history of Duodenal ulcers
What is the mechanism of action of the alpha 1 selective blockers (osin)
Block the peripheral alpha 1 receptors (mostly on arterioles and venules)
What is the effect of Alpha 1 blockers?
1.Reduced Total peripheral resistance and reduced BP
What is another use of the Alpha 1 blockers?
BPH by relaxing the muscles of the bladder and prostate
What are some benefits of Alpha 1 blockers?
Increase HDL lower LDL
Beneficial effect on insulin resistance
What is the preferred patient population for the Alpha1 blockers (osin)?
Healthy Older men with hypertension and BPH
What are the side effects of The selective Alpha1 blockers?
Orthostatic hypertension, first dose should be taken before bed
Sometimes dizziness and vertigo drowsiness and palpitations
When would you use The nonselective alpha blockers Phentolamine and Phenoxybenzamine?
Preoperative to prevent hypertensive crisis in patients undergoing surgery for pheochromocytoma
What is Intristic sympathomimetic activity?
Partial agonist action by adrenoreceptor blockers
What Beta Blockers are known to have ISA activity?
Pindolol and Acebutolol
What is meant by the “Membrane Stabilizing effect?”
The ability of certain Beta Blockers to have a local anesthetic action
Which beta blockers have no membrane-stabilizing activity?
- Timolol
2. Atenolol
Which of the Beta Blockers are Non B1 selective?
Those beginning with letters from N-Z i.e Propranolol, Timolol Pindolol
Which of the Beta Blockers has the Lowest and Highest lipid solubility?
- Highest = Propranolol
2. Lowest = Atenolol
What are the effects of Beta 1 selective beta blockers in normal individuals?
Blocking of myocardial Beta 1 adrenergic receptors results in decreased HR, decreased contractility, thus decreased cardiac output.
What is the effect of Beta Blockers in the kidney?
They Block the Beta1 receptors in the kidney and inhibit the release of Renin
Which Beta Blocker has no effect on Renin release
Pindolol
What would be the effect of Beta Blockers on Peripheral NE?
Decrease the release of peripheral NE by inhibiting presynaptic B adrenergic receptors
When are Beta Blockers most effective?
In cases of high Renin hypertension like is most common in Young and caucasians.
What is the therapy of choice for hypertensive patients who have also had MI, ischemic heart disease or CHF?
Beta Blockers
What are some conditions that are compelling for Beta Blockers?
1,Hyperthyroidism
2.Migranes
What drugs can be used to reduce the risk of a second heart attack?
Beta Blocker i.e Carvedilol, Metoprolol-XL and Bisoprolol
Those Beta Blockers with membrane stabilizing activity can also be used as?
Antiarrhythmic drugs
In what chronic condition is propranolol and all nonselective Beta Blockers contraindicated?
Asthma as they can induce Bronchospasms
How must Beta Blocker Therapy be terminated?
Gradually due to that fact that receptors are upregulated during therapy
Which Long Acting Beta Blocker is considered to be the “Best”
Bisoprolol
If during surgery one discovers and arrhythmia (possibly due to halothane anesthetic) what should be IV administered to the patient?
Esmolol (Brevibloc)
What are the side effects of Beta Blockers?
- Cold extremeties from unopposed alpha adrenergic action which constricts blood vessels
- Bradycardia
- Bronchospasm
- CNS side effects Bad dreams etc
Which calcium channel Blockers are contraindicated with Beta Blockers and why?
Verapamil and Diltiazem for dangerous Bradycardia
What are the metabolic side effects of Beta Blockers?
- Block Glycogenolysis and delay recovery from Hypoglycemia in type 1 diabetes
- Can Block Hormone sensitive Lipase and increase LDL and decrease HDL and increase triglycerides
What is Labetalol?
IV Beta Blocker for treatment of Hypertensive emergencies, Is a non-selective with Alpha-1 receptor antagonism
What is Carvedilol?
3rd Gen Beta Blocker with Alpha-1 antagonist activity, is also an antioxidant that scavenges ROS.
When is Carvedilol used?
Primarily for CHF and HTN
Where is Carvedilol etabolized?
Hepatic (2D6) metabolism
With what drugs should Carvedilol be avoided?
With CYP2D inhibitors like Cimetidine, fluoxetine, quinidine
What is Celiprolol?
Cardio selective + Beta-2 agonism
What is unique about Celiprolol?
Directly vasodilates Blood vessels due to its partial Agonist activity
When is Celiprolol used?
Treatment of HTN and Angina
What is the drug of choice in HTN with Metabolic syndrome?
Nebivolol
