L14- CCB and Sympatholytics Flashcards Preview

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Flashcards in L14- CCB and Sympatholytics Deck (20)
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What are the sympatholytics and generally how do they work?

Reserpine - depletes NE from storage veisicles (blocks VMAT) 

Methyl-DA and Clonidine = inhibit Symp outflow from CNS; central A2 agonists

Met-tyrosine = inhibition of NE synthesis 


How does Reserpine work and what is it used for? adverse effects?

Reserpine selectively and irreversibly binds VMAT2 and blocks it so no Da into vesicles to become NE . Therefore, inactivates NE-releasers bc depletes NE from vesicles

Causes upregulation in adrenoreceptor!!!  

High doses is tranquilizer/sedative. Lower doses anti-HTN

Adverse Effects = increased depression and lower seizure threshold; exacerbation of Parkinsons


Bc lipid soluble, NOT safe for pregnancy bc crosses Placenta  


What are the central A2 agonists and how do they work?

Clonidne and Methyl-Dopa act on brainstem nuclei to decrease the sympathetic activity coming out 


Baroreceptors remain intact! therefore no postural hypotension! 

Clonidine acts on Locus Ceruleus of Pons to inhibit spontaneous firing 


What are other uses for Clonidine?

opiate withdrawal, Anesthetic adjunct, Stimulates GH release


Analogue (Bromolidine) used in the eye to lower IOP


How is Methyl-Dopa used? 

Ingest and needs to be converted to Methyl-NE in the brain to act as a false neurotransmitter and block sympathetic outflow. Taken up and stored and released like neurotransmiter 


FIRST LINE Anti-Hypertensive in pregnancy! does not reduce maternal CO or flow to placenta 


What are the adverse effects of central A2 agonists?

Drowsiness, Somnolence



Withdrawal and exacerbation of HTN and MI: up-regulation of sympathetic outflow onto system that up-regulated receptors in response to decreased input leads to greatly raised BP and can lead to ischemia  (do NOT stop suddenly taking, need to wean off) 


What is Moxonidine and how does it work? 

[not used in US] 

Acts on Imidazoline receptors in Lateral Retiucate Nucleus and stimualtes A2 causing reduced BP without the adverse effects of withdrawal or dry mouth 


What is Met-tyrosine and how is it used?

Competitive inhibitor of tyrosine Hydorxylase and stops NE synthesis at the rate limiting step! 


Used for management of Catecholamine secreting tumors


What are the 2 main classes of calcium channel blockers? What drugs are in these classes?

Dihydropiridines (DHPs) = Nefidipine or Amlodipine -"ipines" 


Non-DHPS = Verapamil and Diltiazem 


What are the targets of the Calcium Channel Blockers?

Target the pore-forming A1 sub-units of the L-type Calcium channels 1.2 and 1.3

1.2 in Cardiac cells, SM, and neurons

1.3 in SA node, cochlear hair cells, neurons 


How do the CCB act on vascular SM?

RELAX vascular SM


Nifedipine > Verapamil > Diltiazem 


Describe the binding affiniy for the non-DHP CCB 

"Frequency Dependent" 

Bind better at Cardiac cells! 

Cardiac cells are phasic and so intermittently switching between C and O conformation. Non-DHP bind more effectively to O so increased O when higher rate and can bind more frequently 


Describe the binding affinity for the DHP CCB

"Voltage Dependent"

Bind more to vascular SM

Vascular SM in tonic depolarization so alternating between O and I conformations, DPH bind more tightly to I (inactivated) form and so tends to be in more tonically depolarized cells in SM. 



Which CCB classes act more as cardiodepressors and which more as vasodilators?

Cardiodepression seen more in Non-DHP bc "Frequency Dependent"


Vasodilation seen more in DHP bc "Voltage Dependent" 


What are the adverse effects of DHP CCBs? 

Hypotension, Flushing Headache

Reflex Sympathetic Activation! acts to increase CO in response and therefore increase O2 demand on heart which could be bad in cardiac ischemia - therefore combined with Beta-blocker to reduce angina that would result from ischemic effects. 


Swollen Ankles - changes capillary dynamic  


What are the adverse effects of Non-DHP CCBs?

LV Dysfunction, AV block


DO NOT give in combination with Beta-blockers bc will severely cardiodepress the heart 

(unlike DHP CCB which give with Beta-Blockers to prevent Reflex Sympathetic activation) 

Verapamil causes constipation 


How are the CCB metabolized?

In liver by Cyp450 Cyp3a4!!!


Drug interactions with Statins, Erythromycin, antifungals, Protease inhibitors, grapefuit juice to all increase CCB levels bc comepetetive substrates for Cyp3a4


Interactions can reslut in severe Hypotension or Bradycardia 


What is Amlodipine?

Long acting Calcium channel blocker - DPH used in primary HTN


used for AA and elderly 

Long half life and protects against Sympathetic reflex!!! better than short-acting 


What drugs Prolong QT?

Some Risky Meds Can PRlong QT

Some Risky Meds Can Prolong QT

Protease Inhibitors (-navir)
Quinidine (Class 1a…Also Class 3)