L14 Flashcards
What is the sympatholytic drug class?
Inhibits post-gang sympa nerve
Sympa - lytic (cut)
Which sympatholytic drug works be depleteing NE in storage vesicles?
Reserpine = adrenergic neuron blocker/depleter
What are the 2 central A2 agonist drugs?
Methyldopa
Clonidine
= X sympa outflow from CNS
Which drug inhibits NE synthesis to stop sympathetic activity?
Metyrosine
Reserpine mechanism
x VMAT2
Blocks dopamine into the vesicle - no NE synthesis
Is reserpine hydrophilic or phobic?
Philic = lipid soluble
Crosses BBB, placenta
What is the recovery time when you withdraw reserpine?
Slow - weeks
B/c depletion of NE was gradual, the recovery and re-synthesis will be slow
What are drug interactions with reserpine?
X NE releasers
- Duh, nothing there to release
↑sen to pharm NE or norad receptor agonists
- Receptors have been hypersensitized while NE has been low
What is the difference between low and high dose reserpine?
Low = PNS sympatholytic High = CNS action = sedative
What is the clinical use of reserpine?
Anti-HTN
Reserpine adverse effects
Associated with high dose (CNS)
- ↑depression
- ↓ seizure threshold
- Potential CNS depressors (alcohol)
Mechanism of clonidine
Directly acts to increase A2 receptors in brainstem
Mechanism of methyldopa
Methyldopa –> MeDopamine –> MeNE
Conversion @ brainstem where MeNE will work
Net effect of A2
↓sympa outflow to CV
Won’t get the ability to increase HR, CO, contractility etc
Do baroreceptor reflexces change with central A2 agonists?
NO
Use of methyldopa
HTN during preg
Dosing methyldopa
In general need higher doses because competes with other AAs for transport into the brain
Clonidine dosing, excretion & clinical use
Short t1/2 - given long acting formulations Renal excretion NOT for anti-HTN Use - Opiate withdraw - Anesthetic to induce drowsiness - GH release
Central A2 agonist shared adverse SE
Drowsiness
Dry mouth
Withdraw excess sympa outflow
Metyrosine mechanism
Block tyrosine hydroxylase (tyrosine –> DOPA)
Rate lim step
Use metyrosine
CA secreting tumor management
2 types of Ca channel blockers - include specific drugs for each
Dihydropyridines
Non-dihydro
- Verapamil
- Diltiazem
Ca2+ blocker effects
ALL = ARTERIAL vasodilation - ↓afterload
- Includes coronary artery dilation
No changes to Na/H2O
Cardiodepressant = non-dihydros
What tissues do Ca2+ channel blockers work in? What is the specific receptor
Voltage sens L type Ca channel Tissues effects are isotype dependent 1.2 = cardiac, smooth muscle 1.3 = SA node, cochlea Both neuronal
3 non-cardiac uses of CCBs
- Relax uterus pre-term
- Manage vertigo
- Neuroprotective @ CNS to limit stroke damage
Regulate L type Ca channels
- Membrane potential
- Feedback via Ca sensitive K channels to repolarize the membrane and limit Ca entry - Neurohormones
- NE activates B receptors in heart for slow inward Ca current
Where do DHP vs non-DHP bind the receptor to effect action
non-DHP - open, cardiac actions - freq dep
DHP - inactivated, vascular actions - voltage dep
Explain the cardiac effects of non-DHP CCBs - be specific
SA node: ↓HR via ↓automaticity
AV node: ↓conduction velocity
↓muscle contractility
Adverse SE DHPs
Hypotension, flushing, headache
Reflex sympa activation - give long acting forms or w/ BBs
Swollen ankles due to changes in cap perm to H2O
Adverse SE for non-DHPs
LV dysfxn
AV block
This why never use w/ BB - same adverse events
GI constipation
How are CCBs inactivated
P450 enzymes in liver If give with other drugs metabolized this way and overwhelm the enzymes, see ↑↑ plasma CCB levels Symptoms: - DHPs = hypotension - nonDHPs = bradycardia
