Ca Channel Antagonists HTN Flashcards
Ca is key is what processes?
Contractility of skeletal, cardiac and SM
Release of neurotransmitters from vesicles by exocytosis
In resting conditions intracellular calcium is? Extracellular?
Low
High
These calcium levels are achieved by?
Active efflux pumps
Active reuptake of calcium into sarcoplasmic reticulum
Voltage-gated Ca channels
Open in response to depolarization of cell membrane
Three types of Voltage-gated Ca channels
L type T type (transient, tiny) N type (neuronal)
L type
Long lasting large channels
Cardiac, SM, SA and AV nodal cells
-Located on the plasma membrane
Agonists-mediated Ca release
results from activation of IP3 by an agonist to release intracellular Ca from storage sites (SR)
Receptor-operated Ca channels
Receptor forms a channel and the channel opens when the receptor is occupied by a ligand
- NMDA receptor
What initiates a contraction?
Entry of calcium into the smooth muscle cell or myocardial cells
So calcium enters the SM cell, now what?
Ca complexes with calmodulin to activate MLCK
MLCK phosphorylates myosin causing an interaction between myosin and actin
Myosin and actin are?
The main cells involved in contraction of a cell
What is different between cardiac and SM cells?
SA and AV do not contract, they generate impulses that spread throughout the heart
Calcium helps generate the impulses
Calcium Channel Blockers Dihydropyridines
- End in dipine
Calcium Channel Blockers Non- Dihydropyridines
Diltiazem
Verapamil
CCB MOA
Inhibit L type calcium channels leading to decreased peripheral resistance and reduced BP
Resting State
Closed by ready to open
Waiting for potential change in the membrane
Open State
Open channel and calcium is entering the cell
Inactivated (Closed) state
Closed and not ready to open
Even if there is a change in potential, the channel will not open
Channel is trying to recover
Dihydropyridines MOA
Prefer the closed channel – they bind and stabilize it so the recovery process takes much longer
Where are the most closed channels?
Vasculature- Arterial muscle cells
Non-dihydropyridines MOA
Prefer the open channels – bind and force them to close with a slow recovery period
Where are the most open channels?
Myocardium
Work mainly on SA and AV
CCB Cardiovascular effect
Inhibit L type channels and reduce contraction of SM cells → vasodilation , contraction of cardiac myocites (inotropic effect), and pacemaker rate in SA and conduction velocity in AV node (chronotropic effect)
What exactly occurs in the vasodilatory effect?
Decrease peripheral resistance and vascular resistance
Increased blood flow
Non-dihydropyridine decrease?
Vessel tone
Heart rate
AV conduction
Non-dihydropyridine increase?
Blood flow
Peripheral vasodilation
Dihydropyridine decrease?
Vessel tone
Dihydropyridine increase?
Blood flow
Peripheral vasodilation
Heart rate
heart contractility
CCB uses?
HTN
Angina pectoris
Superventricular arrhthmia
Migraine
Verapamil and Diltiazem Adverse Effects
Major: Cardiodepression
Mod: HYPOtension, AV node blockade, peripheral edema, liver enzyme elevation
Minor: headaches, facial flushing dizziness, constipation
DHP Amlodipine Adverse Effects
Edema, dizziness, flushing, gingivial hyperplasia, CV, CNS, GI
CYP3A4 inhibitors: HYPOtension, kidney failure
- Long term = increased risk of breast cancer
Alpha 1 Adrenergic Receptor Blocker
End in -zosin
Doxazosin (Cardura)
Terazosin (Hytrin)
Prazosin (Minipress)
Alpha 1 Adrenergic Receptor Blocker MOA
Blocks in arteries and veins
Probable blockage of adrenoreceptors
Alpha 1 Adrenergic Receptor Blocker Effects
Decreased peripheral resistance
Decrease cardiac preload (venous return)
Supress sympathetic outflow in CNS
Decrease LDL, TG and increased HDL
Alpha 1 Adrenergic Receptor Blocker Adverse Effects
First dose effect – postural/orthostatic HYPOtension
Define First dose effect – postural/orthostatic HYPOtension
When you change positions, you experience a drop in BP which makes you feel dizzy, unconscious, and not get enough blood to the brain so you might faint
How does the body prevent all the blood going to your legs when you stand up?
Vasoconstriction
Central Alpha 2 Adrenergic Receptors Agonists
Clinidine (Catapres)
Guanfacine (Tenex)
Guanebenz (Wytensin)
Methyldopa (Aldomet)
Central Alpha 2 Adrenergic Receptors Agonists MOA
Activation of central alpha2 receptors (CV control centers) –> suppression of sympathetic outflow from the brain
Possible stimulation of presynaptic alpha 2 receptors and decrease NE release
Clonidine/Guanfacine Caution
50% excreted unchange in the urine so watch in renal insuf.
Clonidine Effects
Decrease BP
Decrease HR
Decrease intraocular pressure
Clonidine Adverse Effects
Sedation and dry mounth
Sexual dysfunction (hyperprolactinemia)
Bradycardia
Withdrawal rxns
Methyldopa
PRO-DRUG
Delayed peak effects for 6-8 hours –> duration = 24 hours
Methyldopa adverse effects
Sedation and dry mounth Sexual dysfunction (hyperprolactinemia) Bradycardia Withdrawal rxns Hepatoxicity Hemolytic anemia
Methyldopa is beneficial in?
Pre-eclampsia
Reserpine Sympatholytic Drug
Interferes with function of SNS
Normally there is recycling of NE and Epi
VMAT2 picks up NE/Epi and takes it back to be reused
Reserpine BLOCKS VMAT2 via irreversible binding
Reserpine Adverse Effects
Increase sodium and water retention
Sedation and inability to concentrate
Depression and suicidal thoughts (depletion of Epi)
Reserpine Effects
Lowers BP via cardiac output and peripheral resistance
Direct vasodilator
Hydralazine (Apresoline)
Minoxidil (Loniten)
Hydralazine Effects
Decrease in peripheral resistance
Minimal effect on veins (no postural hypotension)
Hydralazine Adverse Effects
Drug-induced lupus syndrome
Increased sodium and water rentention
Headache, HYPOtension, tachycardia, angina pectoris
Hydralazine Caution
Aggravation of myocardial ischemia –> steals blood from dying regions
Minoxidil MOA
PRO-DRUG
Activates ATP dependent potassium channels in SM and causes an efflux of K from cells leading to relaxation of the SM
Minoxidil Effects
Dilation of arterioles and decreased peripheral resistance
Minoxidil Adverse Effects
Increased retention of sodium and water
Tachycardia, angina pectoris, myocardial ischemia
Hypertrichosis (stim hair growth)
