Calcium Channel Blockers, Beta Blockers, Alpha Blockers

β blockers indications

Hypertension

Arrhythmias

Heart failure

Migraine prophylaxis

Anxiety

β blockers oppose the function of the ______ _____ _____

Sympathetic nervous system

β blockers act as antagonists of the ____ ___ ___ response

Fight-or-flight

The impact of β-adrenergic signaling is _______ _________

Context dependent

Action potentials start in the ________ cells of the heart

Pacemaker

An influx of ______ into the cell causes an increase in ______ ______

Cations; membrane potential

High membrane potential eventually surpasses the ______ ____, generating an ______ ______

Threshold potential; electrical impulse

Electrical impulses are shared to non-pacemaker cells via ___ ______

Gap junctions

β-adrenergic receptors are found on ______ and ___ _____ cells

Pacemaker; non-pacemaker

β-adrenergic receptors are activated by _______ and/or ___________

Epinephrine; norepinephrine

_-_____ bind to the β receptor, swapping out GDP for ____ to become activated

G-proteins; GTP

Activated G proteins activate ______ ______

Adenylyl cyclase

Adenylyl cyclase will convert ATP to _____

cAMP

cAMP will activate ______ _____ __

Protein kinase A (PKA)

Activated PKA phosphorylates _-___ _____ _____

L-type calcium channels

L-type calcium channels increase the amount of calcium inside the cell, increasing ______ _____ in pacemaker cells or _______ in non-pacemaker cells

Conduction velocity; contractility

β-blockers MOA

Inhibit the activation of β-receptors

Inhibiting β-receptors decreases ______ and ______

Conductance; contractility

Non-selective (1st generation) β1-2 blocker drugs

Timolol

Propanolol

Sotalol

Selective (2nd generation) β1 blocker drugs

Atenolol

Esmolol

Metoprolol

Acebutolol

Bisoprolol

Non-selective (3rd generation) β1-2 & a1 blocker drugs

Carvedilol

Labetalol

α-blockers indications

Hypertension

Urinary retention

Benign prostatic hyperplasia

Kidney stones

Pheochromacytoma

α-blockers oppose the function of the ________ ______ ______

Sympathetic nervous system

α-blockers act as antagonists of the _____ __ _____ response

Fight or flight

α1-receptors are found near exclusively in _______ _______ _____ _____ ____

Peripheral vascular smooth muscle cells

α1-receptors are ________

Excitatory

α2-receptors are found in the _______ ______ _____

Central nervous system

α2-receptors provide _______ feedback, ________ the release of epinephrine/norepinephrine

Negative; decreasing

α2-receptors are ________

Inhibitory

Calcium moves across smooth muscle cell membranes through _-___ ______ ______

L-type calcium channels

Calcium activates ________

Calmodulin

Calmodulin activates ____ ______

CAM kinase

CAM kinase phosphorylates _____

MLCK

MLCK phosphorylates _____ _____, which induces ______ of smooth muscle cells

Myosin heads; contraction

_______/________ bind to α-receptors

Epinephrine; norepinephrine

The binding of epinephrine/norepinephrine causes a __________ ______ in the receptors, allowing for docking of a _______ G-protein

Conformational change; stimulatory

G-protein exchanges ___ for ___ to become activated

GDP; GTP

Activated G-protein activates ________ __

Phospholipase C (PLC)

PLC cleaves membrane bound ___ into ___ and ___

PIP2; DAG; IP3

DAG activates ______ ____ _

Protein kinase C (PKC)

PKC enhances ______ ____ phosphorylation and smooth muscle cell ________

Myosin head; contraction

IP3 binds to its receptor, causing the release of _____ into the cytosol and enhancing _________

Calcium; contraction

α-blocker MOA

Inhibit activation of α-receptors

Inhibiting the activation of α-receptors decreases ________ of ______ _____ cells

Contractility; smooth muscle

Selective α1 receptor blocker drugs

Terazosin

Prazosin

Tamsulosin

Doxazosin

Nonselective α1-2 receptor blocker drugs

Phenoxybenzamine

Phentolamine

Which nonselective α1-2 receptor blocker is an allosteric modulator?

Phenoxybenzamine

Which nonselective α1-2 receptor blocker acts at the active site?

Phentolamine

ACE and ATII are critical in the maintenance of _____ _______

Blood pressure

ACE and ATII typically work when the body is experiencing ___________

Hypotension

ACE is produced most prominently by the _________ cells in the _____

Endothelial; lungs

ATII is an incredibly potent __________

Vasoconstrictor

Decreased blood pressure is sensed by the ___________ cells of the ______

Juxtaglomerular; kidney

When low blood pressure is sensed by juxtaglomerular cells, they release ______

Renin

The liver constantly produces ___________

Angiotensinogen

Renin cleaves an amino acid from _________ to produce __________ _

Angiotensinogen; angiotensin I

ATI moves through the circulatory system until it encounters ____ and is enzymatically converted to __ __

ACE; ATII

3 sites where ATII acts

Vascular smooth muscle

Posterior pituitary

Zona glomerulosa

In the vascular smooth muscle, ATII causes _______, leading to _____ blood pressure

Constriction; increased

In the posterior pituitary, ATII causes release of ____-_____ _____, which acts on the kidney to increase ______ _______

Anti-diuretic hormone (ADH); water reabsorption

In the zona glomerulosa, ATII causes release of ______ which increases ______ and therefore _____ ______

Aldosterone; sodium; water reabsorption

Increased water reabsorption leads to increased _____ ______, which causes an increase in blood pressure

Blood volume

ACE inhibitors MOA

Prevent the conversion of ATI to ATII

No conversion of ATI to ATII leads to decreased ______, water reabsorption, and ________, which all lead to decreased BP

Sodium; vasodilation

ATII receptor blockers (ARBs) MOA

Inhibit binding of ATII to ATII receptor

ACE inhibitors drugs

Benzapril

Captopril

Enalapril

Lisinopril

ARB drugs

Candesartan

Losartan

Valsartan