Vascular Physiology 4 Flashcards
beta-1 receptor AGONISTS - examples
*epinephrine
*norepinephrine
*isoproterenol
*dopamine
*dobutamine
*phosphodiesterase inhibitors (MOA: inhibition of breakdown of cAMP by blocking phosphodiesterase → cAMP sticks around longer)
-ex: milrinone
beta-1 receptor ANTAGONISTS - examples
beta blockers:
*metoprolol
*carvedilol
beta-1 receptor - functions
*increases heart rate (chronotropy)
*increases contractility (inotropy)
note: there are NO beta-1 receptors in blood vessels
beta-2 receptor - function
vasodilation
beta-2 receptor AGONISTS - examples
*epinephrine
*albuterol
*isoproterenol
beta-2 receptor ANTAGONISTS - examples
beta-blockers:
*carvedilol
*labetalol
*propranolol
beta-blockers - overview & naming conventions
*can help to SLOW DOWN heart rate
*usually end in “-lol”:
-if name starts with A-M, cardioselective for Beta-1
-if name starts with N-Z, non-selective (blocks Beta-1 and 2)
EXCEPTIONS:
*carvedilol and labetalol are non-selective beta-blockers which also block alpha-receptors
*pindolol and acebutolol increase sympathetic activity
alpha-1 receptor - function
vasoconstriction
alpha-1 receptor AGONISTS - examples
*epinephrine
*norepinephrine
*phenylephrine (alpha-1 only)
SELECTIVE alpha-1 receptor ANTAGONISTS - examples
*end in “-zosin”:
-prazosin
-terazosin
-doxazosin
non-selective alpha-blockers
*phentolamine (reversible)
*phenoxybenzamine (irreversible)
alpha-2 receptor AGONISTS - examples
*norepinephrine
*epinephrine
*clonidine
alpha-2 receptor ANTAGONSITS - examples
*yohimbine
*phenoxybenzamine
alpha-2 receptor - functions
*when activated, alpha-2 receptors INHIBIT NEUROTRANSMITTER RELEASE (esp. norepinephrine) from presynaptic neurons
*alpha-2 is a feedback receptor
beta-blockers in RAS pharmacology
*decrease renin release that was due to SNS stimulation (blocks NE)
aliskiren in RAS pharmacology
*direct renin inhibitor
*not used
ACE inhibitors in RAS pharmacology
*end in “-pril (lisinopril, captopril)
INHIBIT angiotensin-converting enzyme (ACE)** → inhibiting production of angiotensin 2 (a vasoconstrictor) → taking away a vasoconstrictor
**INCREASES BRADYKININ (potentiating the effect of a vasodilator)
note - some people develop a cough with ACE inhibitors; some develop angioedema
angiotensin-2 receptor blockers (ARBs) in RAS pharmacology
*end in “sartan” (losartan, etc)
*only block AT1 receptors
effects of BNP (nesiritide) as pharmacology
*renal: get rid of sodium & fluid through urine; inhibits renin release
*adrenal: inhibits aldosterone release
*heart: prevents maladaptive hypertrophy
*blood vessels: relaxes both arterial and venous tone
*DECREASES PRELOAD & AFTERLOAD
sacubitril - MOA
*neprilysn is an enzyme that breaks down BNP and ANP
*sacubitril INHIBITRS NEPRILYSN → BNP and ANP stay around much longer (potentiates the effects of BNP and ANP)
spironolactone (aka eplerenone)
*blocks aldosterone
calcium channel blockers - MOA
*prevent influx of calcium into vascular smooth muscle → less calcium available to facilitate actin-myosin crosslinks → PREVENTS VASOCONSTRICTION
minodoxidil - MOA
*direct arteriolar vasodilator; decreases AFTERLOAD
*opens potassium channels → potassium leaves the cell → hyperpolarization of cell → more DIFFICULT TO OPEN VOLTAGE-GATED CALCIUM CHANNEL → PREVENTS VASOCONSTRICTION
dihydropyridine calcium channel blockers (CCBs)
*end in “-dipine”
*VASODILATE by blocking calcium channels in VASCULAR SMOOTH MUSCLE
*examples: felodipine, amlodipine
DIhydropyridines cause DILATION
non-dihydropyridine calcium channel blockers (CCBs)
*block calcium channels in HEART & BLOOD VESSELS (and everywhere else)
*result in decreased HR and decreased contractility
*great at slowing heart rate, but may decrease calcium influx → decrease inotropy
*examples: verapamil, diltiazem
nitroprusside MOA
*nitroprusside is a powerful arterial & venous DILATOR
*decreases afterload and preload
*SPONTANEOUSLY DEGRADE to give off NITRIC OXIDE → increased cGMP → relaxation
*also gives off CYANIDE, which goes to liver and gets converted to thiocyanate, which is secreted in the urine
nitroglycerine MOA
*nitroglycerin, isosorbide dinitrate, and isosorbide mononitrate are powerful VENOUS DILATORS with some arterial dilation at higher doses
*dilate VEINS > arteries, decreasing PRELOAD
*requires enzymatic conversion with ALDEHYDE DEHYDROGENASE → nitric oxide → increased cGMP → relaxation
nitrates & sildenafil - drug interaction
nitrates & sildenafil do NOT mix:
*nitroglycerin increases cGMP
*sildenafil blocks phosphodiesterase (cGMP is normally broken down by phosphodiesterase)
*giving nitroglycerin to someone who has taken sildenafil in the past 1-2 days → increased cGMP with inability to break it down → may lead to life threatening HYPOTENSION/very low vascular tone
vasodilator drugs - overview
*venodilators: nitrates (nitroglycerine, isosorbites) [decrease PRELOAD]
*mixed vasodilators: nitroprusside, ACE inhibitors/ARBs, alpha-receptor blockers, alpha-2 agonist, sacubitril, nesiritide
*arterial dilators: hydralazine, minoxidil, calcium channel blockers [decrease AFTERLOAD]
atropine & effects on acetylcholine
*acetylcholine normally results in endothelium-mediated vasodilation
*atropine BLOCKS acetylcholine → VASOCONSTRICTION
dopamine - overview
*low levels of dopamine circulate in the bloodstream
*dopamine itself is a precursor for norepinephrine & epinephrine
*there are several different dopamine receptors
low-dose dopamine - pharmacology
*at low doses, dopamine activates D-receptors:
-at D1 in renal arteries → renal artery dilation (may help eliminate extra fluids)
-D receptors in the heart → increased contractility & elevated heart rate
high-dose dopamine - pharmacology
*at higher doses, dopamine becomes converted to norepinephrine & epinephrine (might as well just give them NE)
methyldopa
*safest medication to lower blood pressure during pregnancy
*acts in 2 ways:
1) inhibits DOPA decarboxylase → prevents synthesis of dopamine, NE, and epi
2) gets converted to alpha-methyl-norepinephrine → activates alpha-2 receptor → prevents NE release
fenoldopam - MOA
*D1 receptor agonist
*dilates systemic vessels, including renal → decreases systemic vascular resistance (SVR)
*helps to diurese (eliminate) excess fluid
“pressors” to increase blood pressure
*pressors cause vasoconstriction → increase blood pressure
*examples:
-epinephrine
-norepinephrine
-dopamine
-phenylephrine
-vasopressin
epinephrine vs. norepinephrine
*epi: beta1 & beta 2 > alpha1 (boards love you to know that epi binds to beta2)
*NE: alpha1 = beta1 (boards love you to know that NE binds to alpha 2)
dose-related effects of epinephrine
*low doses: mostly beta-2 activation (vasodilation)
*at increasing doses, starts activating alpha-1 → vasoconstriction at higher doses
dose-related effects of norepinephrine
*NE initially binds to alpha-2 → decreased endogenous NE and epi → decreased HR
*after time, NE starts activating alpha-2
*NE causes increased SYSTOLIC & DIASTOLIC BP
antagonists & multi-receptor pressors
*when many different receptors are available, the pressors bind to the ones available based on their affinity for it
*when an ANTAGONIST (ex. beta blocker, alpha blocker) blocks certain receptors, it forces the pressors to bind to the ones that are available:
-when a BETA-BLOCKER is given, all the available epi/NE bind to alpha-1 receptors → vasoconstriction & increased BP
-when an ALPHA-BLOCKER is given, all the available epi/NE bind to beta receptors → decreased BP
beta-blockers in pheochromocytoma
*when giving a beta-blocker to someone with an epinephrine-secreting tumor (pheochromocytoma) → excess epi/NE activate alpha-1 → unopposed alpha vasoconstriction → severe hypertension
alpha-blockers in pheochromocytoma
*when giving an alpha-blocker to someone with an epinephrine-secreting tumor (pheochromocytoma) → excess epi/NE activate beta-2 → DECREASED BP, EVEN LOWER THAN WHAT IT WOULD NORMALLY BE
pheochromocytoma & pressors - treatment strategy
1) give phenoxybenzamine FIRST to block alpha-receptors (irreversibly)
2) next, give non-selective beta blockers right before surgery
*these measures prevent hypertensive crisis during the operation from epinephrine release when the surgeon has to touch the tumor
antagonists vs. agonists: acetylcholine receptor
*agonist: acetylcholine (→ vasodilation)
*antagonist: atropine (→ vasoconstriction)
antagonists vs. agonists: alpha 1 receptor
*agonists: phenylephrine, epi, NE (→ vasoconstriction)
*antagonists: phentolamine, phenoxybenzamine, “-azosins” (→ vasodilation)
antagonists vs. agonists: beta-2 receptor
*agonists: epi, isoproterenol (→ vasodilation)
*antagonists: carvedilol, labetalol, propranolol (→ vasoconstriction)
antagonists vs. agonists: calcium channels
*agonist: calcium (→ vasoconstriction)
*antagonists: amlodipine, felodipine, diltiazem, verapamil (→ vasodilation)
antagonists vs. agonists: angiotensin-2 receptor
*agonist: angiotensin-2 (→ vasoconstriction)
*antagonist: angiotensin-2 receptor blockers (ARBs) [end in “-sartan”] (→ vasodilation)
ADEs of sudden discontinuation of clonidine
think excessive sympathetic stimulation:
*rebound hypertension
*diaphoresis
*palpitations
*anxiety
ADEs of digoxin
*yellowish vision
*AV block
*increased potassium
ADEs of ACE inhibitors
*cough
*angioedema
*increased potassium (because they limit the ability of the kidney to get rid of K)
ADEs of ARBs
*increased potassium (because they limit the ability of the kidney to get rid of K)
ADEs of sacubitril
*angioedema
ADEs of alpha-1 antagonists
*postural hypotension
ADEs of beta-blockers
*fatigue (b/c they prevent the conversion of thyroid hormone)
vasodilators & reflexive tachycardia
*when we give a medication (vasodilator) which drops our systemic vascular resistance (SVR), then our body responds by increasing cardiac output via INCREASED HEART RATE (tachycardia)
