Cardiovascular agents II Flashcards
Central nervous system neurotransmitters include
epinephrine, norepinephrine, dopamine, serotonin, GABA, acetylcholine
Naturally occurring neurotransmitters are known as
endogenous
Natural catecholamines include
epinephrine, norepinephrine, & dopamine
Synthetic catecholamines include
isoproterenol & dobutamine
Potency for alpha adrenergic agonists
norepinephrine>epinephrine>isoproterenol
Potency for beta adrenergic agonists
Isoproterenol> epi> norepi
Alpha 1 receptors are found in
Postsynaptic- vasculature, heart, glands, and guts
Alpha 1 agonist cause
vasoconstriction and relaxation of the GI tract
Alpha 2 receptors (presynaptic) are found in
presynaptic- peripheral vascular smooth muscle, coronaries, & the brain
Activation of presynaptic alpha 2 receptors causes
inhibition of norepi release and inhibition of sympathetic outflow leading to decreased BP, HR, and inhibition of CNS activity
Alpha 2 receptors (postsynaptic) are found in
coronaries & CNS
Activation of postsynaptic alpha 2 receptors cause
constriction, sedation, and analgesia
The sedation caused by dexemetedomidine is called
a negative feedback loop
Beta 1 receptors are found in
myocardium, SA node, ventricular conduction system, coronaries, & the kidney
The activation of beta 1 receptors causes
increase in inotropy, chronotropy, myocardial conduction velocity, coronary relaxation, and renin release
Beta 2 receptors are found in
vascular, bronchial & uterine smooth muscle; smooth muscle in the skin, myocardium, coronaries, kidneys, & GI tract
Activation of beta 2 receptors causes
vasodilation, bronchodilation, uterine relaxation, gluconeogenesis, insulin release, & potassium uptake by the cells
Direct vs. indirect acting synthetic catecholamines
direct- act directly at the receptor site
indirect- cause change in NT release or reuptake
Indirect acting synthetic catecholamines can cause
depletion of catecholamine stores & tachyphylaxis
Ephedrine acts as a
direct and indirect catecholamine
Phenylephrine is a
pure alpha agonist--> vasoconstriction duration of action: 5-20 minutes can cause reflex bradycardia bolus dose 50-100 mcg infusion: 20-100 mcg
In a patient with a HR of 52 & BP of 70 what medication would you give?
ephedrine because it has room to increase the HR & blood pressure
B1 antagonists and calcium channel blockers work on
heart rate & contractility
Drugs that act on venous tone include
alpha 1 antagonists, ACEI, ARBs, and nitroprusside
Drugs that work on Na/H20 retention include
diuretics, ACEI, ARBs
Drugs that act via direct innervation in the peripheral vascular system include
alpha 1 antagonists & alpha 2 agonists
Drugs that act as circulating regulators of SVR include
alpha 1 antagonists, alpha 2 agonists, ACEI, & ARBS
Drugs that acta as local regulators of SVR include
endothelin antagonist, nitroprusside, ACEI, and ARBs
Alpha 2 agonists are used for
sedation and analgesia
The best way to improve oxygenation through bronchodilation is by
giving more gas
can also give beta 2 agonists
Adrenergic receptors are
all alpha & beta receptors are GPCR receptors
increase in CAMP causes a response
Alpha 1 agonists acts on the
Vascular smooth muscle (blood vessels, sphincters & bronchi)–> contraction
Iris (radial muscle)–> contraction (dilates pupils)
Pilomotor smooth muscle–> erects hair
Prostate & uterus–> contraction
Heart–> increases force of contraction (B1 is more important though)
Alpha 2 agonists act on
platelets–> aggregation
VSMC–> contraction (post-synaptic) OR dilation (presynaptic, CNS)
GI tract–> relaxation (presynaptic)
CNS–> sedation & analgesia via decreased SNS outflow from brain stem
adrenergic & cholinergic nerve terminals (presynaptic)–> inhibits transmitter release (decreased BP & HR)
Dopaminergic 1 agonists act on
smooth muscle–> post synaptic location; dilates renal, mesenteric, coronary, & cerebral blood vessels
Dopaminergic 2 agonists act on
nerve endings–> pre-synaptic- modulates transmitter release; N/V
Beta 1 agonists act on
heart–> increase force & rate of contraction, chronotropy, & inotropy
kidneys–> stimulation of renin release
Beta 3 agonists act on
fat cells–> activates lipolysis; thermogenesis
Beta 2 agonists act on
Respiratory, uterine, vascular, GI, GU (visceral smooth muscle)–> promotes smooth muscle relaxation
mast cells–> decreased histamine release
skeletal muscle–> potassium uptake, dilation of vascular beds, tremor, increase speed of contraction
liver–> glycogenolysis
pancreas–> increased insulin secretion
adrenergic nerve terminals–> increased release of NE
Alpha 2 agonists are considered to be
inhibitory
cause decreased CAMP and decreased norepinephrine release
Alpha 1 agonists are considered to be
excitatory
cause increased Ca2+ –> calmodulin activation–> smooth muscle contraction
Major function of alpha 1 receptors includes
contraction of smooth muscle and sphincters
Major function of alpha 2 receptors inludes
decreased transmitter release at nerve endings
Major function of beta 1 receptors includes
increased heart rate & force on cardiac muscle & increased renin secretion of kidney
Major function of beta 2 receptors includes
relaxed smooth muscle in the bronchi
gluconeogenesis, glycogenolysis of the liver
Major function of beta 3 receptors includes
increased lipolysis of adipose
Major function of dopamine 1 receptors include
relaxation of renal vascular smooth muscles (higher doses activates B1 & alpha 1 receptors)
Classes of drugs to treat hypertension include:
sympathetic nervous system drugs, renin-angiotensin-aldosterone system, and endothelium derived mediator and/or ion channel modulators
Drugs that treat hypertension in the sympathetic nervous system class include
Beta antagonists, alpha 1 antagonists, mixed alpha/beta antagonists, centrally acting alpha 2 agonists
Drugs that treat hypertension in the renin-angiotensin-aldosterone system class include
angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, and diuretics
Drugs that treat hypertension in the endothelium derived mediator and/or ion channel modulators include
direct vasodilators (nitroprusside, hydralazine) calcium channel antagonists potassium channel opener
Goal of high blood pressure treatment is
age 60 or older<150/90 with no diabetes or kidney disease
Age 18-59 year old with no comorbidities and 60 and older with diabetes and/or chronic kidney disease <140/90
First line treatment for high blood pressure is
thiazide diuretic unless there is a “compelling indication”
most patients will require at least 2 medications to reach goal
Medications that treat hypertensive crisis include
nitroprusside, nitroglycerin, labetalol, and fenoldapam
Hypertensive crisis is
diastolic pressure >120 w/ evidence of end organ failure
goal is to decrease DBP 100-105 asap
Medications that treat hypertensive urgency include
clonidine
Hypertensive urgency is considered to be
diastolic pressure >120 without evidence of end organ damage
goal is to decrease DBP to 100-105 within 24 hours
Alpha antagonists work by
binding selectively to alpha receptors and interfere with the ability of catecholamines to cause a response
Competitive alpha antagonists include
phentolamine, prazosin, Yohimibine
Noncompetitive alpha antagonists include
phenoxybenzamine (binds covalently)
Clinical uses of alpha 1 antagonists include
hypertension, BPH, & pheochromocytoma
cause smooth muscle relaxation, decreased PVR, and BP
Mixed alpha and beta antagonists include
labetalol and carvedilol
B1= beta 2>alpha 1> alpha 2
Beta antagonists that have a greater affinity for beta 2 than beta 1 include
butoxamine
Beta antagonists that have equal affinity for beta 1 & beta 2 include
propranolol, nadolol, timolol
Beta antagonists that have higher affinity for beta 1 than beta 2 include
metoprolol, atenolol, and esmolol
Alpha antagonists that have higher affinity for alpha 1 than alpha 2 include
prazosin, terazosin, doxazosin alpha 1»»>alpha 2
phenoxybenzamine alpha 1> alpha 2
Alpha antagonists that have equal affinity for alpha 1 and alpha 2 include
phentolamine
Alpha antagonists that have higher affinity for alpha 2 than alpha 1 include
yohimbine, tolazoline
CV affects of alpha 1 antagonism includes
decreases PVR and lowers BP
postural hypotension due to failure of venous vasoconstriction upon standing
CV affects of alpha 2 antagonism include
increase norepinephrine release from nerve terminals results in tachycardia due to stimulation of beta receptors in the heart
Alpha 2 antagonists effects include
miosis, increased nasal congestion, GU effects- blockade in prostate and bladder cause muscle relaxation and ease micturation