Adrenergic Receptor Antagonists

Front 1

Pheochromocytomas tx

Back 1

-nonselective antagonism of a-receptors

-these tumors of the adrenal medulla cause excessive secretion of EPI and NE

Front 2

What are alpha-1 selective antagonists primarily used for?

Back 2

-primary hypertension
-benign prostatic hyperplasia

Front 3

Some common clinical applications of beta antagonists include?

Back 3

-hypertension
-ischemic heart disease
-arrhythmias
-endocrinologic disorders
-neurologic disorders

Front 4

"EPI reversal"

Back 4

-when you give an a-antagonist such as phentolamine in the presence of EPI --> lowering of BP not inc as is normally seen b/c a1 vasoconstriction is blocked and B2 vasodil in sk m is unopposed--> fall in periph R and BP

Front 5

alpha-antagonists on the heart causes 2 responses

Back 5

1. reflex response to the a-antagonist induced drop in BP causing an inc symp outflow and tachycardia via B1s
2. The presynaptic a2s on adrenergic nerve terminals normally decrease NE release but instead --> inc NE--> + chrono and inotropic

Front 6

Blockade of a1 receptors on veins can result in?

Back 6

Orthostatic Hypotension*

also miosis, nasal stuffiness, and incontinence

Front 7

Alpha antagonists selectivity:

a1>>>>a2

Back 7

1. Tamsulosin
2. Prazosin
3. Terazosin
4. Doxazosin

Front 8

Alpha antagonists selectivity:

a1>a2

Back 8

Phenoxybenzamine

Front 9

Alpha antagonists selectivity:

a1=a2

Back 9

Phentolamine

Front 10

Alpha antagonists selectivity:

a2>>a1

Back 10

1. Rauwolscine
2. Yohimbine
3. Tolazoline

Front 11

Phentolamine

Back 11

-potent reversible, compet and non selective a-antag (short duration of act)
-primary given in mgment of hypertensive crisis (esp due to excessive catechoamine release associated w/ surgery for phaeochromocytoma)

Front 12

Net results of administration of Phentolamine, other actions, and AEs

Back 12

-result: vasodil, inc CO, and HR
*little BP effect on pts w/ essential hypertension
-also inhib serotonin receptors and act muscarinic & histamine receps
-Severe tachy, arrhythmias, myocardial ischemia, headaches

Front 13

Phenoxybenzamine

Back 13

-irreversible, slight a1>a2 antagonist
-can inhib NE reuptake, hist, ACh, & serotonin receptors
-dec supine and erect BP--> oral (48hr) b/c a-recep must be replaced
-can cause reflex tachy which is inc due to presynap a2 blockade

Front 14

Therapeutic uses and AEs of Penoxybenzamine

Back 14

-prim used in tx of hyperT due to pheochromocytoma
-management of sx like sweating and hyperT and preop use for removal of pheochromocytoma
-Postural hypoT, tachy, nasal stuffiness, sex dysfxn, fatigue, n

Front 15

Prazoline
Doxazolin
Terazosin

overview and half life of each

Back 15

-3, 9-12, 22 respectively
-highly selective antagonist of a1
-produces periph dilation of arterioles and veins and dec periph R usually w/out reflex tachycardia
-dec stand/supine BP w/ greater effect on diastolic

Front 16

Therapeutic uses of Prazosin

Back 16

-mngment of mild/mod hyperT in Raynaud's syndomre
-relieve sx of urinary obstruction in BPH (esp pts w/ comorbid hyperT)
-reduces pre/afterload-->improve of CO in pts w/ HF
-postural hypoT, dizzines, sleepy, headache, lack of E, nausea

Front 17

Tamsulosin

Back 17

-a1 select antag but struct diff from prazosin (9-15 hrs, metab in liver)
-a1A and a1D --> higher potency for inhib prostate SM contract and less pot at vasc SM
-preferred if BPH pt has experienced postural hypoT but in pts w/ comorb hyperT, use prazosin

Front 18

Yohimbine

Back 18

alkaloid derived from bark of tree
-a2 selective--> no clinical use although inhib of presynap a2 can be theoretically useful in tx of autonomic insufficiency
-antidiuretic effect and produces inc HR, BP, anxiety, agitation
-help in male sex performance?

Front 19

Selectivity of beta adrenergic receptor antagonists:

B1 = B2 >/= a1 > a2

Back 19

Labetalol
Carvedilol

Front 20

Selectivity of beta adrenergic receptor antagonists:

B1 >>> B2

Back 20

-Metoprolol
-Acebutolol
-Alprenolol
-Atenolol
-Betaxol
-Celiprolol
-Esmolol

Front 21

Selectivity of beta adrenergic receptor antagonists:

B1 = B2

Back 21

Propranolol
Carteolol
Penbutolol
Pindolol
Timolol

Front 22

Selectivity of beta adrenergic receptor antagonists:

B2>>>B1

Back 22

Butoxamine

Front 23

Overview of Beta Antagonists

Back 23

-competitive antagonists @ B-receps
-prototype is non-select propranolol
-B1 are called cardioselective
-never completely selective--> inc [drug], selectivity diminishes
-clinically for tx of hyperT, angina, arrhyths, MI, glaucoma, migraines

Front 24

How can B antagonists be partial agonists?

Back 24

-can inhibit activity of B receptors in presence of high [catecholamine] but moderately activate the receptors in the absense of endogenous agonists
-*Intrinsic sympathetic activity (ISA)

Front 25

Why is the partial agonist aspect of B-antagonists clinically relevant?

Back 25

-by preventing bradycardia or negative inotropy for a pt at rest and during times of inc symp activation blocking undesirable increases in cardiac load

Front 26

Short term administration of B-blocker like propranolol

Back 26

-dec CO due to a reduced contractility and rate--> transient reduction in BP--> activating baroreceptor reflex--> inc symp outflow--> periph R will in due to blockade of B2s-->inc influence of a1s on vasc R--> inc arterial P-->decrease in diastolic P

Front 27

Chronic use of B-blockers

Back 27

-TPR returns to initial values or is decreased in the presence of hyperT
-mechanism unknown, but delayed fall in periph R and persistent reduction of CO accounts for much of the antihyperT act of drugs

Front 28

What do B-blockers do to kidney?

Back 28

-reduce release of renin which may contribute to their antihyperT actions

Front 29

How do B-blockers affect cardiac rhythm and automaticity?

Back 29

-reduce sinus rate, dec spontaneous rate of depo of ectopic pacemakers, slow conduction in atria and AV node, and inc the functional refractory period of AV

Front 30

How are B-blockers actions on rhythmicity of the the heart clinically advantageous?

Back 30

-tx of supraventricular and ventricular arrhythmias

Front 31

B-blockers and tx of acute MI

Back 31

-decreased mortality of 25%
-mechanism not clear but may be bc of decreased O2 demand of heart redistribution of myocardial blood flow and antiarrhythmic actions

Front 32

Why are B-blockers useful in the tx of angina?

Back 32

-bc they can improve the relationship btwn cardiac O2 supply and demand
-they reduce cardiac work

Front 33

Beta-Blockers and the respiratory system

Back 33

-non-selective agents block B2 in bronchial SM, can lead to life threatening bronchoconstriction in pts w/ asthma or COPD
-B1 select at [high] maybe problems
-mixed like celiprolol (B1 antagonist /B2 agonist) hold some promise

Front 34

B-blockers and metabolic effects

Back 34

-non-selective inhibit symp NS stim inhibiting glycogenolysis and gluconeogenesis
-caution in pts w/ insulin dep diabetes
-B1 preferable, but all B-blockers mask tachycardia associated w/ hypoglycemia, warning in diabetics

Front 35

Chronic use of B-blockers and cholesterol concentrations

Back 35

-increase in [VLDL] and decrease in [HDL] both are undesirable in CVD
-LDL levesl usually dont change but a decline in the HDL/LDL ratio increases the risk of CAD
-use agents that are partial agonists

Front 36

B-blockers effects on the eye

Back 36

-reduce IOP especially in glaucoma
-decrease in production of aq humor
-combo of a muscarinic agonist pilocarpine and timolol is used
-B-blockers may block some Na+ channels

Front 37

B-blockers and hyperthyroidism

Back 37

-can control the excessive catecholamine action which causes supraventricular tachycardia which can precipitate heart failure

Front 38

B-blockers and migraines

Back 38

-reduce the frequency and intensity of migraine headaches
*do not prevent or stop a migraine when it has already started
-reduce performance anxiety