Adrenergic Receptor ANTAGONISTS

Question 1

Alpha Receptor Antagonists

1. Nonselective example?
2. Alpha 1 selective example?

Answer 1

1. phentolamine
2. prazosin

Question 2

Beta Receptor Antagonists

1. Non-selective (first generation) example?
2. Beta 1 selective examples?
3. Non-selective (third generation) example? Why are they used?

Answer 2

1. propranolol
2. esmolol and metoprolol
3. Carvedilol and labetalol (used because they have additional vasodilator activities)

Question 3

IGNORE Alpha adrenergic receptors mediate several functions:

1. Receptor and action on smooth muscle?
2. CNS receptor effect?
3. Presynaptic receptor effect?
4. Vagal effect? Why?
5. Two other basic effects?

Answer 3

1. Alpha 1 (some alpha 2) and contraction of arterial and venous smooth muscle
2. Suppress sympathetic output
3. Inhibit NE and ACh release
4. Increase vagal tone as reflex effect in response to increased BP
5. Facilitate platelet aggregation and regulate glucose/lipid metabolism (Alpha 2)

Question 4

Alpha 1 receptor antagonists:

What does it do to catecholamines normal effect? Effect?

Answer 4

Inhibits catecholamine mediated vasoconstriction in arteries and veins –> reduces peripheral vascular resistance and BP. The decreased BP causes reflex increases in HR, CO, as well as fluid retention.

(inhibits vasoconstriction and increased BP in response to sympathomimetic amines)

Question 5

Alpha 2 antagonists

What is an unwanted effect of alpha 2 antagonists?

Answer 5

Increases sympathetic outflow to the heart and blood vessels resulting in an increase in BP

Question 6

What can alpha receptor antagonists do to the amount of glucose released?

Action on insulin release? Receptor?

Answer 6

Reduce glucose release

Facilitates insulin release; alpha 2

Question 7

Haloalkylamines

1. The drug associated?
2. Affects what receptors? How?
3. Primary results stem from blockade of receptors on ___ ___.

Answer 7

1. Phenoxybenzamine
2. Both alpha 1 and 2; irreversible
3. smooth muscle

Question 8

Phenoxybenzamine

1. Main action?
2. Impair pressor response to catecholamines resulting in?

Answer 8

1. DECREASE TPR, INCREASE CO (reflex), and possible tachycardia (from alpha 2 block)
2. hypotension, hypovolemia, and vasodilation

Question 9

Phenoxybenzamine

Therapeutic uses?

Answer 9

Pheochromocytoma (catecholamine secreting tumor that causes severe hypertension) in preparation to remove it (bc it will release catecholamines during surgery) to control episodes of severe hypertension and injury to the myocardium

Question 10

Phenoxybenzamine

Adverse effects? Why?

Answer 10

Due to low BP –> postural hypotension with reflex tachycardia and other arrhythmias

Due to impaired smooth muscle contraction of the vas deferens/ejaculatory ducts –> inhibition of ejaculation

Question 11

Imidazolines

1. Drug example?
2. Receptor antagonists? Mechanism?
3. CV effects?

Answer 11

1. Phentolamine
2. Both (nonselective); competitive inhibition
3. similar to phenoxybenzamine: Decreases TPR, Increases CO, possible tachycardia

Question 12

Phentolamine

Other than CV effects - what else can this cause?

Answer 12

Block 5HT receptors, release histamine (from mast cells), block K+ channels, stimulate GI smooth muscle, enhance gastric acid secretion (not good)

Question 13

Phentolamine

Therapeutic uses:

1. In regards to pheochromocytoma?
2. In regards to clonidine?
3. In regards to MAOIs?
4. What are 2 additional uses?

Answer 13

1. Decrease excessive hypertension and relieve pseudo-obstruction of the bowel
2. Withdrawl of clonidine results in hypertensive crisis (this decreases hypertension)
3. With tyramine ingestion hypertensive crisis occurs (results in a decrease of hypertension)
4. (a) prevents dermal necrosis after the leakage of an alpha agonist (b) intracavernous injection for ED

Question 14

Phentolamine

Adverse Effects/Contraindications?

Answer 14

1. Hypotension
2. Reflex cardiac stimulation with tachycardia, cardiac arrhythmias, ischemia, and MI
3. GI stimulation resulting in abdominal pain/nausea (caused by increased motility by blocking SNS and increased vagal effects) and exacerbation of peptic ulcer

Question 15

Alpha 1 receptor antagonists? (5)

Answer 15

Prazosin, Terazosin, Doxazosin, Alfuzocin, Tamsulosin

Question 16

Prazosin

1. Receptor antagonist?
2. Pharmacological effects? Potent inhibitor of?
3. Why are these better: what do they not cause?

Answer 16

1. Alpha 1
2. Antihypertensive; cyclic nucleotide PDE (vasodilator)
3. Little postural hypotension, does NOT result in reflex tachycardia, no change in CO

Question 17

Prazosin

Therapeutic effects?

Answer 17

Hypertension, CHF (doesnt prolong life!), BPH and associated lower urinary tract

Question 18

Prazosin

Adverse effects and contraindications?

Answer 18

Primary first dose effect: marked postural hypotension and syncope within 30 to 90 minutes after an initial dose (because its very potent and causes increased vasodilation)

Question 19

Terazosin

1. Potentcy compared to prazosin? Pharmacological effects?
2. Duration of action?
3. Therapeutic uses?
4. Adverse effects and contraindications?

Answer 19

1. Less potent; antihypertensive with no tachycardia or increase in CO, still a PDE inhibitor
2. 18 hours
3. Hypertension, better than prazosin for BPH (induces apoptosis in prostatic smooth muscle cells)
4. Primary first dose effect: marked postural hypotension and syncope within 30 to 90 minutes after an initial dose

Question 20

Doxazosin

1. Same as _____. Pharacological effects?
2. Duration of action?
3. Therapeutic use?
4. Adverse effects and contraindications?

Answer 20

1. Prazosin; Antihypertensive with no increase in CO or tachycardia, PDE inhibitor
2. 36 hours
3. Hypertension, better than prazosin for BPH (induces apoptosis in prostatic smooth muscle cells)
4. Primary first dose effect: marked postural hypotension and syncope within 30 to 90 minutes after an initial dose

Question 21

Alfuzosin and Tamsulosin

1. Pharmacological effects?
2. Therapeutic uses?
3. Specific effect with Tamsulosin?
4. Adverse effects and contraindications?

Answer 21

1. Same as prazosin (except alpha 1a receptor antagonist): antihypertensive, no tachycardia or increase in CO, PDE inhibitor
2. BPH
3. Treats BPH with little effect on BP and thus less likely to cause orthostatic hypotension
4. Abnormal ejaculation

Question 22

Beta adrenergic receptor antagonists have efficacy in the treatment of what 5 things?

Answer 22

Hypertension, ischemic heart disease, acute MI, CHF, and certain arrhythmias

Question 23

What is an example of a pure competitive beta receptor antagonist (no ability to activate beta receptors)?

Answer 23

Propranolol

Question 24

Beta 1 selective antagonists? (5)

Answer 24

Metoprolol, atenolol, acebutolol, bisoprolol, and esmolol

Question 25

Partial agonists have what sort of activity? How do these work? Examples? (6)

Answer 25

Intrinsic sympathomimetic activity (ISA); activate beta receptors partially in absence of catecholamines but less than a full agonist. Pindolol, Acebutolol, Penbutolol, Carteolol, Labetolol, and Celiprolol

Question 26

What drugs are used for beta-blockade independent, local anesthetic, or membrane stabilizing activity?

Answer 26

Propranolol, acebutolol, carvedilol (some pindolol, metoprolol, betaxolol, and labetolol)

Question 27

Drugs with combined alpha 1 and beta blockade?

Answer 27

Labetalol, carvedilol, bucindolol

Question 28

Beta blockers with additional vasodilating properties? (10)

Answer 28

carvedilol, labetalol, bucindolol, celiprolol, nebivolol, nipradilol, carteolol, betaxolol, bopindolol, and bevantolol

Question 29

General beta antagonist cardiovascular effects? When are these effects greater?

Answer 29

Slow HR, decrease myocardial contractility, and these effects are greater when the SNS is activated vs the effects seen at rest

Question 30

Beta receptor antagonist effects on CO: 1. Short term administration with propranolol results in what? 2. Long term administration with propranolol? 3. With beta1/alpha1 antagonists or beta antagonists with vasodilator properties - what occurs with CO and TPR?

Answer 30

1. DECREASED CO with compensatory TPR 2. TPR returns to its initial values (goes down) 3. CO is maintained with a greater fall in peripheral resistance

Question 31

Beta receptor antagonist effect on Heart rate? (4)

Answer 31

Reduce sinus rate, decrease spontaneous rate of depolarization of ectopic pacemaker (proarrythmic - bad), slow conduction in the atria and in the AV node, increase the functional refractory period of the AV node

Question 32

Beta antagonist CV effects during dynamic exercise: 1. HR/Contractility effects? 2. CO? 3. Work capacity? 4. Glucose metabolism and lipolysis? 5. Cardiac O2 supply to demand? Important in who?

Answer 32

1. Decreases exercise induced increase in HR and myocardial contractility 2. Less affected bc of an increase in SV 3. Decreased (not as bad with beta 1 selective agent) 4. Decreases activation 5. Net improvement, important in CAD patients

Question 33

Beta antagonist antihypertensive effect?

Answer 33

Lowers BP in patients with hypertension but not in patients with normal BP

Question 34

Beta receptor antaconist effect on the pulmonary system: 1. Normal individual? 2. COPD individuals?

Answer 34

1. Little effect 2. Can cause life-threatening bronchoconstriction (less likely with beta1 selective or ISA antagonists)

Question 35

Normal effect of catecholamines? Nonselective beta blockers: 1. Effect on diabetes? 2. Metabolism of fat? 3. Effect on cholesterol?

Answer 35

Promote glycogenolysis and mobilize glucose in response to hypoglycemia 1. Delay recovery from hypoglycemia 2. Block glycogenolysis and decrease release of FFA 3. Reduce HDL, increase LDL, and increase Triglycerides

Question 36

Beta 1 Antagonist metabolic effects: 1. Exceptions to cholesterol? 2. Blunt what hypoglycemic symptoms? 3. Function in insulin sensitivity? 4. Exceptions?

Answer 36

1. Beta 1 antagonists can improve lipid profiles in dyslipidemic patients (celiprolol, carteolol, nebivolol, carvedilol, and bevantolol), also chronic use of celiprolol, carvedilol, and carteolol reduce triglycerides 2. tremor, tachycardia, and nervousness 3. Decrease 4. Vasodilating beta receptor antagonists may increase insulin sensitivity in patients with resistance: celiprolol, nipradilol, carteolol, and carvedilol

Question 37

Clinical Therapeutic applications of beta receptor antagonists? (name drugs if available)

Answer 37

1. Hypertension 2. Angina - propranolol, metropolol, celiprolol 3. MI - propranolol (post MI) or metropolol (acute MI) 4 Ventricular arrhythmias 5. CHF 6. Pheochromocytoma - propranolol 7. Migraine 8. Emergency beta block - esmolol (perioperative) 9. Open angle glaucoma - esmolol

Question 38

Third generation beta blockers have vasodilatory actions: 1. __ adrenergic receptor blockade ( ____ ) 2. Increased production of \_\_\_ 3. __ agonist properties. 4. __ entry blockade( \_\_\_\_\_) 5. Opening of ___ channels 6. Antioxidant action ( \_\_\_\_\_)

Answer 38

1. alpha 1; carvedilol 2. NO 3. Beta 2 4. Ca++; carvedilol 5. K+ 6. carvedilol

Question 39

Carvedilol activities are great for what disease?

Answer 39

CHF

Question 40

Beta antagonist adverse effects: CV system: 1. Can induce ____ in susceptible patients 2. Exacerbate heart failure in what patients? 3. Can cause life threatening ____ in patients with heart blocks.

Answer 40

1. CHF 2. patients with compensated HF, acute MI, or cardiomegaly 3. bradycardia

Question 41

Beta antagonist adverse effects: CV system: 1. Not recommended with ____ ( calcium antagonists) or _____ agents that impair ___ node function or ___ conduction. 2. What else can occur? Why? (1 thing) 3. What occurs with abrupt discontinuation of the drug? why?

Answer 41

1. verapamil; antiarrhythmic; sinus; AV 2. Cold extremities - due to excessive vasoconstriction from beta block in limbs 3. Exacerbate angina and may increase the risk of sudden death because of receptor upregulation and hypersensitivity

Question 42

Beta antagonist adverse effects: Pulmonary function 1. What occurs in patients with bronchospastic diseases? 2. Which drugs are less likely to induce bronchospasm? 3. Contraindicated in patients with \_\_\_\_.

Answer 42

1. Life threatening increase in airway resistance 2. Beta 1 selective antagonists or ISA at beta 2 3. asthma

Question 43

Beta antagonist adverse effects: CNS effects?

Answer 43

Fatigue, sleep disturbances (including insomnia and nightmares) and depression

Question 44

Beta antagonist adverse effects: Metabolism: 1. Delay recovery from? 2. Use caution in what patients? What agents are preferable?

Answer 44

1. Insulin-induced hypoglycemia 2. Diabetics; Beta 1 selective antagonists

Question 45

Beta antagonist adverse effects: Overdose: 1. How can poisoning manifest itself? 2. What should severe bradycardia be treated with? 3. Role of glucagon? 4. What could treat hypotension?

Answer 45

1. hypotension, bradycardia, prolonged AV conduction times, widened QRS complex, seizures, and depression may occur 2. Atropine 3. Acts as a positive chronotropic and inotropic factor on the heart and is independent of interactions with beta adrenergic receptors and thus can stimulate increased HR 4. large doses of isoproterenol or alpha receptor agonist