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Flashcards in Adrenergic II Deck (67):
1

What are sympatholytic drugs?

Sympatholytic drugs are adrenergic receptor antagonists and they act by blocking the postganglionic function of the sympathetic nervous system.

2

How do sympatholytic drugs block sympathetic action?

3 mechanisms to block:
1) Decrease sympathetic outflow from the brain
2) Suppress nerve terminal NE:
a) Inhibit synthesis
b) Deplete NE granules
c) Suppress the release of NE
3) Block postsynaptic receptors

3

Describe the qualities of irreversible receptor antagonists.

Irreversible antagonists:

1) Do not dissociate => phenoxybenzamine
2) Their antagonism outlasts the presence of the compound
3) The block is insurmountable/not overcome by NE

4

Describe the characteristics of reversible receptor antagonists.

Reversible antagonists:

1) Dissociate from the receptor and produce an equilibrium blockade
2) The block disappears as free drug is metabolized
* Examples => phentolamine and prazosin

5

What is the function of α-adrenergic receptor blockers?

Vasodilation and lowering BP

6

What type of α-adrenergic receptor blocker is used clinically?

α1-AR selective blockers are used clinically.

They are used for vasodilation and reduction in arterial pressure => clinically used for HTN and BPH
- There is no reflex tachycardia in these drugs are decrease in cardiac function
- Prototype drug: Prazosin

7

What are the uses of nonselective α-adrenergic receptor blockers?

Non-selective α-adrenergic receptor blockers:

1) Phentolamine = reversible and rarely used
2) Phenoxybenzamine (Dibenzyline) => irreversible, used in peripheral vasospasm
* Adverse reactions: hypotension and tachycardia

8

What are the cardiovascular effects of β1 blockers?

1) Reduce heart rate
2) Delay AV conduction
3) Decrease rate of depolarization
4) Decrease force of contraction
5) Decrease oxygen consumption
6) Decrease BP
7) Inhibit renin release

9

What are the cardiovascular effects of β2 blockers?

1) Vasoconstriction in arterioles
2) Increased airway resistance
3) Decreased glycogenolysis and gluconeogenesis
4) Inhibit insulin release

10

What are the properties of β-AR blockers?

1) Selectivity => peripheral vascular disease and diabetes
2) Partial agonist activity
3) Action as a local anesthetic
4) Lipid solubility

Pharmacokinetic properties
1) Metabolism in the liver and kidney
2) Elimination half life, bioavailability
3) Well absorbed after oral administration=> peak concentration at 1-3 hours
4) Extensive hepatic metabolism => half lives from 3-10 hours
- Gradually taper doses if discontinuing as receptor up regulation with blockade

11

What considerations need to be made with β-AR blockers?

1) Drug interactions with anti-hypertensives => verapmil, digoxin
2) Caution with airway disease, diabetes and heart failure

12

What are the primary indications for β-AR blockers?

Primary indications for β-AR blockers:
1) Hypertension
2) Arrythmias
3) Ischemic heart disease

13

What are secondary indications for β-AR blockers?

Secondary indications for β-AR blockers?
1) Hyperthyroidism
2) Glaucoma
3) Migraine
4) Anxiety

14

What is Prazosin (Minipress)?

Prazosin is a sympatholytic drug used to treat high blood pressure, anxiety, PTSD, and panic disorder.

Costs range from $4-$2 per month

15

What is the drug class for Prazosin?

Pharmacologic class => selective alpha-1 adrenoceptor blocker
Therapeutic class => antihypertensive, treatment of BPH (benign prostatic hyperplasia), treatment of Raynaud’s syndrome, treatment for kidney stones

16

Describe the pharmacodynamics of Prazosin.

Blocks alpha-1 receptors on arterioles and veins, thereby inhibiting NE-mediated vasoconstriction and venoconstriction

17

Describe the pharmacokinetics of Prazosin.

Available po (Per Os => by mouth) or transdermal
-Variable oral bioavailability (~60%)
- Onset 2 h => duration 12-24 h
- Extensively metabolized in liver

18

What toxicity is associated with Prazosin?

Prazosin toxicity:
Excessive hypotension with passing out => especially orthostatic and patients on diuretics

19

What are the pertinent Prazosin interactions?

Prazosin interactions: additive effects with most other antihypertensives, especially diuretics

20

What special considerations should be made with Prazosin?

Considerations:
- Start gradually and at bedtime => to avoid first-time passing out
- Male patients with BPH?

21

What dose/route should Prazosin be given?

Prazosin route/dose:
-As mono therapy => begin with1 mg tid, advance to 20 mg per day divided tid (ter in die => 3 times/day)

22

What should be monitored in patients on Prazosin?

BP, weight, edema

23

What is Tamsulosin/Flomax?

Tamsulosin is an alpha blocker, which works by relaxing bladder neck muscles and muscle fibers in the prostate itself to make it easier to urinate.

Costs range from $5-$70 per month

24

What drug class is Tamsulosin?

Pharmacologic class => selective alpha-1 adrenoceptor blocker
Therapeutic class => treatment of obstructive symptoms of BPH

25

Describe the pharmacodynamics of Tamsulosin.

Pharmacodynamics:
- Selectively blocks alpha-1 receptors, but preferentially in the prostate
- This leads to relaxation of smooth muscles in the bladder neck and prostate, improving urine flow, and reducing obstructive symptoms of BPH venoconstriction

26

Describe the pharmacokinetics of Tamsulosin.

Pharmacokinetics:
-Completely absorbed after oral ingestion
- >90% metabolized by CYP 450 enzymes
- Half-life about 6 hours, but duration of action up to 15 hours due to slow absorption

27

What toxicity is associated with Tamsulosin?

Toxicity:
- Excessive hypotension with syncope => especially orthostatic and especially in patients on diuretics
- Allergic reactions
- Decreased libido

28

What are pertinent Tamsulosin interactions?

Interactions:
-Additive effects with most other antihypertensives, especially diuretics

29

What special considerations should be made for patients on Tamsulosin?

Considerations:
- Rule out carcinoma of prostate before beginning treatment
- Do not crush or chew tablets, as that will speed up absorption
- Can also be used to treat spasm of ureter in patients with kidney stones

30

What is the appropriate dose/route for Tamsulosin?

Dose/route:
- For symptoms of BPH, 0.4 mg po (by mouth) qd (1/day) or bid (2/day); similar doses for renal colic

31

What should be monitored in patients on Tamsulosin?

BP

32

What is Phentolamine/Regitine?

Phentolamine is a reversible nonselective alpha-adrenergic antagonist used primarily for the control of hypertensive emergencies, most notably due to pheochromocytoma.

33

What drug class is Phentolamine?

Pharmacologic class => non-selective, competitive alpha-adrenergic receptor blocker
Therapeutic class => antihypertensive drug for patients with pheochromocytoma

34

Describe the pharmacodynamics of Phentolamine.

Pharmacodynamics:
- Blocks alpha-1 and alpha-2 adrenergic receptors at presynaptic and postsynaptic alpha receptors, decreasing preload and afterload

35

Describe the pharmacokinetics of Phentolamine.

Pharmacokinetics:
- Only comes in IV formulation, so F=100%
- Plasma half-life about 20 min after IV dose

36

What toxicity is associated with Phentolamine?

Toxicity:
-Excessive hypotension with syncope => especially orthostatic and especially in patients on diuretics
- Allergic reactions
- Decreased libido

37

What are pertinent Phentolamine interactions?

Interactions:
- Additive effects with most other antihypertensives, especially diuretics

38

What special considerations should be made for patients on Phentolamine?

Considerations:
- Rule out carcinoma of prostate before beginning treatment
- Do not crush or chew tablets, as that will speed up absorption
- Can also be used to treat spasm of ureter in patients with kidney stones

39

What are the indications/route/dose for Phentolamine?

Indications:
- Aid in Dx of pheo
- Treatment of intra-op HTN during pheo removal surgery;
- Prevention of dermal sloughing after extravasation of NE infusion
- Hypertensive crisis from sympathomimetic amines (discuss tyramine-MAO interaction)

Dose/Route:
- Dose 5 mg IV, then titrate, repeat as needed

40

What should be monitored in patients on Phentolamine?

BP

41

What is Atenolol/Tenormin/Metoprolol/Toprol?

Atenolol is a Beta-1 receptor antagonist used in cardiovascular disease, primarily in the treatment of hypertension.

Class runs $4/$52 for atenolol to $100 for Toprol XL

42

What drug class is atenolol?

Pharmacologic class => specific β1-adrenoceptor blocker Therapeutic class => antihypertensive, antiarrhythmic, primary and secondary prevention of MI, anti-anginal

43

Describe the pharmacodynamics of atenolol.

Pharmacodynamics:
- Binds directly to β1-receptors, with a preference for beta-1 over beta-2
- Leading to lower blood pressure via several potential mechanisms (less cardiac output, less activation of the RAA system)
- Recent evidence suggests less effective in preventing strokes than other drugs (reason why used less as initial mono-therapy)

44

Describe the pharmacokinetics of atenolol.

Pharmacokinetics:
- Available po (by mouth) or iv
- Variable oral F
- Onset 1-2 hours h, duration 12-24 h
- Can be given once per day
- Renally excreted (longer half-life)
- Metoprolol has hepatic metabolism (and shorter half-life)

45

What toxicity is associated with atenolol?

Toxicity:
- Excessive hypotension
- Bradycardia
- Heart block can worsen severe CHF (but indicated for mild to moderate CHF)
- Worsen bronchospasm in severe asthmatics

46

What interactions should be considered for patients on atenolol?

Interactions:
- Additive effects with most other antihypertensives
- Additive AV block with CEBs

47

What special considerations should be taken for patients on atenolol?

Considerations:
- May be especially useful in HTN patients with exertional angina, MI, atrial fibrillation
- Watch out for abrupt withdrawal
- May no longer be “first line” drug for essential HTN unless other indications exist (recent data)
- Metoprolol (needs to be taken several times per day) has more data for use in patients s/p MI

48

What is the dose/route/indication for atenolol?

Indication:
- For treatment of hypertension
Dose/route:
- 25-100 mg per day, in one or two doses

49

What should be monitored in patients on atenolol?

BP, HR, exercise tolerance

50

What is Propranolol/Inderal?

Propranolol is a sympatholytic non-selective beta blocker.
- Sympatholytics are used to treat hypertension, anxiety and panic.
- It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.
- $4 up to $108 for Inderal

51

What is the drug class for Propranolol?

Pharmacologic class => non-specific β-adrenoceptor blocker
Therapeutic class => antihypertensive, antiarrhythmic, primary and secondary prevention of MI, anti-anginal

52

Describe the pharmacodynamics of propranolol.

Pharmacodynamics:
- Binds directly to β1-receptors and β2 receptors, leading to lower blood pressure via several potential mechanisms (less cardiac output, less activation of the RAA system)
- Recent evidence suggests less effective in preventing strokes than other drugs

53

Describe the pharmacokinetics of propranolol.

Pharmacokinetics:
- Available po or iv; variable oral F
- Onset 1-2 hours h, duration 12-24 h
- Can be given once per day
- Renally excreted (longer half-life)
- Metoprolol has hepatic metabolism (and shorter half-life)

54

What toxicity is associated with propranolol?

Toxicity:
- Excessive hypotension
- Bradycardia
- Heart block can worsen severe CHF (but indicated for mild to moderate CHF)
- Worsen bronchospasm in severe asthmatics

55

What interactions should be considered for patients on propranolol?

Interactions:
- Additive effects with most other antihypertensives
- Additive AV block with CEB’s

56

What special considerations should be considered for patients on propranolol?

Considerations:
- May be especially useful in HTN patients with exertional angina, MI, atrial fibrillation
- Watch out for abrupt withdrawal
- May no longer be “first line” drug for essential HTN unless other indications exist (recent data)
- Metoprolol (needs to be taken several times per day) has more data for use in patients s/p MI

57

What are the indications/dose/route for propranolol?

Indications:
- For treatment of hypertension
Dose/route:
- 25-100 mg per day, in one or two doses

58

What should be monitored in patients on propranolol?

BP, HR, exercise tolerance

59

What is Labetalol/Trandate/Carvedilol/Coreg?

Labetalol is a mixed alpha/beta adrenergic antagonist, which is used to treat high blood pressure especially in pregnancy-induced hypertension, pheochromocytoma, and hypertensive crisis

- class cost $4 (carvedilol generic) to $26 per month

60

What is the drug class of labetalol?

Pharmacologic class => mixed alpha- and beta-receptor blocker
Therapeutic class=> antihypertensive, treatment of CHF

61

Describe the pharmacodynamics of labetalol.

Pharmacodynamics:
- Reduces BP by blocking access of NE to beta-receptors and alpha-1 receptors, thereby lowering BP by several different mechanisms
-Patients differ in degree of beta-blockade vs alpha-blockade

62

Describe the pharmacokinetics of labetalol.

Pharmacokinetics:
- Excellent absorption but high first-pass effect, leading to F~25%
- Onset 1-2 hours after po, 2-5 minutes when given iv
- Extensively metabolized in liver by IID6

63

What toxicity is associated with labetalol?

Toxicity:
- Avoid in patient with bradycardia, heartblock, CHF, asthma, shock
- Use with caution in patients with cardiomyopathy, pheochromocytoma: Pregnancy Class D

64

What interactions should be considered in patients on labetalol?

Interactions:
- Additive effects with most other antihypertensives

65

What special considerations should be made for patients on labetalol?

Special considerations:
- Use reduced doses in patients with impaired liver function
- Dizziness is most troubling early side effect
- Most often used for hypertensive crises (as with nitroprusside)

66

What are the indications/route/dose for labetalol?

Route/Dose:
- Most commonly given iv with initial small boluses of 20 mg, followed by continuous infusion at 2 mg/min
- Not usually given po for chronic treatment
- 80 mg thrice daily, or 240 mg SR once daily

67

What should be monitored in patients on labetalol?

BP, HR