1
Q
What occurs when agonists bind to one of the 3 beta receptor subtypes? (3)
A
- Activates adenylyl cyclase to produce caMP
- Enhances Ca++ influx
- Chronotropic, inotropic, and dromotropic effects
2
Q
What is the selectivity of beta-antagonists dependent on?
A
Selectivity is dose dependent, which is lost at high doses of antagonists
3
Q
Can competitive antagonists be displaced by higher doses?
A
yes
4
Q
4 general benefits of beta blockers?
A
- May restored receptor responsiveness such as after desensitization from catecholamines (tachyphylaxis)
- Protect myocytes from perioperative ischemia and infarction
- Some may decrease arterial vascular tone and reduce afterload
- Decrease CO and inhibit renin release
5
Q
Where do beta blockers delay conduction speed through?
A
The AV node
6
Q
Which phase of depolarization do beta blockers effect?
A
decrease phase 4 depolarization
7
Q
What would be the benefit of increasing diastolic perfusion time?
A
Gives more time for the perfusion of coronary arteries
8
Q
4 Indications for Beta blocker administration?
A
- Excessive SNS stimulation from things such as noxious stimulus or acute cocaine ingestion
- Thyrotoxicosis
- Cardiac Dysrhythmias
- SCIP
9
Q
Surgical Care Improvement Protocol (SCIP) for beta blockers
A
Beta blockers should be administered within 24 hours to all patients who are at risk for myocardial ischemia and patients who are already on beta-blockade therapy
10
Q
3 examples of b1 selective agents?
A
- Atenolol
- Metoprolol
- Esmolol
11
Q
Are all B1 receptors in the myocardium?
A
No, 75% of them are
12
Q
Do B1 selective agents cause vasodilation or increased diastolic filling time?
A
No vasodilation but they do increase diastolic filling time
13
Q
Cardiac selectivity, clearance route, active metabolites, elimination half time, protein binding and adult iv dose of propranolol?
A
Cardiac Selectivity: no Clearance: hepatic E 1/2: 2-3 hours Protein binding: highly (small Vd) IV dose (mg): 1-10mg Active metabolites: yes
14
Q
Cardiac selectivity, clearance route, active metabolites, elimination half time, protein binding and adult iv dose of metoprolol?
A
Cardiac Selectivity: yes Clearance: hepatic E 1/2: 3-4 hours Protein binding: low IV dose (mg): 1-15 mg Active metabolites: no
15
Q
Cardiac selectivity, clearance route, active metabolites, elimination half time, protein binding and adult iv dose of atenolol?
A
Cardiac Selectivity: yes Clearance: renal E 1/2: 6-7 hours Protein binding: low IV dose (mg): 5-10 mg Active metabolites: no
16
Q
Cardiac selectivity, clearance route, active metabolites, elimination half time, protein binding and adult iv dose of esmolol?
A
Cardiac Selectivity: yes Clearance: plasma hydrolysis E 1/2: .15 hours (~9min) Protein binding: low IV dose (mg): 10-80 mg Active metabolites: no
17
Q
What receptor effect does propranolol (inderal) have?
A
Pure beta (B1=B2),there is no sympathomimetic activity
18
Q
What is the difference per person of plasma concentration with inderal?
A
20x difference per person, oral doses range from 40mg-800mg/day
19
Q
What other drugs does inderal have an effect on?
A
decreases clearance of amide LA’s and opioids
20
Q
Which beta antagonist is the most B1 selective?
A
Atenolol (Tenormin)
21
Q
What patients is tenormin useful for in the pre and postoperative setting?
A
Non-cardiac surgery in CAD patients, reduces complications for 2 years
22
Q
Does tenormin potentiate insulin-induced hypoglycemia?
A
no
23
Q
Why does tenormin show less fatigue than other beta blockers?
A
it does not enter the CNS
24
Q
How is tenormin usually given?
A
5mg every 10 minutes IV
25
What are the two po forms of metoprolol
1. Tartrate elimination 1/2 time is 2-3 hours, bid, qid dosing
2. Succinate elimination 1/2 time is 5-7 hours, qd dosing
26
How is lopressor usually dosed?
1mg q 5 min IV in blocks of 5mgs
27
What does the selectivity of metoprolol (loppressor) give us?
bronchodilator, vasodilation and keeps metabolic effects of B2 receptors intact
28
Therapeutic effect and offset of esmolol (brevibloc)?
TE: 5 minutes
Offest: 10-30 minutes
29
What is esmolol useful in treating?
intraoperative noxious stimulu
30
Initial dosing of brevibloc?
20-30mg IV
31
Drug interactions with cimetidine?
decreases 1st pass metabolism of metoprolol, causing it to last much longer
32
Drug interaction of beta blockers when concurrently administered with Ca++ channel blockers?
bradyarrhythmias and heart failure
33
Drug interaction of beta blockers and insulin?
Potentiate insulin effects and prevents glycogenolysis (B2 agonist activity), want to administer B1 antagonists instead of B2
34
Interaction of beta antagonists with anesthesia? (3)
Potential additive myocardial depression, greatest with enflurane, least with isoflurane, not significant between 1-2 MAC
35
2 examples of mixed beta/alpha antagonists
1. Labetolol
| 2. Carvedilol
36
Receptors that labetalol effects?
selective alpha 1, non-selective b1 and b2 antagonist effects
37
What is the beta to alpha blocking ratio in IV form of labetalol?
1:7
38
How does labetalol reduce systemic BP and what reflex is attenuated?
Reduction in SVR due to alpha 1 and b2 antagonistic effects, reflex tachycardia is attenuated by beta 1 blockade
39
maximum effect time for IV labetalol?
5-10 minutes
40
Usual dose of labetalol?
2.5-5 mg IV may increase to 10mg IV
41
2 most common uses for sympathomimetics?
1. Increase myocardial contactility
| 2. Increase systemic BP
42
2 effects that may be seen in sympathomimetics lacking B1 specificity?
1. Intense vasoconstriction
| 2. Reflex bradycardia
43
MOA of sympathomimetics? (3)
1. Activate directly or indirectly beta or alpha adrenergic G protein receptors
2. cAMP enhance calcium influx to increase cytoplasmic concentrations
3. Actin and myosin interact more forcefully
44
4 direct acting sympathomimetics?
epinephrine, norepinephrine, phenylephrine, dopamine
45
Action of indirect sympathomimetics?
Evoke the release of norepinephrine from postganglionic sympathetic nerve endings
46
Most common indirect sympathomimetic?
Ephedrine
47
5 effects seen with epinephrine?
1. Alpha 1 and 2
2. Cutaneous, splanchnic and renal bed vasoconstriction
3. 2-10x more potent than norepinephrine in renal vessels
4. B1 mediated increased HR and CO
5. B2 mediated skeletal muscle vasodilation and bronchodilation
48
Single dose of epinephrine and how long does it last?
2-8mcg lasts 1-5minutes
49
Infusion dose of epinephrine and what receptor it primarily effects?
1. 1-2mcg/min B2
2. 4cg/min B1
3. 10-20mcg/min Predominantly alpha
50
Effects of Ephedrine?
Direct and indirect acting on alpha and beta adrenergic receptors
51
4 characteristics of Ephedrine use
1. Used in Inhaled or injected anesthetics sympathetic depression
2. BP response much less intense, last 10x longer than epinephrine
3. Causes increases in systolic, diastolic, heart rate and CO
4. tachyphylaxis indicated depleted norpei stores
52
What is the preferred sympathomimetic for parturients?
ephedrine, especially for hypotension s/p SAB, and does not effect uterine blood flow
53
What did phenylephrine show in comparison to ephedrine in parturients?
equal BP response but higher umbilical pH in neonates
54
Where does phenylephrine exert its effects more?
Venoconstriciton > arterial constriction
55
Why does phenylephrine show less potency and longer lasting effects than epinephrine?
1. Principally stimulates alpha 1 receptors
| 2. Indirectly releases small amount of norepinephrine
56
3 instances in which phenylephrine is used to treat hypotension from?
1. SNS blockade by regional anesthesia
2. Inhaled/injected anesthetics
3. CAD and AS d/t no tachycardic effects
57
What side effect is seen with phenylephrine?
reflex bradycardia
58
What does vasopressin stimulate?
Vascular V1 receptors to cause arterial vasoconstriction
59
Effect of vasopressin on renal-collecting duct?
Increases its permeability, causing increased water to be reabsorbed
60
What is vasopressin effective in?
1. Reversing catecholamine-resistant hypotension
| 2. ACE-I resistant hypotension
61
Side effects of Vasopressin? (3)
1. Coronary artery vasoconstriction
2. Stimulate GI smooth muscle to cause abd pain and N/V
3. Decreased platelet counts and antibody formation
62
What ion does Nitric Oxide cause a reduction in?
Decreased intercellular Ca++ ions, causing vasodilation
63
7 instances in which Nitric Oxide is involved
1. Cardiovascular tone relaxation
2. Platelet regulation
3. CNS neurotransmitter
4. GI smooth muscle relaxation
5. Immune modulation
6. Effector molecule for volatile anesthetics
7. Pulmonary artery vasodilation
64
How do nitro-vasodilators work to reduce systemic blood pressure?
1. Decreased SVR (arterial vasodilators)
| 2. Decreased venous return (venous vasodilators), which helps to alleviate pulmonary/systemic congestion
65
Effect of sodium nitroprusside?
causes relaxation of arterial and venous vascular smooth muscle
66
Describe the onset and duration of sodium nitroprusside
Immediate onset, transiet duration, requires arterial line monitoring and continuous administration
67
Effect of sodium nitroprusside on oxyhemoglobin?
dissociated immediately upon contact, causing methemoglobin and releases cyanide and NO
68
Initial dose and titrated dose of sodium nitroprusside?
Initial: 0.3mcg/kg/min
Titrated: 10mcg/kg/min
69
Uses of SNP?
1. Production of controlled hypotension in Aortic surgery
2. Production of controlled hypotension in Pheochromocytoma
3. Production of controlled hypotension in Spine surgery
4. HTN emergencies in carotid surgery
70
When do we see Cyanide toxicity with SNP use?
With higher IV doses
71
Why do Cyanide radicals accumulate with SNP use?
Sulfur donors/methemoglobin is exhausted
72
When should we suspect cyanide toxicity in patients who SNP is being used?
1. Increased doses needed
2. Increased mixed-venous sats (tissues not oxygenating)
3. Metabolic acidosis
4. CNS dysfunction/change in LOC occurs
73
What does nitroglycerin act on and what does it cause?
Acts on venous capacitance vessels and large coronary arteries causing venous pooling, relaxation of arterial vascular smooth muscle in high doses
74
Relate tachyphylaxis and nitroglycerin (3)
1. Dose dependent and duration dependent (24 hours0
2. Limit vasodilation
3. Drug free interval 12-15 hours reverses tolerance, but may see rebound ischemia
75
Initial dose of nitroglycerin
0.5-1 mcg/kg/min or IVP boluses
76
What is the effect of nitroglycerin in acute MI?
receives pulmonary congestion, reduces O2 requirements and limits MI size
77
4 instances in which nitroglycerin is useful
1. Acute MI
2. Acute HTN
3. Controlled Hypotension (less potent than SNP)
4. Sphincter of Oddi spasm
78
What is hydralazine?
Direct, systemic arterial vasodilator
79
Effect of hydrazine? (2)
1. Decreases ITP (inositol triphosphate), reducing Ca++ release
2. Extreme hypotension, rebound tachycardia
80
Onset time of hydralazine?
peak plasma concentration 1 hour
81
Initial dose of hydralazine?
2.5mg IV
82
Which Ca++ channel blockers have selective AV node effects?
Phenylalkylamines and Benzothiazepines
83
Which Ca++ channel blocker has selective arteriolar bed effects?
Dihydropyrmidines
84
MOA of Ca++ channel blockers?
1. Bind to receptor on voltage-gated L-type calcium channels
| 2. Decreases calcium influx, inhibits excitation-contraction coupling
85
Effects of CCB? (4)
1. Decreased vascular smooth muscle and contractility
2. Peripheral vasodilation d/t reduction in SVR and systemic blood pressure
3. Increased coronary blood flow
4. Decreased speed of conduction through the AV node
86
Which CCBs show reduction in HR?
Verapamil and diltiazem
87
Which CCB shows the greatest coronary artery vasodilation?
nicardipine
88
Which CCBs show marked peripheral artery dilation?
nifedipine and nicardipine
89
Which CCBs do not effect the SA node or AV node conduction?
nifedipine and nicardipine
90
Describe nicardipine's effect on hypertension?
provides short term control
91
Dose, increase titration, decrease dose of nicardipine?
1. 5 mg/hour (50mL/hr)
2. Increase 2.5 mg/hr (25 mL/hr) to max of 15 mg/hr (150 mL/hr)
3. Decrease to 3 mg/hr
92
How much nicardipine is decreased 30 minutes after D/C?
50% drug decrease 30 minutes after D/C
Advanced Pharmacology 2
flashcards
Decks in class (5)
# Cards
