Pharmacology adjuncts - test 4 Flashcards
1
Q
3 subtypes of beta receptors:
A
- G protein coupled
- Occupied by agonists
- Occupied by antagonists (competetive antagonists)
2
Q
When beta receptors are occupied by an agonists, it activates adenylyl cyclase to ____ ___; this enhances __ ____ and has what effects?
A
Produce cAMP; enhances Ca+ influx
- produces chronotropic, inotropic, and dromotropic effects
3
Q
How do beta-antagonists work?
A
- have a selective affinity for B-adrenergic receptors
- prevent catecholamines/other sympathomimetics from binding on heart, airway smooth muscles, blood vessels
4
Q
What happens with chronic administration of beta-antagonists?
A
Causes upregulation of receptors
5
Q
After β receptor desensitization from prolonged catecholamine exposure, what drug class can restore receptor responsiveness?
A
β-blockers
6
Q
How do β blocker protect myocytes from perioperative ischemia?
A
By ↓O₂ demand on the heart
7
Q
What affect does beta antagonists have on vascular tone and cardiac output?
A
- Some may decrease arterial vascular tone and reduce afterload
- Decrease CO and inhibit renin release
8
Q
How will beta blockers affect cardiac action potentials?
A
Decreases phase 4 slope
- decreases rate of spontaneous depolarization
- decreases dysrhythmias during ischemia and reperfusion
9
Q
Indications for giving beta blockers:
A
- Excessive SNS stimulation (noxious stimuli, acute cocaine ingestion)
- thyrotoxicosis
- cardiac dysrhythmias
- essential hypertension
- SCIP
10
Q
How do beta blockers affect diastolic perfusion time?
A
It increases diastolic perfusion time
11
Q
What is SCIP?
A
Surgical Care Improvement Protocol
- beta blockers must be given within 24 hours of surgery for patients at risk for myocardial ischemia or already on beta blockade therapy
12
Q
What percent of beta receptors in myocardium are B1 specific?
A
75%
13
Q
Do B1 selective agents cause vasodilation?
A
No
14
Q
Which drug is the prototypical B antagonist?
A
Propanolol (Inderal)
15
Q
Propanolol B1 and B2 activity:
A
B1 = B2
16
Q
What are some negatives of using propanolol?
A
- Bradycardia lasts longer than negative ionotropic effects
- Decreases clearance of opioids and amine LAs
17
Q
Which drug is the most B1 selective?
A
Atenolol (Tenormin)
18
Q
When is atenolol useful?
A
Pre/post non-cardiac surgery in CAD patients
- decreases complications (myocardial ischemia) for 2 years
19
Q
Other benefits to using atenolol:
A
- Does not appear to potentiate insulin-induced hypoglycemia
- Doesn’t enter CNS (in large amounts) - less fatigue
20
Q
How is atenolol usually given?
A
5 mg q 10 minutes IV
21
Q
B1 and B2 effects of metoprolol:
A
- Selective B1
- Bronchodilator, vasodilator, and metabolic effects of B2 receptors intact
22
Q
What are the two PO formulations for metoprolol?
A
- Tartrate: E1/2 time 2-3 hours (bid or qid dosing)
- Succinate E1/2 time 5-7 hours (qd dosing)
23
Q
How is metoprolol usually dosed?
A
1mg q 5 minutes IV - in blocks of 5 mg
24
Q
What is esmolol useful to treat?
A
Intraoperative noxious stimuli (intubation)
- versus lidocaine or fentanyl
25
What do you caution for if you give esmolol with cocaine or epi?
Pulmonary edema/collapse
26
How is esmolol metabolized?
Plasma cholinesterases
27
What is the inital dose of esmolol?
Usually 20-30 mg IV
28
What two scenarios would you wanna give a beta selective antagonist?
- Diabetes: interferes with glycogenolysis and potentiates insulin
- Airway: potentiates bronchospasm and ventilatory depression
29
Which volatile anesthetic will cause the greatest potential additive myocardial depression with beta antagonists? which will cause the least?
- Greatest with enflurane
- Least with isoflurane - would want to use iso in patients with preexisting myocardial ischemia
- *not significant between 1-2 MAC
30
How do agonists at alpha 1 receptors work?
- Increase synthesis of 2nd messengers (IP3): increases Ca+ release from SR
- Affect vascular smooth muscle
- Determine arteriolar resistance, venous capacity and BP
31
How do agonists at alpha 2 receptors work?
Decrease release of norepi from presynaptic nerve terminals (brain stem)
32
Phenylephrine mimics norepi but less ____ and ____ ____
Less potent and longer lasting
- indirectly releases a small amount of norepi
33
How is phenylephrine useful in treating hypotension?
- SNS blockade by regional anesthesia
- Inhaled/injected anesthetics
- Very useful in CAD and AS - no tachycardia
- Commonly used both IVP and IV drip
34
What is one negative of using phenylephrine?
It can cause reflex bradycardia
35
What receptors does labetalol work on?
- Selective a1
- non-selective B1 and B2 antagonist effect
36
What is the beta to alpha blocking ratio for labetalol?
Beta to alpha = 7:1
37
How does labetalol lower systemic BP?
Decreases SVR
- reflex tachycardia attenuated by beta blockade
38
What is the dose and max effect of labetalol?
- Dose = 2.5-5 mg IV; may increase to 10 mg IV (d/t tachyphylaxis)
- Max effects of IV dose is 5-10 minutes
39
What are sympathomimetics used for most often?
- Increase myocardial contractility
- Increase systemic blood pressure
40
Sympathomimetic agents lacking B1 specificity may...:
- Cause intense vasoconstriction
- Reflex-mediated bradycardia
41
MOA of sympathomimetics:
- direct or indirectly activates beta or alpha adrenergic G protein coupled receptors
- cAMP enhance calcium influx to the cytosol
- Actin and myosin interact more forcefully
42
Give examples of direct acting sympathomimetics:
Epi, Norepi, phenylephrine, dopamine
43
How do indirect sympathomimetics work?
Evoke the release of norepi from postganglionic sympathetic nerve endings
44
Which drug is an indirect acting sympathomimetic?
Ephedrine
(phenylephrine a little)
45
Mr. Spencer is in your preoperative holding room, scheduled for a CABG x 4 this am. You realize that he has not had his beta blocker this am. Which beta-blocker will you administer?
Metoprolol - longer acting
- not propanolol (not specific)
- not esmolol (too quick, not cardioprotective)
- not carvedilol (PO)
- not labetalol (shorter acting and peripheral effects)
46
You are in the process of extubating a patient immediately following a left carotid endarterectomy. His blood pressure is 210/64. Which of the following drugs would be most desirable?
Esmolol - fast acting beta 1 to focus on SBP
47
What is the prototype catecholamine?
Epi!
48
How long does a single bolus dose of 2-8 mcg of epi last?
1-5 minutes
49
What receptors do infusions of epi work on?
- 1-2 mcg/min = beta 2
- 4 mcg/min = beta 1
- 10-20 mcg/min = mostly alpha
50
Comparison of sympathomimetics
51
Ephedrine is commonly used in sympathetic depression from what?
Why?
- inhaled/injected anesthetics
- BP response much less intense - lasts 10x longer than epi
52
Why does tachyphylaxis happen with ephedrine?
It depletes norepi stores
53
When might ephedrine be given IM?
In OB - if they're hypotensive from the spinal, IM forms of 50 mg can be given to support BP through c-section
54
How does vasopressin work?
- Stimulates vascular V1 receptors to cause arterial vasoconstriction
- increases renal-collecting duct permeability (water is reabsorbed)
55
When might vasopressin be a good choice?
- Reversing catecholamine resistant hypotension
- ACE-I resistant hypotension
56
CV side effects of vasopressin:
Coronary artery vasoconstriction
57
GI side effects of vasopressin:
Stimulate GI smooth muscle
- abd pain
- N/V
58
Other side effects of vasopressin:
Decreased platelet counts and antibody formation
59
How does nitric oxide work?
cGMP inhibits calcium entry into smooth muscle and increases uptake by endoplasmic reticulum
60
What is nitric oxide involved in?
- CV tone relaxation
- Platelet regulation
- CNS neurotransmitter
- GI smooth muscle relaxation
- immune modulation
- pulmonary artery vasodilation
61
How do nitro-vasodilators decrease systemic blood pressure?
-↓ SVR - arterial vasodilators; treat effects of vasoconstriction
-↓ venous return - venous vasodilators; alleviate pulmonary/systemic congestion
61
62
What are two examples of nitro-vasodilators?
- Sodium nitroprusside
- Nitroglycerin
63
How does sodium nitroprusside work?
Causes relaxation of arterial and venous vascular smooth muscle
64
What is the onset and duration like for sodium nitroprusside?
Immediate onset, transient duration
- requires continuous administration
- requires invasive arterial monitoring
65
What does Nitroprusside dissociate on contact with?
What is the result?
Dissociates on contact with oxyhemoglobin → methemoglobin, NO, and cyanide released
66
What is the dosing for nitroprusside?
Initial dose: 0.3 mcg/kg/min
Titrated to 2 mcg/kg/min
67
What is sodium nitroprusside used for?
Production of controlled hypotension:
- Aortic surgery
- Pheochromo
- Spine surgery
Hypertensive emergencies
- carotid surgery
68
When does cyanide toxicity occur with giving SNP?
- With higher IV doses
- Cyanide radical accumulates d/t sulfur donors/methemoglobin exhaustion
69
When would you suspect cyanide toxicity when using SNP?
- Needing increased doses of SNP
- Increased mixed-venous sate (tissues aren't using oxygen)
- Metabolic acidosis
- CNS dysfunction/change in LOC
70
What does nitroglycerin act on?
Acts on venous capacitance vessels and large coronary arteries
- venous pooling
- relaxation of arterial vascular smooth muscle (high doses)
71
Can you develop tachyphylaxis to nitroglycerin?
Yes
- dose dependent and duration dependent
- limits vasodilation
- drug free interval 12-25 hours reverses tolerance
72
Dosing for nitroglycerin:
5-10 mcg/min infusion and titrate
73
Why is nitroglycerin useful for acute MI?
Relieves pulmonary congestion, decreases O2 requirements, limits MI size
74
Why is nitroglycerin useful for controlled hypotension?
Less potent than SNP
75
Why is nitroglycerin useful for retained placenta?
Nitro helps placenta to release and stops bleeding
76
How does hydralazine work?
Direct, systemic arterial vasodilator
- Decreases ITP, decreases Ca+ release
77
What negative effects can hydralazine cause?
Extreme hypotension, rebound tachycardia
78
Hydralazine onset:
Half life:
Initial dose:
Peak plasma concentration 1 hour
- 1/2 life = 3-7 hours
- Initial dose = 2.5 mg
79
What are the 3 types of calcium channel blockers and what are they selective for?
- Phenylalklylamines: selective for AV node
- Benzothiazepines: selective for AV node
- Dihydropyrimidines: selective for arteriolar beds
80
MOA of calcium channel blockers:
- Bind to receptors on VG calcium ion channels (l-type, main pathway)
- Decrease calcium influx - inhibits excitation-contraction coupling
81
Effects of CCB:
- Decrease vascular smooth muscle contractility (peripheral vasodilation and increased coronary BF)
- Decreased speed of conduction (through the AV node)
82
What is nicardipine used for?
Short term control of hypertension
83
Dosing for nicardipine:
5 mg/hr
- increase 2.5 mg/hr x4 to max of 15 mg/hr
84
___% of nicardipine decreases 30 minutes after d/c
50%
85
Which antihypertensive works primarily through altering venous capacitance?
Nitroglycerin
- hydralazine and SNP are arterial
86
Your end-stage COPD patient needs emergent blood pressure control in the ICU. Which of the following medications might worsen his PaO2 the most?
Sodium nitroprusside: oxy = cyanide and methmaglobin
*nitroglycerin would help lungs from NO vasodilation
*hydralazine would not give emergent control
87
Your physician is closing the neck incision following an uneventful right carotid endarterectomy. You have reversed the muscle relaxant and the patient is spontaneously breathing at 20/min; BP 140/90 and climbing, HR 84 and climbing. Your 1st intervention is:
Give narcotic (25 mcg of fentanyl) - give short acting first then give longer acting (dilaudid/morphine)
88
Comparison of CCB:
