Pharm Flashcards
1
Q
Alpha 1
A
Vasoconstricts vascular smooth muscle, GU contraction, GI relaxation, gluconeogenesis, glycogenolysis
2
Q
Alpha 2
A
Decreased insulin secretion
Platelet aggregation
Decreased NE release
Vasoconstriction of vascular smooth muscle
3
Q
Beta 1
A
Increased cardiac contractility HR AV conduction Increased renin secretion Increased contractility Arrhythmias
4
Q
Beta 2
A
Relaxation of vascular smooth muscle Bronchial relaxation GI/GU relaxation Gluconeogenesis Glycogenolysis
5
Q
Dopamine 1
A
Dilation of vascular smooth muscle (renal, mesentery, coronary, renal tubules, natriuresis)
JGCs increased renin release
6
Q
Dopamine 2
A
Inhibits NE release
May constrict renal and mesenteric smooth muscles
7
Q
Volatile agents
A
All are cardiac depressants - amplified in diseased tissue
Affect L-type Ca+ channels located in SR of myocardial cells. This decreases contractility and prolongs isovolumetric relaxation time
8
Q
Coronary steal
A
With volatile applied, vasodilation occurs in healthy tissues and “steals” the flow from ischemic tissue to areas with enough perfusion
- Isoflurane most known for this
- Sevo and Des cause coronary artery dilation
9
Q
BP effect of volatile agent
A
All with dose-depend responses
- With increased MAC, lower BP but maintain CO
- Least concerning is with NO
- At high Des flows, increase sympathetic stimulation (Rule of 24)
10
Q
Rule of 24
A
Flows x % of gas
< 24 = sympathetic circulation less than with > 24
11
Q
Pulmonary blood flow / effect of volatile gas
A
Halothane causes pulmonary vasoconstriction d/t catecholamine release
- Iso and Halothane inhibit vaso-endothelial response to hypoxia through K-channel activation
- Sevo and Des have no effect
12
Q
Baroreceptor reflex/effect of volatile gas
A
All agents attenuate
Halothane/enflurane more than others
Suppression of reflex arc at all components - no reflex HTN
13
Q
Under cardiac surgery/effect of volatile gas
A
Avoid Des d/t cost and length of surgery; also increased SNS stimulation which increases myocardial oxygen consumption
Avoid Nitrous d/t air bubbles I n vasculature and SNS stimulation
Volatiles better than TIVA bc protective cardiac effects to decrease size of infarct during ischemic events
14
Q
Anesthesia pre-conditioning/effect of volatile gas
A
Dose dependent
Protective mechanism correlating with infarction, before ischemia occurs - volatiles can be protective after this “stunning” event
This works through mitochondrial K/ATPases and GCPRs
15
Q
Propofol
A
Inhibits L-type Ca+ channels to decrease Ca+ release from SR; causing negative inotropic effects
Decreases O2 stress so better with MI (as adjunct)
Decreases SVR, vessel-autoregulation altered, and pulmonary vasculature is sensitive to catecholamines
Decreases baroreceptor reflex
CV collapse can occur in shock or trauma states - can decrease BP by 40%
Increase in lipid levels - MI risk
Decrease CBF/CMR O2 consumption and help prevent emboli transfer
16
Q
Thiopental
A
Decreases contractility MAP unchanged, HR increases Increased O2 consumption Decreased CO Cerebro-protective
17
Q
Midazolam
A
0.05-0.2 mg/kg for induction Little variation in BP CI stays the same No analgesia properties - need Fentanyl (2 mcg/kg) Long 1/2 life
18
Q
Etomidate
A
0.3 mg/kg max
Burns with injection
Myoclonus increases O2 consumption
Adrenal/Cortisol suppression major concern
Most cardiac static induction agent
Instability can occur with high doses or with valvular issues
19
Q
Ketamine
A
Dissociative anesthesia
Increase CI/HR/SVR/MAP through sympathetic stimulation
If catecholamine stores are low, then negative inotropic effect
Drug of choice for cardiac tamponade
20
Q
Precedex
A
HTN with bolus dosing can occur
Increases SVR, then low BPHR
Should get loading dose to reach steady state
21
Q
Opioids
A
- Ischemic preconditioning
- Endogenous opioids decrease sympathetic outflow
- Administered with MI can improve survival outcomes by decreasing afterload and providing coronary artery dilation
- Exogenous opioids depress the outward K+ flow, which causes bradycardia
- Large doses prolong the QT interval.
- All levels are decreased during CPB
22
Q
Which opioid protects against reperfusion injury?
A
Morphine
Increases post-pump contractility after CPB
23
Q
Which opioid at large doses can lead to ventricular arrhythmias
A
Fentanyl
24
Q
Which opioid can decrease BP? How?
A
Morphine due to histamine release. Can mitigate with administration of H1 antagonist
Sufenta can also lower BP - good with induction
25
Which opioid is exception to bradycardia rule?
Meperidine due to it's similarity to atropine
26
Cardiac Bypass effects on circulation
- 1.5 –2L of priming fluid in the CPB machine that mixes with pt blood
- Pt HCT drops to 25% and increases plasma volume by 50%
- Causing an immediate reduction in circulating free drug and proteins
- Heparin causes release of chemicals that bind competitively to plasma proteins as well, which increases free drug concentration.
- Acid/base changes during CPB that alter ionized vs. non-ionized forms of drugs
- Blood flow is decreased during CPB
27
Non-pulsatile CPB is associated with . . .
Altered tissue perfusion and acidosis
This causes basic drugs to become trapped in acidic tissue wand will redistributed during the rewarming phase and become biologically active as pH normalizes
28
Hypothermia during CPB reduces. . .
hepatic and renal enzyme function
Therefore, metabolic drug clearance decreases.
Decreased perfusion to the kidneys slows renal drug excretion. GFR drops by 65% at 25 degrees C
29
Are NMB needed during CPB?
No. Cooling slows nerve conduction and slows cholinesterase enzyme activity. Given the protein decrease, NMB like rocuronium enjoy increased free drug levels
30
Barbiturates and Propofol during CPB
concentration decrease on CPB initiation
31
Benzos and CPB
Concentration decreases when starting CPB. They are highly-protein bound.
32
CPB and binding of drugs
CPB actually binds several drugs. The CPB oxygenator known to bind lipophilic drugs
(including PIA, induction agents, and opiates).
The lungs are bypassed and basic drugs can be held by the lungs and act as a reservoir for release once systemic perfusion returns.
33
Drugs used for ischemia
Nitrates (vasodilator)
Ca+ blockers (vasodilator and cardiac depressant)
Beta Blockers (cardiac depressant)
34
Atherosclerotic angina
Classic angina - 90% of cases
Associated with plaques that occlude coronary arteries
Rest usually results in relief
Precipitated by exertion
35
Vasospastic angina
```
Rest angina
<10% of cases
Reversible spasm of coronaries
Spasm may occur during any time - even sleep
May deteriorate into unstable angina
```
36
Unstable angina
Acute Coronary Syndrome
Increase frequency and severity of attacks
Combo of plaques, platelet aggregation at plaques, vasospasm
Precursor to MI
37
Nitrate tolerance, tachyphylaxis
Loss of effect of a nitrate vasodilator when exposure is beyond 10-12 h
38
Intramyocardial fiber tension
Filling pressure Force exerted by myocardial fibers, especially ventricular fibers at any given time
(PVR, HR, EF, Venous tone, Blood volume)
A primary determinant of O2 requirements
39
Contractility is mostly controlled by
Sympathetic flow
40
Faster HR, diastole is . . .
shortened, reducing time the ventricles are filled
41
NO is produced by . . .
breaking down arginine by enzymes called nitric oxide synthase (NOS) into citrulline and NO. This primarily occurs by isoform of 3 of NOS, found in endothelial cells.
NO is not stored in cells and must be made when needed
By using drugs that metabolize into NO, we can reap the benefits of NO
Inhibit platelet aggregation
42
NTG
| MOA
Releases NO, increases cGMP and relaxes vascular smooth muscle
43
NTG
| clinical application
Acute angina pectoris
| ACS
44
NTG onset and dose
rapid
5-10 mcg/min is a standard starting dose.
Angina relief is typically 75-150mcg/min but may require up to 600mcg/min.
Arterial dilation at 150mcg/min
45
NTG
| interactions
Do not use with right sided infarct bc preload dependent
Do not used with phosphodiesterase inhibitors because causes profound hypotension
Do not use as preemptive for ischemia during induction bc causes hypotension
Can cause headache, tachycardia
Arterial dilation at higher doses, causing drop in BP. While infusing intravenous NTG for ischemia, if hypotension occurs, add phenylephrine. May cause reflex in HR and contractility that can increase O2 consumption, but adding a BB can mitigate this.
46
NTG and pulmonary artery vasodilation
Can inhibit Hypoxic Pulmonary Vasoconstriction and Can worsen intrapulmonary shunting
47
Ca+ channel blockers
| MOA
reduce myocardial oxygen demand by depressing contractility, HR and BP. Also dilate coronary arteries
Blocks L-type Ca+ channels in smooth muscle and heart
Decreases intracellular Ca+
Work at SA and AV nodes
Inhibit platelet aggregation
48
Ca+ Channel Blockers
| clinical application
Angina
HTN
AV nodal arrhythmias
Migraine
49
Ca+ Channel Blockers types
4 classes:
1. DHPs - nifedipine, nicardipine, amlodipine.
2. Benzothiazepinesinclude - diltiazem.
3. Phenylalkylamines - verapamil.
4. Diarylaminopropylamineether - Bepridilis
50
DHPs
potent arterial dilator with little venodilating effects, which causes a reflexive tachycardia.
Used as anti-hypertensive
Antianginal effects come from reduced myocardial oxygen requirements from afterload reduction and coronary artery dilation.
51
What is the most potent coronary dilatory?
Nifedipine
52
Phenylalkylamines
has less potent arterial dilation and less reflex tachycardia concern.
Used for effects on conduction pathway of the heart to slow tachyarrhythmias
53
What is the least potent vasodilator CCB?
dilt
54
CCB side effects
```
Hypotension
dizziness
flushing
nausea
edema
```
Diltiazem & verapamil also cause bradycardia and myocardial depression.
55
What is the most potent dilator of the DHP CCBs?
Nicardipine
56
Verapamil side effects
Increase digoxin levels
When combined with BB, the risk of AV block and myocardial depression increases
Metabolized by liver
57
Clevidipine
Metabolized by nonspecific tissue esterases and is very short acting
58
Beta blockers
reduce oxygen consumption through lowering HR, BP, and contractility
If can't administer NTG and BB due to BP, BB take precedence
reduce insulin release and suppress glycogenolysis and gluconeogenesis
May cause bronchospasm
59
Beta blocker MOA
Blocks sympathetic effects on heart and BP
Reduces renin release
Reduce MI size
Chronic BB therapy causes upregulation of beta receptors, and when held cause reflex effects
60
BB
| clinical application
```
Angina
HTN
Arrhythmias
Migraine
anxiety
```
61
Mixed BB
Some BB –acebutolol, carteolol, penbutolol, pindololare
- are partial agonists (meaning they don’t reach the same physiologic maximum at receptors) and also competitively antagonist.
- There is less CO and HR reduction than seen with full antagonists.
- Benefit in COPD patients as there is less B2 antagonism
62
Lipid soluble BB
```
produce CNS effects
metabolized by liver
propranolol
labetalol
metoprolol
```
63
Lipid insoluble BB
atenolol, nadolol, acetbutolol, and sotalol
Renal excretion
64
Propranolol
Most lipid soluble
Most CNS effects
Non-selective BB (B1 and B2)
1 mg dose
65
Metoprolol
1st selective BB
30x affinity for B1 vs B2
1-2 mg doses
66
Esmolol
B1
9 minute half life
Prolonged/high use can produce methanol, toxic alcohol
- loading dose of 0.5mg/kg followed by infusion of 0.05-0.3mg/kg/minute
67
Labetalol
5-10 x > BB than Alpha 1 blocker
Partial B2 agonist
peripheral vasodilator that lacks reflex tachycardia
68
Other antianginal drugs
| Ranolazine
Blocks late Na+ current in myocardium, reduces cardiac work
Can cause QT prolongation
69
Other antianginal drugs
| Ivabradine
Blocks pacemaker Na+ current in SA node, reduces HR
70
Baroreceptor reflex
Primary autonomic mechanism for BP homeostasis
Involves sensory input from carotid sinus and aorta to the vasomotor center and output via the parasympathetic and sympathetic motor nerves
71
Catecholamine reuptake pump
Nerve terminal transporter responsible for recycling norepi after release into the synapse
72
Catecholamine vesicle pump
storage vesicle transporter that pumps amine from cytoplasm into vesicle
73
Essential HTN
HTN of unknown etiology/Primary htn
74
False transmitter
Substance stored in vesicles and released into synaptic cleft but lacking the effect of the true transmitter - i.e. norepi
75
HTN emergency
Accelerated form of severe HTN associated with rising BP and progressing damage to vessels and end organ180/110
Needs to be treated immediately
- Nitroprusside, nicardipine, clevidipine, fenoldopam
76
Postganglionic neuron blocker
drug that blocks transmission by an action in the terminals of the postganglionic nerves
77
Rebound HTN
Elevated BP resulting from loss of antihypertensive drug effect
78
Reflex tachy
Tachy resulting from lowering of BP mediated by the baroreceptor reflex
79
Sympatholytic
Drug that reduces effects of the sympathetic NS
80
When pressures rise above 115/75 . . .
Double the risk for CV M & M for each 20/10 mmHg increase.
81
Diuretics for HTN
Thiazides
loop
K+ sparing diuretics
82
Thiazides
| MOA
HCTZ, Chlorthalidone
Block Na/Cl transporter in DCT
10 mmHg decrease in BP
83
Thiazide toxicities/interactions
Hypokalemia
Hyperglycemia
Hyperuricemia
Hyperlipidemia
84
Loop diuretics
| MOA
Furosemide, Torsemide
| Block Na/K/2Cl transporter in thick ascending loop
85
Loop toxicities/interactions
Hypokalemia
Hypokalemic metabolic acidosis
Hypovolemia
ototoxicity
86
K+ sparing
| MOA
inhibit Na+ reabsorption in Distal Collecting Duct, which indirectly increases the K+ excreted
Contraindicated in pts with hyperkalemia
87
Angiotensinogen
Angiotensinogen is made by the liver and found in the blood. When renin is released, it cleaves angiotensinogen peptide into angiotensin I.
When angiotensin 1 comes into contact with angiotensin converting enzyme (ACE) (found in the endothelium of the vasculature), cleaved into angiotensin II.
88
ACE inhibitors
block conversion of AT1 to AT2
| Frontline drug for HTN
89
ACEI toxicities/drug interactions
- dry cough that bradykinin elicits.
- angioedema not associated with dose changes (said differently, it can occur years into a stable therapy).
- hyperkalemia/contraindicated with bilateral renal artery stenosis.
- can produce severe hypotension in the anesthesia patient.
- teratogens.
90
ARBs MOA
They bind to the AT1 receptor and directly inhibit the vasoconstrictive effects of angiotensin II.
91
ARBs toxicities/interactions
Hyperkalemia
| Teratogen
92
Renin antagonist
Aliskiren
Renin inhibitor, reduces angiotensin I synthesis
Can cause angioedema, renal impairment
93
Alpha 1 antagonists
competitively block NE at the post synaptic alpha 1 receptors.
- causes vasodilation
- Side effects are orthostatic hypotension, fluid retention, reflex tachycardia.
- front line drug for BPH.
- Prazosin , Doxazosin, terazosin, Tamsulosin
94
Methyldopa
| Sympathoplegic
prodrug that is converted to its active drug in the brain.
95
Clonidine
| Sympathoplegic
Agonist at alpha 2 receptor
In CNS results in decreased SANS outflow
Inhibits NE release
Sedation, dry mouth, depression
Severe rebound htn if suddenly stopped; treat with alpha 1 antagonist
96
Sympathoplegic
reduce cardiac output, SVR.
| The body compensates with salt and water retention.
97
Hydralazine
MOA
Side effects
Causes release of Nitric acid by endothelial cells
Causes arteriolar dilation
Side effects: lupus like syndrome, tachycardia, salt and water retention
98
Minoxidil
Prodrug, sulfate metabolite opens K+ channels, causing arteriolar smooth muscle hyperpolarization and vasodilation
Side effects: tachycardia, salter and water retention, hair growth
99
Nitroprusside
Release NO from drug molecule
Arterial and venous dilation
Side effects: Cyanide toxicity
100
Fenoldopam
D1 agonist
Causes arteriolar dilation
Excessive hypotension
Used for renal insufficiency
Side effects: hypotension
101
Drugs used in HF
Positive inotropic drugs
Vasodilators
Misc
102
Positive inotropic drugs
Glycosides - Digoxin
Beta agonists- (dobutamine, isoproterenol, dopamine, epinephrine, norepinephrine, milrinone)
Vasodilators - Nipride
Misc - Loops, ACEI, BB
103
catecholamine
dihydroxyphenylethylamine derivative, polar molecule, that is readily metabolized
104
decongestant
an alpha agonist drug that reduces conjunctival, nasal, or oropharyngeal mucosal vasodilation by constricting bv in mucosa
105
Mydriatic
drug that causes dilation of the pupil; opposite of miotic
106
Sympathomimetic
drug that mimics stimulation of the sympathetic autonomic NS
107
Epinephrine
| MOA and side effects
alpha 1
alpha 2
Beta 1, 2, 3
Agonist
Side effects: HTN, arrhythmia, MI, pulm edema
108
Norepinephrine
| MOA and side effects
Alpha 1, 2
Beta 1
Agonist
Used for profound vasodilation
Vasospasm, tissue necrosis, arrhythmias
109
Dopamine
| MOA and side effects
D1
Alpha 1, 2
Beta 1, 2, 3
Agonist
Relatively weak inotrope
Start higher if need inotropy, low doses cause vasodilation
arrhythmias
110
Isoproterenol
| MOA
B1, 2, 3
Agonist
Nebulizer in acute asthma, AV block
111
Dobutamine
B1 agonist
| Acute HF to increase Co
112
Heart failure
HF is when the CO doesn’t meet oxygen demands of tissues.
CHF means both L and R heart failure
Comes from injury/death of heart tissue or remodeling and decline in function. The body’s response is sympathetic and activates the RAAS system, which eventually fails.
113
Explain how RAAS system is activated in HF
Kidney juxtaglomerular cells release renin in response to decreased BP or renal perfusion. The end result is AT2 vasoconstriction, aldosterone release, and antidiuretic hormone release. The increased effects of salt and water retention increase SVR and in the later CHF causes pulmonary congestion and hemodynamic decompensation.
The RAAS system is also known to cause cardiac remodeling. AT1 receptors are thought to mediate the remodeling on the heart.
114
Why are ACEI first line treatment in HF?
They are vasodilators.
They increase the amount of NO, bradykinin and prostacyclin circulating, all of which are vasodilators in addition to reducing the amount of the vasoconstrictor angiotensin II.
They decrease the amount of aldosterone and ADH.
They attenuate angiotensin II induced remodeling.
115
Aldosterone levels remain high in HF pts despite use of ACEI and ARBS. . .
thought to come from hypomagnesemia. Low magnesium stimulates aldosterone secretion.
Spironolactone and eplerenone. Eplerenone is better tolerated with less hyperkalemia.
116
Why are BB indicated in HF?
- improve systolic function
- help reverse remodeling
- Lower heart rate and therefore myocardial O2 consumption.
- Beta blockers are cardiac depressants.
- Clinical benefit of BB in HF patients takes 3 months
- Third generation BB have efficacy in HF patients and include labetalol and carvedilol.
-The ACC/AHA and European Society of Cardiology recommend BB use in all HF patients with reduced EFS (<40%) who are on ACEI or ARBs.
117
Carvedilol and HF
Carvedilol is a first line drug that increases insulin sensitivity, has antioxidant effects, and have Beta3 activity.
118
Hydralazine in HF
Hydralazine combined with isosorbide dinitrate reduced preload, afterload, improves regurgitant valves, improves exercise capacity and prolongs survival in HF patients.
It also interferes with remodeling.
-most impactful on African Americans
119
HF pts with symptomatic fluid overload should . . .
be optimized with diuretics before beginning BB
120
What is the only positive inotropic drug approved for HF and how does it work?
Digoxin
acts by inhibiting myocardial sarcolemmal Na/K-ATPase and thereby increasing intracellular Na+. This indirectly inhibits the Na/Ca exchanger to retain Na at the expense of extruding Ca, making contractions more efficacious from increase calcium retention.
Digoxin slows AV nodal conduction rates and can also be used in Afib.
It has a narrow therapeutic index and toxicity occurs from increased intracellular calcium. PVCs warning sign of toxicity
121
HF pts at risk for thromboembletic events. why?
Stasis in the hypokinetic heart.
also associated with afib
122
What antihypertensive is NOT used in HF pts?
Ca+ channel blockers
123
Acute CHF pt
Vasodilators (like morphine, NTG) reduce ventricular filling pressures and SVR while increasing SV and CO. They work especially well when afterload is the issue (post MI HTN).
Nesiritide is an analogous to BNP and serves as a negative feedback mechanism for AT2, NE, and endothelin. It acts by increasing cGMP levels causing arterial and venous dilation. It is very renal toxic and short-term use only
Inotropes including dobutamine or milrinone can also be used in the acute HF. These are phosphodiesterase inhibitors and increase cAMP
124
Group 1 A antiarrhythmic
Na+ channel blocker
Slow conduction velocity and PM activity
*Prolong AP
Use for atrial and ventricular arrhythmias
Procainamide
125
Group 2 antiarrhythmic
BB - block sympathetic activation
Slow PM activity
Slow phase 4 depolarization by reducing cAMP (decreased Na/Ca conductance) and PR prolongation
Esmolol
Propanolol
126
Group 3 antiarrhythmic
K+ channel blockers
| Amiodarone
127
Group 4 antiarrhythmic
Misc
| adenosine
128
Group 1 B antiarrhythmic
Highly selective use
Na blockade
*Shorten AP risk for R on T torsade's
Minimal effect in normal tissue
-Ventricular arrhythmias and digitalis induced arrhythmias
Lidocaine
129
Group 1 c antiarrhythmic
Selective use of Na channel blockade
Slowed conduction velocity and PM activity
*Unchanged AP
WPW syndrome
Used in refractory arrhythmias
130
Vasoplegic syndrome
vasopressin and methylene blue can be given
NE and phenylephrine will increase RH afterload from pulmonary vascular constriction
