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Pharm II > Vasodilators and Antihypertensives > Flashcards

Vasodilators and Antihypertensives Flashcards

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1
Q

What are some reasons for perioperative hypertension?

A 
Inadequate anesthesia
Airway manipulation
Hypercarbia
Hypoxia
Medications
Aortic cross clamp
Hypervolemia
Hypothermia
Pain
Pre-existing disease states
Type of procedure being performed
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2
Q

What is the primary cause for perioperative hypertension?

A

Increased sympathetic discharge with systemic vasoconstriction

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3
Q

What are come complications from perioperative hypertension?

A 
CVA
MI
Ischemia
LV dysfunction
Arrhythmias
Increased suture tension
Hemorrhage
Pulmonary edema
Cognitive dysfunction
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4
Q

Idiopathic hypertension accounts for how much of all hypertension?

A

95%

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5
Q

For idiopathic hypertension, the renin-angiotensin system is important in ___, but not for ___

A

Control

Development

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6
Q

How does idiopathic hypertension develop?

A

Initially, SVR is normal, increased BP is due to increased CO
SVR increases to prevent the increased BP from being transmitted to the capillary bed where it would affect cell homeostasis

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7
Q

Do most systemic vasodilators increase or decrease resistance in the pulmonary circulation?

A

Decrease

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8
Q

What is the mechanism of action for vasodilators?

A 
Direct smooth muscle dilatation (production of intracellular NO, calcium channel blockers)
Alpha-1 antagonists (prazosin and labetalol)
Ganglionic blockers (trimethaphan)
Alpha-2 agonists (clonidine, alpha-methyldopa)
ACE inhibitors (captopril and enalapril)
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9
Q

How are vasodilators classified?

A

According to their predominate effect on the circulation:

  • Arterial dilators (resistance circulations)
  • Venodilators (capacitance circulation)
  • Balanced vasodilators
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10
Q

How do arterial dilators work?

A

Dilate the arterial resistance circulation, decrease afterload and enhance CO when myocardial contractility is impaired. Most arterial vasodilators work on systemic and pulmonary arterioles

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11
Q

How do venodilators work?

A

Dilate the venous capacitance circulation and decrease preload, pulmonary congestion, and edema

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12
Q

How do balanced vasodilators work?

A

Dilate the arterial and venous systems and decrease preload and afterload

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13
Q

What are some examples of arterial dilators?

A

Hydralzine
ACE inhibitors
Nicardipine

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14
Q

What is an example of a balanced dilator?

A

Nitroprusside

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15
Q

What is an example of a venodilator?

A

Nitroglycerine

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16
Q

What are the primary effects of vasodilators?

A

Act primarily to cause systemic vasodilatation and decrease afterload

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17
Q

T/F: Pure arteriole dilator causes maximal effects on preload

A

False, causes minimal effects of preload

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18
Q

Are there pure venodilators?

A

No, not available

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19
Q

What is the only “pure” pulmonary vasodilator?

A

Inhaled NO

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20
Q

What are the indications for vasodilators?

A 
Hypertension
Low CO (must maintain preload)
Valvular insufficiency
Coronary and cerebral vasospasm
Pulmonary hypertension
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21
Q

When does the LV get perfused?

A

70-90% of the coronary artery perfusion to the LV occurs during diastole

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22
Q

What governs perfusion?

A

Aortic diastolic pressure

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23
Q

In the presence of ischemic heart disease, the ___ ___ are maximally dilated and coronary perfusion is largely ___ dependent

A

Collateral arteries

Pressure

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24
Q

What is the formula for coronary perfusion pressure?

A

Transmyocardial gradient (TMG) = Aortic diastolic pressure (ADP) - LVEDP or PCWP

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25
What is coronary steal?
Narrowed coronary arteries are always maximally dilated to compensate for the decreased blood supply. Dilating the other arterioles causes blood to be shunted away from the coronary vessels
26
Which drugs can help treat myocardial ischemia?
Nitroglycerine Calcium channel blockers Sodium nitroprusside
27
How does Nitroglycerine work?
Venodilation decreases venous return and filling pressures - Relative increase in coronary perfusion pressure facilitates subendocardial and collateral blood flow - Wall tension and myocardial O2 demand decrease - Mild arteriolar dilatation may decrease BP and cause a reflex increase in HR
28
How do calcium channel blockers work for myocardial ischemia?
All are coronary and systemic vasodilators May produce myocardial depression Useful to treat coronary vasospasm
29
What are some adverse effects to vasodilators?
- Acute hypotension in hypovolemic patients - Older patients more sensitive to vasodilatation because of an attenuated baroreceptor reflex and impaired reflex tachycardia - Rebound hypertension when abruptly discontinued - Hypoxemia from reversal of hypoxic pulmonary vasoconstriction - Increased CBF, increased ICP, and decreased CPP in patients with a closed head injury or intracranial hypertension - Salt and water retention - Adverse effects on MvO2
30
What are the nitrovasodilators?
Nitric oxide | SNP and NTG
31
___ spontaneously generates NO while ___ requires a cofactor to release NO in smooth muscle
SNP | NTG
32
SNP receives an electron from oxyhemoglobin and dissociates immediately releasing,
Methemoglobin NO 5 cyanide molecules
33
How does NO work?
Activates guanylyl cyclase leading to the formation of cGMP in vascular smooth muscle cells. cGMP inhibits calcium entry into smooth muscle cells and produces vasodilitation
34
What are the effects of nitric oxide?
Vasodilator Relaxes other smooth muscle Increases blood flow to parts of the lung exposed to NO and decreases pulmonary vascular resistance
35
What are the clinical application for NO?
Hypoxic respiratory failure Pulmonary artery hypertension Cardiopulmonary resuscitation
36
How do you administer NO?
Inhalation as a gas Dosed in ppm -NO is stored as a compressed gas that is mixed with nitrogen: 100 or 800 ppm. Dose: 18 ppm
37
What is the toxicity and adverse interactions for NO?
- React with oxygen to form nitrogen dioxide (NO2): pulmonary irritant that can decrease lung function - Can induce the formation of methemoglobin: hemoglobin that cannot bind to oxygen - Monitor NO2 and methemoglobin levels during administration
38
What is an alternative strategy to NO?
PDE (isoform 5) inhibitors - Inhibit PDE that degrades cGMP in vascular smooth muscle - Results in the prolongation of the duration of NO-induced cGMP elevations - Approved for the treatment of PAH
39
How does SNP act as a balanced vasodilator?
- Direct action on vascular smooth muscle - Decreased MAP and MPP - Decreases LA and LV filling pressures - Decreased afterload promotes forward flow in MR and AI - May dilate coronary arteries (coronary steal) - No direct myocardial depression
40
Does SNP increase or decrease cerebral blood flow and ICP?
Increase
41
What happens with abrupt discontinuation of SNP?
Reflex tachycardia and hypertension
42
Does SNP cause and increase or decrease in renal blood flow?
Decrease
43
What is the dose for SNP?
- Start with 0.1-0.2 mcg/kg/min IV - Recommended max dose 0.5 mg/kg/hr (8-10 mcg/kg/min) for 10 mins - Over 2-4 mcg/kg/min, add a second drug (BB, trimethopham)
44
What are some misc. facts about administration of SNP?
- Requires placement of aline - May be administered peripherally - Protect from light - Mix in D5W
45
What are the pharmacokinetics of SNP?
- Onset: <1 min - Duration: 5-10 mins - Peak: 2-3 mins - Half life: 2.7-7 days
46
What are the CNS side effects of SNP?
``` Restlessness Apprehension Muscle twitching HA Dizziness ```
47
What are the CV side effects of SNP?
Profound hypotension Palpitations Fluctuations in HR Retrosternal discomfort
48
What are some other side effects of SNP?
``` N/V Abdominal pain Nasal stuffiness Increased serum creatinine Thiocyanate/cyanide toxicitiy ```
49
What are the advantages to using SNP?
Immediate onset Short duration Reduced myocardial O2 demand
50
What are the disadvantages to using SNP?
``` Reflex tachycardia Cyanide toxicity Intrapulmonary shunting Precipitous drop in BP is possible Photodegradation Methemogloninemia Coronary steal Enhanced bleeding Cerebral vasodilator ```
51
What is the hyperdynamic response to SNP?
Progressive widening of the arterial pulse pressure | Increase in HR
52
How do you treat the hyperdynamic response to SNP?
BB to suppress reflex tachycardia, narrow the pulse pressure and be able to treat the hypertension with a lower dose of SNP
53
What is the metabolism of SNP?
Can break down to 5 cyanide molecules: - CN can react with methemoglobin to form cyanomethemoglobin - CN can be converted to thiocyanate in the liver or kidneys by the rhodanase enzyme (requires thiosulfate) - CN may inactivate cytochrome oxidase in cells (changes cells from aerobic to anaerobic metabolism)
54
Toxicity of SNP depends on what?
- How rapid the drug is given (max dose should not be infused for longer than 10 mins) - Total amount given: > 2 mcg/kg/min can lead to accumulation of cyanide and cyanide toxicity
55
When does cyanide intoxication occur?
When the detoxification pathways are overwhelmed by the rapid administration of SNP. CN enters the cell and binds and inactivated Fe3 cytochrome oxidase and blocks cellular use of oxygen (cytotoxic anoxia)
56
What is acute cyanide toxicity associated with?
Tachyphylaxis Increasing SvO2 Metabolic acidosis Cardiac dysrhythmias
57
How does thiocyanate/cyanide toxicity present itself?
``` Hypotension Blurred vision Fatigue Metabolic acidosis Pink skin Absence of reflexes Faint heart sounds ```
58
What are the therapeutic, toxic and fatal doses of thiocyanate?
Therapeutic: 6-29 mcg/ml Toxic: 35-100 mcg/ml Fatal: >200 mcg/ml
59
What are the normal, toxic and fatal doses of cyanide?
Normal: 2 mcg/ml Fatal: > 3 mcg/ml
60
How do you treat cyanide toxicity?
Stop infusion, administer 100% O2 Give bicarb Administer 3% sodium nitrite 4-6 mg/kg slowly IV Administer sodium thiosulfate 150-200 mg/kg IV over 15 mins
61
T/F: Thiocyanate cannot be removed with dialysis
False, can be removed with dialysis
62
Methemoglobin reductase converts what?
Methemoglobin to hemoglobin
63
How much methemoglobin is produced with a SNP dose of 1 mg/kg?
10% methemoglobin
64
How do you convert methemoglobin back to hemoglobin?
Methylene blue 1-2 mg/kg IV over 5 mins
65
What are the side effects of methemoglobin?
- HA, NV, palpitations, abd pain | - Worsening intrapulmonary shunt
66
Thiocyanate inhibits the uptake and binding of iodine and may cause what with chronic use?
Hypothyroidism
67
SNP reverses what?
Hypoxic pulmonary vasoconstriction
68
T/F: thiocyanate is a metabolite
True
69
NTG requires what to release NO?
A cofactor such as a cysteine (a thiol)
70
NTG increases ___ blood flow relative to ___ blood flow
Endocardial | Epicardial
71
Does NTG dilate or constrict meningeal vessels?
Dilate, caution with increased ICP
72
Does NTG increase or decrease renal blood flow?
Decreases renal blood flow with decrease in systemic BP
73
What are the indications of NTG?
Ventricular failure Hypertension Ischemic heart disease
74
How is NTG metabolized?
Metabolized by glutathione nitrate reductase in the liver | Nitrite ion oxidizes Hgb to methemoglobin
75
How does the body build a tolerance to NTG?
Tolerance in arterial vessels can occur with chronic administration but not in the venous vessels
76
What is the IV dose of NTG?
Initial: 0.5 mcg/kg/min (we use 5 mcg/min) Titrate to desired hemodynamic response Small IV bolus dose for uterine relaxation
77
What is the sublingual dose of NTG?
0.3-0.8 mg (bypasses a lot of first-pass effects)
78
What is the pharmacokinetics of NTG?
Onset: 1 min Duration: 3-5 mins Half-life: 1-4 mins
79
What are the adverse effects of NTG?
``` Postural hypotension Tachycardia HA Dizziness Weakness Methemoglobinemia ```
80
What are the contraindications to using NTG?
``` PDE5 inhibitors Narrow angle glaucoma Head trauma, cerebral hemorrhage Severe anemia Hypotension ```
81
What are the advantages to using NTG?
``` Rapid onset Short duration Coronary vasodilator Decreased myocardial O2 consumption No major toxicities No coronary steal Reduced PVR ```
82
What are the disadvantages to using NTG?
``` Decreased diastolic BP Reflex tachycardia Possible hypotension Variable efficacy Tachyphylaxis Methemoglobinemia Intrapulmonary shunting Prolonged bleeding time ```
83
How does Hydralazine work?
Direct-acting dilator of vascular smooth muscle due to hydralazine-related interference with calcium ion transport
84
What does Hydralazine do clinically?
``` Decreases SVR (decreases dBP more than sBP) Increases CO HR and SV Effect on arterioles greater than veins so minimal risk for orthostatic hypotension ```
85
Does rebound hypertension occur with hydralazine?
No but ICP increases significantly
86
What are the advantages to Hydralazine?
Maintains/increases cerebral blood flow | Increased CO and SV
87
What are the disadvantages to hydralazine?
``` Reflex tachycardia Reduced pressor response to ephedrine Drug interactions Sodium and water retention (increases renin activity) Longer duration of action ```
88
What are the CNS side effects to Hydralazine?
HA Dizziness Tremor Vertigo
89
What are the CV side effects to Hydralazine?
``` Palpitations Angina Tachycardia Flushing Reflex tachycardia ```
90
What are the GI side effects to Hydralazine?
``` Anorexia NV Abd pain Paralytic ileus Diaphoresis ```
91
What other side effects can occur with Hydralazine?
``` Anemia Agranulocytosis Nasal congestion Muscle cramps Edema Sodium and water retention ```
92
Who do you want to avoid Hydralazine with?
Patients with CAD, increased ICP, lupus
93
What is the dose of Hydralazine?
5-20 mg IV
94
What are the pharmacokinetics of Hydralazine?
Onset: 10-20 mins Peak: 30-60 mins Duration: 3-6 hrs Half-life: 3-7 hours
95
T/F: Tachyphylaxis does not occur with hydralazine
False, tachyphylaxis may occur
96
Activation of alpha 1 receptor increases intracellular calcium causing what?
Smooth muscle contraction Peripheral vasoconstriction Bronchoconstriction
97
What else does activation of alpha 1 receptor do?
Inhibits insulin secretion (stimulates glycongeloysis and gluconeogenesis) Mydriasis GI relaxation
98
Alpha 2 receptor activation inhibits neuronal firing in the CNS and PNS causing what?
Hypotension Bradycardia Sedation Analgesia
99
What else does alpha 2 receptor activation do?
Decreased salivation and secretions Decreased GI motility Inhibit renin release, increase GFR, increased NA and H2O secretion Decreased insulin release
100
What are some of the alpha1 antagonists?
Phentolamine Phenoxybenzamine Prozosin (minipres)
101
How do alpha1 antagonists work?
Block the effect of endogenous catecholamines on arterial and venous constriction
102
What are some side effects of alpha1 antagonists?
Hypotension Nasal congestion Orthostasis
103
How does Phentolamine work?
Alpha adrenergic blockade and direct-acting vasodilator | Greater arterial than venous
104
What clinical effects does Phentolamine do?
Decreases afterload and preload Promotes greater EF and CO Decreases PVR Used for vasoconstrictor infiltrate
105
What is the dose if phentolamine is used for a vasoconstrictor infiltrate?
5-10 mg in 10 ml NSS
106
Does phentolamine increase or decrease airway resistance?
Decrease in and improves asthma symptoms
107
What are the uses for phentolamine?
Hypertension secondary to pheochromocytoma Clonidine withdrawal hypertension Erectile dysfunction Extravasation of catecholamines
108
What is Phenoxybenzamine (dibenzyline)?
Prototype alpha1 antagonist | Irreversibly binds to the receptor
109
What is the use of Phenoxybenzamine?
Long-term preop treatment to control the effects of pheochromocytoma (chemical sympathectomy) Relieve ischemia in PVD Improve flow in patients with BPH
110
How does Phenoxybenzamine work?
Reduced PVR to reduce BP Secondary increases in NE d/t alpha2 blockade can increase HR and CO Crosses the BBB
111
What are the side effects of Phenoxybenzamine?
CNS: sedation, depression, tiredness, lethargy, HA GI: N/V CV: postural hypotension, tachycardia, arrhythmias
112
What are the pharmacokinetics of Phenoxybenzamine?
Half-life: 24 hours | Duration of action: 4 days
113
What is Prazosin (minipres)?
Oral selective alpha1 antagonist Peripheral vasodilator (arteries > veins) Increases HR Improves urinary flow
114
What is clonidine?
Central acting alpha-2 agonists that leads to inhibition of sympathetic outflow Decreases release of sympathetic neurotransmitters Inhibits renin release
115
What are the pharmacokinetics of clonidine?
Rapidly and completely absorbed from po dosing with peak in 60-90 mins Half life: 9-12 hours Patch takes 2 days to reach full potential
116
What are the adverse effects of Clonidine?
Drowsiness Dizziness Dry mouth Orthostasis
117
What are the uses for Clonidine?
Premedication (sedation, anesthetic sparing effect) Regional anesthesia Postop analgesia Analgesia for labor Chronic pain Prevention/treatment of drug withdrawal and postop shivering
118
What are clonidines effects on anesthesia?
- Reduces propofol and thiopental requirements - Alternatives to N2O for shortening induction time and attenuating the adrenergic response to intubation during inhaled anesthesia - Supplement of regional blocks
119
What are the clinical effects of clonidine?
Decreases HR, BP, CO and SVR (baroreceptor reflexes are preserved)
120
Abrupt cessation of clonidine may lead to what?
Rebound hypertension
121
Clonidine withdrawal manifests how?
``` Excessive hypertension Tachycardia Restlessness Insomnia HA Nausea ```
122
Which alpha-2 agonist is almost as potent as NE?
Alpha-Methyldopa (Aldomet)
123
What is Alpha-Methyldopa metabolized to?
Alpha-methylepinephrine in the CNS which acts at Alpha-2 receptors to decrease sympathetic outflow
124
What is the use of Alpha-Methyldopa?
Treatment of hypertension during pregnancy (usually 3rd trimester)
125
What is the dose for Alpha-Methyldopa?
500 mg to 2 gm in 4 divided doses po or IV
126
What are the side effects of Alpha-Methyldopa?
``` Sedation, HA, dizziness Fluid retention Orthostatsis, bradycardia Hepatic necrosis Dry mouth, diarrhea, NV Positive coombs test, hemolytic anemia, bone marrow suppression, impotence, rash ```
127
What are the alpha 2 agonists?
Clonidine Alpha-Methyldopa Precedex
128
Relatively selective alpha2 agonist for continuous IV sedation in ICU
Precedex
129
T/F: Precedex has an analgesic effect
False
130
What can Precedex be used for as a preop med?
Anxiolytic Sympatholytic Analgesic Sedative
131
What can Precedex be used for intraop?
``` Reduces the stress response Improved respirations Hemodynamic stability Improves efficacy of anesthetics Increased recovery time Less pain meds necessary ```
132
What does Precedex help with postop?
May reduce opiate use by as much as half, reduced postop shivering
133
T/F: Precedex has amnestic effects
False
134
What is the dosage of precedex?
Bolus 0.5-1 mcg/kg over 5-10 mins (4mcg/mL in 5 ml syringe) | Follow with IV infusion of 0.5-1 mcg/kg/hr
135
What are the adverse effects of precedex?
NV Bolus: HTN, bradycardia Infusion: Hypotension
136
Which drug is unsafe to administer for >24 hours continuous infusion?
Precedex
137
What do ACE inhibitors do?
Block the conversion of angiotensin I to angiotensin II preventing vasoconstriction
138
Are ACE inhibitors primarily venous or arterial vasodilators?
Arterial vasodilators
139
Risk of acutre renal failure in the intra and postop periods in patients on what?
ACEIs or ARBs
140
How do ACE inhibitors work on your renal function if your baseline BP is hypertensive?
decreased renal vascular resistance improves RBF and GRF
141
How do ACE inhibitors work on your renal function if your baseline BP is normotensive?
If BP is decreased, renal function may deteriorate because compensatory efferent arteriolar constriction mediated by angiotensin II is blocked and decreased glomerular filtration pressure and GFR may result in acute hyperkalemia
142
What type of patients do you avoid giving ACEI's to?
Decreased renal function or renal artery stenosis
143
What is the initial dose of Vasotec?
1.25 mg IV q 6 hours
144
What are the advantages to ACE inhibitors?
Minimal side effects | CHF, bronchospasm, hypokalemia, hyponatremia, and rebound HTN not seen with abrupt withdrawal
145
What are the side effects of ACE inhibitors?
Cough Congestion Rhinorrhea Angioedema
146
Is it safe to use ACE inhibitors during pregnancy?
No, causes fetal morbidity and mortality
147
What are the angiotensin II receptor antagonists?
``` Losartan (Cozaar) Irbesartan (Avapro) Valsartan (Diovan) Olmesartan (Benicar) Telmisartan (Micardis) Eprosartan (Teveten) ```
148
What are the advantages of Angiotensin II Receptor Antagonists?
Save hemodynamic effects and uses and ACEI Less cough/angioedema Available PO, no IV yet
149
What are the types of dopaminergic agonists?
DA1 (renal vasodilation and naturesis) DA2 (presynaptic)--> inhibit NE release and promote vasodilatation. Attenuate the beneficial effects of DA on renal blood flow
150
What is a Dopaminergic agonist?
Fenoldopam (Corlopam)
151
What is Colopam?
Selective DA1 agonist with moderate affinity for presynaptic alpha2 receptors
152
Does Colopam have any beta or alpha effects?
No beta or alpha1 or DA2 effects
153
What do Colopam do clinically?
Decreases SVR and renal vasculature resistance resulting in decreased BP and increased LVEF and RBF
154
Does Corlopam increase or decrease RBF?
Dose-related increase in RBF. As effective as SNP in controlling BP with the added benefit of increased RBF
155
Is Dopamine or Corlopam more potent?
Colopam is 10-100 times more potent than Dopamine
156
What are the uses for Corlopam?
Short term (<48 hours) management of severe hypertension
157
T/F: Corlopam is renal protective
False, may preserve RBF and UO but NOT renal protective
158
What is the max dose of Colopam?
0.5-0.8 mcg/kg/min | Do not bolus!
159
Is an aline required for Corlopam?
No, can use a peripheral IV as well
160
What are the cautions with using Corlopam?
Dose related tachycardia with infusions >0.1 mcg/kg/min Hypokalemia may occur Cost may limit its utility

Pharm II (8 decks)

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