I. Anti-Hypertensive Drugs and Vasodilators Flashcards
1
Q
What percent of hypertensive patients suffer from “essential HTN”?
A
90%
2
Q
Essential HTN meaning?
A
HTN that occurs without an identifiable cause; unknown etiology
3
Q
Secondary HTN
A
HTN resulting from an underlying condition
4
Q
Secondary HTN examples
A
Pheochromocytoma, thyroid disease, kidney disease, diabetic nephropathy, glomerular Disease, Cushing syndrome, aldosteronism, sleep apnea (not getting enough oxygen damages blood vessels making it harder for vessels to control pressure, also the nervous system release chemicals that cause htn), obesity (more blood flow leads to HTN).
5
Q
Drugs that cause sodium and water retention, ultimately increasing BP
A
- NSAIDs (especially in kidney and heart patients: they inhibit prostaglandins which
Have vasodilatory effects, therefore vasoconstriction occurs and increases bp/prostaglandins help maintain renal blood flow and inhibition disrupts renal blood flow and electrolyte regulation, ultimately leading to increased BP). - anti diuretics
- steroid hormones (corticosteroids: mineralocorticoids, not glucocorticoids): increase Na reabsorption in the renal tubules
- anti hypertensives ( diuretics must be co-prescribed to blunt the sodium - water retention)
6
Q
Drugs used to treat HTN
A
- Direct VD
- Beta Blockers
- Ca Channel blockers
- ACE-I/ARBs
- Diuretics
- Alpha Antagonist
- Other VD
7
Q
Vascular smooth muscle contraction is primarily dependent on ____.
A
Calcium
8
Q
Describe the cascade that occurs that leads to vasoconstriction of smooth muscle (alpha-1 MOA):
(Non-ppt)
A
- GQ protein complex activates Phospholipase C
- Phospholipase C hydrolyzes PIP2 to IP3 & DAG
- IP3 activates the Sarcoplasmic Reticulum to cause release of Calcium
- Calcium causes contraction
9
Q
___ is a second messenger that mediates smooth muscle relaxation in response to various vasoactive agents such as nitric oxide (NO). :
(Non-ppt)
A
cGMP (cyclic guanosine monophosphate)
cGMP-mediated smooth muscle vasodilators are drugs that promote vasodilation by increasing the effect of cGMP
10
Q
What are some examples of cGMP-mediated smooth muscle vasodilators?
(Non-ppt)
A
- Hydralazine
- Nitroprusside
- Nitrates (angina pectoris = Nitroglycerin)
11
Q
.cGMP-mediated smooth muscle vasodilators are used to treat:
(Non-ppt)
A
- HTN
- Heart Failure
- Angina Pectoris
12
Q
Nitrates are prodrugs. They need to be converted to ____.
(Non-ppt)
A
Nitric Oxide
13
Q
Nitric Oxide Mechanism of Action (non-ppt)
A
- Nitric Oxide Synthase is present in Endothelial Cells
- Nitric Oxide Synthase uses L-Arginine & O2 to synthesize Nitric Oxide
- N.O. Diffuses to adjacent SM cells in Tunica Media where it binds and activates Guanylyl Cyclase
- Guanylyl Cyclase converts GTP to cGMP
- .cGMP is a second messenger that induces relaxation in smooth muscle cells
- .cGMP production results in vasodilation and decrease in BP
N.O. also acts to inhibit there effects of calcium independently of cGMP, although the mechanism is not completely understood
14
Q
Nitrates should not be given to ____.
(Non-ppt)
A
Patients taking erectile dysfunction medication (“-afil”) - PDE5I
*ED meds block Phosphodiesterase 5 (PD5) which is responsible for converting cGMP to GMP; therefore, there will be an excessive fall in BP = MI = Death.
15
Q
Hydralazine causes vasodilation by what mechanism?
(Non-ppt)
A
Increasing production of cGMP in SM cells, thereby reducing afterload
16
Q
Hydralazine dilates ____ more, while nitrates dilate ___ more. (Non-ppt)
A
- arteries (Hydralazine)
- veins (nitrates)
Therefore, causes a larger decrease in afterload, but less of a decrease in preload
17
Q
Hydralazine is intended to treat:
A
Acute hypertensive emergencies
Es: preeclampsia or HTN in pregnancy
18
Q
Hrydralazine & Nitrates are often prescribed to treat:
(Non ppt)
A
Chronic heart failure
19
Q
Hydralazine can cause what side-effect?
A
Reflex tachycardia
can choose to treat with Beta blockers
AVOID in pts with CAD
Drug-Induced systemic Lupus Erythematosus
Slow Acetylators may experience Hydralazine Toxicity (break down drug too slowly)
20
Q
Nitroprusside is used to HTN emergencies; what is its MOA?
(Non-ppt)
A
- Interacts with oxyhemoglobin
- Produces Nitric Oxide, Methemoglobin, and Cyanide
- NO stimulates Guanylate Cyclase in SM to produce cGMP
- .cGMP causes equal VD of peripheral arteries and veins
- Reduces both Pre-Load (vein VD) and afterload (arteries VD)
Patients are at risk for acute Cyanide poisoning: Headache, Vertigo, Confusion, Seizures, Coma, Death
21
Q
Treatment for cyanide poisoning (non ppt)
A
- Hydroxocobalamin (Injectable B12)
- Sodium nitrite + Sodium thiosulfate
22
Q
What are some examples of Central Anti-Adrenergics? (Non-ppt)
A
- Clonidine
- Dexmetetomidine (Precedex)
- Guanabenz
- Guanfacine
Anti-adrenergics: term that refers to drugs that oppose the effects of the SNS Alpha-2-Agonists
23
Q
Clinical uses of peripheral vasodilators?
A
- HTN
- Controlled HoTN (aortic dissections)
- Facilitation of LV (by manipulating afterload and preload)
- Coronary VD
- Pulmonary HTN
24
Q
Nitrovasodilators generate ____ intracellularly, producing vascular smooth muscle relaxation.
A
Nitric Oxide
25
The MOA of nitrovasodilators is an **endogenous/exogenous** process.
Endogenous
26
Nitric oxide is produced from ____ and ____ in the endothelium by ____ (enzyme).
- Oxygen & L-Arginine
- Nitric Oxide Synthase
27
Nitric Oxides production is dependent on ____ as a cofactor.
Calcium
*The increase in intracellular Calcium activates endothelial Nitric Oxide Synthase (NOS); NOS then uses L-Arginine and O2 to produce Nitric Oxide; N.O. Then diffuses into Tunica Media (smooth muscle vasculature) where it activates Guanylate Cyclase to produce cGMP (& PFG, MLCP);cGMP then relaxes smooth muscle via **Calcium Reuptake***
28
Physiologic effects of Nitric Oxide
1. Regulation of SVR and PVR
2. Bronchodilation
3. Decrease platelet activation, aggregation, and adhesion (anti-platelet = bleed risk)
4. Endogenous CNS neurotransmitter mediated by N-MDA receptors
5. Inflammation modulation
29
How does Sildenafil (Viagra) work?
Increases local availability of endogenous nitric oxide = increase in BF
30
NMDA receptor **induces/blocks** nitric oxide synthesis.
Induces
*Ex: Ketamine blocks NMDA receptors; NMDA receptor blockage causes inhibits N.O. Production; therefore, no vasodilation occurs; therefore there is increased SVR = possible increase in BP (and increased HR)*
31
Nitroglycerin is a ____ (prodrug), and must be converted to nitric oxide (active form).
Nitrate
32
Nitroglycerin can also cause ____, but only at HIGH doses. It is also rare because NTG is metabolized quickly.
Methemaglobinemia
*sublingual onset = 3 min (non-ppt)*
*sublingual DOA = 25 min (non-ppt)*
33
Nitric Oxide is rapidly inactivated by ____ and combines to form ____.
- Hemoglobin
- Methemoglobinemia
*Methemoglobinemia is more rare with NTG due to its rapid metabolism; however, MetHgb TOXICTY can occur with SNP at clinically relevant doses*
*Nitric Oxide production is increased by Nitroglycerin (a Nitrate) and Sodium Nitroprusside (Antihypertensive, i.e. NOT technically a nitrate)*
34
T/F: Hydralazine exerts its vasodilatory effects via N.O.
FALSE
Hydralazine is a direct systemic arterial vasodilator and exerts its effects by promoting the *influx (2K in/3Na out = net negative)* of Potassium; this causes hyperpolarization of the cell and muscle relaxation. *True MOA is not fully understood; it is known that cGMP is increased which causes smooth muscle relaxation = vasodilation (non-ppt)*
35
What drug is used to treat hypertensive emergencies such as Preeclampsia?
Hydralazine
36
Which drug can cause an autoimmune-like condition called “Drug Induced Systemic Lupus Erythamatosus*?
Hydralazine
*Red “butterfly” rash on face*
37
“Slow-acetylators” possess an enzyme mutation inhibiting them from breaking down certain drugs such ____, which could lead to sustained hypotension and tachycardia.
Hydralazine
38
Plasma half-life of IV nitroglycerin
3 min
39
The blue cylinder/dial on our anesthesia machines is Nitrous Oxide (N2O), which is an anesthetic and sometimes called “laughing gas.” *Nitric Oxide* is used for:
- pulmonary vasodilation (5-20 ppm)
- bronchodilation
- improved V/Q matching
- run as infusion (gas)
40
Clinical scenarios where Nitric Oxide gas may be used?
- Newborn pulmonary HTN
- Adult Respiratory Distress Syndrome (ARDS)
- Cardiac transplant
*Methemoglobinemia can still occur as NO combines with oxyhemoglobin.*
41
Sodium Nitroprusside (Nipride) causes vasodilation of ____ vascular smooth muscle.
**ARTERIAL**
42
Nitroprusside interacts with Hgb, dissociating immediately to form:
- MetHgb
- CYANIDE
- N.O.
43
Metabolism of Nitroprusside yields:
- MetHgb
- Cyanide
- Thiocyanate
44
Clinical uses for Nitroprusside?
1. Controlled Hypotension
2. Hypertensive Emergencies (Pheochromocytoma, Thyrotoxicosis)
3. Cardiac Disease
4. Aortic Surgery
5. Cardiac Surgery
45
Clinical Considerations (S/E) of administering Nitroprusside:
- Cardio: hypotension, reflex tachycardia, decrease pulmonary arterial pressures
- CNS: Increase CBF, CBV, ICP (at <30% MAP)
- Respiratory: Attenuates HPV (via VD)
- Other: Rebound HTN after abrupt discontinuation , Coronary Steal, Decreased platelet aggregation (>3 mcg/kg/min)
46
Which drug is photosensitive?
Nitroprusside
*comes in amber vial, place 250cc bag in protective sleeve, then inject medication*
47
Nitroprusside (Nipride) infusion dose
0.3 - 10 mcg/kg/min
MetHgb toxicity can occur >8 mcg/kg/min
48
Nitroprusside IVP dose
100 mcg
49
Maximum dose of Nitroprusside (10 mcg/kg/min) not to be administered for greater than ____.
10 minutes
50
At what dose of Nitroprusside do you encounter decreased platelet aggregation (bleed risk)?
>3 mcg/kg/min
51
Nitroprusside clinically observed DOA (Weirich anecdotal)?
~2 min *short-acting*
*great for clipping aneurysm or cannulating aorta where acute BP control is needed temporarily*
52
Cyanide Toxicity is a concern with what drug?
Nitroprusside
53
How is cyanide eliminated in the body?
Hepatic elimination at rates <2 mcg/kg/min
54
Signs of cyanide toxicity
- Tachyphylaxis
- Metabolic Acidosis
- Anaerobic Metabolism and lactate formation (inhibits aerobic respiration)
- Increased venous PO2
- lactate concentration >10 mmol/L (non-ppt)*
- cyanide >40 micro moles/L (non-ppt)*
55
Treatment of Cyanide poisoning
1 .100% O2 *despite normal SpO2*
2. NaHCO3 (Sodium Bicarbonate) to correct acidosis
3. **Sodium thiosulphate** (200 mg/kg) over 15 min: removes CN
4. **Sodium Nitrite**: sequesters the cyanide (CN)
56
Thiocyanate Toxicity can occur with what drug if it is ran for extended period? How is is treated/reversed?
- Nitroprusside
- Tx: Stop SNP infusion
57
Thiocyanate Toxicity clinical signs
1. Fatigue
2. Nausea & Vomiting
3. Hyperreflexia (muscles have increased reflex response)/muscle cramps
4. Psychosis (disconnection from reality)
58
Thiocyanate is ____x less toxic compared to cyanide (CN)
100
59
Methemoglobinemia occurs with any substance that increases N.O. (Nitric Oxide, **SNP**, NTG); what is the required dose (IVP & Infusion) of SNP to evoke MetHgb?
~10 mcg/kg
>8 mcg/kg/min
60
MetHgb clinical signs
- Impaired oxygenation despite adequate CO and arterial oxygenation
61
Treatment for Methemoglobinemia
Methylene Blue IVP 1-2 mg/kg
62
Nitroglycerin (NTG) causes what?
1. Dilation of venous capacitance vessels (more so than systemic arterial vasculature)
2. dilates large coronary arteries
63
NTG MOA
NO mediated vasodilation
64
T/F: NTG is susceptible to tolerance after 48 hours.
FALSE
*after 24 hours*
65
T/F: NTG causes increased platelet aggregation
FALSE
Decreased platelet aggregation
66
Nitroglycerin is a good choice to **decrease/increase** pre-load.
Decrease (venous dilation occurs resulting in venous pooling in lower extremities)
*NTG also dilates large coronary arteries improving blood flow/oxygen delivery to heart; this coronary dilation decreases SVR which decreases the workload of the heart, thereby decreasing oxygen consumption.*
67
Nitroglycerin causes mainly ____ dilation.
Venous
68
NTG causes NO to be released through ____ - dependent pathway.
Glutathione
69
NTG causes what side effects?
- Controlled HoTN
- **Cerebral VD: increased ICP, CBF & headache**
- Uterine Relaxation
- Rare risk of MetHbg-emia
70
NTG clinical uses
- Angina Pectoris
- Acute HTN
- ACS
- Cardiac Failure
- Controlled HoTN
- Sphincter of Oddi Spasm *(muscular valve surrounding the exit of the bile duct and pancreatic duct into the Duodenum, opens to allow bile juices to assist with food digestion)*
71
- NTG will dilate sphincter of Oddi if surgeon is trying to cannulate (ERCP procedure)
- Opioids will constrict it
- Glucagon 1 mg will constrict it
72
NTG infusion dose
0.3 - 10 mcg/kg/min
73
NTG sublingual dose
0.3 mg
74
Nitroglycerin transdermal dose
0.6 mg/hr
75
NTG IVP dose
100 mcg
76
Methods of giving NTG
- infusion
- sublingual
- transdermal
- oral spray
- IVP
77
Other name of NTG
Nitrobid
78
Beta 1 blockers decrease ____ formation, ultimately leading to ____.
-cAMP
-increased reuptake of Calcium (less Calcium = less contraction)
79
B1 Blockers are what type of antagonists?
Competitive
80
Beta blockers decrease CO via ____ & ____.
- decreasing contractility (negative inotropy)
- decreasing HR (negative chronotropy)
81
Beta blocker side effects:
- Bradycardia
- AV Heart Block
- CHF exacerbation *(the maintenance of CO depends in part on sympathetic drive)*
- HoTN
- Reduced Myocardial Oxygen Demand
82
Which type of beta blocker can allow for bronchospasm and therefore should both be given to at-risk asthmatics?
Non-selective (e.g. propranolol)
*block Beta 2 which then inhibits bronchodilation*
83
Atenolol, Esmolol and Metoprolol are all what type of beta blockers?
Beta 1 “Selective”
84
Labetalol & Carvedilol (non-selective beta blockers) are what ratio alpha:beta
1:7
*this is counterintuitive, b/c Labetalol has far greater impact on the BP (alpha) compared to HR/Contractility (Beta)*
*maybe affinity for alpha receptor is far greater than beta???*
85
ACE-I are effective against HTN caused by ____
Increased renin
86
What do ACE-I block?
1. The conversion of Angiotensin 1 to Angiotension 2
(This ultimately blocks the release of Calcium from SR = NO VC = decreased BP)
*- If not blocked, Angiotensin 2 acts on AT1 receptors
- Activates Phospholipase C
- Phospholipase C increases DAG & IP3
- DAG & IP3 INCREASE Calcium release from SR = VASOCONSTRICTION
- Also increases release of NE & inhibits its uptake*
2. Aldosterone release is blocked (Aldosterone: Na & H2O retention)
(This results in reduced Na & water retention = decreased BP)
87
Why do we not want our patients to take ACE-I prior to surgery?
Because it will inhibit our ability to increase BP during the procedure
*Under anesthesia, sympathetic responses are diminished = unable to increase BP*
*ACE-I block the ability of the body to VC through RAS pathway = unable to increase BP*
88
If a patient takes ACE-I or ARB prior to surgery, this suggests patient will likely be profoundly hypotensive throughout the case and unable to compensate. What medications will likely be first go-to’s?
Tier 2 HoTN Tx:
- **Calcium Chloride**
250-500 mg
- *Vasopressin will not be effective b/c it acts along the RAS pathway*
Tier 3 HoTN Tx:
- **Neo Drip**
40-100 mcg IVP
.2-.5 mcg/kg/min
Tier 4 HoTN Tx:
- Epi:
10 mcg IVP
.03-.1 mcg/kg/min
- Levophed:
10 mcg IVP
.03-.1 mcg/kg/min
**Hang Albumin**
89
ACE-I out of system in how long?
~24 hours
90
Why can ACE-I cause coughing?
- ACE converts Bradykinin to an inactive peptide.
- If ACE is inhibited, then bradykinin will accumulate.
- **Bradykinin causes coughing**
- If pt is sensitive to cough, then they can be prescribed an ARB (Angiotensin Receptor Blocker) *Therefore, ACE is allowed to convert AT1 to AT2, then the ARB blocks AT2 receptors = pathway is blocked later still decreasing BP*
91
Examples of ACE-I
“-pril”
Captopril (Captopen)
Enalapril (Vasotec)
Lisinopril (Prinivil)
92
Onset comparison of ACE-I
Captopril:15-30 min
Enalapril: 60-120 min
Lisinopril: 60 min
93
DOA comparison of ACE-I
Captopril: 6-10 hr
Enalapril: 18-30 hr
Lisinopril: 18-30 hr
94
ACE-I contraindications
1. Renal artery stenosis (Decreased RBF = risk of CRF) [BQ]
2. Pregnancy
95
ACE-I side-effects
1. Diarrhea
2. Dry cough
3. Edema
4. Bronchospasm
5.Hyperkalemia
96
ARBs MOA
- competitively block AT2 receptors
1. Blocks AT2 VC
2. Blocks Aldosterone release
3. Blocks water reuptake
97
ARBs do/do not potentiate bradykinin
Do not
98
Examples of ARBs
“-sartan”
-Valsartan
-Losartan
-Candesartan
99
Three chemical structures of Calcium Channel Blockers
1. Phenylalkylamines
2. Dihydropyridines (DHPs)
3. Benzothiazepines
100
Calcium channels blockers MOA
1. CCBs bind to receptors on voltage gated calcium ion channels to ensure channel closure
2. Results in a reduction of intracellularly calcium
101
Phenylalkylamines occlude the calcium channels in the *open/closed* state.
Open
102
Phenylalkylamines act on ___ via calcium channel inhibition and cause____.
- the heart
- **decreased contractility, rate**, and coronary and peripheral vasodilation
103
Examples of Phenylalkylamine (CCB):
Verapamil (Calan)
104
Verapamil IVP
2.5-10 mg q. 15-30 min
Max = 20mg
105
Verapamil clinical use:
- SVT
- Angina
- Essential HTN
- Symptomatic hypertrophic cardiomyopathy
106
Verapamil’s active metabolite has what relative potency?
1/5th - 1/10th
107
Verapamil half life
5 hours
108
Verapamil should be given with caution to what patients?
CHF
109
Verapamil two major effects
1. Vasodilation
2. Negative inotropy (decreased contractility)
3. Negative Chronotropy (decreased rate)
*RATE DRUG*
110
CCB: modulation of ion channel prevents calcium entry intracellularly
Dihydropyrimidines
111
Dihydropyrimidines (DHP)are used mainly to treat ____.
Systemic HTN
112
DHP can cause reflex increase in ____ & ____, as well as a decrease in ____.
- CO
- HR
- afterload
113
Patients on DHP (CCB) and ACE-I may develop marked and refractory ____ under GA.
Hypotension
114
DHP (CCB) examples:
- Nicardipine (Cardene)
- Nifedipine (Procardia)
- Amlodapine (Norvasc)
115
Nicardipine half life and infusion dose:
- short 1/2 life
- 0.5-10 mcg/kg/min OR 5-10 mg/hr
116
Nicardipine considerations (S/E)
- Minimal myocardial depression
- Decreased SVR
- Coronary artery VD
- Tocolysis
117
What DHP (CCB) has not depression of SA or AV node?
Nifedipine
118
Nifedipine treatment for:
- coronary artery vasospasm 2/2 CABG
- prevention of cerebral arterial vasospasm 2/2 SAH
119
DHP (CCB) that is PO only and is prescribed for its anti-ischemic effects after MI:
Amlodipine
120
DHP (CCB) are primarily ____ agents.
Anti-hypertensive
121
Benzothiazepines (CCB) are primarily ____ agents.
Rate-controlling
Non-DHP
122
Benzothiazepines MOA
Block Calcium influx into heart and smooth muscle and therefore decrease HR and contraction oat SA and AV nodes
123
Benzothiazepine example
Diltiazem (Cardizem)
124
Diltiazem is used to treat what EKG abnormality?
A-Fib (fast irregular HR)
….or other SVT
125
Diltiazem IVP
.25 mg/kg
126
Diltiazem infusion dose
5-15 mg/hr
127
Diltiazem uses:
- peripheral arterial dilation
- Essential HTN
- SVT
- Angina
128
If performing a neuro case or any case where increased ICP is to be avoided, what anti-hypertensive agents should be avoided and which are more appropriate?
- AVOID: Nitric Oxide agents (NTG, SNP); these can cause headaches which increase ICP/CBF (plus MetHgbemia, CN poisoning, etc.)
- Preferred: Calcium Channel Blockers have a safer profile (e.g., Nicardipine); do not dilate cerebral vessels
*Nicardipine is used frequently*
129
Clinical considerations of Calcium Channel Blockers:
1. Cautious administration in hypovolemic and patients with poor LV function
2. Potentiation of NMB
3. Verapamil and Diltiazem have potent LA activity
4. Verapamil causes cardiac collapse whe administered concurrently with Datrolene
5. May increase plasma concentration of Digoxin
130
What two CCB may lower the threshold for LA toxicity ?
1. Verapamil
2. Diltiazem
NON-DHP
131
Where are alpha 2 receptors located relative to neuronal synapses?
Presynaptic and Postsynaptic
132
Major effects of Alpha 2 agonists
1. Sedation
2. Analgesia
3. Hypotension
133
Alpha 2 agonists MOA
1. Inhibits adenylyl cyclase, Calcium, and Potassium Ion channels
2. Result is reduction of cAMP = decrease in Calcium levels = decreased BP & hyperpolarization (decrease in cardiac conduction?)
134
Clonidine & Precedex are *centrally-acting alpha-2 agonists* that bind to ____ in order to ____.
- Pre-syaptic alpha 2 receptors
- decrease NE release (via negative feedback loop) which decreases sympathetic tone.
- decreased NE release in brain causes sedation (also benefits for ADHD pts)
135
Clonidine and Precedex clinical effects:
- Sympatholytic
1. Decrease BP
2. Decrease HR
- Sedation
- Anxiolysis
- Analgesia
- Antisialagogue
- *minimal respiratory depression*
136
Precedex cautions:
- most providers avoid initial bolus dose (opting for infusion) IOT avoid HoTN and Bradycardia (produced by vagal stimuli)
- abrupt discontinuation of leads to **Rebound HTN**
137
Other uses of alpha-2 agonists
1. Opioid withdrawal
2. Adjunct to regional
3. Analgesia
138
Alpha Antagonist examples
- Phentolamine (Regitine) [non-selective]
- Phenoxybenzamine (Dibenzylene) [non-selective]
- Prazosin (Minipress) [alpha 1 selective]
- Terazosin (Hytrin) [alpha 1 selective]
139
Alpha Antagonists are used almost exclusively for the treatment of:
Pheochromocytoma
*block the actions of catecholamines*
140
Alpha 2 blockage leads to:
NE release and increase in HR
141
Phosphodiesterase Inhibitors (PDEIs) increase levels of cAMP/cGMP and activates cardiac ____ channels/
Calcium
142
PDEIs cause an influx of calcium into the cell which leads to ____ & ____.
- increase in HR
- increased force of contraction (inotropy)
- increased relaxation speed (lusitropy)
143
increase in cAMP = ____.
Increase in cGMP = ____.
Increased cAMP: increased Calcium = increased contractility (positive inotropy)
- Increased cGMP: vasodilation (decrease in preload/afterload)
144
Whenever a PDEI is given, what should be given with it?
Vasoconstrictor IOT to offset vasodilation effects of PDEI
145
PDE 3 Inhibitors
- Amrinone (Inocor)
- Milrinone (Primacor) *more common*
146
Amrinone is what type of drug
Selective PDE 3 Inhibitor
147
What does Amrinone cause
Dose-dependent inotropy and VD
148
Amrinone loading dose
0.5-1.5 mg/kg
149
Amrinone infusion dose
2-10 mcg/kg/min
150
Milrinone causes:
- positive inotropy
- vasodilation
151
Which PDEI is used in acute LV dysfunction?
Milrinone
152
Milirinone loading dose
50 mcg/kg
Hint: He made his first Mil at 50
153
Infusion dose Milrinone
0.5 mcg/kg/min
154
When is PDE 3 like Milrinone used?
IOT make tachycardic:
- Whenever pt has weak heart/LV dysfunction (coming of CPB, EF < 20%)
- Elicit arrhythmia (A-Fib) IOT ID abnormal paths
*Isuprel and Dobutamine can also be used for similar effects*
155
Non-Selective PDEI
- Theophylline
~found green/black tea
~Tx bronchospasm due to asthma
~GERD can occur due to gastroesophageal relaxation
~Narrow therapeutic index
- Caffeine
- Theobromine
156
PDE 5 Inhibitors are selective for ____ in the lung and corpus cavernosum.This causes ____.
- cGMP
- pulmonary vasodilation & erections
157
PDE 5 Inhibitors examples:
- Sildenafil (Viagra)
- Tadalafil (Cialis)
158
*Rule of 5’s* initial infusion doses for vasoactive agents
Epi/NE/REMI: 0.05 mcg/kg/min
Neo/SNP/NTG: 0.5 mcg/kg/min
DA/Dobutamine: 5 mcg/kg/min. (DA = Dopamine)
Esmolol/Labetalol: 50 mcg/kg/min
159
Hydralazine is a _____..
*Potent* systemic arterial vasodilator
160
Hydralazine MOA
Promote efflux of Potassium which leads to hyperpolarization and muscle relaxation
*Potassium (+) out of cell makes cell more negative, less able to reach action potential*
161
Hydralalazine can cause what side effects:
- Reflex tachycardia
- Rebound HTN
- Used commonly in PIH?
162
Hydralazine concentration
20 mg/cc
163
Hydralazine IVP
5-10 mg IVP
164
Hydralazine onset & DOA
Onset: 10-20 min
DOA: 3-8 hours
165
Give Hydralazine ____ min before end of case to allow for onset IOT to thwart increased BP.
25-30 min
166
If you give Labetalol to treat anticipated spike in BP at emergence, give it ____ min before.
5 min (one cycle of cuff)
167
Weirich suggested emergence protocol for antihypertension:
30 min out: Hydralazine 5 mg (Opens Potassium Channels = VD)
*K Channels stay open, K exits the cell via concentration gradient, cell loses positivity, hyperpolarizes, no action potential, no vasoconstriction.*
10 min out: Labetalol 10mg (Blocking Alpha 1 = VD)
5 min out: Start Cardene gtt (Blocking Calcium Channels = VD)
168
Hydralazine draw up method (Weirich)
3cc Saline + 1 cc Hydralazine = 5 mg/cc
169
What PDEI is good for coronary and cerebral vasodilation/prevent vasospasm?
Papavarine
170
Magnesium acts as a ____. How does it do this?
- CCB
- Stimulates production of VD
- Reduces Prostaglandins (inflammatory markers)
- Increases N.O.
171
____ is a first line treatment for pre-eclampsia and eclampsia.
- Magnesium
- Hydralazine (non-ppt*)
*Magnesium is also administered to stop premature labor = **Tocolytic***
172
Normal pulmonary arterial pressure (PAP)
23-30 mmHg
173
Pulmonary arterial pressure equation
PAP = LAP + (CO x PVR)/80
**know for test**
174
Pulmonary HTN caused by 3 factors
1. Increased LAP (left atrial pressure)
2. Increased CO
3. Increased PVR
175
Other pulmonary vasodilators
1. Inhaled NO (or iNO)
2. PDE5 Inhibitors (Sildenafil)
3. CCB (Diltiazem & Verapamil)
4. PGE1: neonates with CHD to maintain PDA latency
5. PGI2: Primary Tx for Pulmonary HTN (Prostaglandins)
*not tested*
176
Sildenafil & Tadalafil are what type of PDEIs?
PDE Type 5 Inhibitors
HINT: Sildenafil (**V**iagra) = Type **V**
177
What type of PDEI is Milrinone and Amrinone?
PDE Type 3 Inhibitor
HINT: “**mil**li = **3** decimal places *(1 milliliter = .001L)*
178
Caffeine, Theophylline, Theobromine, Paraxanthine are all what kind of PDEI?
Non-Selective PDEI
179
Caffeine Fun Facts (non-ppt)
- Causes increased Ca release via PDEI pathway by increasing cAMP = *Increased force of contraction & Increased BP due to VC of vessels*
- Binds and blocks Adenosine receptors: causes increased neuronal activity, Increases NE, constricts vessels = *Increase in HR & Alertness*
~Adenosine causes sleepiness, decreased neuronal activity, decreased HR, VD
- Relieves headaches due to increased Adenosine (VD causes increased CBF) = *VC reduces BF & relieves headache*
180
What alpha antagonist put patients at increased risk of fall due to orthostatic HoTN and dizziness?
Terazosin
