Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

AS - N929 Pharmacology II > Cardiovascular II > Flashcards

Cardiovascular II Flashcards

1
Q

Nitrovasodilators

A

NO donors:

  • Nitroglycerin NTG
  • Sodium nitroprusside
  • Nitric oxide
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Nitric Oxide NO

A

Endogenous gas messenger formed from L-arginine
NOT stored
Lipophilic - easily crosses membranes
Reactive & labile free radical

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Nitric Oxide PK

A

Oxidation to NO (nitrate or nitrite) → Hgb nitrosylation

Half-life SECONDS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Nitric Oxide

Protective Biological Roles

A 
Vasodilator - smooth muscle relaxant
Neurotransmitter
Immune cytotoxicity
Inhibits platelet aggregation
Cytoprotection 
↓cell adhesion & proliferation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Nitric Oxide

Pathogenic Biological Roles

A

Neuronal injury NMDA
Cell proliferation
HoTN → shock
Inflammatory tissue injury

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Organic Nitrates

A

Nitroglycerin NTG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Nitrovasodilators

Organic Nitrates & Sodium Nitroprusside MOA

A

NO release results in GC activation in vascular smooth muscle → cGMP formation → vascular smooth muscle relaxation & vasodilation

Organic nitrates require metabolism to release NO
NTG tolerance effect r/t metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Sodium Nitroprusside

A

Nitrovasodilator (NO donor)
Direct-acting & non-selective peripheral vasodilator
Unstable - light & temperature sensitive
Deterioration results in change to bluish color (normal color faint brownish tint)
IV infusion via pump

Diluted in dextrose 5%
Admin shortest duration possible to avoid toxicity*
*Discontinue after 10 minutes at max infusion rate no ↓BP d/t cyanide toxicity risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Sodium Nitroprusside

MOA

A

Relaxes arterial AND venous vascular smooth muscle
Limited effect on non-vascular smooth muscle & cardiomyocytes

SNP interacts w/ oxyhemoglobin to dissociate & form methemoglobin →
Methemoglobin releases NO & cyanide →
NO activates guanylate cyclase in the vascular muscle ↑cGMP →
cGMP inhibits Ca2+ entry into vascular smooth muscle & INCREASES ↑Ca2+ uptake into the smooth endoplasmic reticulum
Vasodilation via NO

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Sodium Nitroprusside PK

A

1 Fe+, 5 cyanide, & 1 NO group
Direct-acting peripheral vasodilator → arterial & venous smooth muscle relaxation

Spontaneous breakdown to NO + cyanide (LIGHT SENSITIVE)
Metabolism - cyanide combines w/ sulfur groups to form thiocyanate & renal excretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Sodium Nitroprusside

Dose

A

0.3-10 mcg/kg/min IV
DO NOT INFUSE MAX DOSE > 10 MINUTES

  • Requires continuous IV admin to maintain therapeutic effects
  • Extremely potent
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Sodium Nitroprusside

Onset

A

< 2 minutes

Immediate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Sodium Nitroprusside

DOA

A

1-10 minutes SHORT
Half-life 2 minutes

Thiocyanate half-life 2-7 days (prolonged w/ impaired renal function)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Sodium Nitroprusside

Metabolism

A

Renal excretion as metabolites 1° thiocyanate
Also exhaled & excreted via feces

Transfer an electron from oxyhemoglobin Fe+ to SNP → MetHgb + unstable SNP radical
SNP radical breaks down → all 5 cyanide ions are released
Cyanide ion reacts w/ MetHgb to form cyano-methemoglobin (non-toxic)
Remainder metabolized in liver & kidneys → converted to thiocyanate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Sodium Nitroprusside

Clinical Indications

A

HTN crisis ↓BP to prevent/limit end-organ damage 1-2 mcg/kg bolus
Controlled HoTN during surgery → reduce bleeding when indicated
Acute and/or decompensated CHF 0.3-0.5 mcg/kg/min (do not exceed 2 mcg/kg/min)
Cardiac disease ↓LV atfterload
Acute MI → improve CO w/ LV failure present & low CO post-MI *Limited use d/t coronary steal effect - altered blood flow results in diversion away from ischemic areas

USE A-LINE TO MONITOR RESPONSE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Sodium Nitroprusside

Drug Interactions/Contraindications

A

Antihypertensive drugs d/t additive effects
ABSOLUTE CONTRAINDICATION - selective PDE 5 inhibitors (Sildenafil) → profound potentiation, potential life-threatening HoTN and/or hemodynamic compromise, cGMP accumulation d/t inhibiting breakdown
Guanylate cyclase stimulating drugs ↑cGMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Sodium Nitroprusside PD

A

CNS ↑CBF/ICP caution w/ carotid disease
CV - direct venous & arterial vasodilation
↓arterial/venous pressure, SVR, afterload (CHF or acute MI potential ↑CO d/t ↓afterload), ↓venous capacitance ↓VR, ↓BP (SBP/DBP) ↓coronary perfusion, ↑HR (baroreceptor-mediated response), ↑contractility (↑intracoronary steal in damaged areas associated w/ MI), no significant effects on non-vascular smooth muscle & cardiac muscle
Pulm - HPV attenuation
Heme - NO inhibits platelet aggregation ↑bleeding time
Renal - vasodilation w/o significant Δ GFR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Sodium Nitroprusside

SIDE EFFECTS

A

Profound HoTN - potential to impair end-organ perfusion
Cyanide toxicity
Methemoglobinemia
Thiocyanate accumulation
↑serum creatinine (transient)
↑ICP, headache, dizziness, restlessness, palpitations, flushing, GI upset/nausea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Cyanide Toxicity

A

Adverse effect r/t sodium nitroprusside administration
Occurs d/t high plasma thiocyanate concentrations

Dose/duration related >2 mcg/kg/min
*Consider when patient demonstrates resistance to HoTN effects or previous responsive now unresponsive (tachyphylaxis) at 2-10 mcg/kg/min
Tissue anoxia & anerobic metabolism
Venous hyperoxemia - tissues cannot extract O2
Lactic acidosis
Confusion & death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Cyanide Toxicity

Treatment

A

Immediately discontinue SNP
FiO2 100% (regardless SpO2)
Admin Na+ bicarbonate to correct metabolic acidosis
Sodium thiosulfate 150 mg/kg over 15 minutes (sulfur donor to convert cyanide to thiocyanate)

Severe toxicity Na+ nitrate 5 mg/kg
→ converts Hgb to MetHgb then converts cyanide → cyanometHemoglobin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Methemoglobinemia

A

RARE adverse effect r/t sodium nitroprusside administration

Hgb Fe2+ (ferrous) oxidized to Fe3+ (ferric) → impaired oxygen affinity → reduced O2 delivery to tissues → hypoxia

Reversal agent = Methylene blue 1-2 mg/kg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

When to consider methemoglobinemia as differential diagnosis?

A

Patients w/ impaired oxygenation despite adequate CO & arterial oxygenation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Thiocyanate

A

Cleared via kidneys in 3-7 days

Less toxic than cyanide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Thiocyanate Toxicity

A

Accumulation adverse effect r/t sodium nitroprusside administration

↑risk associated w/ prolonged infusion
Renal impairment
Neurotoxicity - tinnitus, miosis, & hyperreflexia
Hypothyroidism d/t impaired iodine uptake

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Thiocyanate Toxicity | S/S
CNS hyperreflexia, confusion, & psychosis Fatigue & tinnitus Nausea/vomiting Miosis seizures → coma
26
Phototoxicity
Mix SNP w/ 5% glucose to protect from light exposure Continuous light exposure → SNP converted to aquapentacyanoferrate Prevention - wrap the solution & tubing in foil or dark plastic bag
27
Nitroglycerin | MOA
Organic nitrate NO released via cellular metabolism - glutathione-dependent pathway *Requires thiols (sulfur group) NO release stimulates GC → cGMP formation → vascular smooth muscle relaxation & peripheral vasodilation 1° action site = VENOUS capacitance vessels Mildly dilates arteriolar resistance vessels Admin IV, sublingual, translingual spray, transdermal patch, OR ointment
28
Nitroglycerin PK
Extensive hepatic 1st pass effect 90% after PO admin Sublingual route to avoid 1st pass Hepatic metabolism - denitrate via glutathione-organic nitrate reductase to glyceryl dinitrate → mononitrate
29
Nitroglycerin | Dose
125-500 mcg/kg/min IV
30
Nitroglycerin Onset/DOA - IV - Sublingual - Translingual Spray - PO XR - Topical - Transdermal
``` IV immediate/3-5min Sublingual 1-3min/>25min Translingual 1-3min/>25min PO extended release 60min/4-8hrs Topical 15-30min/7hrs Transdermal 30min/10-12hrs ```
31
Nitroglycerin | Clinical Indications
Angina - Acute angina SL - Prevention long-acting PO, transdermal, or ointment - Venodilation ↓VR ↓RV & LVEDP ↓MVO2 ``` HTN - periop, HTN emergencies, postop HTN (after coronary bypass) Controlled HTN intraop Non-STEMI Acute MI (limits damage) Heart failure/low-output syndromes ```
32
Nitroglycerin | Relative Contraindications
Volume depletion, HoTN, brady/tachycardia, constrictive pericarditis, aortic/mitral stenosis, inferior wall MI & RV involvement
33
Nitroglycerin PD
1° action site at venous capacitance vessels = ↓preload & MVO2 Arterial resistance vessels - minimal ↓afterload & MVO2 Myocardial arteries ↑MVO2 supply d/t vasodilation CV ↓VR ↓RV & LVEDP ↓CO Ø SVR ↑coronary blood flow to ischemic subendocardial areas Bronchial smooth muscle relaxation → bronchial dilation Impairs HPV Inhibits platelet aggregation *Tolerance after 8-10 hours results in diminished effectiveness
34
Nitroglycerin | SIDE EFFECTS
``` Throbbing headache ↑ICP Orthostatic HoTN, dizziness, syncope Reflex tachycardia (baroreceptor reflex) Flushing, vasodilation, & venous pooling ↓CO Methemoglobinemia (rare) ```
35
Phosphodiesterase
Enzymes that breakdown cyclic nucleotides Regulate intracellular levels cAMP & cGMP (2nd messengers - endogenous pathways) Numerous sub-families x11 differ in localization & potential therapeutic targets Inhibitors boost cyclic nucleotide levels via preventing breakdown Older non-selective drugs that inhibit PDE include Caffeine & Theophylline
36
PDE 3 Inhibitor
-rinone Broad distribution cAMP & cGMP substrate Action site = heart & vascular smooth muscle Cardiac contractility & platelet aggregation Inotrope + peripheral vasodilation ↑contractility
37
PDE 3 Inhibitor | MOA
Milrinone - inhibits PDE3 Prevents cAMP breakdown to AMP (inactive form) ↑2nd messenger cAMP
38
cAMP
*Enhances the biological effect* Ca2+ channel activation ↑cytosolic Ca2+ → actin-myosin-troponin interaction → + INOTROPY cAMP-dependent protein kinase ↑phosphorylated phospholamban → augmented Ca2+ SR uptake → VASODILATION
39
Milrinone
PDE 3 inhibitor
40
Milrinone | MOA
Inhibits cAMP breakdown | ↑intracellular Ca2+
41
Milrinone | Onset
IV 5-15 minutes Half-life 3-6 hours *Only parenteral
42
Milrinone | Metabolism
>80% excreted renally unchanged
43
Milrinone | Clinical Indications
Acute heart failure or severe CHF Cardiogenic shock (off-label) Heart transplant bridge or post-op (off-label)
44
Milrinone PD
``` + inotrope ↑cardiac contractility Vasodilation Minimal chronotropic activity Dilates pulmonary vasculature ```
45
Milrinone | SIDE EFFECTS
Arrhythmias | HoTN
46
PDE 4 Inhibitor
Broad distribution CV, neural, immune & inflammatory function cAMP substrate Indications include ↓inflammation & remodeling associated w/ COPD
47
PDE 5 Inhibitor
-afil Broad distribution cGMP substrate Action site = vascular smooth muscle (erectile tissue, lung, retina) Vascular smooth muscle relaxation at lungs Pulmonary HTN & erectile dysfunction
48
PDE 5 Inhibitor MOA
Sildenafil - inhibits PDE5 Prevents cGMP breakdown to GMP (inactive form) ↑2nd messenger cGMP
49
RAAS
Renin-Angiotensin-Aldosterone system Angiotensinogen + renin → angiotensin I + converting enzyme (ACE) → angiotensin II → aldosterone ↑preload OR vascular smooth muscle constriction ↑afterload Aldosterone causes ↑H2O + Na+ retention
50
What secretes renin?
The JG cells in the renal afferent tubules | Secretion stimulated via ↓BP or Na+ load
51
ACE
Angiotensin converting enzyme | Converts angiotensin I → angiotensin II
52
Angiotensin II
Causes vasoconstriction at angiotensin II type 1 GPCRs receptor Aldosterone secretion ↑ADH ↑proximal tubule Na+ reabsorption
53
Angiotensin II PD | Type 1 vs. 2 Receptors
AT1R - Blood pressure regulation - Body-fluid balance regulation - Vasoconstriction - Inflammation - Platelet aggregation/adhesion - Reactive oxygen species production - Proliferative - Hypertrophy - Fibrosis AT2R - Natriuresis - Neuronal activity - Vasodilation - Anti-inflammation - Pro-apoptotic - Anti-oxidative - Anti-hypertrophic - Anti-fibrotic
54
Aldosterone
Steroid hormone secreted via adrenal cortex Regulates gene expression ↑Na+ reabsorption H2O retention & K+ excretion
55
RAAS Pathways Inhibition
``` β1 adrenergic antagonist - Metoprolol Renin inhibitor ACEi -pril Angiotensin II receptor antagonist ARBs -sartan Aldosterone antagonist - Spironolactone ```
56
ACE Inhibitors
-pril ↓angiotensin II → vasodilation, ↓remodeling (heart failure), ↓aldosterone (↓Na+/H2O ↑K+ retention), ↑sympathetic output, ↑natriuresis ↑bradykinin → vasodilation, cough, angioedema
57
Bradykinin
Endogenous peptide Stimulates NO & prostacyclin formation Vasodilation (heart, kidney, microvascular beds) Inflammatory actions ↑capillary permeability → angioedema
58
Bradykinin | DOA
Elimination 1/2 time 16 seconds
59
ACEi
Angiotensin converting enzyme inhibitors -pril Lisinopril, Enalapril, Benazapril Captopril (prototype)
60
ACE Inhibitors | MOA
Block angiotensin I → angiotensin II Prevents vasoconstriction Prevents aldosterone secretion ↓Na+ & H2O retention
61
ACE Inhibitors PK
Commonly pro-drugs (Enalapril & Ramipril) inactive when administered & require metabolism → active form 1° renal excretion Commonly combination drugs + diuretic ↑UOP
62
ACE Inhibitors | Clinical Indications
HTN, CHF (systolic dysfunction), & mitral regurgitation Post-MI More effective in diabetes mellitus patients - diabetic neuropathy Delay renal disease progression
63
ACE Inhibitors | Drug Interactions
K+ sparing diuretics & supplements K+ retention → hyperkalemia
64
ACE Inhibitors | Contraindications
Renal artery stenosis - potential to develop renal failure d/t efferent arteriole constriction Pregnancy - teratogenic
65
ACE Inhibitors PD
↓BP → HoTN, syncope, & possible 1st dose effect ↓GFR ↑BUN/creatinine & renal dysfunction ``` Dry cough (reversible) bradykinin-related Angioedema 1% ``` Teratongenic - causes fetal malformations & contraindicated in pregnancy
66
ACE Inhibitors | SIDE EFFECTS
``` Cough C1 esterase deficiency - contraindication Angioedema/agranulocytosis Proteinurea/potassium excess Taste change Orthostatic HoTN Pregnancy CONTRAINDICATION (fetal renal damage) Renal artery stenosis CONTRAINDICATION Increases renin Leukopenia/liver toxicity ```
67
ARBs
Angiotensin receptor blocker -sartan Losartan (prototype) Similar PK/PD to ACEi
68
ARBs MOA
Competitive antagonist at AT1 receptor Blocks angiotensin II effects mediated at AT1 receptor Does NOT block bradykinin breakdown → no bradykinin accumulation
69
ARBs | Metabolism
Hepatic via CYP2C9
70
ARBs | Clinical Indications
Same as ACEi
71
ARBs Drug Interactions
Interactions w/ K+ sparing diuretics & supplements K+ retention → hyperkalemia
72
ARBs Contraindications
Renal artery stenosis | Pregnancy
73
ARBs PD
Similar effects to ACEi | Less frequent cough & angioedema (rare)
74
ACEi vs. ARBs
No difference in HTN efficacy ARBs less likely to be discontinued (main reason ↓dry cough 1% vs. 4%) Longer history available w/ ACEi ARBs no comparison vs. placebo
75
Aldosterone Antagonist MOA
Spironolactone Competitive antagonist at mineralocorticoid receptors (1° renal + heart, blood vessels, & brain) Blocks gene transcription - coding Na+ channels
76
Spironolactone MOA
Aldosterone antagonist | Off-target effects include blocking androgen & progesterone receptors
77
Aldosterone Antagonist PK
Hepatic metabolism | Spironolactone - active metabolites w/ elimination 1/2 life 12-20 hours
78
Aldosterone Antagonist | Clinical Indications
HTN & heart failure K+ sparing diuresis 1° hypoaldosteronism Spironolactone off-label uses acne, hirsutism, & PCOS
79
Aldosterone Antagonist | Drug Interactions
Other K+ sparing drugs (ACEi or ARBs) K+ supplements NSAIDs ↑renal risks
80
Aldosterone Antagonist PD
↑Na+ & H2O excretion → mild diuresis | ↑K+ reabsorption
81
Aldosterone Antagonist | SIDE EFFECTS
Hyperkalemia Spironolactone - hepatic, renal, Steven-Johnson, toxic epidermal necrolysis, GI, gynecomastia, menstrual irregularities
82
Hydralazine MOA
Direct vasodilator Release NO from endothelial cells Inhibits Ca2+ release from sarcoplasmic reticulum
83
Hydralazine PK
Extensive 1st pass effect 25% bioavailability Half-life 1.5-3 hours
84
Hydralazine | Clinical Indications
↓BP HTN - combination therapy + β-blocker & diuretic to limit SNS effects Heart failure ↓ejection fraction
85
Hydralazine | Contraindications
Coronary artery disease | Mitral valve disease
86
Hydralazine PD
``` Arteriole vasodilation Minimal venous effects ↓SVR ↓↓DBP > ↓SBP ↑HR reflex tachycardia ↑SV/CO ```
87
Hydralazine | Side Effects
``` Headache Palpitations, sweating, flushing Reflex tachycardia & tolerance/tachyphylaxis Angina w/ EKG changes Nausea Na+ & H2O retention Lupus erythematous (reversible) ```
88
Hydralazine | Contraindications
Coronary artery disease | Mitral valve disease
89
Minoxidil
Direct arterial vasodilator | ↑K+ efflux from vascular smooth muscle → hyperpolarization & vasodilation
90
Nitric Oxide PK

AS - N929 Pharmacology II (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions