EXAMS 2 Flashcards
1
Q
functional unit of the kidney
A
The nephron
2
Q
5 mains regions of the nephron
A
- Glomerulus
- Proximal convoluted tubule
- Loop of Henle
- Distal convoluted tubule
- Collecting duct
3
Q
three basic function of the renal
A
- Cleansing of extracellular fluid (ECF) and maintenance of ECF volume and composition
- Maintenance of acid-base balance
- Excretion of metabolic wastes (drugs/toxins)
4
Q
renal filtration
A
- Occurs at the glomerulus
- All small molecules get filtered
5
Q
renal absorption
A
- 99% of water, electrolytes and nutrients undergo reabsorption via active transport
6
Q
renal active tubular secretions
A
- Located in proximal convoluted tubule
- Excrete products into lumen of nephron
7
Q
where in the regions of the nephron does filtration occur
A
glomerus
8
Q
where in the regions of the nephron does active tubular secretion occur
A
- Located in proximal convoluted tubule
- Excrete products into lumen of nephron
9
Q
what are the most abundant electrolytes in filtrate
A
sodium and chloride.
SODIUM AND CHLORIDE ARE ABSORBED IN DIFFERENT AMOUNTS based on the location in the nephron
10
Q
how does diuretics work?
A
Diuretics work by disrupting reabsorption of electrolytes (Na and Cl)
11
Q
proximal convoluted tubule (PCT)
A
- High reabsorptive capacity
= 65% of filtered Na+ and Cl- reabsorbed here
= 100% of filtered K+ and bicarbonate reabsorbed here
- Water flows freely
12
Q
what percentage of filtered sodium and chlorine are rebasorbed in the proximal convoluted tubule
A
65%
13
Q
what percentage of filtered potassium and bicarbonate are rebasorbed in the proximal convoluted tubule
A
100%
14
Q
where does water flow freely in the nephron?
A
proximal convoluted tubule
15
Q
which of the limbs of the loop of henle is freely permeable to water
A
descending limb
16
Q
which of the limbs of the loop of henle IS NOT permeable to water
A
ascending limb
17
Q
which of the limbs of the loop of henle does filtrate become VERY concentrated
A
descending limb
18
Q
which of the limbs of the loop of henle does filtrate become LESS concentrated
A
ascending limbs
19
Q
what does not leave the descending limb
A
sodium and chloride
20
Q
….% of sodium and chloride are rebasorbed in the ………. whereas …..% of sodium and chloride are rebabsorbed in the ……..
A
65% of sodium and chloride are reabsorbed in the proximal convoluted tube, whereas the 20% of Na and Cl rebasorbed in the ascending limb
21
Q
early segment of distal convulated tubule (DCT)
A
- Freely permeable to water
- 10% of Na and Cl reabsorbed here
22
Q
late segment of distal convulated tubule (DCT)
A
- Na can be exchanged for K
- Process stimulated by hormone called aldosterone
- Part of Renin-angiotensin-aldosterone system
23
Q
where can sodium be exchanged for potassium
A
late segment of distal convoluted tubule (DCT)
THIS PROCESS IS STIMULATED BY ALDOSTERONE HORMONE which is part of the renin-angiotensin-aldosterone system
24
Q
what are direutics
A
drugs that increase urine output
25
what diurectics are more effective
Diuretics that work EARLIER in the nephron are more effective
26
Increases in urine are directly related to??
Increases in urine are directly related to how much reabsorption of Na and Cl are blocked
27
most diuretics work by....
Most work by blocking reabsorption of Na and Cl at some point in the nephron. Remember, water follows salt!
28
Applications of diurectics
- Treatment of hypertension
| - Edema associated with heart failure, kidney failure, and cirrhosis
29
classes of diuretic
- loop diuretics
- thiazide diuretics
- potassium-sparing diuretics
- osmotic diuretics
30
what are the potassium-sparing diuretics
- Aldosterone antagonists
| - Non-aldosterone antagonists
31
Most effective class of diuretics
- loop diuretics
32
mechanism of action of loop diuretics
- Block sodium and chloride reabsorption in the ascending Loop of Henle
- 20% of Na and Cl typically reabsorbed here, inhibition leads to profound diuresis
33
loop diuretics drugs
- Furosemide
- Torsemide
- Bumetanide
- Ethacrynic acid
```
Oral= 60 mins
IV= 5 minutes
```
34
indication of loop diuretics
- Congestive heart failure
Pulmonary edema
Peripheral edema
- Hypertension
35
adverse effects of loop diuretics
- Hypovolemia/dehydration
- Electrolyte abnormalities
Hyponatremia, hypochloremia, hypokalemia, hypomagnesemia, hypocalcemia
- Hypotension
- Ototoxicity
- Hyperuricemia
36
drug interactions of loop diuretics
- Digoxin
- Ototoxic drugs
- Potassium-sparing diuretics
- Lithium
- Anti-hypertensive drugs
- NSAIDs
37
monitoring points for loop diuretics
* Avoid taking before bedtime
* Monitor urine output
* Watch for signs of dehydration
* Give IV doses SLOWLY to avoid ototoxicity
* Caution in patients with a sulfa allergy
* Monitor urine output
* Can be given safely to patients with a sulfa allergy
38
Thiazide Diuretics
Lesser diuretic effect than loop diuretics
39
mechanism of actions of thiazide diuretics
- Block reabsorption of Na+ and Cl- at the early segment of the distal convoluted tubule (DCT)
- 10% of Na and Cl reabsorbed from DCT; inhibition leads to diuresis
40
drugs of thiazide diuretics
- Hydrochlorothiazide (HCTZ)
- Chlorothiazide
- Chlorthalidone
- Metolazone
41
indication of thiazide diuretics
- Hypertension (first-line)
- Edema
- Diabetes insipidus
42
drugs interactions of thiazide diuretics
- Digoxin
- Potassium-sparing diuretics
- Lithium
- Anti-hypertensive drugs
- NSAIDs
43
adverse effects of thiazide diuretics
```
- Electrolyte abnormalities
Hyponatremia, hypochloremia, hypokalemia, hypomagnesemia
- Dehydration
- Hyperglycemia
- Hyperuricemia
```
44
route for thiazide diuretics
oral EXCEPT chlorothiazide
chlorothiazide = IV
45
monitoring points for thiazide diuretics
- Avoid dosing before bedtime
- All agents equally effective
- Monitor for ADEs especially related to electrolyte abnormalities
- Caution in patients with a sulfa allergy
46
therapeutic effects of potassium-sparing diuretics
- Small amount of diuresis
- DECREASE potassium excretion
- Reduce cardiac remodeling
47
Aldosterone Antagonists drug of potassium-sparing diuretic
Spironolactone
48
Non-aldosterone Antagonists drug of potassium-sparing diuretic
- Amiloride
| - Triamterene
49
mechanism of spironolactone
Blocks aldosterone in the distal convoluted tubule
- Aldosterone typically causes sodium retention and potassium excretion.
- Increased excretion of sodium and retention of potassium
50
indications of spironolactone (PO)
- Hypertension and edema
- Heart failure
- Acne
- Polycystic ovarian syndrome
51
adverse effects of spironolactone
- Hyperkalemia
| - Endocrine effects
52
drug interaction of spironolactone
- Thiazide and loop diuretics
| - Agents that raise potassium
53
mechanism of action of amiloride and triamterene (PO)
- Direct inhibitor of the Na/K ion exchange transporter
| - Increased excretion of sodium and retention of potassium
54
indications of amiloride and triamterene
- hypertension
| - Edema
55
adverse effect of amiloride and triamterene
hyperkalemia
56
drug interactions of amiloride and triamterene
- Thiazide and loop diuretics
- Agents that raise potassium
same as spironolactone
57
implications with mannitol
ONLY GIVEN BY IV
- Inspect the product prior to administration
- Mannitol can crystalize
- Must be administered through a 0.22 micron filter to remove microcrystals
58
what is mannitol
Osmotic diuretic made of a 6-carbon sugar
59
mechanism of action of mannitol
- Filtered by the glomerulus
- Does NOT undergo reabsorption and remains in the lumen
- Increased osmotic pressure keeps water from being reabsorbed
60
indications of mannitol
- Reduce elevated intracranial pressure
| - Reduce elevated intraocular pressure
61
adverse effect of mannitol
- Edema
| - Electrolyte imbalances
62
Drugs Impacting the Renin-Angiotensin-Aldosterone-System (RAAS)
- Angiotensin converting enzyme inhibitors (ACE-i)
- Angiotensin II receptor blockers (ARB)
- Direct renin inhibitors (DRI)
- Aldosterone antagonists
63
role of the RAAS system
- The RAAS system plays critical role in regulating blood pressure, blood volume and fluids and electrolytes
64
key compounds of the RAAS
- Angiotensin
- Aldosterone
- Renin
65
what is renin of the RAAS
Enzyme that starts the whole RAAS pathway
66
renin are produced by the kidney in response to?
- Low blood pressure
- Low blood volume
- Low blood sodium content
67
renin release is suppressed when......
- Low blood pressure, volume and sodium content return to normal
68
three subtypes of angiotensin
angiotensin I, II, III
69
Angiotensin I:
inactive; converted into angiotensin II by angiotensin-converting enzyme (ACE)
70
Angiotensin II:
- Powerful vasoconstrictor (increases blood pressure)
- Stimulates release of aldosterone (increases blood pressure)
- Causes remodeling and hypertrophy of the myocardium
71
Angiotensin III
effects incompletely understood
72
function of aldosterone
- Stimulates Na+ retention and K+ excretion in the distal convoluted tubule
- Na+ retention leads to water retention which increases blood pressure
- Causes pathologic remodeling and hypertrophy of the myocardium
73
what does Na+ leads to? and causes what?
Na+ retention leads to water retention which increases blood pressure
74
Angiotensin Converting Enzyme Inhibitors (ACE-i) drugs
- Lisinopril (PO)
- Enalapril (PO)
- Enalaprilat (IV)
- Captopril (PO)
- Benazepril (PO)
* Generally well-tolerated
* All agents are equally efficacious
75
Angiotensin Converting Enzyme Inhibitors (ACE-i) are very effective for treating?
- Hypertension
- Heart failure
- Diabetic nephropathy
76
mechanism of action Angiotensin Converting Enzyme Inhibitors (ACE-i)
- inhibit angiotensin converting enzyme (ACE) from converting angiotensin I to angiotensin II
- Inhibit kinase II from converting bradykinin to an inactive form
77
increase in bradykin results in
- vasodilation
- cough
- angioedema (RARELY)
78
decrease in angiotensin II results in
- vasodilation
- decrease blood volume
- decrease cardiac and vascular remodeling
- potassium retension
fetal injury
79
pharmacokinetics of ACE- inhibitors
- All administered orally (EXCEPTION: enalaprilat is IV)
- Long half-lives (EXCEPTION: captopril)
- Renally excreted
80
adverse effects of ACE-inhibitors
- First-dose hypotension
- Dry cough
- Hyperkalemia (high potassium levels)
- Renal failure in patients with bilateral renal artery stenosis
- Fetal injury
- Angioedema
81
ACE-Inhibitors indication
- hypertension
- heart failure
- myocardial infarction
- diabetic nephropathy
- Prevention of MI, stroke and death in patients at high risk for CV disease
82
Angiotensin II Receptor Blockers mechanism of actions
block angiotensin II from binding to its receptor
83
Angiotensin II Receptor Blockers physiologic effects
- Vasodilation
- Decrease production of aldosterone
- Reduce cardiac remodeling
- Dilation of renal blood vessels
84
Angiotensin II Receptor Blockers drugs
- Losartan
- Valsartan
- Telmisartan
- Olmesartan
all PO
85
Angiotensin II Receptor Blockers (ARB) therapeutic uses
- Hypertension
- Heart failure
- Diabetic nephropathy
- Myocardial infarction
- Prevention of MI, stroke and death in high risk patients
86
adverse effects of Angiotensin II Receptor Blockers (ARB)
- Angioedema
- Fetal harm
- Renal failure
87
Direct Renin Inhibitors (DRI) drug
Aliskiren (PO)
88
Direct Renin Inhibitors (DRI) mechanism of action
binds to renin and prevents it from cleaving angiotensinogen to angiotensin I
89
Direct Renin Inhibitors (DRI) physiologic actions
- Vasodilation
- Decrease production of aldosterone
- Reduce cardiac remodeling
- Dilation of renal blood vessels
same as Angiotensin II Receptor Blockers
90
adverse effects of Direct Renin Inhibitors (DRI)
- Angioedema
- Dry cough
- Diarrhea
- Hyperkalemia
- Fetal injury
91
indications of Direct Renin Inhibitors (DRI)
Hypertension
92
Aldosterone Antagonists mechanism of action
blocks aldosterone from binding to receptors in kidney
93
Aldosterone Antagonists physiologic effects
- Decrease Na+ reabsorption and increase reabsorption of K
- Decrease blood pressure and blood volume
- Reduce pathologic remodeling of the heart
94
drugs of Aldosterone Antagonists
Eplerenone (PO) =
Selective for aldosterone receptors
Spironolactone (PO) = NON-selective
95
Aldosterone Antagonists indications
Hypertension
| Heart failure
96
Aldosterone Antagonists adverse effects
Hyperkalemia
Diarrhea
Gynecomastia
97
Physiology of Calcium Channels
Calcium channels are gated pores in the cytoplasmic membrane
98
locations of calcium channels
- Vascular smooth muscle (stimulates contraction)
- Heart
Myocardium = increase force of contraction
SA node = increase heart rate
AV node = increase conduction velocity which increases heart rate
99
Classification of Calcium Channel Blockers (CCBs)
1. Dihydropyridines
- several drugs
- works only on vascular smooth muscle
2. Non-dihydropyridines
- two drugs
- Work on heart and vascular smooth muscle
100
Dihydropyridine Calcium Channel Blockers drugs
- Amlodipine (PO)
- Nifedipine (PO)
- Felodipine (PO)
- Nimodipine (PO)
- Nicardipine (IV)
- Clevidipine (IV)
IV 5 to 10 mins
PO= 12 to 24 hours
101
Dihydropyridine Calcium Channel Blockers mechanism of action
block calcium channels in the vascular smooth muscle
MINIMAL effects on the heart
102
indications of Dihydropyridine Calcium Channel Blockers
Angina pectoris
| Hypertension
103
hemodynamic effects if Dihydropyridine Calcium Channel Blockers
- Vasodilation of the arteries and arterioles which decreases blood pressure
- Vasodilation cardiac vasculature which increases myocardial perfusion
- Reflex tachycardia
104
first line iv medications for hypertension
Nicardipine
| Clevidipine
105
monitoring points for Dihydropyridine Calcium Channel Blockers
- DDI with beta-blockers
- Toxic doses can affect the myocardium
- Nimodipine is ONLY indicated for SAH
- Nicardipine and clevidipine are first-line IV medications for hypertension
106
Non-dihydropyridine Calcium Channel Blockers drugs
- verapamil ( both mouth and IV )
- diltiazem ( both mouth and IV)
oral 1-2 hours
IV - 5 minutes
107
Mechanism of action of Non-dihydropyridine Calcium Channel Blockers
block of calcium channels in the vascular smooth muscle AND heart
108
Hemodynamic effects: of non-dihydropydrine calcium channel blockers
- Vasodilation of the arteries and arterioles which decreases blood pressure
- Vasodilation cardiac vasculature which increases myocardial perfusion
- Blockade of the SA and AV node which decreases heart rate
- Decreased force of myocardial contraction
109
indications of non-dihydropydrine calcium channel blockers
- Angina pectoris
- Hypertension
- Cardiac dysrhythmias
110
monitoring points for non-dihydropydrine calcium channel blockers
* DDI with digoxin and beta-blockers
* Possible interaction with grapefruit juice
* Monitor BP, ECG and heart rate
* Do not crush or chew ER products
111
adverse effects of non-dihydropydrine calcium channel blockers
```
Constipation (verapamil)
Dizziness
Flushing
Headache
Bradycardia
AV nodal block
Peripheral edema
```
112
Classification of Hypertension (HTN)
- primary/essential = NO IDENTIFIABLE
| - secondary = IDENTIFIABLE CAUSE
113
Why is hypertension so dangerous?
- Increases risk of heart disease and stroke
- Increases risk of irreversible kidney damage
- Often asymptomatic (the “silent killer”)
114
overall management of hypertension
- Diagnose (Primary vs Secondary)
- Evaluate for factors that increase CV risk and target organ damage
- Treatment Goals
- Therapeutic Management
115
drug therapy of hypertension
- Many different options
Treatment algorithms to guide decisions
- Different mechanisms of action can be combined to have stronger effect or synergistic effect
- Combine with lifestyle changes
116
hypertensive emergency
- end organ damage
Need to rapidly decrease BP over one hour
- Requires IV medications
- Sodium nitroprusside, labetalol, clevidipine, nicardipine
117
hypertensive urgency
- no end organ damage
Decrease BP gradually over 24 hours
- Can use IV or PO medications
118
chronic hypertension
```
- Discontinue all category X drugs
ACE-i
ARBs
DRI
Preferred drugs: labetalol, methyldopa
```
119
Preeclampsia and Eclampsia
- Disorder characterized by HTN and proteinuria after 20 weeks gestation
- Presence of seizures = eclampsia
- Serious risks to the mother and fetus
- Treatment
Labetalol
Magnesium(anticonvulsant)
Deliver baby (if possible)
120
pathophysiology of heart failure
Step 1: Myocardial dysfunction
Step 2: Activation of the RAAS system
Step 3: Activation of the neurohormonal system
Step 4: Remodeling of ventricular myocardium
121
The normal compensatory systems of the body make the issue worse:
* RAAS system → fluid accumulation
| * Neurohormonal system → cardiac remodeling
122
Angiotensin Receptor Neprilysin Inhibitor drugs
- Valsartan/sacubitril
Valsartan -> ARB
Sacubitril -> neprilysin inhibitor
123
what is neprilysin
Enzymes that break down natriuretic peptides
124
ONLY 3 FDA-approved for HF
Bisoprolol
Carvedilol
Metoprolol
125
inotropes
Added in very severe heart failure
126
three agents of inotropes
Digoxin ( PO or IV)
Dobutamine (IV)
Milrinone (IV)
- All inotropes are given IV
EXCEPTION digoxin which can be given PO or IV
127
digoxin mechanism of action
- Inhibition of the Na/K/ATPase pump
↑ intracellular Ca concentrations
↑ force of contraction
128
role of potassium digoxin
- Competes with digoxin for binding to Na/K/ATPase
- If K levels low = ↑ digoxin binding
- If K levels high = ↓ digoxin binding
129
low potassium levels impact on digoxin
↑ digoxin binding
130
high potassium levels impact on digoxin
↓ digoxin binding
131
digoxin physiologic effects
- Increased cardiac output
- Suppresses renin release in the kidneys → ↓ activation of the RAAS pathway
- Alters electrical activity in the heart → ↑ vagal responses
132
pharmakokinetics of digoxin
- Well absorbed and distributed into tissues
- High levels reached in cardiac tissues
- Long half-life
133
dosing of digoxin
Loading dose
| Maintenance dose
134
Monitoring points for digoxin
digoxin = last line defense
```
Narrow therapeutic index
DRUG LEVELS (0.5-0.8 mcg/mL)
```
135
adverse effects of digoxin
- Cardiac dysrhythmias
- GI symptoms
- Fatigue
- Visual disturbances
136
dobutamine mechanism of action
- Beta-1 & beta-2 activation
↑ force of contraction
↑ heart rate
- Place in therapy =
Acute decompensated heart failure
137
Adverse effects/ Monitoring parameters of dobutamine
Arrythmias
| BP and HR monitoring
138
Milrinone mechanism of action
- Phosphodiesterase-3 inhibitor
↑ cyclic AMP → ↑ myocardial contractility
Vasodilation
place in therapy = Acute decompensated heart failure
139
Adverse effects/ Monitoring parameters of milrinone
Arrythmias
| Hypotension
140
two types of dysrhythmia
- Tachydysrhythmia = Dysrhythmia where rate is increasing
- bradydysrhythmia
Dysrhythmia where rate is decreasing
Drugs are used to treat dysrhythmias BUT can also predispose patients to dysrhythmias
141
SA node
pacemaker of the heart
142
AV node
getaway for impulse to reach the ventricles; delays impulse travel
143
His-Purkinje System
conduct electrical impulse to the ventricles
144
Properties that Generate an Impulse
AUTOMATICITY
- Heart’s ability to generate an electrical impulse
- SA node has the fastest rate of automaticity
CONDUCTIVITY
- Ability of cardiac tissue to transmit electrical impulses
- Orderly, rhythmic transmission of impulses needed to generate effective contractions
145
4 classifications of antidysrhythmic drugs
```
Class I: Sodium Channel Blockers
Class II: Beta-blockers
Class III: Potassium Channel Blockers
Class IV: Calcium Channel Blockers
Other: digoxin and adenosine
```
146
Class I; Sodium Channel Blockers
Class IA
- Disopyramide
- Quinidine
- Procainamide
Class IB
- Lidocaine
- Mexiletine
Class IC
- Flecainide
- Propafenone
- ↓ conduction velocity in the atria, ventricles and His-Purkinje system
- Similar in action and structure to local anesthetics
- Effects are secondary to sodium channel blockade
147
adverse effect of quinidine
Diarrhea (33%)
| Cinchonism = hearing loss, tinnitus, dizziness, flushing, and blurry vision
148
Procainamide( CLASS IA) adverse effect
- Systemic Lupus Erythematosus reaction
- Blood dyscrasias
- Arterial embolism
149
adverse effect of lidocaine (CLASS IB)
- CNS effects
- Toxic doses:
Seizure
Respiratory arrest
150
monitoring points of lidocaine (CLASS IB)
- Narrow therapeutic index
- Monitor: drug levels
- Make sure you’re using the correct product!
151
monitoring points for Flecainide (CLASS IC)
↑ mortality in post-MI patients with asymptomatic Vtach
152
Class II: Beta-blockers DRUGS
```
Propranolol
Acebutolol
Esmolol
Sotalol
= 4 approved
```
Metoprolol
Labetalol
Bisoprolol
Carvedilol
153
physiological effects of Class II: beta-blockers
Physiologic effects:
↓ automaticity in SA node
↓ conduction velocity through AV node
↓ myocardial contractility
154
indications of Class II: beta-blockers
Sinus tachycardia
| Atrial fibrillation/flutter
155
Propranolol adverse effect
- AV block
- Sinus arrest
- Hypotension
- Bradycardia
156
monitoring points for Propranolol
- Give IV SLOWLY to avoid hypotension
| - Monitor: HR, BP, ECG
157
adverse effect of esmolol
- AV block
- Sinus arrest
- Hypotension
- Bradycardia
158
monitoring points for esmolol
- VERY fast acting
- Short half-life
- Monitor: HR, BP, ECG
159
monitoring points for sotalol
- Also causes blockade of K channels; can be considered
- Class III
- Monitor: HR, BP, ECG
160
Class III: Potassium Channel Blockers
- amiodarone (PO/IV)
- dronedarone (PO)
- sotalol (PO)
- Ibutilide
- Dofetilide
161
adverse effects of Amiodarone (CLASS III)
- Toxicity – lungs, liver, eyes, thyroid
| - Photosensitivity
162
monitoring points for amiodarone (CLASS III)
- Hypotension
| - Give through 0.22 micron filter
163
adverse effects of dronedarone (CLASS III)
- Photosensitivity
| - Hepatotoxicity
164
monitoring points for dronedarone (CLASS III)
Contraindicated in pregnancy
165
monitoring points for dofetilde (CLASS III)
Initiated therapy in the hospital
166
Monitoring points for Sotalol (CLASS III)
Class II and III agent – do NOT use like a typical beta-blocker
167
Adenosine mechanism of action
- ↓ automaticity of SA node
- ↓ conduction through the AV node
- Prolonged PR interval
168
indication of adenosine
- Termination of supraventricular tachycardia (SVT)
| - NOT for treatment of afib or aflutter
169
pharmacokinetics of adenosine
- EXTREMELY short half-life (2 to 10 seconds)
| - Must be given IV push
170
adverse effects of adenosine
- Momentary asystole
| - Chest discomfort
171
Drug interactions of adenosine
- Methylxanthines (E.g. theophylline) – block adenosine receptors
172
Types of Angina
- chronic stable
- variant (prinzmetal's)
- unstable
173
what is chronic stable angina
- Caused by coronary artery disease (CAD), in which PLAQUES cause PARTIAL occlusion of the vessel
174
what are chronic stable angina triggered by
- Increase in physical activity (most common)
- Emotional excitement
- Large meals
- Cold exposure
175
treatment approach for chronic stable angina
- Decrease myocardial oxygen demand
| - Increase myocardial oxygen supply
176
non-drug interventions of chronic stable angina
- Avoid precipitating factors
- Smoking cessation
- Exercise
- Healthy diet
177
Therapeutic agents: chronic stable angina
All medications work by decreasing myocardial oxygen demand
- Organic nitrates
- Beta-blockers
- Calcium channel blockers
-/+ ranolazine
178
what is variant angina
Caused by coronary artery SPASM (VASOSPASM) which decreases blood flow resulting in decreased oxygen supply
179
variant angina precipitating factors
NO precipitating factors
- Can occur at rest, while sleeping, or during normal activity
180
treatment approach for variant angina
- Decrease Incidence and severity of attacks with drug therapy that increase oxygen supply
181
therapeutic agents variant angina
- Calcium channel blockers
- Organic nitrates
- Beta-blockers and ranolazine are INEFFECTIVE
182
INEFFECTIVE Beta-blockers and ranolazine is part of what angina
variant angina
183
what is unstable angina
CAD complicated by vasospasm.
- a plaque ruptures causing a clot that partially occludes the vessel
- Medical emergency with higher risk of death than stable angina
184
Presentation of unstable angina
- Symptoms at rest
- New-onset exertional angina
- Intensification of existing angina
185
therapeutic approach unstable angina
- Maintain oxygen supply
| - Decrease oxygen demand
186
Therapeutic Options unstable angina
```
- Anti-ischemic therapy:
Organic nitrates
Beta-blocker
Oxygen
IV morphine
- Anti-platelet therapy:
Aspirin
Clopidogrel, ticagrelor or prasugrel
```
187
Nitrates mechanism of actions
- Converted to nitric oxide using sulfhydryl group
| - Acts primarily on cells of vascular smooth muscle (VSM)
188
nitrates physiologic effects
- Vasodilation
GREATER EFFECTS ON VEIN than arteries
- Nitroglycerin is the oldest and most commonly used
189
nitroglycerin Mechanism of action in STABLE angina:
- Vasodilates veins which REDUCES VENOUS RETURN to the heart and REDUCES preload leading to decreased oxygen demand
190
nitroglycerin Mechanism of action in VARIANT angina:
- Relaxes spasms in the coronary arteries which helps increase oxygen supply
191
pharmacokinetics of nitroglycerin
```
- Extremely lipid soluble
Allows it be administered by uncommon routes (ie. transdermal, ointments, sprays, sublingual)
- Rapidly metabolized by the liver
Large first-pass effect
- Short half-life (5-7 minutes)
```
192
adverse effect of nitroglycerin
- Headache
- Orthostatic hypotension
- Reflex tachycardia
193
drug interactions of nitroglycerin
- Anti-hypertensive agents
- Phosphodiesterase-5 (PDE5) inhibitors
Sildenafil (Viagra), Tadalafil (Cialis) and Vardenafil (Levitra)
- Beta-blockers
- Non-dihydropyridine calcium channel blockers
194
Isosorbide mononitrate (ER)
given twice daily
195
Isosorbide dinitrate (IR)
given three times daily
196
what are Ranolazine
first-line or add-on therapy to beta-blockers, CCBs or nitrates
197
adverse effects of ranolazine
- QT prolongation
- Elevation in BP
- Constipation, dizziness, nausea, headache
198
drug interactions ranolazine
- CYP3A4 inhibitors
- QT prolonging drugs
- CCB - can inhibit CYP 3A4 - ecept amlodipine
199
myocardial infarction complete block
STEMI
200
myocardial infarction incomplete block
NSTEMI
201
routine therapy of STEMI
```
M = morphine
O = oxygen
N = nitroglycerin
A = aspirin
B = beta- blockers
```
202
Adjuncts to Reperfusion Therapy ANTICOAGULANTS
- heparin
- fondaparinux
- bivalirudin
203
Adjuncts to Reperfusion Therapy ANTIPLATELETS
- thienopyridines
- glycoprotein IIb/IIa inhibitors
- Aspirin
204
lipoprotein class
```
VLDL = probably contribute to atherosclerois
LDL = bad cholesterol = contribute to atherosclerosis
HDL = protect against atherosclerosis
```
VLDL is triglyceride
LDL AND HDL are cholesterol
205
HMG-CoA Reductase Inhibitors drugs
- Atorvastatin
- Rosuvastatin
- Lovastatin
- Pravastatin
- Simvastatin
206
HMG-CoA Reductase Inhibitors pharmacokinetics
- Administered orally
| - Metabolized by the liver (CYP3A4
207
drug-drug interaction HMG-CoA Reductase Inhibitors
- other lipid-lowering drugs
- Drugs that inhibit CYP3A4
CONTRAINDICATED IN PREGNANCY
208
counseling points for HMG-CoA Reductase Inhibitors
- Take medication in the evening at bedtime
- Maximal effects seen in 4 to 6 weeks
- Continue treatment lifelong
209
adverse effects of HMG-CoA Reductase
```
Mild headache, rash, GI disturbances
Myopathy and rhabdomyolysis
Possible with ALL statins
Measure CK at baseline and repeat if patient complains of muscle pain and weakness
Hepatotoxicity
Rare
Measure LFTs at baseline
Memory Loss
Transient
True incidence and correlation unclear
Cataracts
```
210
Bile Acid Sequestrants mechanism of action
- Bile acids are needed for re-uptake of cholesterol into the blood stream
- BAS binds to bile acids and prevent their physiologic action
211
Bile Acid Sequestrants
- Decrease LDL (15-30%)
- Increase HDL
- Possible transient increase in TG
212
Ezetimibe mechanism of action
- Decrease reabsorption of cholesterol in the small intestines
213
Ezetimibe effects on lipids
- Decrease Total cholesterol
- Decrease LDL (19%)
- Decrease TG (5-10%)
- Possible modest increase in LDL
214
indication of Ezetimibe
- Adjunct therapy for decrease LDL
215
adverse effects of ezetimibe
- well tolerated
| - rare - myopathy and rhabdomyolis, hepatitis
216
drug to drug interactions of ezetimide
- Statins
- Fibrates - increase risk of gallstones
- Bile acid sequestrants
217
drugs of bile acid sequenstants
- Colesevelam
- Cholestyramine
- Colestipol
218
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9 Inhibitors)
- Alirocumab
| - Evolocumab
219
Mechanism of action: Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9 Inhibitors)
- PCSK9-inhibitors PREVENT the binding of PCSK9 to LDLRand enhances clearance of LDL
220
adverse effects of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9 Inhibitors)
- Hypersensitivity reactions
| - Immunogenicity = Body may develop antibodies to the drug itself
221
Niacin
- B2 vitamin, also called nicotinic acid
- As a vitamin, products are not regulated by the FDA
- Thought to it may help decrease LDL and TG levels
- Niacin has not been shown to improve CV outcomes in patients, thus no longer recommended for use
222
niacin adverse effects
flushing
223
DDI fibric acid derivatives
increase risk of myopathy when combined with a statin
224
fibric acid derivatives drugs
Gemfibrozil
Fenofibrate
Fenofibric acid
Most effective drugs for lowering TG levels
Also known as ‘fibrates’
No proven mortality benefit
Third-line agents for lowering lipid levels
225
fish oil drugs
- Lovaza
- Vascepa
Goal to have 1 gram/day minimum beneficial oils to maintain a healthy heart:
Docosahexaenoic acid (DHA)
Eicosapentaenoic acid (EPA)
Effective for lowering TGs (20-50%)
Used as adjunct therapy for lowering TGs
Counseling points:
Can cause fishy burps, can freeze capsules to help prevent this
226
Stage C heart failure
Symptoms AND structural heart damage
227
drugs of stage C and D heart failure
ACE-i/ ARB/ARNI drugs
- Beta-blocker diuretics
- /+ digoxin or aldosterone antagonist
228
stage D heart failure
Refractory HF requiring specialized intervention
