Final Exam Flashcards
(190 cards)
1
Q
Organic Nitrates MOA
A
compound denitrated by ntALDH, forms NO which signals for release of cGMP, leading to decreased [Ca++]i and vasodilation
2
Q
Effects of Organic Nitrates
A
Primary action is venodilation - significant decrease in preload.
Coronary artery dilation
Some arteriolar dilation - decreased afterload
Net result: decreased oxygen demand, and in some situations, increased oxygen supply
3
Q
Organic Nitrate metabolism
A
high 1st pass effect = limited oral bioavailability
metabolized by glutathione-organic nitrate reductase
4
Q
Sub-lingual and nasal Organic Nitrates
A
EX: SL nitroglycerin, SL isosorbide dinitrate, inhalant amyl nitrite
ra[id onset, short DOA
used to relieve acute angina
5
Q
Oral and Dermal Organic Nitrates
A
nitroglycerin ointment, nitroglycerin dermal patches, oral isosorbide dinitrate.
slow onset, longer DOA
used for prophylaxis of angina
6
Q
Organic Nitrates Side Effects
A
Orthostatic hypotension
Tachycardia (SNS activation)
Throbbing headache (“Monday disease”, can develop tolerance)
Dizziness, flushing of skin
7
Q
Organic Nitrates Contraindications
A
PDE5 inhibitors (ED) - both promote vasodilation via separate mechanisms = potentiated effects
8
Q
Main Uses of Organic Nitrates
A
Stable angina and Variant angina that is not associated with atherosclerosis
9
Q
Effects of Calcium Channel Blockers
A
blocks receptor-mediated Ca++ channel, decreases [Ca++]i. Voltage-gated channel can still be activated
Decreases oxygen consumption by decreasing contractility and heart rate and causing relaxation of coronary smooth muscle cells (relieves vasospasms)
10
Q
“Others” class of Ca Channel Blockers
A
Verapamil and Diltizem
Cardiac»_space; Vascular effects
Primary effects are to decrease HR, contractility, and conduction velocity, all of which decrease oxygen demand on the heart.
Safer choice for pts with stable angina than dihydropyridines
11
Q
Dihydropyridines
A
Nifedipine, amlodipine, felodipine
Primary effect is to decrease afterload, which decreases oxygen demand.
BUT if you lower BP too fast, trigger SNS response = increased oxygen demand. (tempers effectiveness)
short acting nifedipine should not be used as monotherapy for unstable or chronic stable angina
long acting nifedipine, amlodipine, and felodipine are more slowly absorbed, and are not as likely to cause reflex tachycardia.
This class CAN be used for angina, just have to be cautious of what type is used
12
Q
Net Effects of Ca Channel Blockers
A
Decreased oxygen demand
Decreased vasospasms
13
Q
Main Uses of Ca Channel Blockers
A
Variant and Stable Angina
14
Q
Ca Channel Blockers Side Effects
A
Bradycardia Heart Block (AV node) Dizziness and edema Flushing (vasodilation) Constipation (reduced GI motility)
15
Q
Beta-Blockers used in Angina
A
B1 Selective - metoprolol and atenolol
Nonselective - propranolol and nadolol
Do not usually use ones with ISA
16
Q
Effects of Beta blockers
A
reduces inotropy (contractility) and chronotropy (HR), leading to overall reduction in oxygen demand.
Slight increase in coronary flow to ischemic areas, not consistent (increased oxygen supply)
Net: decreases oxygen demand, slight increase in blood flow (and oxygen supply)
28-40% reduction in mortality
17
Q
Main anti-anginal uses of B-blockers
A
Stable and Unstable angina.
CAUTIOUS use in pts with ischemia induced CHF
18
Q
Contraindications of B-blockers
A
Variant angina (unchecked alpha-receptor effects)
19
Q
B-blocker side effects
A
Cardiovascular effects: bradycardia, heart failure, low exercise tolerance
Rebound effect: upregulated receptor number can cause an increase in HR or BP, causing more angina
Bronchospasms (B2 antagonists)
CNS effects (lipophilic B2 antag): fatigue, depression, vivid dreams/nightmares
20
Q
Ranolazine (Ranexa) MOA
A
blocks the “late Na+ current” curing cardiac AP.
Decreasing [Na+]i will decrease [Ca++]i, reduces ventricular stiffness and therefore oxygen consumption
21
Q
Angina Pectoris
A
Pain resulting from myocardial ischemia, usually originates in chest and ratiates to arm
22
Q
Myocardial Ischemia
A
oxygen demand»_space; oxygen supply in heart
23
Q
Myocardial Infarction
A
Myocardial Cell Death following prolonged ischemia
24
Q
Stable Angina (classical or effort)
A
Most common type of angina
Etiology: atherosclerosis
Symptoms: angina with exertion, relief at rest
Goal of therapy is to decrease oxygen demand
Drugs: long-acting nitrates, Ca blockers, B blockers, combo therapy, surgery
25
Variant angina (Prinzmetal's)
Etiology: vasospasms of coronary artery, which may or may not be associated with atherosclerosis.
Symptoms: pain independent of rest or exertion. Length depends on how long the vasospasm lasts.
Therapy goal is to decrease severity and frequency of vasospasms.
Drugs: nitrates, Ca blockers, combo therapy
26
Unstable Angina
Etiology: recurrent formation of platelet clots, usually associated with plaque and often compounded by local vasospasms.
Symptoms: *prolonged* pain at rest, change in character, frequency, or duration of stable angina
goal of therapy is aggressive anticoagulants, vasodilators, etc.
This type of angina usually signifies an impending MI
Drugs: anticoagulants, thrombolytics, nitrates, Ca blockers, B blockers, combo therapy, surgery.
27
Uses of anticoagulants
Diseases: unstable angina (and acute coronary syndromes), Afib, Pulmonary embolism, DVT, HF, stroke
Procedures: angioplasty, valve replacement, hemodialysis, indwelling catheters, assist devices, heart/lung machine
28
Pathophysiology of Acute Coronary Syndromes
fibrous cap covering plaque ruptures, causing platelet activation and aggregation, leading to thrombus
29
Important drug targets in clotting pathway
Vitamin K
Factor Xa
Factor IIa (thrombin)
30
Heparins MOA
binds to circulating antithrombin and increases affinity for thrombin and factors IXa and Xa 1000x. This complex is then rapidly removed by liver.
Not orally active, given IV/SC. Active site is the pentasaccharide sequence (has to be sulfated in a certain order to be active)
31
Fondaparinux (Arixtra)
Most basic form of heparin, only consists of the pentasaccharide sequence, therefore only binds and inactivates Xa.
Given SC
Eliminated primarily unchanged in urine
Contraindicated in pts with CrCl <30mL/min (and pts with animal allergies, isolated from pigs)
-T1/2 17-21h, effect lasts 2-4 days after discontinuing
less likely to cause thrombocytopenia
32
Types of Heparins
Unfractionated: full length heparin. Inactivates Xa and IIa equally. Increased risk of allergies, major bleeding, and thrombocytopenia. F=0.3
Low Mol-Wt Heparin: fractionated heparin, inactivates factor Xa > IIa. slightly lower risk of allergies, major bleeding, and thrombocytopenia. F=0.9
Fondaparinux: smallest version of heparin (pentasaccharide sequence only). Only inactivates Xa. Greatly reduced risk of allergic reactions, major bleeding, or thrombocytopenia. F = 1. Much more expensive than others.
33
(unfractionated) heparin side effects
Bleeding - dose related
Thrombocytopenia
Osteoporosis with long term use (relatively rare)
34
(unfractionated) heparin contraindications
Active bleeding (ulcers, tumors, trauma, etc.)
Coagulopathies
Hypersensitivity to pork products
35
Apixaban (Eliquis)
Newer, Direct acting, reversible Xa inhibitor
In phase 3 trials (delayed approval)
Prevent venous thromboembolism
no routine monitoring required
36
Rivaroxiban (Xarelto)
First orally active direct Xa inhibitor, once daily dosing is possible
approved for prophylaxis of DVT in pts undergoing knee or hip replacement surgery
slightly higher bleeding incidence than heparin
does not require routine monitoring
37
Lepirudin (Refludan)
Direct thrombin inhibitor, recombinant version of hirudin (leeches)
most potent thrombin inhibitor known
neutralizes clot-bound thrombin (unlike heparin)
Main use: pts with heparin induced thrombocytopenia
38
Bivalirudin (Angiomax)
direct thrombin inhibitor
small synthetic peptide (20aa's)
beter tissue/clot penetration
main use: pts with unstable angina undergoing angioplasty (alternative to heparin)
39
Dabigatran (Pradaxa)
Orally available, direct thrombin inhibitor, for prevention of stroke in pts with afib.
Just as effective as warfarin, may challenge warfarin as dominant oral anticoagulant.
(GI bleeding significantly higher with 150mg vs 110mg or warfarin)
40
Warfarin MOA
Vitamin K antagonist - inhibits Vitamin K epoxide reductase. reduces amount of VitK available for biological synthesis of clotting factors (II, VII, IX, X)
30-50% effective decrease of functional clotting factors. takes 3-5 days to reach full effect, lasts several days after stopping
41
Warfarin metabolism
extensively metabolized by CYP2C9. Genetic variations lead to variable pt response.
42
Warfarin Interactions
Has a narrow therapeutic index. 99% protein bound.
Dietary Vit K changes
Inhibitors/Inducers of CYP enzymes
All result in variable pt response. Therapy requires constant INR monitoring
43
Warfarin Side Effects
Bleeding - can be correct with Vitamin K administration and/or blood transfusions
Birth defects/abortion
44
Warfarin Contraindications
pregnancy and pre-existing bleeding
45
Anti-platelet drugs
Aspirin
Ticlopidine, Clopidogrel, Prasugrel, Ticagrelor
Tirofiban, Abciximab, Eptifibatide
Effects: prevent platelet activation/aggregation. Mechanisms differ
46
Aspirin MOA
irreversibly acetylates and inhibits COX-1 in platelets. Decreases amount of thromboxane A2 (TXA2) = reduced platelet activation and adhesion.
81mg/day will effectively inhibit platelet formation without causing additional effects
47
ADP antagonists
Inhibit ADP dependent activation and aggregation of platelets, and blocks ADP receptor on platelets
Irreversible: Ticlopidine and Clopidogrel
Reversible: Prasugrel and Ticagrelor (quicker onset than irreversible, greater and more predictible inhibition of ADP0induced platelet activation. Less PG variability, greater efficacy for preventing stent thrombosis. But, greater incidence of life threatening bleeding)
48
Clopidogrel
generally more potent than Ticlopidine, better safety profile. (rare thrombocytopenia/leukopenia)
Prodrug, requires oxidation by CYPs.
Genetic variations in CYP2C19 are associated with reduced drug responsiveness.
49
Prasugrel
MOA: thienopyridine, antiplatelet agent
Reduces rate of thrombotic CV events in pts with unstable angina, NSTEMI or STEMI managed with PCI
Contraindications: pts with history of intracranial hemorrhage, active bleeding, or severe hepatic impairment
BBW: May cause significant or fatal bleeding; contraindicated in pts with active bleeding or history of TIA or stroke
Reversal: platelet concentrate of desmopressin
50
Ticagrelor
Newest oral antiplatelet agent
MOA: reversibly inhibits platelet ADP receptor
Used for prevention of stent thrombosis, cardiovascular death, heart attack in adults with ACS
Contraindications: pts with historyof intracranial hemorrhage, active bleeding, or severe hepatic impairment.
51
Abciximab (Reopro)
Monoclonal antibody against fibrinogen receptor. Approved for high risk post-angioplasty thrombosis. Noncompetitive inhibition, long half life, slow to reverse
52
Eptifibatide (Integrilin)
blocks fibrinogen binding to activated platelets. Proven success in PTCA and unstable angina trials. competitive inhibition, 2.5h half life. quickly reversible.
53
Tirofiban (Aggrastat)
Blocks fibrinogen binding to activated platelets. Short acting, IV use in high risk ACS pts. competitive inhibition, 2h half life, quickly reversible
54
Anti-platelet drugs Side Effects
```
Bleeding (all classes, all drugs) especially in GI tract (aspirin)
GI upset (aspirin)
Ticlopidine: Nausea, Vomiting, Neutropenia, Thrombocytopenia, Skin rashes.
```
55
Fibrinolytic agents
Streptokinase, Alteplase recombinant tPA, Tenecteplase
56
Uses of fibrinolytic agents
dissolve existing fibrin clots by converting circulating plasminogen to plasmin
57
streptokinase MOA
binds to plasminogen, forms enzyme complex which catalyzes conversion of plasminogen to active plasmin
58
Alteplase and Tenecteplase MOA
similar MOAs. Binds to fibrin first, then complex binds plasminogen forming triad.
alteplase = longer infusion time
tenecteplase = shorter infusion time
59
Side Effects of Fibrinolytic agents
bleeding and allergic reactions
60
Contraindications of Fibrinolytic agents
Recent bleeding
Recent surgery or invasive procedures
Severe hypertension
History of stroke.
61
Sources of LDL
```
from VLDLs (endogenous)
From diet (exogenous)
```
62
Removal of LDLs
LDL receptor activity, serves as the mechanism for LDL's to enter cells, thus reducing plasma concentrations.
HDLs also transport LDLs back to liver for enterohepatic recycling
63
Lipoprotein disorders
genetic: familial hypocholesterolemia (defective LDL receptor)
Most common - polygenic hypercholesterolemia (multiple genetic and environmental factors)
64
HMG CoA Reductase Inhibitors MOA
"statins"
Reversible, competitive inhibitors of HMG CoA reductase activity (converting HMG CoA to intermediates and then to cholesterol etc.)
65
Physio Effects of HMG CoA Reductase Inhibitors
reduce cholesterol synthesis in liver
reduce plasma VLDL concentration
reduce plasma LDL concentration
increase LDL receptor # (increased removal from plasma)
results in 20-55% decrease in plasma [LDL]
66
HMG CoA reductase Inhibitor optimal dosing
take at bedtime, cholesterol synthesis increased at night
67
HMG CoA reductase Inhibitor side effects
usually well tolerated, relatively few side effects
Increased liver transaminase
Rhabdomyolysis (rare) with secondary renal failure - can be fatal
68
HMG CoA reductase Inhibitor contraindications
pregnancy (need cholesterol for fetus to make new cells
69
Net result of HMG CoA reductase Inhibitor
decreased cholesterol synthesis in liver, increased LDL receptor activity inliver
20-55% decrease in LDL
5-15% increase in HDLs
70
Bile Acid Binding Resins
cholestyramine, colestipol HCl
71
Bile Acid Binding Resin MOA
resins positively charged, bile salts/acids negatively charged. Resins bind to cholesterol-containing bild acids/salts in intestine.
reduces enterohepatic recirculation of cholesterol
72
Effects of Bile Acid Binding Resin
decreased reabsorption of bild acids/salts
increased bile (and cholesterol) excretion in feces
increased hepatic LDL receptor expression (decrease plasma [LDL])
increased hepatic cholesterol synthesis (tempers therapeutic effect)
73
Bile Acid Binding Resin useful dosing
usually supplied as powder, and drunk as slury. take with meal (more bile secreted into SI)
74
Side Effects of Bile Acid Binding Resin
no direct systemic SE
| Local: bloating, abdominal discomfort, constipation, all leading to compliance issues
75
Bile Acid Binding Resin Drug interactions
binds to other anionic drugs/compounds. Need to dose other drugs 1 hour before or 3 hours after
76
Net Result of Bile Acid Binding Resin
```
increases LDL receptor activity
Increases cholesterol synthesis in liver (limits efficacy)
increases cholesterol loss in feces
15-30% reduction in LDLs
3-5% increase in HDLs
```
77
Ezetimibe MOA
inhibits cholesterol absorption at brust border of intestines. DOES NOT effect absorption of anionic drugs (vit A, D, E, Warfarin, OC's etc.)
78
Ezetimibe clinical use
10mg once a day, with or without food
13% decrease TC
18% decrease LDL
1% increase HDL
79
Ezetimibe Side Effects
rare allergic RXNs, otherwise well tolerated
80
Ezetimibe Combo therapy with statins (Vytorin)
additional 25% decrease in cholesterol
additional 33% decrease in TGs
7-9% increase in HDL
81
Niacin MOA
inhibits TG synthesis in liver, leads to reduced VLDL, which leads to reduced LDL
Increases lipoprotein lipase activity which promotes the clearance of chylomicrons and VLDL TGs
82
Niacin Physio Effects
10-15% decrease LDLs
15-35% increase HDLs (unknown mechanism)
35-50% decrease TGs
83
Niacin Side Effects
```
50% of pts
intense cutaneous flushing (can develop tolerance to this or give aspirin to decrease effect)
GI irritation (large frequent dosing)
hepatic dysfunction (jaundice)
Hyperglycemia
```
84
Niacin use/dosing
often used as adjunct therapy to raise HDLs
| available OTC
85
Niacin contraindications
liver dysfunction
peptid ulcers
diabetic pts
pregnancy
86
Fibric Acid Derivatives
gemfibrozil, clofibrate
87
Fibric Acid Derivative MOA
stimulates the PPAR-alpha, reduces TGs by 50%
88
Fibric Acid Derivatives Physio effects
decreases VLDL synthesis
9% decrease in LDLs
10-20 increase in HDLs
Effective in pts with hypertriglyceridemia
89
Fibric Acid Derivative side effects
gall stones
GI irritation
GI/hepatic tumors
90
Fibric Acid Derivative contraindications
pts on warfarin - increases anticoag effect
91
NEW CETP inhibitors in development: Anacetrapib
40% decrease in LDL
138% increase in HDLs
Acceptable SE profile
Did not produce adverse CV effects and mortality observed with predecessors
92
Class 1A Na Channel Blockers
Procainamide, Quinidine, Disopyramide
93
Class 1A Na Channel Blocker Effects
moderate potency to block Na channel
slows upstroke of AP, Increase AP duration (increases phase 0 and 3)
reduce conduction felocity
increase refractoriness
94
Class 1A Na Channel Blocker uses
atrial and ventricular arrhythmias
95
Important features of Class 1A Na Channel Blockers
drugs preferentially target rapidly depolarizing tissue more than normal tissue
prolonging repolarization = increased refractory period (effective in stopping re-enterant arrhythmias
96
Class 1B Na Channel Blockers
Lidocaine
97
Class 1B Na Channel Blocker Effects
Low potency Na blockers
have highest affinity for Na channels in ischemic cells
reduce phase 0 slope and slows conduction
reduces automaticity and phase 4 slope
increase refractoriness
98
Class 1B Na Channel Blocker uses
ventricular arrhythmias
| ineffective in atrial tissue
99
Class 1B Na Channel Blockers unique features
lidocaine - highly lipophilic
reduces ventricular tachycardias or Vfib after cardioversion
clinical trials = decreased survival after MI when used long term
100
Class 1C Na Channel Blockers
Flecainamide, Propafenone
101
Class 1C Na Channel Blocker effects
high potency Na blockers with some K blocking potential
decreases phase 0 slope and AP conduction
increases AP duration and refractoriness especially in atrial cels at fast rates and AV nodes
102
Class 1C Na Channel Blocker uses
supraventricular arrhythmias (nodal arrhythmias)
103
Class 1C Na Channel Blocker unique features
increases AP duration disporportionately more in atria at fast rates
increases mortality in patients recovering from MI
104
Class 1 Antiarrhythmic Side Effects
```
provoke or increase arrhythmias
exacerbate congstive heart failure
heart block (block AV node)
Hypotension
GI distress
Sedation, tremor, dizziness, blurred vision
nausea, vomiting
```
105
Class 2 antiarrhythmics (B-blockers)
propranolol, sotalol, esmolol
106
Class 2 antiarrhythmic effects
increases AV refractoriness
decreases conduction velocity
increases AP duration (atria, nodal tissue)
107
Class 2 antiarrhythmic uses
atrial tachycardia and ventricular tachycardia
108
Class 2 antiarrhythmic unique features
reduces mortality after MI (new studies say maybe not)
109
Class 2 antiarrhythmic side effects
```
relatively well tolerates
CV: bradycardia, HF, low exercise tolerance
Rebound effect
Bronchospasm (B2)
Sedation (lipophilic B2)
Metabolic effects (increased TGs)
```
110
Class 3 antiarrhythmics
amiodarone (most freq), dronederone, dofetilide
111
Class 3 antiarrhythmic effects
blocks K channels
| increases repolarization phase and AP duration
112
Class 3 antiarrhythmic uses
nost arrhythmias (atrial/ventricular)
113
Class 3 antiarrhythmic unique features
highly lipophilic, concentrates in tissues, therefore very long t1/2 (25-110 days)
SLIGHTLY decreases mortality after MI
114
Class 3 antiarrhythmic Side Effects
75% of pts
hypotension and decreased LV contractility
muscle weakness
hypo/hyperthyroidism
pulmonary fibrosis (rare but can be fatal)
115
Class 4 antiarrhythmics
verapamil, diltiazem (no dihydropyridines)
116
Class 4 antiarrhythmic effects
blocks Ca channels
decreases slope of phase 4, increases AP, decreases automaticity
decreases HR
decreases AV conduction
117
Class 4 antiarrhythmic uses
atrial tachycardias, Afib, AV node arrhythmias
118
Class 4 antiarrhythmic unique features
do not reduce mortality after MI (do not increase either)
| Dihydropyridines are ineffective
119
Class 4 antiarrhythmic side effects
```
mostly with concomitant therapy
hypotension (w/ vasodilators)
sinus bradycardia (w/ B blockers)
Heart block (w/ B blockers)
decreased contractility
constipation
```
120
Adenosine MOA
stinulates adenosine receptors
opens K channels, hyperpolarizes membrane
inhibits pacemaker current in Ca channels
121
Adenosine use
supraventricular rhythms, must be given IV, usually in hospital setting
122
Adenosine side effects
Asystole (transient)
| hypotension
123
Digoxin MOA
increases AV node refractoriness
124
Digoxin uses
AV re-entrant rhythms, atrial fibrilation (HF)
125
Digoxin side effects
```
triggered rhythms
AV block (reduced coordination of contraction)
```
126
Sources of LDL
```
from VLDLs (endogenous)
From diet (exogenous)
```
127
Removal of LDLs
LDL receptor activity, serves as the mechanism for LDL's to enter cells, thus reducing plasma concentrations.
HDLs also transport LDLs back to liver for enterohepatic recycling
128
Lipoprotein disorders
genetic: familial hypocholesterolemia (defective LDL receptor)
Most common - polygenic hypercholesterolemia (multiple genetic and environmental factors)
129
HMG CoA Reductase Inhibitors MOA
"statins"
Reversible, competitive inhibitors of HMG CoA reductase activity (converting HMG CoA to intermediates and then to cholesterol etc.)
130
Physio Effects of HMG CoA Reductase Inhibitors
reduce cholesterol synthesis in liver
reduce plasma VLDL concentration
reduce plasma LDL concentration
increase LDL receptor # (increased removal from plasma)
results in 20-55% decrease in plasma [LDL]
131
HMG CoA reductase Inhibitor optimal dosing
take at bedtime, cholesterol synthesis increased at night
132
HMG CoA reductase Inhibitor side effects
usually well tolerated, relatively few side effects
Increased liver transaminase
Rhabdomyolysis (rare) with secondary renal failure - can be fatal
133
HMG CoA reductase Inhibitor contraindications
pregnancy (need cholesterol for fetus to make new cells
134
Net result of HMG CoA reductase Inhibitor
decreased cholesterol synthesis in liver, increased LDL receptor activity inliver
20-55% decrease in LDL
5-15% increase in HDLs
135
Bile Acid Binding Resins
cholestyramine, colestipol HCl
136
Bile Acid Binding Resin MOA
resins positively charged, bile salts/acids negatively charged. Resins bind to cholesterol-containing bild acids/salts in intestine.
reduces enterohepatic recirculation of cholesterol
137
Effects of Bile Acid Binding Resin
decreased reabsorption of bild acids/salts
increased bile (and cholesterol) excretion in feces
increased hepatic LDL receptor expression (decrease plasma [LDL])
increased hepatic cholesterol synthesis (tempers therapeutic effect)
138
Bile Acid Binding Resin useful dosing
usually supplied as powder, and drunk as slury. take with meal (more bile secreted into SI)
139
Side Effects of Bile Acid Binding Resin
no direct systemic SE
| Local: bloating, abdominal discomfort, constipation, all leading to compliance issues
140
Bile Acid Binding Resin Drug interactions
binds to other anionic drugs/compounds. Need to dose other drugs 1 hour before or 3 hours after
141
Net Result of Bile Acid Binding Resin
```
increases LDL receptor activity
Increases cholesterol synthesis in liver (limits efficacy)
increases cholesterol loss in feces
15-30% reduction in LDLs
3-5% increase in HDLs
```
142
Ezetimibe MOA
inhibits cholesterol absorption at brust border of intestines. DOES NOT effect absorption of anionic drugs (vit A, D, E, Warfarin, OC's etc.)
143
Ezetimibe clinical use
10mg once a day, with or without food
13% decrease TC
18% decrease LDL
1% increase HDL
144
Ezetimibe Side Effects
rare allergic RXNs, otherwise well tolerated
145
Ezetimibe Combo therapy with statins (Vytorin)
additional 25% decrease in cholesterol
additional 33% decrease in TGs
7-9% increase in HDL
146
Niacin MOA
inhibits TG synthesis in liver, leads to reduced VLDL, which leads to reduced LDL
Increases lipoprotein lipase activity which promotes the clearance of chylomicrons and VLDL TGs
147
Niacin Physio Effects
10-15% decrease LDLs
15-35% increase HDLs (unknown mechanism)
35-50% decrease TGs
148
Niacin Side Effects
```
50% of pts
intense cutaneous flushing (can develop tolerance to this or give aspirin to decrease effect)
GI irritation (large frequent dosing)
hepatic dysfunction (jaundice)
Hyperglycemia
```
149
Niacin use/dosing
often used as adjunct therapy to raise HDLs
| available OTC
150
Niacin contraindications
liver dysfunction
peptid ulcers
diabetic pts
pregnancy
151
Fibric Acid Derivatives
gemfibrozil, clofibrate
152
Fibric Acid Derivative MOA
stimulates the PPAR-alpha, reduces TGs by 50%
153
Fibric Acid Derivatives Physio effects
decreases VLDL synthesis
9% decrease in LDLs
10-20 increase in HDLs
Effective in pts with hypertriglyceridemia
154
Fibric Acid Derivative side effects
gall stones
GI irritation
GI/hepatic tumors
155
Fibric Acid Derivative contraindications
pts on warfarin - increases anticoag effect
156
NEW CETP inhibitors in development: Anacetrapib
40% decrease in LDL
138% increase in HDLs
Acceptable SE profile
Did not produce adverse CV effects and mortality observed with predecessors
157
Class 1A Na Channel Blockers
Procainamide, Quinidine, Disopyramide
158
Class 1A Na Channel Blocker Effects
moderate potency to block Na channel
slows upstroke of AP, Increase AP duration (increases phase 0 and 3)
reduce conduction felocity
increase refractoriness
159
Class 1A Na Channel Blocker uses
atrial and ventricular arrhythmias
160
Important features of Class 1A Na Channel Blockers
drugs preferentially target rapidly depolarizing tissue more than normal tissue
prolonging repolarization = increased refractory period (effective in stopping re-enterant arrhythmias
161
Class 1B Na Channel Blockers
Lidocaine
162
Class 1B Na Channel Blocker Effects
Low potency Na blockers
have highest affinity for Na channels in ischemic cells
reduce phase 0 slope and slows conduction
reduces automaticity and phase 4 slope
increase refractoriness
163
Class 1B Na Channel Blocker uses
ventricular arrhythmias
| ineffective in atrial tissue
164
Class 1B Na Channel Blockers unique features
lidocaine - highly lipophilic
reduces ventricular tachycardias or Vfib after cardioversion
clinical trials = decreased survival after MI when used long term
165
Class 1C Na Channel Blockers
Flecainamide, Propafenone
166
Class 1C Na Channel Blocker effects
high potency Na blockers with some K blocking potential
decreases phase 0 slope and AP conduction
increases AP duration and refractoriness especially in atrial cels at fast rates and AV nodes
167
Class 1C Na Channel Blocker uses
supraventricular arrhythmias (nodal arrhythmias)
168
Class 1C Na Channel Blocker unique features
increases AP duration disporportionately more in atria at fast rates
increases mortality in patients recovering from MI
169
Class 1 Antiarrhythmic Side Effects
```
provoke or increase arrhythmias
exacerbate congstive heart failure
heart block (block AV node)
Hypotension
GI distress
Sedation, tremor, dizziness, blurred vision
nausea, vomiting
```
170
Class 2 antiarrhythmics (B-blockers)
propranolol, sotalol, esmolol
171
Class 2 antiarrhythmic effects
increases AV refractoriness
decreases conduction velocity
increases AP duration (atria, nodal tissue)
172
Class 2 antiarrhythmic uses
atrial tachycardia and ventricular tachycardia
173
Class 2 antiarrhythmic unique features
reduces mortality after MI (new studies say maybe not)
174
Class 2 antiarrhythmic side effects
```
relatively well tolerates
CV: bradycardia, HF, low exercise tolerance
Rebound effect
Bronchospasm (B2)
Sedation (lipophilic B2)
Metabolic effects (increased TGs)
```
175
Class 3 antiarrhythmics
amiodarone (most freq), dronederone, dofetilide
176
Class 3 antiarrhythmic effects
blocks K channels
| increases repolarization phase and AP duration
177
Class 3 antiarrhythmic uses
nost arrhythmias (atrial/ventricular)
178
Class 3 antiarrhythmic unique features
highly lipophilic, concentrates in tissues, therefore very long t1/2 (25-110 days)
SLIGHTLY decreases mortality after MI
179
Class 3 antiarrhythmic Side Effects
75% of pts
hypotension and decreased LV contractility
muscle weakness
hypo/hyperthyroidism
pulmonary fibrosis (rare but can be fatal)
180
Class 4 antiarrhythmics
verapamil, diltiazem (no dihydropyridines)
181
Class 4 antiarrhythmic effects
blocks Ca channels
decreases slope of phase 4, increases AP, decreases automaticity
decreases HR
decreases AV conduction
182
Class 4 antiarrhythmic uses
atrial tachycardias, Afib, AV node arrhythmias
183
Class 4 antiarrhythmic unique features
do not reduce mortality after MI (do not increase either)
| Dihydropyridines are ineffective
184
Class 4 antiarrhythmic side effects
```
mostly with concomitant therapy
hypotension (w/ vasodilators)
sinus bradycardia (w/ B blockers)
Heart block (w/ B blockers)
decreased contractility
constipation
```
185
Adenosine MOA
stinulates adenosine receptors
opens K channels, hyperpolarizes membrane
inhibits pacemaker current in Ca channels
186
Adenosine use
supraventricular rhythms, must be given IV, usually in hospital setting
187
Adenosine side effects
Asystole (transient)
| hypotension
188
Digoxin MOA
increases AV node refractoriness
189
Digoxin uses
AV re-entrant rhythms, atrial fibrilation (HF)
190
Digoxin side effects
```
triggered rhythms
AV block (reduced coordination of contraction)
```
