CPEE Test 2 Flashcards
1
Q
What’s the role of NO in VSM relaxation
A
- Activates Guanylyl Cyclase which creates cGMP
- cGMP activates myosin light chain phosphatase which takes a phosphate off of myosin light chain
- Dephosphorylated myosin light chain leads to relaxation of VSM and vasodilation.
2
Q
Which drugs are the Organic Nitrates
A
-Nitroglycerin and Isosorbide dinitrate
3
Q
Nitroglycerin
A
- Prodrug converted to NO by ALDH2 (inhibited by alcohol and some decrease in activity among asian population)
- ALDH2 deactivation by NO leads to tolerance
- Primary effect is venous dilation –> decreased preload
- Reverses ST segment depression but no survival benefit in MI
- Orthostatic hypotension, reflex tachycardia, flushing headaches
- Sublingual tablet for fast relief (fast effect short duration of action)
- Patch or oral formulation for prophylaxis (longer duration of action and slower acting)
- DON’T TAKE WITH ED drugs.
4
Q
Isosorbide Dinitrate
A
- Prodrug that is converted to isosorbide mononitrate which contributes to its efficacy.
- Longer duration of action that NTG
- Used when NTG and Beta blockers or CCB aren’t effectively controlling Angina.
5
Q
Calcium Channel Blocker Drugs
A
- Dihydropyridines: Nifedipine
- Non-dihydropyridines: Verapamil and diltiazem
6
Q
Calcium Channel Blockers action
A
- Block inward flow to Calcium through voltage gated L-type Channels
- Verapamil and diltizem work at nodal tissue (decrease heart rate) as well as cardiac and VSM
- Dilators on coronary and peripheral VSM –> decrease in preload
- Prophylaxis (due to long duration of action) to reduce NTG consumption.
- Useful in Vasospasm seen in Prinzmetal angina.
- Efficacy in treating angina = to beta-blockers, but no survival benefit.
7
Q
Nifedipine
A
- Dihydropyrimidine
- Causes reflex tachycardia so it shouldn’t be used
- Less depression of myocardial contractility and minimal effects on SA node
- CYP 3A4 (avoid grapefruit juice
8
Q
Diltiazem and Verapamil
A
- Same action as Nifedipine with added SA and AV node effects (decreased heart rate and contractility)
- less potent vasodilators
- Diltiazem produces less cardiac depression and is generally tolerated better than Verapamil.
- DONT USE IN SICK SINUS SYNDROME OR AV NODAL BLOCK
9
Q
Adverse effects of Nifedipine, Diltiazem and Verapamil
A
- Bradyarrhythmias (VER and DIL)
- Reflex Tachy (NIFE)
- Cardiac Depression (VER and DIL)
- Flushing with peripheral edema (NIFE)
- Constipation in geriatrics (Ver)
10
Q
Beta-Blockers
A
-Propranolol
11
Q
Propranolol
A
- Beta blocker
- Decreases: HR, Contractility, Systemic BP
- Works by decreasing afterload
- Decreases mortality by decreasing sudden cardiac death
- Goal is to get resting HR at 55bpm and upper limit is 110 bpm
- Not useful in Prinzmetal due to unopposed alpha 1 activity
- Reduces frequency and severity of stable angina attacks
- Can precipitate acute M.I. after sudden withdrawl
- Don’t use with B1 agonists
12
Q
Ranolazine
A
- Antianginal effects w/o changing heart rate or Blood pressure
- Stops Calcium overload in ischemic myocytes by inhibiting sodium influx which is later exchanged for calcium
- Prophylaxis against angina
- Used for refractory angina because it prolongs QT interval.
13
Q
1st line Antihypertensives
A
Thiazide diuretics, ACE inhibitors, ARBs, CCBs
14
Q
3rd line Antihypertensives
A
Beta blockers, Loop diuretics, Alisikiren, Alpha 1 blockers,, vasodilators, Centrally acting alpha-2 agonists, Reserpine, Aldosterone antagonist.
15
Q
Thiazide
A
- Chlorthalidone
- Anti hypertensive not hypotensive
- Initially increase renal secretion of Na+ and H20 but TPR increases due to sympathetic reflex and activation of RAAS
- Later on decrease TPR, probably lack of sodium –> altered Na/Ca exchange in VSM
- No change in HR or CO
- Low dose mono therapy for stage I (10-15mmHg 4-6 weeks after onset of therapy)
- reduce Na retention caused by vasodilators
- Partially effective in volume dependent HTN
- Hypokalemia, Hyperuricemia, ED
16
Q
Loop Diuretics
A
- Furosemide
- mostly malignant HTN and volume dependent patients w/ renal disease
- Ototoxicity
17
Q
RAS System drugs
A
- Captopril (ACE inhibitor)
- Losartan (ARB)
- Eplerenone (Aldosterone agonists)
- Aliskiren (Renin inhibitors)
18
Q
ACE inhibitor
A
- Captopril
- Inhibits Ang I –> Ang II conversion decrease TPR
- Antihypertensive (effective even in patients with normal PRA)
- First dose phenom
- Doesnt interfere with cardiovascular reflexes or bronchial asthma.
- Reduce risk of HTN associated cardiovascular mortality
- hyperkalema, cough, angioedema, teratogenicity
19
Q
ARBs
A
- Losartan
- AT1 receptor antagonists
- Alternative for patients who don’t like ACEI
- No cough or angioedema
20
Q
Aldosterone antagonists
A
- Eplerenone
- selective aldosterone antagonist (more selective in this regard than spironolactone)
- Promotes Na and H2O excretion in kidney
- Prevent reverse cardiac remodeling
- Used for additional decrease in BP in Pts taking ACEI or ARB
- HYPERKALEMIA
21
Q
Direct Renin inhibitor
A
- Aliskiren
- Blocks angiotensinogen –> ATI
- Used alone or in combo
- hyperkalemia
22
Q
Calcium Channel Blockers
A
Nifedipine, Verapamil, Diltiazem
- Blocks voltage gated L-Ca channels in VSM –> decrease TPR
- Ver and Dil slow HR
- First line for mild to mod HTN
- Nif used for PAH
23
Q
Vasodilators
A
Nitroprusside, Hydralazine, Minoxidil, Epoprostenol, Bosentan
24
Q
Nitroprusside
A
- Decomposes to release NO w/ enzyme (no tolerance)
- Arterial and venous dilation
- Immediate effect with short DOA (unstable and light sensitive in solution)
- Produces CN- that is metabolized in liver by rhodanase (thiosulfate antidote)
- Hypertensive emergencies, hypotensive during surgery, need to give furosemide to avoid edema
- Excessive vasodilation and hypotension, cyanide, hypothyroidism (thiocynate accumulations)
25
Q
Hydralizine
A
- ARTERIOLAR dilation to decrease TPR
- High first pass metabolism, NAT-2 inactivates drugs (slow acetylators)
- SEVERE HTN 3rd line, HTN crisis
- Combo w/ isosorbide dinitrate for CHF/HTN in AA
- Reflex tachy, lupus like syndrome in slow acetylators
26
Q
Minoxidil
A
- Arterial Dilation via K+ efflux –> membrane hyperpolarization
- Reflex increase in HR and contractility
- Prodrug, liver –> minoxidil sulfate
- Seldom used unless extreme HTN due to side effects
- Rogaine
- Edema due to Na and H2O retention (diuretic), Pericardial effusion, Reflex tachycardia (beta blocker), Hypertrichosis
27
Q
Prostacyclin
A
- Epoprostenol
- Mimics endogenous PGI2 on VSM, binds to GPCR and stimulates cAMP synthesis
- Vascular relaxation, suppresses VSM growth, inhibits platelet agg.
- used in PAH to increase short term survival
- Flushing, headache, nausea, increased risk of bleeding
28
Q
Endothelin-1 Antagonist
A
- Bosentan
- Endothelin 1 is endothelial derived vasoconstrictor peptide (POTENT)
- induces inflammation, fibrosis, and prolif of VSM, levels elevated in PAH
- Antagonist at ETa and ETb receptors
- PAH treatment but use limited due to toxicity
29
Q
Sympatholytics
A
-Clonidine and methyldopa
30
Q
Centrally acting Alpha 2 adrenergic agonists
A
- Clonidine
- Decrease sympathetic outflow, pre-synaptic alpha 2a receptors in medulla decreased CO and TPR
- produces compensatory sodium and H2O retention
- Antihypertensive for patients who haven’t responded to other drugs
- Sedation, dry mouth, sex dysfunction, postural hypotension
- abrupt withdrawal symptom
31
Q
Methyldopa
A
- -> Methyl-NE
- similar to clonidine but no rebound effect, hemolytic anemia
- use during pregnancy
32
Q
Beta-Blockers
A
- Propranolol, metoprolol, atenolol (last 2 are cardioselective)
- Reduces CO (initial decrease in BP)
- Inhibits beta-1 mediated release of renin
- CNS reduces sympathetic outflow
- no longer recommended unless there is a specific indication (MI, CHF, SIHD) or intolerance to first line agents
- Less effective in AA and geriatrics
- Brady, bronchoconstriction, reduced exercise capacity, sex dysfunction
33
Q
Alpha Blockers
A
- Terazosin
- Block Alpha 1 on VSM
- Salt and water retention
- Used as antiHTN add on
- first dose effect, reflex tachy, nasal congestion, inhibition of eject
34
Q
HMG-CoA Reductase inhibitors: MOA and effects
A
- Atorvastatin (Lipitor)
- Compet inhib of HMG CoA reductase (rate limiting step in cholesterol synth)
- Increase LDL hepatic receptors –> increased removal of LDL
- enhance clearance and production of LDL precursors (VLDL IDL)
- 20-55% dec LDL
- 20% dec Triglycerides
- 5-10% incr HDL
- 1st line hypercholesterolemia due to elevated LDL
35
Q
HMG-CoA Reductase inhibitors: Potential cardioprotective effects, PK, drug interactions, Adverse effects
A
-Cardioprotective effects: Dec C-Reactive protein
-Anti inflam
-Enhance NO synth
-Stabilize plaque
-Reduce lipoprotein agg
-reduce plate agg
Pharmkinects: Orally, at night, extensive 1st pass metabolism, excreted by liver into bile
Drug interactions: Other statins
Adverse effects: GI irritation, headache and rash, hepatotoxicity, myopathy (creatine phosphokinase) NO PREGNANCY!
36
Q
Fibric Acids: MOA and effects
A
- Fenofibrate
- agonists at PPAR-alpha
- Inc. FA Oxidation
- Inc. act of lipoprotein lipase
- Reduce expression ApoC-III –> inc. clearance of VLDL
- ApoA-I and ApoA-II expression –> inc. HDL levels
- Inhib of coag and incr. fibrinoylsis
- Total effects: Dec. VLDL lowering Triglycerides and incr. HDL
37
Q
Fibric Acids: Uses, PK, Drug interactions, and adverse effects
A
- Fenofibrate
- Uses:
- Type III hyperlipoproteinemai
- Severe Hypertriglyceridemia (risk for pancreatitis)
- Hypertriglyceridemia with low HDL
- PK: absorbed rapidly and efficiently, T1/2 1-20 hrs, excreted as glucuronides
- Interactions: warfarin effects may be incr., w/ statins myositis and myopathy
- Adverse Effects: GI disturbances, skin rash, utricaria, hair loss, myalgias, fatigue and headache
- NO PREGNANCY RENAL AND HEPATIC FAILURE
38
Q
Bile Acid Binding Resins
A
- Colesevelam
- Prevents bile acid reabsorption in the intestines –> incr. breakdown of hepatic cholesterol to bile acids
- Also increases hepatic LDL receptors like statins, but accompanied by increase in HMG CoA activity
- Lower LDL levels (10-20%) with a small increase in HDL levels (5%)
- Familial or primary hypercholesterolemia w/ very high LDL usually used with Statin
- Not absorbed after oral administration stays in GI tract
- Bloating, dyspepsia, and Constipation, steatorrhea
39
Q
Niacin: MOA
A
- Inhibits lipolysis of TGs in adipose tissue which reduces hepatic TG synthesis
- Inhibits both the synthesis and esterification of FA’s which leads to decrease of TG synthesis. Dec. TG synthesis –> dec. Hepatic VLDL production –> decreased LDL
- Decreases fractional clearance of HDL ApoA-I (makes HDL)
40
Q
Niacin: Effects, uses, PK, and Adverse effects
A
- Effects: rapidly lowers TG levels, more gradual lowering of LDL levels, increases HDL
- Uses: Hypertriglyceridemia and elevate LDL, useful in patients with Hypertriglyceridemia and low HDL
- PK: Readily absorbed in all part of intestinal tract, short T1/2, metabolized in the liver and excreted unchanged
- Adverse effects: Myopathy, flush, GI disturbances, Hepatic toxicity, ulcer, hyperglycemia, hyperuricemia
- Pregnancy, hepatic disease, ulcer, arthritis
41
Q
Ezetimibe (Zetia)
A
- Inhibits intestinal absorption of cholesterol, reabsorption of cholesterol excreted in bile, inhibits cholesterol transport protein NPC-1L1
- Primary effect is to reduce LDL levels
- Primarily used with Statins but study shows no more efficacy than solo statins
- Orally, feces, 22% conjugated in liver glucuronidation
- Fibrinates = increase Ezetimibe levels increase levels of cholelithiasis
- Niacin incr. levels which incr. risk of myopathies
- Warfarin = incr. prothrombin time
- Diarrhea
42
Q
Drugs used for altered automaticity
A
-Na+ and Ca+ channel blockers (Reduce phase 4 depolarization rate and reduce excitability)
43
Q
Drugs used for EAD
A
-Reduce K+ channel blockers or and Na+ and Ca+ channel blockers (increase rate of repolarization or suppress depolarization)
44
Q
Drugs for DAD
A
-Na+ or Ca+ channel blockers (reduce Ca+ overload)
45
Q
Reentry Fast tissue
A
-Na+ channel blockers (Decrease excitability and prolong refractory period) K+ channel blocker (prolong APD and prolong refractory period)
46
Q
Reentry Slow tissue
A
-Ca+ Channel blockers (decrease excitability and prolong refractory period)
47
Q
Class IA antiarrhythmics
A
Na+ channel blockers with 1-10 second dissociation.
- Moderate reduction in rate of depolarization and conduction velocity in normal cells
- Prolong refractory period and APD (K+ effect)
- Widen QRS and QT
- Low [K+] leads to increased pro arrhythmic effects
48
Q
Quinidine
A
- Class IA
- Blocks Na+ and K+ channels
- Alpha adrenergic blockade
- Anticholinergic
- Maintain Sinus rhythm in A fib and A flutter
- Suppresses supraventricular and ventricular tachycardias
- Prolongs QT –> incr. risk of torsades
- Incr. levels of digoxin
49
Q
Procainamide
A
- Class IA
- N-Acetyl procainamide blocks K+ but not Na+ channels which prolongs QT leading to Torsades
- Lupus like syndrome in slow acetylators
50
Q
Disopyramide
A
- Class Ia
- Stronger anti-cholinergic effects than quinidine
- Neg. Inotropic effects (Bad in CHF)
51
Q
Class Ib Antiarrhythmics
A
- Na+ channel blockers
- Fast dissociation (less than 1 second)
- Minimal phase 0 and conduction velocity reduction in normal cells. (Functions more on ischemic cells
52
Q
Lidocaine
A
- Class Ib
- Selective for ventricular over atrial cells
- Acute IV therapy for ventricular arrhythmias after MI (Not effective against Atrial arrhythmias
- Seizures with rapid IV administration
- Depression of Cardiac function
- Local anesthetic
53
Q
Class IC
A
- Very long dissociation (greater than 10 seconds)
- marked effect on rate of phase 0 depolarization and conduction in normal cells
- small effect on APD and refractory period
- Widens QRS and prolongs PR and QT intervals
54
Q
Flecainide
A
- Class Ic
- Blocks Na+ channels (selective for cells with a high rate but also blocks cells with a normal rate more than class Ia and Ib
- Blocks K+ channels (prolongs refractory periods)
- Suppresses Suprvent tachyarrhythmias
- Life threatening vent arrhythmias
- increases mortality in patients recovering from MI
- Blurred vision
- Proarrhythmic especially in the presence of severe heart disease
- Blocks Ca + channels and suppresses LV function
55
Q
Propafenone
A
- Class IC
- Beta-adrenergic blockade
- flecainide and propafenone are metabolized by CYP2D6 but only propafenone levels are increased in the blood in slow CYP2D6 metabolizers
56
Q
Class II
A
- Beta Blockers
- Metroprolol
- Blocks Beta-1 adrenergic receptor regulated activity of Ca++ and K+ channels in myocardium
- Blocks sympathetic influence on cardiac automaticity
- Blocks sympathetic induced EAD and DAD
- Increases refractory period at AV node (incr. PR interval)
- Decreases mortality after MI (only other drug amiodarone)
- SA and AV node block
- Sudden withdrawal may worsen angina and arrhythmias
- Decrease vent. function
57
Q
Class III
A
-K+ Channel blockers (prolong APD) MECHANISM: -Blocks K+ leading to prolonged refractory period -Blocks Na+ channels Decreased excitability -Blocks Ca++ channels -Prolongs PR, QRS and QT intervals USES: -Refractory vent tachycardia or fib -Maintain sinus rhythm in a fib SIDE EFFECTS: Pulmonary fibrosis with long-term use Thyroid dysfunction (Hypo or Hyper) Other: Lipophilic long half life Many drug interactions due to inhibition of CYP 3A4 2C9 and P-glycoprotein
58
Q
Sotalol
A
- Class III K+ Channel blocker
- Non-selectiv Beta blocker that also blocks K+ channels
- Approved for patients with vent tachy, severe a flutter, or a fib
- Torsades in overdose
59
Q
Dofeltilide
A
Class III K+ channel blocker
- Potent and pure K+ channel blocker (no extra cardiac effects)
- Restricted distribution to main sinus rhythm in patient w/ A fib
- Torsades
60
Q
Class IV
A
-Ca++ Channel blockers
-Verapamil
MECHANISM:
-Blocks Ca++ Channels and decreases slow tissue automaticity and excitability
-Effects similar to Beta-blockers
-Depresses AV node conduction
USES:
-Control vent rate in atrial flutter fib
-Supravent tachy due to AV node reentry
EFFECTS:
-Depresses Cardiac force of contraction (NO CHF)
-Constipation most common side effect
OTHER:
-Interaction with other drugs that inhibit AV and SA node (beta blockers and digoxin)
61
Q
Adenosine
A
MECHANISM: -Stimulates A1 GCPR --> Dec cAMP -Activate K channels in SA and AV leading to Hyperpolarization -Reduces AV node Ca++ currents -Increases PR interval USES: -Acute termination of AV node reentry -WPW syndrome (don't use with A FIB) Effects: -Relatively safe due to short action, brief asystole -Flushing and metallic taste Other: -IV -Inactivated by adenosine deaminase -interaction with caffeine
