i) Discuss 6 agents that may cause drug induced torsade de pointes and ii)treatment of torsade de pointes.

1.    Quinidine
2.    Ibutilide (Corvert®)
3.    Dofetilide (Tikosyn®)
4.    Phenothiazines
5.    Antihistamines
6.    Antidepressants
(ii)    Treatment = drug of choice is magnesium

Name some properties of Class 1a Antiarrhythmics

Class 1a Toxic Effects:  

Quinidine =

Procainamide =

Disopyramide = 

1)  Class 1b Antiarrhythmic Properties

2)  Name the 2 most commonly prescribed and their properties

1) Used for emergent ventricular arrhythmias
Very similar in action to Ia
Fast “on/off” action = best effect on greatly increased heart rate

1)  Class Ic Properties

2)  Name 2 1c drugs

1)Class II properties

2) Name some

1)  Class III Properties

2)  Name some specific Class III and their properties

1) Block potassium channels to prolong refractory period

1)  Class IV Properties

2)  Potential Downsides?

1)  Which drug blocks AV Nodal reentry halting paroxysmal supraventricular tachycardia (PSVT)

2)  T or F..it has a very long half life

3)  T or F...causes a temporary flatline?

1)  Adenosine (Adenocard ®)

2)  False  only 10 seconds so it must be injected very rapidly for desired effect.

3) T

Atrial Fib or FlutterRates
1)  Fib = atrial BPM=?

, ventricular response usually 120 – 180 BPM; irregular
2)  Flutter = atriam BPM=?
3)  Ventricular response in multiples of ___

1) 400 – 600 BPM

2)  280 – 320 BPM

3)  300

1:1 = VR 300 BPM
2:1 = VR 150 BPM
3:1 = VR 100 BPM

i)  post MI

iii)  Ic

iv)  3

Just say no to drugs (maybe a Betablocker....if the pain is really severe but that is IT)

....nothing what's the mada witchu?

1)  Ventricular Tachycardia is considered SUSTAINED if it is greater than how many seconds?

2)  Nonpharm Txs?

3)  Pharm Txs? 

1) 30

1)  What is the Drug of Choice to treat Torsades De Pointe?

2)  What types of ion deficiencies are associated with this condition?

1)  Drug of choice for treatment is MAGNESIUM (2 grams of Mag will set you free)

2)  Hypokalemia...hypomagnesium

Receptors and their fcts:

Vasoconstriction

Increase HR and contractility

Increases HR and contractility AND VASODILATION

Receptors and their fcts:

V1

DA

 

Vasoconstriction

Vasodilation

1)  Intravascular volume deficit (hypovolemic, hemorrhagic)

2)  Myocardial failure (cardiogenic)

3)  Peripheral vasodilation (septic, anaphylatic, neurogenic)

1)  T or F

With Alubumin there is No difference in 28 day mortality when compared to NS for resuscitation of critically ill patients (SAFE trial)
2)  What is Comparable to 5% albumin but
Less expensive

 

1)  True...but there IS a difference in cost...ALBUMIN is much more pricey

2)  Hetastarch,  but avoid in intracranial hemorrhage due to risk of decreased factor VII activity and watch out for renal damage (limit to 1.5 L a day to avoid damage here...large starch molecules)

1) Rank these in order of Vasoconstrictiveness Fcting:

 Dopamine

Isoproterenol 

Phenylephrine

Isoproterenol

Dobutamine

Norepinephrine

2) T/F HR effectiveness follows this same order?

PNEDDI or

 Phenylephrine (most alpha)

Norepinephrine

Epinephrine

Dopamine

Dobutamine

Isoproterenol (most beta)

2) False Inverse...most beta-like are more effective HR effectors. 

With Dopamine DOSING is Essential to Desired Effect

1)   < 5 mcg/kg/min =____ and ___  receptor activation 

2)  5 to 10mcg/kg/min = beta 1 adrenergic effects...WHAT WOULD THIS MEAN?

3) > 10 mcg/kg/min = _____ adrenergic effects

1)  DA1 and DA2 (vasodilation)

2)   Increased cardiac contractility and heart rate

3) alpha 1...Increased vasoconstriction

Inotropic Agents (alter the strength of cardiac contractions) we discussed are:

Dobutamine
Milrinone
Isoproterenol

T or F  Dobutamine

1)  Increases CO

2)  Vasoconstricts

3)  Is a Beta 1 and 2 antagonist?

4)  Tachyarrhythmia, arrhythmias, and tachycardias may be adverse effects

True

False it vasodilates

False it is a beta 1 and beta 2 agonist

True

1)  Milrinone is  administered how?

2)  Maintenance dosing needed?

3)  What might we have to adjust for?

4)  What is the mechanism of action for Milrinone

5)  What are some adverse side effects?

1) 50 micrograms/kilogram over 10 minutes

2)   Yes....0.375 to 0.75 mcg/kg/minute...

3)  Renal Insufficiency

4)  Phosphodiesterease inhibitor...increases CO and reduces after-load via vasodilation

5)  Hypotension, Ventricular arrhythmias, Thrombocytopenia

1)WHy might corticosteroids help us with shock therapy?

1)They upregulate the sympathetic nervous system which help the other drugs effective (prevent a tolerance to drug efficacy)

Vasopressin

1) Mechanism(3)

2) Dosing

3) Adverse effects:  

1) i)Increase in SVR (systemic vascular resistence) via V1 receptor mediated vasoconstriction

ii) Increase responsiveness to catecholamine
iii)Inhibition of of vascular smooth muscle nitric oxide production

2)  0.01 – 0.04 units/min

3)  Decreased splanchnic blood flow
•    Arrhythmias
•    Peripheral necrosis
•    High dose = cardiotoxic

1)How does PAD usually present clinically?

2)  What are  Treatment goals?

3) Whare are the 2 drugs we talked about for Tx PAD?

1) Intermittent claudication..usually resolves with rest and is exacerbated by exercise.

2)  Reduction of confounding variables
Increase walking distance, walking duration, pain-free walking
Improvement of comorbid conditions

3) Cilostazol and Pentoxifylline

How does Pentoxifylline work?

How well does it work?

1)Alters RBC flexibility so they may squeeze by the blockage areas

2)   Not very well...but LOPA (leave old people alone)

Drug Therapy for HF depends on ACC/AHA stages...

1) for Stage A

2) for Stage B

3) for Stage C

B (Patients with structural HD but no HF symptoms) = ACEI + β blocker

C (Patients with structural HD and current HF symptoms) = ACEI + β blocker + digoxin + diuretics ± aldosterone antagonist ± ARB or dihydroperidine Ca channel blocker ± nitrates

1)  In what 2 ways does the ACE inhibitor Fct?

1)  Blocks Ang 1 from becoming Ang 2...causes vasoconstriction of renal arterioles...hench raising systemic blood pressure

2)  Decreases the production of Aldosterone...which is responsible for Na reabsorbtion

ULTIMATELY these effects reduce cardiac remodeling, fibrosis, apoptosis, hypertrophy, vasoconstriction, sodium and water retention

Beta-Blockers (class II) and HF

1)  Not all are equal...which 3 should we stick with ?

2)  Outcomes good for which HD patients?

3)  mechanism? 

1) Carvedilol
Metoprolol XL
Bisoprolol

2)  Stable (gives them fewer hospitalizations and increases survival rates)

3)  Act to decrease teh Sympathetic Nervous System.

1)  ACE Inhibitor side effects?

2)  Any difference in Heavy and Light dosing?

1)  Side effects
COUGH!!!... (due to prevention of breakdown of Bradykinin.)
Angioedema …uncommon
Hyperkalemia…RX diuretics…
Renal dysfunction

 2) ATLAS Low dose vs. high dose
No difference in mortality
24% lower hospitalization in the high dose group…KEEPS PEOPLE OUT OF THE HOSPITAL>>>better quality of life.
 

1)  Why do pts on ACE inhibitors need diuretics?

2)  What do we watch for?

3)  T/F  Diastolic HF requires higher diuretic dosages?

4)  Rank the following diuretics in potency

Torsemide   Bumetanide   Furosemide
 

1)  Hyperkalcemia due to natriuresis

2) Hypokalcemia 

3)   False

4)  Bumentanide>Toresemide>Furosemide

Digoxin is a positive inotropic drug used for over 200 years for rate control...it is more often used for its neurohormonal effects.   1)  In small doses (~ ___-___ng/ml) it can be helpful, but it has many side effects that must be monitored.2)  These are...

1)  0.5– 1

2)   Diarrhea, nausea, vomiting, mental status changes, visual disturbances (yellow and green visual rings), fatigue, ventricular arrhythmias, AV block

1)Aldosterone Antagonists are good for which group according to the RALES trial ?

2)They may reduce mortality by up to ___%

3)  Mechanism?

4) What do 10-20% of pts develop?

5)  If using with ACE inhibitors..what do we watch out for?

1)Add in patients with NYHA III – IV  SEVERE SYMPTOMATIC DZ
2)  30%

3)  i)Potassium Diuretic ii)  Mineralocorticoid blockers. iii)Decreases collagen deposition during cardiac remodeling

4)Gynecomastia (Bob...Bob had bitch tits)

5)  Hyperkalemia

1)  Angiotensin II Receptor Blockers (ARBs) are good for which group of HF pts?

2) Nitrates and Hydralizines are good for which group

3)  Specifically, which group does better on Nitrates/Hydralazines than ACEI or ARBs

1)  Those who cannot deal with the cough

2)  those who cannot be tx with ACEI or ARBs

3)  African Americans

1)  How do Nitrates work?

2)  How do Hydralazines work?

3)  Common side effects of both include

1)  Nitrates = vasodilatation (increased cGMP in smooth muscle) = preload reduction
2)  Hydralazine = arterial smooth muscle vasodilator = SVR reducation

3) Headache, nausea, vomiting

Decompensated Heart Failure (body's compensation mechanisms no longer suffice)

1)  What is subset I

2)  What is subset II..how do u treat?

3)  What is subset III

4)  What is subset IV

1)  Dobutamine should be used on which subset of DHF pts?

2)  What do we need to watch for?

3) Can we easily ween these pts off Dobutamine? 

1)  III (Dry failure)

2) Tachycardia 

3)  No...you can send them into HF

1)Milrinone is used to Tx which Class of DHF?

2)  Increases____ levels to act as a positive intropic agent

3)  T/F...Short half-life

4)  Side effects?

1) III

2) cAMP

3) False, Long half life

4)  Hypotension, thrombocytopenia, arrhythmias

Nitropurside:

1)  Mechanism?

2)   Relationship to other inotropic agents?

3)Side effects?

1)  mixed arterial-venous vasodilator

2)  Causes  greater drop in preload

3) SEVER HYPOTENSION, CYANIDE and THIOCYANATE toxicity, Rebound Hypertension

Nitroglycerin and DHF

1) which subset is this the "mainstay for?

2)  T/F Short half-life?

3)  T/F Tolerance develops quickly

4)  Side Effects?

1)  II (preload reduction for "wet subset")

2) True

3)  True

4)  Headache, tachyphylaxis, hypotension

VT and DTE:

1) t/f ...Unfractionated Heparin can beabsorbed well subcutaneously?

2)  side effects?

3)  What do we need to monitor? (4 things)

1)  IV

2) HIT,osteoporosis, alopecia, suppressed aldosterone production

3)  aPTT (activated partial thromboplastin time)

ACT (activated clotting time)

Anti-factor Xa activity

Plasma Heparin concentrations

1)  T/F ..LMW Heparin can is okay to be absorbed subcutaneously?

2)  T/F it has a shorter half-life than Unfractionated?

3) requires less monitoring?

4)  If factor Xa needs to be checked do so  __ hours after bolus.

1)  True

2) False...longer halflife than unfractionated..give bid

3) True must more specific with a 4:1 (Xa:IIa ratio) compared to unfractionated.

4) 4

1)  Fondaparinux (Arixtra)

2)  T/F no direct effect on thrombin 

3)  T/F ..Short half life

4)  Eliminated through the ____ unchanged?

5)  What is the major problem with this drug?

1)  More selective pentasaccharide anticoagulant selectively and directly inhibits factor __activity.

2)  T

3) False...long

4) urine

5)  It binds irreversibly...watch for bleeding

Direct Thrombin inhibitors:

1)  Name the 3 marketed in US

2) Which binds irreversibly?

1)Lepirudin

Bivailirudin

Argatroban

 2)  Lepirudin

Lepirudin

1)  What is its advantage?

2)  What is the disadvantage

1)  undergoes Hoffman reduction so we don't need to worry about the liver or kidneys (for those that are damaged)

2)   Up to 40% of pts develop Antibodies to Lepirudine when treated for 10 days

1)  What is the target group for Bivailirudin (Angiomax) therapy?

2)  How does Argatroban bind to thrombin?

3) What is the name of teh drug not currently marked in the US but similiar in mechanism to Argatroban?

1)  Only approved for treatment of patients undergoing percutaneous transluminal angioplasty (PTA)

2)  Reversibly binds only to the active catalytic site of thrombin

3) Ximelagatran

1)  What is the most widely prescribed Anticoagulant in North America?

2)  How does it work?

3)  T/F...very narrow therapeutic index?

4)  Most pts can start at __ mg a day

5)  Why not safe for pregnant women?

1)  Warfarin...=Rat poison

2) Inhibits vitamin K reductase....decreases factors VII, IX, X, II protein C and Protein S.

3) True 

4)   Five

5)  Fetal hemorrhagic and teratrogenic complications

1) Which -mycins does Warfarin interact with?

2)Which antiarrhythmic drug does it intereact with?

3)  Which antifungals?

1)  Erythro and Neo

2)   Amiodarone

3) Miconazole, Metronidazole, Itraconazole

1)  Warfarin users must eat foods high or moderately high in Vit__ sparingly and consistently.

2)  What is the Goal INR for most Warfarin users?

3)  How long do you have to wait for peak Warfarin effects to take hold?

1)  Vit K (brussels sprouts cabbage, collard greens)

2)  2-3

3)  3-5 Days

Thrombolytic Therapy:

1)  What is only  used in strokes?

2)   __ hours after first symptoms present, there is no difference in using tPA vs. placebo according to the NINDS trial.

3)  How is it administered usually?

4)  T/F it also decreases teh risk of intracerebral hemorrhage

5)  Any difference in mortalities with tPA and Placebo?

1)  Tissue Plasminogen activator or Alteplase®

2) 3 hours

3) IV

4)  True ...(0.6% tPA) vs 6.4% (placebo)

5) No

1)  How does tPA work?

2)  Derivatives of tPA include (2)

3) Which has a longer half-life

4)  If candidate is cleared for tPA administration, what dosage do you give them?

1)  Selectively activates firbrin-bound plasminogen

2)  Reteplase and Tenecteplase

3) Tenecteplase (1 bolus)

4)0.9mg/kg over 1 hour (bolus 10% of dose)
KNOW THIS DOSING
 

Stroke... Secondary Prevention you use what for....

1) 1st line?

2) Cardioembolic?

3)  All?