Nitrates, Viagra/CHF/Antiarrhythmics Flashcards
Low Dose Aspirin/NSAID Interaction
- Concomitant NSAID intake may reduce ____ effects of low dose aspirin.
- Both ASA and NSAID compete for ____ in the platelet.
- NSAID effect on inhibiting platelet aggregation is only ____
- ASA not binding to platelet is converted to salicylic acid which lacks ____ activity.• Aspirin inhibits COX and so does NSAID > blunting of the antiplatelet effects
○ Platelet cannot regenerate ____, while other cells can
○ Accept that the binding of aspirin to COX is an irreversible chemical bond (whether it’s COX1/2); while the endothelial cells can regenerate
• Taking an NSAID for chronic TMJ, while on cardioprotective doses of aspirin > clinically important
cardioprotective COX1 short lived antiplatelet COX1
ASA
T1/2 = ____; ____
SA
T1/2 = ____; as active as ____, inactive as ____
Conjugated metabolite
____
• Aspirin has an active metabolite > SA > every bit as active as aspirin as a pain reliever, but lacks \_\_\_\_ activity ○ Give an NSAID and low dose aspirin, there will be competition for COX1 in the platelet, and some of COX1 will be occupied instead of \_\_\_\_, it will be with ibuprofen - only reversibly binds (a couple of hours) § By this time, aspirin that hasn't bound > SA > lacks antiplatelet activity • Trying to stagger to maintain cardioprotection ○ Take first dose of aspirin early in the morning, then wait an hour until you start dosing with a \_\_\_\_ ○ Doing this over months, do not know how effective this strategy will be ○ On the package insert > aspirin/NSAID > both used at same time4 may inhibit cardioprotective use • 81mg of aspirin (low dose) > there's a tiny chance of \_\_\_\_ (1:4000)
1 hour active 3 hours analgesic antiplatelet inactive antiplatelet NSAID GI bleed
Antithrombotics
• aspirin
- blocks ____ (salicylic acid lacks antiplatelet)
• dipyridamole
- ____ inhibitor
- decreases ____ uptake
• ticlopidine (Ticlar®) • clopidogrel (Plavix®) • prasugrel(Effient®) - prodrugs - metabolized to active form by CYP - \_\_\_\_ receptor inhibitor - \_\_\_\_ outlasts t1/2 - clopidogrel most dependent on metabolism by \_\_\_\_ – potency subject to individual patient distribution of CYP2C19 isozymes - all used to for \_\_\_\_ with or without aspirin, \_\_\_\_ angina, and before PCTA during MI
• Ticagrelor( Brilinta®)
- ____ receptor inhibitor
• Aspirin is targeting thromboxane • See a lot of clopidogrel ○ ADP receptor antagonist on platelets ○ Inhibits activation ○ People at serious risk of an MI, or had one before and have unstable angina may be on this durg w/wo aspirin • 10% of individuals are aspirin \_\_\_\_ ○ Put on clopidogrel • Ticlopidine first on market, Clop has fewer drug interactions • Ticagrelor ○ Same mechanism as clopidogrel
CO PDE adenosine irreversible ADP P2Y12 action CYP2C19 MI prevention unstable reversible ADP P2Y12
resistant
Abciximab (ReoPro)
• t1/2a = ____ min; t1/2b = 30 min
• Platelet function recovers over ____ hours
• Low levels of IIb/IIIa blockade present for up to ____ days
Also: ____ (Integrilin®), tirofiban (Aggrastat®)
Indication: to reduce ____ complications to PTCA and ____. Given by ____ infusion.
• \_\_\_\_ ○ Has to be given IV, will not see someone walk into your practice and that they're on this • Used in the \_\_\_\_ to prevent complications form PTCA (percutaneous transluminal coronary angioplasty - this was a balloon, now it's a stent) • Atherectomy - endo on the carotid arteries; carotids are blocking with occlusive strokes, and CV surgeons will rotoruter the carotid artery > risk ○ During the procedure you may slightly injure the BV, or you dislodge platelet material > you can throw a clot which can go to your lungs or your brain ○ Given the drug during the procedure to prevent a clot from forming • T1/2a and t1/2b - add them up and total half life ○ Alpha - 50% of cleared blood ○ Beta - taking into account elimination of the drug ○ Example of the drug where the half-life is short, but the actions are very long • Iib/IIIa - bridge receptors between platelets
10 48 10 eptifibatide atherectomy IV
monoclonal ab
hospital
Role of ADP receptors in platelet activation and aggregation
• Platelet aggregation involves lots of chemicals ○ Can block \_\_\_\_, ADP receptors, \_\_\_\_ receptors § Rheopro does all of this
TXA
IIb, IIIa
Anticaoagulants
Intravenous
• heparin - binds to ____ - complex binds and inhibits ____
• enoxaparin - ____ molecular weight heparin (LMWH) Decrease in immune mediated ____
• Work on the clotting cascade, can have platelet effects but not directly; thrombin stimulates platelet aggregation (cross-talk) • No-one is coming in on these • When taking blood samples for a study - flush the catheter with \_\_\_\_, which prevents blood coagulation > binds to something that opposes one of final steps in the clotting cascade > antithrombin III > opposes thrombin ○ Makes antithrombin III \_\_\_\_ more powerful ○ Large molecule; issue with all these drugs > enhance bleeding • Enoxaparin ○ Smaller version of heparin § Lower \_\_\_\_ with it; one of immune mediated responses that you saw with heparin, you can get severe bleeding: thrombocytopenia (very lower platelets) § See this less with low MW heparin; typically a \_\_\_\_ drug > knee-replacement surgery
antithrombin III thrombin thrombocytopenia heparin 100x antigenicity hospital
Anticoagulants
Oral
• ____
• dicumarol
•Reduces liver synthesis of
Factors ____ by 30-50%
•Reduces activity of Factors by 10-40%
• You will see people on these ○ Classic oral anticoagulant • Inhibit the synthesis of \_\_\_\_ dependent clotting factors ○ Active form of vitamin-K is reduced vitamin K ○ Antidote for someone bleeding in stomach/brain from warfarin is \_\_\_\_ (IV) § Competitive inhibition • Warfarin hits multiple clotting factors ○ TI of \_\_\_\_ (5x the effective dose is lethal - may be even lower) ○ Has such a low TI and how it behaves in body [???]
warfarin II, VII, IX and X vitamin-K vitamin-K 5
Warfarin: Pharmacokinetic and Pharmacodynamic Pathways
• Warfarin is a \_\_\_\_ compound ○ Exists as L and R handed isomer ○ The \_\_\_\_ isomer is 5x more potent as an anticoagulant ○ The S isomer is only processed by a single cyto p450, while the weaker is detoxified by multiple isoforms • If block \_\_\_\_ with grapefruit/erythromycin - 1A1 and 2 ar eopen and it's the weaker isomer • If you knock of \_\_\_\_ > then the S warfarin has nowhere to go and it cannot be processed ○ \_\_\_\_ and metronidazole inhibits 2C9 § Fluconazole is a major antifungal; also penetrates the BBB - people with opportunistic fungal infections § Metronidazole > major antibiotic for anaerobic infections, and combined with amox/penicillin (punches holes in wall) • \_\_\_\_ is the ultimate site of warfarin ○ \_\_\_\_ ○ Left with hypofunctional factors, but there are other proteins involved in this clotting cascade that remain hypofunctional
racemic S 3A4 2C9 fluconazole VKORC1 vitamin-K epoxide receptor complex 1
Plasma protein binding characteristics of various drugs and the potnetial result of their displacement
Wafarin
% protein bound: ____
Displacement result: ____
Tolbutamide, chlorpropamide, glyburide
% protein bound: ____
Displacement result: ____
Phenytoin
% protein bound: ____
Displacement result: ____
• Warfarin is one of highly protein bound drugs ○ When drugs are bound to plasma proteins > not free to interact with receptors ○ If you decrease binding by giving a displacer like an \_\_\_\_, chloral hydrate > decrease plasma protein binding of warfarin to 96% > now you have \_\_\_\_% free (increasing it 4x) • Prescribing ibu/naproxen > already on a drug that inhibits vitamin K dependent clotting factors, now you're gonna give something that temporarily wacks the platelets > increase risk of \_\_\_\_ two additive by distinct mechanisms of action, regardless of protein binding ○ Can also thin the blood via other mechanisms
99 bleeding 90-99 hypoglycemia 90 cns depression, ataxia
NSAID
4
GI bleeds
Dabigatran etexilate
Direct ____ inhibitor
Use: Stroke prevention in patients with ____
-European Approval, April, 2008: -Canadian Approval June, 2008 -US Approval, October 2010
MW: 627.7 (471.5) Route: Oral
t1/2: 8 h Bioavailability: %
• Flood of new oral anticoagulants • Instead of multiple CF, they tend to hit \_\_\_\_ ○ If only hit one, there's less bleeding • There has been bleeding episodes • With warfarin you have the INR; with these you don'y get an \_\_\_\_ ○ With a fib (2.2-2.5) ○ Surrogate measure of blood coagubility (consistency of cherry koolaid - 9) • Targets only thrombin ○ Essential for converting \_\_\_\_ (the clot) ○ NOTHING TO TREAT THE \_\_\_\_ ○ Used at high risk for heart attacks and strokes • Atrial fib: atria beating like jello and forms clots
thrombin atrial fibrillation one INR fibrinogen to fibrin fibrillation
Rivaroxaban (Xarelto®)
____ inhibitor Use:
- prevention of ____ and ____ after major orthopedic surgery -Stroke in patients with ____ -European Approval, July, 2008, 2011 -November, 2011 US Approval
MW: 435.9
Route: Oral
t1/2: 5.7 – 9.2 h Bioavailability: 60-80%
• Clot formed in leg and then it breaks off and it ends up in pulmonary vessel > becomes lethal ○ Concern after major orthopedic surgery, get them up quickly ○ Prevent DVTs from blood stagnation ○ Also treats a fib
factor Xa
DVT
pulmonary embolism
Apixaban (Eliquis®)
____ inhibitor Use:
-Stroke in patients with ____
-European Approval, May, 2012
-US Approval, Dec 2012
MW: 459.5
Route: Oral
t1/2: 9 – 14 h
Bioavailability: ~50%
Excretion: 75% billiary, 25% renal
• Can come in on these drugs and they're more likely to bleed ○ Won't give an advil, will give \_\_\_\_ § No antiplatelet effects
factor Xa
atrial fib
acetominophen and hydrocodone
Fibrinolytics (all given iv or through iv catheter)
Lyse thrombus in ____ or ____. Not employed for ____.
• tissue plasminogen activator (Alteplase®)
• streptokinase
• anistreplase
• Emergency drug administered in the hospital for a MI or an occlusive stroke ○ How to know occlusive and not bleeding stroke > take a \_\_\_\_ scan § Thread a catheter to blockage and locally deliver a drug • Strepokinase and anistreplase ○ Ani is streptokinase (product of a \_\_\_\_) and is tied to plasminogen, and \_\_\_\_ will lyse clots ○ Will activate plasmin wherever it is located > if plasminogen is buried in a clot and will lyse it, but if it's in the BS it will also activate it • The beauty of TPA ○ Need much less (\_\_\_\_ less) to activate plasminogen that's bound to fibrin (in a clot), then plasminogen that's floating around the plasma ○ Major problem with these two: you \_\_\_\_ out ○ TPA is highly \_\_\_\_ for activating plasminogen when it goes to plasmin and will lyse clots § Plasminogen that's already in a clot ○ No one will walk in on this; but if someone is having a heart attack you will take this > within first hour or two you will prevent major damage
MI occlusive stroke hemorrhagic stroke CAT fungus plasmin 400X bleed selective
VIAGRA
• Interaction between NG-like drugs, and sublingually you have the largest interaction; still can demonstrate with the oral ones • \_\_\_\_ inhibitors ○ \_\_\_\_ ○ Not only specific for male sexual organ
PDE-5
vasodilator
Risk factors for erectile dysfunction include many of the same risks for cardiovasuclar disease!!!
- ____
- High Cholesterol – High LDLs, low HDLs
- ____
- Smokers
Bottom line: Many patients with erectile dysfunction will also have ____ and may require acute or chronic nitrates to treat angina.
• Interaction between nitrates and male erectile dysfunction drugs • Why are people on both nitrates and ED drugs ○ The risks for male ED are seen to be some of the same risks as having CAD • People started looking > men on ED became sexually active, had chest pain and had a dose of nitro and their BP fell > organs were not perfused as well
hypertension
diabetics
CAD
How do these drugs work and why has the combo lead to severe hypotension?
Nitrates: ____ (Nitrostat®), isorbide dinitrate (Isordil®)
PDE5 Inhibitors: ____ (Viagra®), Tadalafil (Cialis®) Vardenafil (Levitra®)
• The nitrates are \_\_\_\_ > not just the coronaries, it's all over the place • Male ED drugs > work on the same pathway but a little differently > block \_\_\_\_ ○ The end result, one drug increases \_\_\_\_, and the other is blocking its breakdown > can get an \_\_\_\_ effect (vasodilation everywhere, and a drop in BP, with a \_\_\_\_)
nitroglycerin sildenafil NO donors cGMP additive reflex tachycardia
• These studies showed how powerful the nitrates were
• 7 days of isorbide to prevent angina attacks, and now they take a single dose of sildenafil > massive change in ____
○ BP goes way down with the viagra (dropped ____ mmHg)
○ Isorbide is still a powerful hypotensive pill (dropped ____ mmHg)
• 7 days of placebo or viagra, and followed by NG
○ Placebo: 30% of people had BP systole less than 85 (not standing up for a while)
○ On cialis: ____% of people had BP systole less than 85 mmHg
○ Effect of cialis, can still see some at ____ hours, if dose 24 hours after the last cialis dose > you still have 41% vs 32% and at hours it’s over
systolic BP 52 25 45 24 48
Congestive heart failure
a disorder in whcih the heart loses its ability to pump blood efficiently throughout the body
decreased CO
- heart failure occurs when CO is inadequate to provide the oxygen needed by the body
• Systole failure and diastolic failure ○ SF - deficiency pumping blood \_\_\_\_ ○ DF - \_\_\_\_ are inadequately filling • In congestive failure, sometimes both are happening • Retaining fluid, gasping for air ○ Used to be a death sentence
out
heart chambers
Hemodynamic consequences of myocardial ischemia/infarction
• Major cause is \_\_\_\_ ○ Lose contractile mass, heart dies ○ As you get sicker, more obstruction to the coronaries
myocardial ischemia
Congestive heart failure common causes
• Major cause is \_\_\_\_, but really bad \_\_\_\_ that's untreated can cause CHF, bc heart is working against really tight BV and being sympathetically stimulated and ventricles enlarge in order to overcome but eventually it fails • \_\_\_\_ > heart valves and hearts • Hypertensive crisis • \_\_\_\_ is a lot worse than hypothyroid ○ Hypo is easier to manage ○ Excessive thyroid is driving the \_\_\_\_ nervous system and will have adverse effects on the heart
MI hypertension bacterial endocarditis hyperthyroid symp
Congestive heart failure
Most common signs and symptoms
- ____
- edema
- ____
- chest congestion• Enlarged chambers of heart > specifically the ____, but eventually that fails and the people just cannot walk a couple of steps
○ Fluid retention in lungs and legs
fatigue
shortness
ventricles
Starling mechanism
• As you increase the pressure in the ventricles, it spits out more blood up to a point
• In CHF, the starling curve is much ____ > can never reach the old one
○ The drugs don’t regain normalcy, but they’re not ____
lower
symptomatic
Digitalis glycosides -Digoxin • Natural product of the \_\_\_\_ plant • Recognize that something is an antiplatelet agent and not an antihypertensive Sugar connected to a \_\_\_\_
foxglove
steroid structure
Digitalis mechanism
- Ca2+ released from SR into the sarcoplasm by RyR2 receptor
- Ca2+ reuptake into SR via Ca2+-ATPase, SERCA2
- Excess Ca2+ removed from sarcoplasm by sarcolemal Ca2+- ATPase or by high capacity Na/Ca exchange protein, NCX
- Driving force for NCX is Na+ electrochemical potential across the sarcolemal membrane, 3Na+/1Ca2+
- Inhibition of Na+/K+-ATPase increases intracellular Na+ reducing Ca2+ extrusion by NC• Digoxin and digitoxin block the ____ pump
○ This pump after an AP, whether it’s cardaic or nerve > excess of Na+, and excess of K+ potassium and this pump gets rid of the excess and counterbalances with K+
○ If you block this, it slows down the ____ extrusion
§ Increased Ca++ staying in the SR of cells of heart > increases the ____ of contraction
• If you dose this right you don’t get an increase in rate > also have ____ effects > has effects that kind of turn on the parasymp nervous system at the same time
○ Can increase CO without increasing ____
○ If you increase HR in a weak heart > will make situations worse
• When you go on this drug, you’re ____ for a week (digitalized)
○ One dose does not ____ all
○ Dose titrate up, and get to point of early toxicity and dose you back down
Na+K+ ATPase Ca+ force parasympathomemetic HR hospitalized fit
Starling mechanism: effect of digitalis
• Pushes the starling curve up ○ More in some people, less in other people • Compare digoxin and digitoxin ○ Same mechanism (Na+K+ ATPase) ○ More \_\_\_\_ - better perufsion to organs, and to kidney > indirect \_\_\_\_ effect (remove some of the excess water)
CO
diuretic
Digoxin protein binding: \_\_\_\_ t1/2: \_\_\_\_ excretion: \_\_\_\_ metabolism: \_\_\_\_ therapeutic (cxn): \_\_\_\_ oral bioavailability: \_\_\_\_
Digitoxin protein binding: \_\_\_\_ t1/2: \_\_\_\_ excretion: \_\_\_\_ metabolism: \_\_\_\_ therapeutic (cxn): \_\_\_\_ oral bioavailability: \_\_\_\_
25% 36-48 h kidney, 60% unchanged 1-2ng/mL 70-80%
97% 4-7 d kidney, 32% extensive, liver >10 ng/mL 100%
Digitalis glycosides: comparative pharmacology
• Major differences: \_\_\_\_ • \_\_\_\_ is more likely to be involved in drug interactions ○ Oral bioavailability (how much makes into BS) is \_\_\_\_ • Somebody that has poor renal function, \_\_\_\_ depends on the kidney for elimination more than digitoxin
pharmacokinetics
good
digoxin
Digitalis Glycosides: Adverse Effects
• Cardiac toxicity – ____ and ventricular arrhythmias - AV blockade may be useful in control of ____
secondary to atrial tachycardia Therapeutic Index = ____
• Nausea, vomiting (stimulation of \_\_\_\_ • Loss of appetite • \_\_\_\_ • Headache • Fatigue, drowizness • Abdominal pain • Occasionally produces \_\_\_\_ • \_\_\_\_ in men Overdose treatment: \_\_\_\_ (Digibind)
• Major toxicity: can get a blockade of the AV node > \_\_\_\_ • The way people die from this drug > push the heart a little too much > ventircular arrhythmias • Nausea and vomiting are \_\_\_\_ signs of too much digoxin ○ It can stimualte the chemoreceptor trigger zone • Salivation (\_\_\_\_) ○ Patients drool a lot • Don't leave the dental lamp in patient's eyes ○ Patients will have \_\_\_\_ • Gynecomastia ○ Enlarged breasts in men • Overdose treatment ○ A low TI (4X effective dose is lethal in 50% of individuals) ○ Mab developed agaisnt digitalis glycosides § Given \_\_\_\_ § Someone with ventricular arrhythmias □ Will get \_\_\_\_ and digibind (emergency only) • Don't blast patients with epinephrine ○ Use a local that has a decent duration of action without epi § 3% \_\_\_\_
av bloackade ventricualr arrhytmias 4 cheoreceptor triggering zone salivation visual disturbances gynecomastia fab antibody fragment
ventricular arrhythmias
early
parasympathomemetic
photophobias
IV
antiarrhythmias
mepivocaine
Other Agents
b-Blockers - ____, carvedilol
Vasodilators:
• ____
• ACE Inhibitors
b-Agonists (____, dopamine)
Diuretics
PDE Inhibitors - ____, milrinone
• B-blockers ○ People who had \_\_\_\_ and angina and they kept the dose of B blocker low > they were living longer ○ Too much can make it worse, but it seems like giving a low dose protects the heart against excessive epinephrine ○ Metoprolol is \_\_\_\_, carvedilol also used often (not cardioselective - cannot give to someone who has upper airway problems bc it blocks \_\_\_\_ receptors; but also blocks \_\_\_\_ receptors, and \_\_\_\_ seems to help in CHF) • Alpha-blockers ○ \_\_\_\_ • ACE inhibitors ○ (ARBs) ○ Mild \_\_\_\_ ○ Indirectly increase \_\_\_\_ cb they block aldo receptors on adrenal cortex ○ \_\_\_\_ slowing down effects ○ Mild \_\_\_\_ before dig they go to these because they don't have a TI or 3/4 • B agonists ○ \_\_\_\_ situation ○ If goes into ER they will die (drowning in own fluids) > give these IV just to get the heart going temporarily and get the fluid out > once crisis passes then switch them to the more conventional drugs ○ Stimulate \_\_\_\_ receptors and also open up renal vasculature (getting rid of water and sodium) • Diuretics ○ \_\_\_\_ are used the most (ferusoimide, and acid) ○ Major issue: xerostomia, but the main concern is low \_\_\_\_ > \_\_\_\_ § Often on potassium supplements, or ones that spare K+ • PDE inhibitors ○ Not PDE-5 like ED drugs, but these drugs have \_\_\_\_ effects; will only see a cardio prescribing these
metoprolol
alpha-blockers
dobutamine
amrinone
CHF cardioselective b2 alph1 vasodilation
vasodilation
vasodilation
H2O/Na+ excretion
sympqathetic
CHF
emergency
B1
loops
K+
cardiac arrythmias
vasodilatory
Pathophysiology of CHF
• If work on systolic side: pump better and fill better • Not this \_\_\_\_! • Shows that with decreased CO > decreased renal blood flow > retain water and sodium > edema • Digitalis doesn't just work on enhancing preload, but it's working on this side too ○ Going on in both \_\_\_\_ of equation
clean
sides
Remove Cells
• ____
• CirculatingStemCells
• ____
Isolate/Prepare Cells
Inject Cells
* Area of the heart that has been damaged, by a heart attack, and now right into the heart \_\_\_\_ stem cells to regenerate/repair the area * Or thread a \_\_\_\_ down the coronaries, and shoot into the coronaries; or use the catheter to get to that area and release those stem cells * Not seen as \_\_\_\_ to care - hasn't happened yet
bone marrow stem cells myoblasts transplant catheter standard
Antiarrhythmic agents • Drugs do one of four things: ○ Depress \_\_\_\_ conductance ○ Depress \_\_\_\_ conductance ○ Block \_\_\_\_ ○ Mess around with a bunch of channels, including \_\_\_\_
Na+
Ca++
beta-blockers
K+ channels
Sodium channel mechanism
• Sodium, calcium and potassium ____ is important in heart muscle
• How drugs that block Na+ channels work in cardiac muscle; how they get to a supposed receptor
○ These channels can exist in a ____ stage
○ When channels open, m gate opens and h gate stays where it is, and the drug form inside out can get ot the receptor (at least ones that block sodium)
○ But even in inactivated sate (m open and h closed), drugs are really ____ (like locals) > they can actually get into the membrane, and get to the receptor
§ Why can’t they get ot receptor in resting state? Idk, maybe m gate is close enough by that it’s not letting the drug int here
conductance
resting
lipophilic
Cardiac action potential
• This is a single cardiac AP • This isn't the SA node; cardiac muscle • \_\_\_\_ channel opens up • Why do we get dip, then plateua ○ This is \_\_\_\_, which opens up > repolarizing ○ Quickly \_\_\_\_ opens up > equal effect from both potassium and calcium ○ Eventually the Ca+ close, K+ remain open > more reploraization § Goes in to out (K+), and the cell becomes hyperpolarized
Na+
K+
Ca++
Cardiac anatomy, AP morphology and ECG
• When in \_\_\_\_ region in atria > you don't get the typical AP in the contractile cells ○ Self-pacing ○ The contractile muscle needs signals from SA and AV node • Second is running down bundle of His and \_\_\_\_ • It's difficult to match it up perfectly • Will not dictate how drugs are used
SA node
purkinje fibers
Prcoess of Reentry
• Easiest way to explain mech of cardiac arrhythmia > too much \_\_\_\_ drive > release of too many catecholamines > shoot a PVC (autonomic) ○ B-blockers > a lot of autonomic system overdrive > leading to arrhythmia, would make you think that something that \_\_\_\_ the action of the sympathetic nervous system would work • Imbalance between \_\_\_\_ that are trying to put heart back into resting state and Ca+ and Na+ channels ○ Can be due to \_\_\_\_ • Reentry phenomenon ○ Purkinje fibers running down both sides, and typically one thing that happens is you get a branching > signals going in one direction, and electrical signals in another direction > hit each other, and that \_\_\_\_ the activity ○ When you get damage on one twig or the other > twig becomes blocked > and cannot clash with each other > the impulse/electrical drive that normally wipes out by the opposing twig is now left to run \_\_\_\_ > powerful enough to jump over the block > circle movements where the \_\_\_\_ is no longer in contorl > automaticity of the contractile muscle that's driving the heart > theory of reentry ○ Different arrhythmias may be more dpeendent on one than the other
sympathetic
blocks
K+ channels
damage
ends
wild
SA node
• A fib > drugs that are good, but they will also be on anticoagulants
○ A lot of ____, sometimes you cannot even see them
p waves
• Ventricular tachycardia > rapid, ventricular rate and you can see that it’s still kind of a repeated pattern > when get into ventricular fib > heart looks like a bowl of jello > little impulses all over the place > no drug that will reverse this > ____ is the only thing that will reverse it
cardioversion
Normal and abnormal cardiac rhythms
• Torsades de pointes ○ Form of \_\_\_\_ that you can see with cardiac damage, but can also see with adverse drug interactions ○ First nonsedating antihistimine (seladane) > terfanidine is processed by 3A4, but grapefruit juice blocks conversion to fexofenidine (allegra), but \_\_\_\_ built up > ventricular arrhythmias (torsades) > not a fixed rate, it's really wild • For ventricular arrhythmias the emergency drug is \_\_\_\_, and torsades is \_\_\_\_ to it and it can rapidly go into \_\_\_\_ ○ Torsades is just as bad as \_\_\_\_
ventricular arrhythmia terf IV lidocaine resistant ventricular fibrillation rhabdomyelysis
Classification of Antiarrhythmic Drugs
I. Sodium Channel Blockade
A. ____ phase-0 depression and slow conduction (____+)*; usually prolonged ____
Agents: ____, procainamide,diso- pyramide, moricizine
B. ____ phase-0 depression and slow conduction (____+); usually ____ repolarization
Agents: ____, mexiletine, pheny- toin, tocainide
C. ____ phase-0 depression and slow conduction (3+ to 4+); little effect on repolarization
Agents: ____, flecainide, propafenone, indecainide
II. b-Adrenergic Blockade `
Agents: ____, acebutolol, esmolol, others
III. Prolong Repolarization
Agents: ____, bretylium, sotalol
IV. Calcium-Channel Blockade
Agents: ____, diltiazem
moderate
2
repolarization
quinidine
minimal
0 to 1
shorten
lidocaine
marked
encainide
propranolol
amiodarone
verapamil
