Anti-arrhythmics Flashcards
(77 cards)
1
Q
Beta adrenergic receptors in heart, vascular SM, kidney?
A
B1
B2
B1
2
Q
B1 receptor agonist effect in heart?
A
increase in contractile force (myocardium), increase in HR (SA, AV nodes) – via inc cAMP and inc intracellular calcium
3
Q
B2 receptor agonist effect in vasculature?
A
smooth muscle relaxation via inc cAMP and dec intracellular Ca
4
Q
Epi and NE affinities for B1, B2, and alpha receptors?
A
- NE void of activity at B2 (high dissociation constant) at therapeutic doses
- Epi has equal affinity at B1, B2
- same affinities for alpha receptors
5
Q
Consequences of vascular alpha1 receptor activation?
A
inc IP3, DAG and inc intracellular calcium = vasoconstriction
6
Q
How does concentration affect the effects of epinephrine on vascular alpha1 and beta2 receptors?
A
- low conc = B2 activation (Kd = 800 nm)
- high conc = A1 activation (Kd = 5000 nm)
7
Q
What reflex responses do drugs that INC and DEC BP have?
A
- INC: trigger reflex slowing of heart via M2 receptors
- DEC: trigger reflexing increase in HR via B1 receptor
8
Q
What is oral epi not used?
A
rapid metabolism in gut via MAO
9
Q
What type of drug is Terazosin?
A
- Alpha1 blocker in vasculature, prostate
- 2nd line HTN drug
10
Q
What drug type is phenylephrine? Uses?
A
- alpha1 agonist = pressor effect
- raise BP in shock/sepsis/surgery
- Tx of orthostatic hypotension
11
Q
What are 3 B1 agonists are used to provide inotropic support in acute Tx of shock and HF?
A
- milrinone, dopamine, dobutamine
- IV, acute care only
12
Q
What distinguishes first, second and 3rd gen beta blockers?
A
- first = B1, B2
- second = B1 only
- third = either alpha blocker also or novel effects unrelated to beta blockade
13
Q
Two AE’s associated with B2 blockade?
A
bronchospasm/inc in airway resistance
exacerbation of PVD
14
Q
5 uses of B blockers?
A
- HTN
- ischemic HD (dec O2 consumption)
- supraventricular tachyarrhythmias (block of SA/AV B1 receptors)
- HF
- following MI (dec O2 consumption)
15
Q
What are the only two B blockers approved to Tx HF?
A
- metoprolol
- carvedilol
- improve outcomes and dec morb/mort
16
Q
Proposed mechanisms of B blockers in HF Tx?
A
- B1R upregulation
- antagonism of enhanced sum activity
- blockade of hypertrophic growth/ROS gen
17
Q
CNS and cardio AE’s of all B blockers?
A
CNS: sedation, fatigue, impairment
CARDIO: hypotension, bradycardia
18
Q
Which nonselective B blocker has a long 24 h half life?
A
Nadolol (propranolol was 1st useful BB)
19
Q
Two selective BB widely used?
A
metoprolol and atenolol
20
Q
Two BB that also block alpha activity?
A
Carvedilol (HF) and Labetalol (HTN)
21
Q
Novel effects of carvedilol (HF)?
A
- block alpha
- block Ca channels
- inc NO
- antioxidant
22
Q
Novel effects of nebivolol?
A
- inc NO
- vasodilator
- good in HTN
23
Q
What are the consequences of excess stim of beta receptor?
A
- inactivation of receptor function
- desensitization via G protein uncoupling from receptor (receptor phosphorylated)
- down regulation = loss of receptors from cell surface
- role in HF
24
Q
Difference between rhythm and rate control?
A
Rhy restores and maintains a completely normal heart beat (more effective, but toxic) - targets voltage-gated Na/K channels
Rate slows ventricles and improves CO (atria still fibrillate - still clot risk) (more modest, but safe) - targets B receptors or L type Ca channels
25
Difference between mono and poly VTAC? Ex of poly?
- mono has single origin/pathway
| - poly = electrical pathways are wandering around ventricles --> Torsades de Points
26
How are the classes organized? (Vaughn Williams)
```
I = Na+ block
II = B block
III = K+ block
IV = Ca block
```
27
What classes are effective in rate control?
affect AV node --> II, IV, digoxin
28
What drug is effective in AV-RT?
adenosine
29
What classes are effective in rhythm control?
I, III
30
How do rhythm control drugs work? ECG effects?
- Na block slows gen of ventricular AP
- K block of rapid and slow channels slows depolarization and prolongs cardiac AP (prolonged refractory period, widened QT interval)
- prolonged PR by II, IV (slowed AV conduction)
31
Which current is easily blocked by many drugs and can cause cardiac toxicity? Ex?
- rapid K+ depolarizing current
| - erythromycin
32
How do rate control drugs work? ECG effects?
- B block reverses acceleration of AV node AP's by SYM tone
- Ca channel block slows generation of AV AP's
- Prolonged QT (slowed ventricular repolarization)
- -> IA (intermediate) only because it also blocks K+ channels
- Widened QRS (slowed V conduction)
33
Cause, consequence and Tx of EAD?
- abnormally long AP (K+ blocker tox)
- Torsade de pointes (polymorphic VTAC)
- shorten AP (IV Magnesium, inc HR)
33
Cause, consequence and Tx of DAD?
- toxic cytosolic Ca levels (ischemia, + inotropic drug overstim)
- PVC, monomorphic VTAC
- relieve Ca overload
33
Drug of Class IB?
- lidocaine (weakest Na+ channel block)
- short DOA
- injection, hepatic elim, local anesthetic
33
Drug of Class IB?
- lidocaine (weakest Na+ channel block, smallest - inotropic effect)
- short DOA
- injection, hepatic elim, local anesthetic
34
Cardiac uses of lidocaine?
Suppress VTAC once they appear, particularly following MI
34
Cardiac uses of lidocaine?
Suppress VTAC once they appear, particularly following MI
35
Preferential effects of Na+ channel blockers on cardiac myocytes?
- preferentially affects rapidly arrhythmic cells
- drugs bind during AP when channels are open and unbind at rest
- rapidly firing cells leave less time for drug to unbind increasing the # of blocked channels
35
Preferential effects of Na+ channel blockers on cardiac myocytes?
- preferentially affects rapidly arrhythmic cells
- drugs bind during AP when channels are open and unbind at rest
- rapidly firing cells leave less time for drug to unbind increasing the # of blocked channels
36
How do Na+ channel blockers affect reentrant rhythm generation?
- RE currents involves rapidly beating cells
- inhibits abnormal AP conduction in cells participating in a fast rate of reentry current production = blocker accumulation
37
What is a common AE among Class I drugs?
promotion of new monomorphic VTAC = proarrhythmias --> potentially LETHAL
38
How do Na+ channel blockers affect DAD?
- suppress arrhythmias triggered by DAD's by preventing the generation of unusually rapid AP's
39
Risks for pro arrhythmia development with Na+ channel blockers?
- damaged, fibrotic, chaotic hearts have multiple reentry circuits that conduct current with variable AP length and timing = dormant circuits
40
How do Na+ channel blockers contribute to activation of dormant circuits and pro-arrhythmias?
- dormant circuits, AP's are too short and cells are still refractory when depo swings back around
- drugs slow down AP conduction velocity -- since it takes longer for AP to get there, cells are no longer refractory and can depolarize
41
What is the strongest Na+ channel blocker? Class?
Flecainide - IC, oral, hepatic elim
42
What causes the negative inotropic effect of Na+ channel blockers?
Widened QRS complex due to slowed generation of V AP --> heartbeat spreads through the ventricles slowly so contraction isn't as synchronous or forceful
43
Flecainide is DOC for what type of patient?
low-risk AFIB (prophylaxis or termination) -- used as 'pill in pocket'
44
Intermediate strength Na+ channel blocker + K+ blocker? Class?
- procainamide, IA, injection, renal/hepatic elim
45
Quinidine Class IA can be used additionally for:
- malaria (similar to quinine)
| - pseudobulbar affect w/ detromethorphan (uncontrollable laughing/crying in patients with underlying neuro disease)
46
What is procainamide's primary use? Why so limited?
- life-threatening VTAC
| - serious AE's
47
While Na+ channel blockers can activate a dormant reentry current, K+ blockers can de-activate it. How?
- Na+ blockers slow gen of AP's so that origin is no longer refractory when the impulse comes back around
- K+ blockers elongate AP's/refractory period in the circuit so that the origin is still refractory when the impulse comes back around
48
Additional risks associated with Procainamide (besides Na+ pro arrhythmia, - inotropism)?
- K+ channel block pro-arrhyhmias (Torsades de Pointes can develop due to block of rapid K+ current = abnormally prolonged AP's yielding EAD's)
- Long-term oral: bone marrow suppression, SLE
49
What is unique about Sotalol?
both class II (non-selective) and III actions
50
Three ECG effects of Sotalol?
- prolonged QT (K+ channel block)
- prolonged PR (beta adrenergic block)
- dec HR (beta adrenergic block)
(B block has both nodal and myocardial effects)
51
Cause of Sotalol's neg inotropism?
Beta block causes inhibitory effects on HR and AV conduction
52
Three AE's of Sotalol?
- bronchoconstriction/exacerbation of PVD (B2 block)
- inotropism
- proarrhythmia (K+ --> EAD --> TDP)
53
Primary use of Sotalol? Two specific patient sub-groups?
- prophylaxis of AFIB/VTAC
- ischemic disease = beta block useful (dec O2 consumption)
- implantable defib = lowers defib threshold and dec # of shocks
54
Which Class III drug is available in oral AND IV forms? Use? Off label?
- Amiodarone
- IV = suppression of VTAC to prevent cardiac arrest
- Oral = rhythm control in LVH, HF
- AFIB off-label
55
Why is amiodarone such a good anti-arrhythmic?
MULTIPLE targets:
- rapid and slow K+ channel block
- weak Ca and Na channel block
- weak non-competitive antagonist of alpha and beta adrenergic receptors
56
Four long term AE's?
- LOW risk of pro-arrhythmia
- pulmonary tox
- hepatotox
- skin and corneal micro-deposits
- neuropathy -- peripheral and optic nerves
57
What is unusual about the structure of amiodarone? Potential associated AE's?
- IODINE
- Type 1 thyrotoxicosis: inc TH syn
- Type 2: thy inflamm --> TH release
- hypothyroidism: most common; inhibits iodinases that convert T4 to T3
58
What is the DOA of amiodarone?
- LONG half life
- large Vd
- oral Tx requires high loading dose; highly tissue bound during long-term oral use
59
What are two important drug interactions of amiodarone?
- INC warfarin levels: inhibitor of CYP2C9 and CYP3A4
| - INC digoxin levels: inhibitor of P-glycoprotein, a transporter involved in renal and biliary excretion of digoxin
60
What drug class is most often used for rate control and why?
- Class II = beta blockers
| - AFIB -- rate control lets more blood enter V in diastole = INC CO
61
How do beta blockers function? ECG?
- slow AP conduction across the AV node -- some atrial beats will not result in V depolarization
- prolonged P-R interval
62
Two uses of propanolol?
- AFIB
| - V tach (DAD) due to Ca overload from ischemic damage/sympathetic overload = negative inotropic effect
63
What are the Class IV drugs? Two classes?
- dihydropyridine Ca channel blockers = majority
| - non-dihydropyridine Ca channel blockers = verapamil, diltiazem
64
Uses of dihydro Ca channel blockers vs non-dihydro?
- Non's are useful in arrhythmias, but dihydro's are NOT --> only verapamil and diltiazem directly inhibit the SA/AV nodes and cardiac contractility
- Both are useful in angina pectoris, HTN = VASODILATORY EFFECTS
65
What are the two prototype Class IV drugs for RATE control of AFIB?
verapamil and diltiazem
66
How do the Class IV drugs work?
- block L type Ca channels
| - slow the gen of AV nodal AP so each AP takes longer to cross the AV so fewer per min in AFIB
67
What is one non-cardiovascular AE of CCB?
relaxation of smooth GI muscle = hypotension
68
Three important drug interactions of CCB?
- co-admin with other AV inhibitors (beta blockers) could cause complete AV block
- inc DIGOXIN - inhibition of P-glycoprotein (renal and biliary excretion of drug)
- Inc erythromycin levels via inhibition of CYP3A4 --> erythro blocks cardiac K+ channels!
69
What drug is used specifically for episodic Tx of AV-reentry tachycardia? How does it work?
- adenosine IV bolus
- hyper polarizes via K+ channel activation and blocks AV node, stopping reentry to resynchronize fast and slow AV nodal pathways
70
Which adenosine receptor subtype is therapeutic? Location? Effects?
- A1 GPCR: SA/AV nodes; slowed HR, slowed AV nodal conduction
71
Three AE's of adenosine? Why are they usually not a problem?
- cardiac arrest (nodal inhibition)
- chest pressure (bronchoconstriction via A3 receptor in mast cells = histamine release)
- flushing (vasodilation via A2 receptor in vasculature)
- VERY short DOA
72
Specific drug interaction of adenosine?
Dipyridamole (anti-platelet drug) inhibits adenosine uptake (potentiates effects of adenosine on platelets) = INC adenosine levels
