QUESTIONS NOTES

Causes of HTN? - Primary (or essential HTIN) 90-95%, cause unknown

- Secondary: 10%, cause known. Primary (or essential) HTN [Treat underlying cause]
 Kidney abnormalities
 Congenital heart defects (i.e. aorta)
 Narrowing of arteries
Treatment goals for HTN? - Short term goal: Reduce BP
- Long term goal: Reduce mortality due to HTN induced disease (Stroke, CHF, CAD,
Nephropathy, Retinopathy)

Ways of lowering BP? 1. Reduce cardiac output: Beta blockers, Ca2+ Channel antagonists [Not all]
2. Reduce plasma volume: Diuretics
3. Reduce total peripheral resistance [Open up the lumen to reduce BP]: Vasodilators,
alpha1-adrenergic receptor antagonists, ace inhibitors.

Antihypertensive and Lipid-Lowering treatment to prevent Findings: Chlorthalidone is superior to ACE inhibitors, CCBs, and Alpha-adrenergic
heart attack trial (ALLHAT)? antagonists in preventing CVD events.
Chlorthalidone is a diuretic [Only 5 dollars]

Thiazide diuretics general info? -[1st line of therapy for majority of pt – not used in impaired kidney function]
-Lower plasma volume
-Monotherapy for mild to moderate HTN
-ALLHAT: reduction of CVD superior to other agents
-Adjunct agent [Can be used in combination with other meds]
-Most effective in patients with normal kidney function (loss of efficacy with CrCl below 30
ml/min)
[If CrCl is below 30, means impaired kidney function, which means kidneys not processing
as much fluid volume, therefore diuretic is not going to work well]
Thiazide diuretics MOA? - Inhibit NaCl reabsorption from the luminal side of DCT
- Decrease intracellular Na, increase Na/Ca exchange in DCT, increase Ca
-Action of thiazides depends in part on renal PG (prostaglandins) and can be inhibited by
NSAIDS
[Need CrCl greater than 30 ml/min and renal PG production]
Thiazide considerations? - Long-term hypokalemia (increases mortality)
- Include K+ sparing diuretic in therapy.
- Most efficacious in “low-renin” or volume expanded forms of HTN
- Very effective in African American patients
- Mostly well tolerated and cheap.

Drugs interacting with Renin-Angiotensin system? -Ace inhibitors: inhibit Antiogensin II

formation.
-Angiotensin receptor antagonists:
(ARB’s) block Antiogensin receptor
activation.
Both prevent vasoconstriction ultimately
ACEI block conversion of Angiotensin I to
Angiotensin II (Angiotensin I increases
Bradykinin, which increases cough. It’s
not considered an allergy)] ARB’s don’t
have cough.
Systemic Effects of ACE inhibitors - Reduction in: - Increase in:
-Total peripheral resistance - Regional blood flow in vascular beds
- Systolic and diastolic pressure - Large artery compliance
- Mean arterial pressure [arteries and veins]
- Aldosterone secretion
- Cardiac remodeling
Types of Ace inhibitors? - Active Molecules [don’t have to be Prodrugs: [Have to be converted to
metabolized] active form]
-Captopril - Enalapril
-Lisinopril - Fosinopril
-Enalaprilat - Quinapril
[All drugs that end in PRIL are ace inhibitors] - Ramipril
Therapeutic uses of Ace inhibitors?
Side effects of Ace inhibitors?
ACE inhibitors and Renal artery stenosis?
What happens when ACEI are introduced?
Types of Angiotensin Receptor Blockers (ARB’s)
Therapeutic Uses of Antiogensin receptor Blockers?
Direct Renin inhibitors general characteristics?
Adrenergic receptor antagonists
B-Blockers therapeutic uses? MOA?
B-Blockers considerations?
B-Blockers Side effects?
- Initial choice for mild to moderate HTN [Like thiazide diuretics]
- Drug of choice for HTN due to DM
- Most effective in high renin patients
- Most effective in Caucasian patients
- Great for HTN secondary to CHF, arrhythmias, kidney disease
- Efficacy enhanced by diuretics
- Hypotension, cough, hyperkalemia [good reason to use along with diuretics which
diminish K], angioedema, renal insufficiency [SCr increase, if above 30 okay] , teratogenic,
skin rash, neutropenia, proteinuria, ageusia (loss of taste)
- With bilateral renal stenosis, the blood flow is not significantly reduced due to the body’s
response of increasing the efferent arteriolar constrictor tone.
- ACEI will drop the pressure on the efferent side, but filtration is deficient due to lack of
pressure. This is why ACEI are contraindicated on these patients.
- Losartan (Competitive antagonist)
- Valsartan (noncompetitive)
- Candesartan (noncompetitive)
- Irbesartan (noncompetitive)
- Same as ACE inhibitors
- No bradykinin effect (no cough)
- Useful for HTN secondary to CHF
- Used for prevention of re-stenosis after angioplasty
[ACEI and ARB’s are interchangeable for HTN]
- Produce dose-dependent reduction in plasma renin activity and ANG I and II and
aldosterone.
- Produces dose related decreases in BP like ACE inhibitors and ARB’s.
- Can be used in combination with thiazides [Like ACEI and ARB’s]
- Contraindicated in pregnancy. [Like ACEI and ARB’s]
- Associated with diarrhea and rash
- Aliskiren : cost $$ [just have them on two drugs for 10 bucks]
 β-adrenergic receptor antagonists
“β-blockers”
 Non-selective: Propranolol, Nadolol, Timolol, Pindolol, Labetolol
 Cardioselective: Metoprolol, Atenolol, Esmolol, Betaxolol
 α1-adrenergic receptor antagonists
“α-blockers”
[Not used very effective, specially the nonselective ones]:
 Non-selective: Phentolamine, Phenoxybenzamine, Dibenamine
Selective: Prazosin, Doxazosin, Terazosin
 Used as monotherapy
 MOA: reduce cardiac output [Decrease HR]
 reduce renin release [not significant]
 CNS effects: reduce SNS outflow [specially nonselective ones]
 Most effective in high-renin hypertension
 Used in hypertensive patients with coronary insufficiency
 Non-selective and cardioselective drugs are equally effective for lowering BP
 Cheap!
 Intrinsic sympathomimetic activity [if they have asthma, COPD]
Pindolol, Acebutolol, Penbutolol: partial β2-AR agonism
 Mixed antagonism
Labetolol, Carvedilol: β- and α-adrenergic receptor antagonists
 Differences in ability to penetrate CNS
Propranolol readily enters CNS [most CNS side effects]
Sotalol unable enter CNS
 Bradycardia
 Bronchospasm
 Coldness of extremities
 Heart failure
 Contraindicated in insulin-dependent diabetes [because mask symptoms of
hypoglycemia]
  CNS effects
 Increased plasma triglyceride concentration
 Decreased plasma HDL concentration
 Do not use in conjunction with Ca2+ channel blockers, conduction effects in
heart
 NSAID’s blunt β-blocker effects [avoid NSAID’s as much as possible]

Alpha Blockers: Therapeutic uses and MOA  Mechanism of action: block vascular α1-adrenergic receptors,
inhibit vasoconstriction
 decrease total peripheral resistance
 Non-selective blockers used for treatment of hypertensive crisis in
pheochromocytoma
 Selective α-blockers used as monotherapy or adjunct therapy in resistant
patients
[not used in the long run because of development of resistance]
Alpha blockers Side effects?  First dose phenomenon [take first dose at bedtime due to hypotension]
 hypotension
 tachycardia [it’s true for any drug for vasodilation drugs due to homeostasis →
baroreceptor reflex]
 baroreceptor reflex
 GI effects
 Fluid retention [due to vasodilation]
 use with diuretic
 ALLHAT study
Sympatholytics  Centrally acting sympatholytics
 Clonidine
 α-methyldopa
 Guanfacine
 Guanabenz
 Peripherally acting sympatholytics
 Metyrosine
 Guanethidine, Bretylium
 Reserpine

CNS Sympatholytics  α2-AR receptor agonists

 act in CNS to reduce sympathetic neuron firing rate
 nucleus of solitary tract
 C1 neurons of rostral ventrolateral medulla
 act on prejunctional sympathetic neurons in vascular tissue
 autoreceptor on sympathetic neurons
 prevent NE release
 stimulate post-junctional α2-ARs on vascular smooth muscle (I.V. only)

Pharmacokinetics  α-methyldopa is a prodrug, converted to α-methyl-norepinephrine in brain

 short T1/2: 2 hours
 long duration of action: 24 hours
 action prolonged with renal insufficiency
 clonidine, guanfacine, guanabenz enter brain readily
 orally active
 excellent absorption
 clonidine available as sustained release transdermal patch

Therapeutic uses  Reduce BP by lowering TPR and CO

 Peripheral sympatholytics produce marked fluid retention and impairment of
baroreceptor reflexes
 use with diuretic
 α2-agonists effective in ALL patients
 clonidine used in diagnosis of pheochromocytoma: reduces plasma NE < 500
pg/mL in tumor-free patients

Adverse effects  Hypotension

 Sedation: ~ 50% of all patients
 Dry mouth
 Vivid dreams
 Depression
 Withdrawal

Peripheral sympatholytics
Ca2+ channel antagonists
Calcium channel blockers
Direct acting vasodilators
Direct acting vasodilators
NEW POWERPOINT
Oral Anticoagulation Therapy
 hypertension
 tachycardia
 nervousness, excitement
 α-methyldopa specific effects
 heart block
 autoimmune: Lupus, leukopenia
 hyperthermia
 reduced mental acuity
 rarely used
 Metyrosine (or α-methyl-
tyrosine):
 inhibits tyrosine hydroxylase
 rate-limiting enzyme for NE
synthesis
 Bretylium, Guanethidine
 uptaken into NE vesicle
 prevent NE release from vesicle
 Reserpine
 inhibits accumulation of NE into
vesicle
 an initial choice for monotherapy of mild to moderate hypertension
 all antagonists are equally effective for Stage 1 hypertension
 Verapamil and Diltiazem do not cause reflex tachycardia
 directly inhibit cardiac chronotropy
 Effective in low-renin hypertension
 African-americans
 Elderly
 Do not cause fluid retention
• The Non-dihydropyridine CCBs such as verapamil and diltiazem cause less
vasodilation and more cardiac depression than dihydropyridine CCBs. They have
negative effects at the SA and AV nodes, and cause reductions in heart rate and
contractility.
• Dihydropyridine CCB’s such as amlodipine and nifedipine primarily exert there
effect on blood pressure lowering via vasodilation,
 Hydralazine
 liberates NO from vascular endothelium
 decreases TPR
 not used as monotherapy
 bioavailability dependent on genetic factors
 adverse effects: tachycardia, hypotension, fluid retention, lupus-like syndrome
 only used in severe or refractory hypertension
 Minoxidil
 prodrug of N-O sulfate
 K+ channel opener, reduces smooth muscle contractility
 not used as monotherapy
 long duration of action (~24 hours)
 adverse effects: tachycardia, fluid retention, hypertrichosis
 only used in severe or refractory hypertension
 Warfarin (Coumadin)
 Dabigatran (Pradaxa)
 Rivaroxaban (Xeralto)
 Apixiban (Elaquis)
 Edoxaban (Savaysa)
Warfarin  Vitamin K Antagonist (VKA)
 Excellent oral bioavailability (90%)
 High plasma protein binding ( albumin)
 Metabolized primarily in the liver
Warfarin Pharmacokinetics  Onset of action depends on the
elimination half life of Vit K
dependent clotting factors.
 Peak effect may be delayed up to
72-96 hrs. Due to depletion of
circulating coagulation factors
and decrease in production of
new clotting factors.
 Duration of action of warfarin 2-5
days after last dose. [There is a
lag time when you stop warfarin]
 [Don’t need to know numbers,
but just know the clotting factors
have different half lives]
Warfarin drug interactions

[Sulfamethoxazole need to decrease warfarin by 50%.

[With amiodarone, decrease like 30% of warfarin]
[Hepatic enzyme inducer is Rifampin. Also carbamazepine is a drug inducer. Isoniazid is
enzyme inhibitor so you need to decrease warfarin]
Warfarin Drug Interactions / Increased risk of bleeding  Aspirin
 Clopidogrel……
 NSAIDS
 Fish Oil
 Other anticoagulants
 Acetaminophen greater than 2 grams /day , chronic use [Increase the risk of
bleeding]
Warfarin herbal interactions

[IN general just know that increase or decreases risk?]

Warfarin drug interactions  Keypoints
 Not as critical when warfarin is added to interacting medication.
 Important when interacting agents are initiated or discontinued.

Warfarin disease state interactions
 Diarrhea- Increase INR due to decrease in flora [Because diarrhea decreases
normal bacterial flora in gut. Normal bacteria produces Vitamin K which is used
for clotting]
 Heart Failure- Decreased clearance [puts you at higher risk of bleeding]
 Liver Disease- Decrease clotting factors
 Hyperthyroid- Increased metabolism [Increase metabolism of warfarin]
 Hypothyroid- Decreased metabolism [No warfarin in system so decreased risk of
bleeding]
  Smoking- Increased clearance [of warfarin, increased clotting risk]
[INR is international normalized ratio. It’s how you measure warfarin therapy. Pt with Afib,
INR should be between 2-3. Same with DVT. Warfarin has narrow therapeutic index]
[If someone has INR of 12, give him Vitamin K] [Like broccoli, kale, spinach, can decrease
INR a lot]
Warfarin Diet considerations  Vit. K containing foods
 Green leafy vegatables
 Broccoli
 Collard Greens
 Kale
 Spinich
 Green Tea
 Cranberry
 All can decrease INR
Lab Testing: Monitoring  Intermediate Normalized ratio ( INR)
 Goal for Atrial Fibrillation 2-3
 Goal for some mechanical heart valves 2.5-3.5
 CBC to monitor for internal bleeding if suspected.

Common Indications  Atrial Fibrillation

 VTE ( DVT & PE)
 Valve replacement
 Post MI
 Cardiomyopathy (CHF) [Because there is bad circulation]

Dosing Considerations  Instruct patient to take at night [so the correction can be done that same day
when INR testing]
 Utilize 1 tablet strength
 If taking different doses on various days ensure they are spaced throughout the
week
7.5mg daily except 5mg Mon and Fri
7.5mg daily except 5mg Mon,Wed,Fri
[INR reflects what you did 2 or 3 days ago]
Dose initiation Consideration Lower Dose Higher dose
 Elderly  Hyperthyroid state
 Drug Interactions  High Vit K diet
 Disease state interactions  Drug interactions
 Increased bleeding risk enzyme inducers
 Genetic variations 5mg daily -7.5mg daily
 2mg daily to start

Warfarin dosing  Dosage adjustment based on weekly dose

 Calculate 10-20% of weekly dose.
 Typically, anywhere from 5-20% change in dose based on INR patient specific
factors.

Monitoring ADR’s  Skin necrosis, especially in toes ( usually in first 10 days of treatment. If it doesn’t
then you won’t have it.)
 Bleeding
Hematuria
Melena
Excessive bruising
Bright red blood , gums, rectal
Epistaxis

Antiarrhythmics Cardiac A&P  The heart is composed of 2 atria and 2 ventricles

 Cardiac Muscle is composed of excitatory [cardiac pace makers] and contractile
cells [muscular fibers]
 Both atria and ventricles have excitatory and contractile cells
 Specialized excitatory cells are called pacemaker cells

Pacemaker Cells • Specialized cardiac pacemakers are:
Sinoatrial node (SA) located in right atria
Atrio-ventricular node (AV) located between the atria and ventricles
• His-Purkinje fibers [located just in ventricles] as well as any of the cardiac cells
have the potential to produce spontaneous impulses
Characteristics of SA Node
Characteristics of the AV node
Characteristics of His-Purkinje Fibers
Phases of Cardiac Action Potential
Phases of Cardiac Action Potential
[Shows the same as previous chart]
Phases of the EKG
Phases of EKG
Phases of EKG
• Slow depolarization rate, calcium dependent
• Susceptible to sympathetic stimulation due to cAMP
phosphorylation and calcium channels
• Significant firing inhibition by activation of Vagus nerve due to Ach activation of K
channels
• SA node signals transmit to atrial tissue as well as AV node
• Atrial tissue depolarization is shown by the P-wave of the EKG
• Slow conducting fibers
• Similar action potential to SA node with a slower phase 4 depolarization
• Delay signal transduction to ventricles
• Serve as filter to prevent 1-2 stimulation of ventricles following SA node firing
[prevents failed signals. Like a backup system]
• Can substitute pacemaker activity of SA node should the SA node be blocked

 His-Purkinje fibers are conducting fibers and have pacemaker capacity
 Very fact conducting fibers
 Separate into 2 bundle branches called His-bundle
 The 2 bundles deliver depolarizing signal to ventricles
 Receive signal from AV node
 The rapid firing rate of these fibers is due to a large Na current (phase O
depolarization) and a rapid phase 3 repolarization
 [SA node AV node His purkinje nodes. Na dependent in His Purkinje fibers]
 Phase O- membrane depolarization and activation of fast Na channels
 Phase 1- transient repolarization by transient outward K channels and
consequent inactivation of Na channels [Gates opening and closing. Sequentially]
 Phase 2- activation of slow Ca channel, enhanced contractility, activation of
outward K channels
 Phase 3-inactivation of Ca channels early repolarization by K channels
 Phase 4- late phase repolarization, closure of outward K currents
• The EKG represents the cardiac muscle action potential
• P wave: represents atrial contraction
• QRS complex: Beginning of phase 0 to the end of phase 2. Represents ventricular
activation/contraction.
• T-wave: Phase 3-4 repolarization, represents ventricular repolarization
[Drugs longate QR interval for example]
• R-R interval- heart rate
• PR interval- end of phase 4 to end of phase 0 depolarization
• QRS interval- Duration of ventricular depolarization

EKG waves
Electrical Abnormality
Arrhythmia-Abnormal Cardiac Rhythm
Mechanism of Arrhythmias (1)
Mechanism of Arrhythmias (2)
Classification of Antiarrhythmic Drugs
Classes of Antiarrhythmic Drugs
Class IA Antiarrhythmic drugs and MOA
Class 1A Antiarrhythmic Drugs
Class 1A Side Effects
• ST segment- duration of contractility and repolarization
• QT interval- beginning of phase 0 to the end of phase 4 repolarization. Duration
of action potential
•
• P wave- Atrial conduction
• PR wave- AV conduction
• QRS wave- Ventricular conduction
• T wave- Ventricular repolarization
[Ideas of where we are in EKG]
• Genetic predisposition ( long QT syndrome)
• Drug induced ( Beta adrenergic over activity) [Drugs like Albuterol cause
tachyarrhythmia]
(Dopamine agonists) [Dopamine dependent]
• Electrolyte abnormality [K, Ca, Na affect different parts of the heart]
• Damaged cardiac tissue
Ischemia or Fiber stretch [like in heart failure]
• There are two types of conduction defects:
• Abnormal impulse generation “autonomic” or “spontaneous” [Av node SA node
and purkinje fibers; some people have different sites of where the action
potential starts in the heart]
• Abnormal impulse conduction “re-entry” [ischemic heart tissue, blocks Action
potential, cause the pacemaker AP to recycle through the heart]
• Rate of SA, AV nodal cells
Automaticity of extra-nodal cells
Abnormal signal conduction
 Signal Block
Av block-drug induced or genetic [can be caused by some drugs]
Bundle branch block- blocked branches the bundle
of His
 Re-entry- occurs when an impulse reenter and excites areas of the heart more
than once [usually when there is damaged tissue] Generally damaged tissues
that have higher resting membrane potential than normal tissue.
Anatomical presence of accessory pathway. [ischemic tissue that blocks the
signal]
Vaughan-Williams Classification
• An early classification system that when first conceived very few drugs were
available
• Based on primary MOA of each class with special emphasis on their differential
effects on the cardiac action potential
• [Not very easily categorized. This classification system is old]
• Class I – Primarily block fast Na channel, block other channels also (K, Ca)
• Class II- Beta blockers [Talked a lot in previous diseases]
• Class III- Drugs which prolong the effective refractory period usually by blocking K
efflux channels
• Class IV- Calcium Channel blockers
• Class V- Adenosine, Digoxin, Magnesium [Miscellaneous]
Drugs
 Quinidine
 Procainamide
 Disopyramide
MOA
 Binds to subunit of Na channel
 Prefer open and or inactivated state (state dependent block)
 Anti-muscarinic activity (except procainamide) [Side effect should know it, it’s
dry mouth, decreased urinary output]
increase HR, increase AV conduction
 Some K channel blockade
Properties; [MOA]
• Slow down phase 0 of AP
• Slows conduction velocity
• Increase QRS
Therapeutic application:
Atrial and ventricular arrhythmias
General Side Effects:
  GI: nausea, vomiting, diarrhea
 Pro-arrhythmic: can lead to torsades de pointes [can cause arrhythmia in high
doses. Torsades de pointes means turning on a point]
Specific Side Effects: [Quinidine has the most]
 Anti-muscarinic: Inc. AV conduction, dry mouth, blurred vision (Quinidine)
 Thrombocytopenia (Quinidine)
 Hepatitis (Quinidine)
 Lupus like rash (procainamide)
n-acetyl procainamide metabolite accumulation in renal failure and CHF [Be
careful with patients in renal failure and CHF]

Class 1B Antiarrhythmic Drugs:

• Lidocaine (most common IV antiarrhythmic)
• Mexiletine (orally active congener of lidocaine)
MOA
• Similar to Class 1A [Primarily Na channels]
• Preferred binding to diseased tissue

Class IB Antiarrhythmic Drugs Properties:

• Moderate slowing of phase O and conduction velocity in normal tissue
• No change to QRS in normal tissue
• Decrease QRS duration and refractory period in damaged depolarized myocardial
cells and fast heart rate ( state dependent block)
Therapeutic Application:
Ventricular arrhythmias and digoxin induced toxicity

• Generally, well tolerated

• Neurologic
Class 1B Side Effects Seizure, confusion, tremor
• Other
Hypotension

Class 1C Antiarrhythmic Drugs:

 Propafenone
 Flecainide
MOA
 Markedly slow down Phase 0
 Marked reduction in impulse conduction velocity via blockade of Na channel
 Some effect on repolarization via K channels
 Flecainide: use dependent block, more at fast rates
 Prolong QT and QRS

Class 1C Drugs Therapeutic Application and Side effects Therapeutic Application:

 Life threatening ventricular arrhythmias
 Propafenone can be used in Paroxysmal Supraventricular Tachycardia
Side Effects:
 Pro-arrhythmic: can lead to ventricular arrhythmias in atrial fibrillation of atrial
flutter
 Not used in myocardial ischemia and CHF due to increased mortality
 QT prolongation and torsades de pointes
 Agranulocytosis [Didn’t see this in class 1A or 1B]

Class II Antiarrhythmic Drugs Drugs: [We’re back to B blockers]

• Propranolol, Atenolol, Metoprolol ……..
• Sotalol
• Esmolol ( short t1/2 of 9 min) [Not for HTN because of short half life]

Class II Antiarrhythmic MOA: [Know what B1 receptors do to apply]

• B1- receptor blockade in SA and AV nodes, indirect blockade of Ca influx
• Membrane stabilizing effect
• Dec. AV conduction velocity [AV node works as a filter to try to slow down
impulses]
• Reverse activating effect of cAMP
• Reduce purkinje fiber responsiveness
• Sotolol has K channel blocking activity
• Increase PR interval
Class II Antiarrhythmic Drugs
Class III Antiarrhythmic Drugs and MOA
Class III Antiarrhythmic Drugs
Amiodarone
Amiodarone
Additional effects of Amiodarone
Amiodarone Side effects:
Other Class III drugs
Therapeutic Application [Difference between Afib and A-flutter…]
 Atrial Fibrillation
 Controlling ventricular rate in A-Fib and A-Flutter via AV blockade
Side Effects
 Well tolerated
 AV blockade with overdose
 Bradycardia and decreased contractility
 Hypotension
Drugs:
Amiodarone
Ibutilide
Dofetilide
Dronedarone
MOA:
 Prolongs action potential
 Increase QT delay repolarization in phase 3
 Do not alter phase 0 depolarization
 Increase refractory period
Therapeutic Applications
• Effective in delaying onset of fibrillation
• Ibutilide, dofetilide, drondarone indicated to maintain sinus rhythm after
conversion from A. Fib or flutter [they’re put on these drugs after conversion]
Side Effects:
• Proarrhythmic : QT prolongation and torsades de pointes ( except amiodarone)
• Dofetilide requires close QTc monitoring and electrolyte levels
Unique antiarrhythmic drug with broad spectrum of activity
MOA:
• Blockade of K channel.
• Blocks Na channels
• Weakly blocks Ca channels
• Non-competitive inhibition of b-adrenergic receptors [Also has some beta
activity]
Effects on Action Potential
• Prolongs refractoriness in all cardiac tissue
• Delays AP conduction velocity
• Prolongs PR,QRS,QT intervals
• Inhibits abnormal automaticity in most cardiac tissues
Therapeutic application:
• Atrial and ventricular fibrillation and tachycardias
Pharmacokinetics
• Very lipophilic
• Large volume of distribution
• Very long half life
• Hepatic metabolism
• Drug interactions with CYP3A4 substrates
Side effects:
• Pulmonary fibrosis
• Hypo or Hyperthyroidism
• Hepatic dysfunction
• Peripheral neuropathy, muscle weakness
• Hypotension ( IV use)
• Corneal microdeposits
• Photosensitivity ( blue haze)
[Visual exams every 6 weeks needed]
Dofetilide
• Selective Ik, K channel blocker
• High risk of causing torsade, required QT monitoring [need regular ekgs]
Ibutilide
• Selective IK K channel blocker
• Major toxicity torsade (6% incidence)
Dronedarone

Class IV Antiarrhythmic Drugs
Class IV Antiarrhythmic Drugs
Class V Antiarrhythmic Drugs
Class V Antiarrhythmic
Stroke prevention in A-Fib
Who needs anticoagulation
Anticoagulation for A-Fib
Anticoagulation in Persistent AF
• Contraindicated for patient’s with NYHA Class II
Drugs: [CCBs]
 Diltiazem
 Verapamil
MOA:
 Ca channel blockade only SA and AV nodes
 Non-dihydropyridines ( not used as anti arrhythmics
Therapeutic application:
 Controlling ventricular rate in atrial fibrillation via AV nodal blockade [B blockers
work in AV nodes too. Don’t use B blockers with any CCBs to treat HTN, to avoid
same mechanism of action]
Effect on AP:
• Slow down phase 0 of pacemaker AP
• Slow SA, AV nodal rate, decrease HR
• Increase PR interval
• Decrease amplitude of AP
Side effects:
• Av block with overdose
• Hypotension
[High doses get bradycardic]
Drug:
 Digoxin [works on K channels]
MOA: AV block via muscarinic activation and inc. K efflux . Increase PR interval
Therapeutic use: Ventricular rate control and A. Fib (in CHF)
Side Effects: Inc intracellular Ca. Inc. delay of depolarization worsened by hypokalemia
[Careful with Digoxin, careful with hypokalemia]
Drug: Magnesium, unknown MOA used for Torsade de pointes
Drug: Adenosine
MOA
 Nucleoside analog
 SA AV blockade via activation of Ach sensitive K efflux channels
 Reversal of cAMP effects, dec. CA current
 Increase AV refravtoriness
 Short lived activity
Therapeutic use: Paroxysmal Superventricular Tachycardia (PSVT)
[If you give adenosisne, patients have lots of chest discomfort]
Anticoagulation therapy is necessary to prevent embolism and stroke
• Ineffective atrial contractions increase the likelihood of clot formation.
• Incidence of stroke in patients who do not receive anticoagulation is 5%
• Some risk factors for stroke include: increasing age, female gender, previous
stroke and DM.
• Anticoagulation should be started in patient’s with A-Fib greater then 48 hrs.
• CHF ( 1pt)
• HTN (1pt)
• Age >75yrs (1pt)
• DM ( 1pt)
• Stroke/TIA (2pts) [Means 5.9%]
Anticoagulation prior to cardioversion is important
• Prevents formation of new thrombus or or growth of existing clot, and allows
clots already formed to be organized and adhere to atrial wall
• In order to prevent stroke during or immediately after cardioversion several
weeks of anticoagulation is required before cardioversion is attempted. Approx 3
weeks
Chads2 score 0
• No therapy rather than anticoagulation
 • If therapy desired ASA 75mg-325mg/day (81mg)
Chads2 score 1 : intermediate risk
• Oral anticoagulation rather than ASA
Chads2 score 2 or greater: High risk
• Initiate therapy with LMW heparin, warfarin or DOAC [Direct oral anticoagulant]