Dysrythmia and HTN Drugs Flashcards
Dromotropism definition
Ability to alter the rate of electrical conduction
Refractoriness
Inability of a cell to receive and transmit an action potential
Action potential duration
The time between phase 0 of one action potential to the next.
Increased length = decreased heart rate
Decreased length = increased heart rate
Effective refractory period
Time between phase 0- phase 3 in which the cells cannot initiate another action potential.
Relative refractory period
Time between phase 2-3 in which the cells cannot initiate another action potential except within the presence of an extreme stimulus
What is the normal threshold potential of an AV node action potential?
Approximately -65 mv
Sympathetics influence what cardio tissues?
All of them
- SA/AV nodes: epinephrine binds to B1 receptors, increasing the Ca2+ inward current causing an increasing rate of repolarization in phase 4 (funny current)
- causes tachycardia*
Atrial tissue: epinephrine binds to B1 receptors causing an increasing Ca2+ inward current which results in an increased conduction velocity and contractile
(Positive dromotropic and inotropic effects)
His/purkinje tissues: similar to atrial tissues
Delayed After Depolarizations (DADs)
Appear due to an abnormally elevated intracellular concentration of Ca2+.
At low rates of stimuli (brachycardia), the DADs skip ventricle depolarization since the threshold potential cannot be reached
At high rates of stimuli (tachycardia), the DADs produce spontaneous ventricle depolarizations causing v tachycardia.
Parasympathetics influence which cardiac tissues?
SA/AV node and atrial tissues
- SA/AV: acetylcholine produces a bradycardia effect by increasing phase 3 potassium out of the cell.
- decreases rate of repolarization during phase4*
Atrial tissues: acetylcholine increases the rate of conduction through the atrial muscle (positive dromotropic effect).
NOT ventricular tissues
What is the most common etiology of dysrhythmia?
Acute MI
Ventricular recently
A phenomenon that occurs when ischemic or scar tissue forms, or a boundless of Kent, along the normal conduction pathway.
Action potentials that are post-ERP cant go the normal pathway will ;try to redirect the pathway.
Class 1 dysrhythmic agents
Are all Na+ channel antagonists (blockers)
- blocks the non-nodal (ventricular) conductive tissue in phase 0
Effects:
- slows depolarization (lowers Vmax of phase 0)
- negative dromotropy
- lengthens QRS and QT intervals (1a especially increases QT)
- increases ERP/APD ratio (except lb)
Class 2 dysrhythmic agents
Are all B-blockers (B-adrenergic antagonists)
Class 3 dysrhythmic agents
Are K+ channel antagonists (blockers)
- block all types of cardiac tissue in phase 3
Class 4 dysrhythmic agents
Similar to class 2 except block calcium channels instead of B1 or B2 receptors
class 1a dysrhythmic agent effects (quinidine, procainamide, disopyramide, hydralazine)
moderate binding to the Na+ channels
- also block the potassium channels , delaying repolarization.
- can induce calcium blocking but only at very high doses
Effects:
- prolongs QRS complex
- prolongs QT intervals and valgus nerve effects
- slows phase 0
- increases ERP/APD ratio
Used to treat PVCs, V tach, atrial fibrilation (w/out WPW)
ADRs:
- can induce torsades
- cinchonism (tinnitis, hearing loss, blurred vision)
- hypotension
- SLE in slow acetylators of 1a drugs
Special populations to pay attention to:
- patients who are slow acetylators of 1a drugs
- renally impaired (must lower dosage)
Class 1b dysrhythmic agent effects
Lidocaine, tocainide
Weakest binding to the sodium channels. Actually accelerate the repolarization of conductive tissue (rapid “on-off” kinetics)
Effects:
- shortens the ERP/ADP ratio
- QT interval is shoterned
- no change in QRS
- positive inotropic and dromotropic effects
- MOST EFFECTIVE FOR DIGITALIS and MI INDUCED DYSRHYTHMIA
- also treat V tachycardia, premature ventricular beats and preventing V. Fibrillation
ADRs:
- hypersensitivity
Class 1c dysrhythmic agent effects
Encainide, flecainide, moricizine, propafenone
Strongest blockers of NA+ channels (“slow on-off” kinetics)
Effects:
- strong effects on phase 0 of the action potential of conducting tissues
- lengthen QRS and APD
- no change QT
- CAN STOP HEART THEREFORE ONLY LAST RESORT
MOST USEFUL FOR NON-MI INDUCED VENTRICULAR DYSRYTHMIAS
ADRs:
- prodysrthmic
- hypersensitivity
Class 2 agent effects
Propranolol, acebutalol, esmolol, metoprolol
Bind to B receptors and act as antagonists (also block calcium to a small degree since B-receptors are bound to calcium channels)
Effects:
- inhibit sympathetic activation (NE release)
- decrease Heart rate and cardiac output (negative chronotropic and inotropic)
- slight decrease on stroke volume
- AV nodal conduction is decreased (prolongs PR interval)
- AV nodal refractory is increased (prolongs PP interval)
MOST EFFECTIVE ON SUPRAVENTRICULAR AND DIGITALIS INDUCED DYSRHYTHMIAS AND HTN*
ADRs:
- hypotension
- asystole (@ high doses)
- bronchospasm
- rebound withdrawal (if not removed slowly will cause hypertensive crisis)
Specific patient populations to note:
- contraindicated in pregnant patients
- contraindicated in diabetics
Class 3 agent effects
Amiodarone, ibutilide, sortalol, dofetilide
Prolong repolarization by altering phase 3 of conducting cells and blocking potassium channels.
- amiodarone also can block sodium,calcium and B-receptors*
Effects:
- decrease effluent of K+ (prolonged ERP in all cardiac tissue)
- prolonged QT interval
- no effect on QRS complex
MOST USED FOR A/V FIB AND A FLUTTER.
ADRs:
- pulmonary toxicity
- elevated liver enzymes
- induces thyroid tumors/hypothyroidism
- photosensitivity
- can induce torsades
Certain populations to take note:
- contraindicated in liver impaired patients
- COPD patients (can still use just monitor)
Quinidine specifics
Class 1a drug
- used for atrial flutter/fibrillation, supraventriclar tachycardia, paroxysmal atrioventricular junctional rhythm, atrial/ventricle tachycardia
Effects:
- inhibit Na+ channels moderately (fastchannels only)
- increases ERP
- increases action potential duration
- prolongs QRS and QT intervals
- decreases membrane excitability and automaticity
Pharmacokinetics
- P.O 200-400mg every 4-6 hrs
Adverse effects: (33% of people will discontinue use)
- can causes cinchonism (tinnitis, hearing loss, blurred vision)
- excessive doses cause AV blocks, tachy dysrhythmia
- torsades de pointes via QT prolongation
- hypotension (blocks a1 receptors)
Procainamide specifics
Class 1a used primarily for PATs, A fib/ A flutter (especially prophylacticly)
- 2nd line behind Quinidine.
- can also be used for ventricular tachycardias however not the best
Effects:
- inhibits sodium channels moderately
- does not enter the CNS
PK: metabolized through hepatic N-acetyltransferase activity
- low acetylator activity patients will take longer to metabolize drug and can induce SLE
ADEs:
- arthralgia, fever, pericarditis, skin lesions, lymphadenopathy, anemia, hepatomegaly
- SLE like syndrome if slow acetylator
- torsades (prolongs QT) (less likely to happen compared to quinine)
Lidocaine specifics
Class 1b agent
MOA:
- inhibits sodium channels and inhibits reentry mechanisms (inhibits spontaneous depolarizations in ventricles) through fast sodium channels
- acts preferably on ischemic tissue and shortens the ERP (allowing the normal conduction pathways to work again)
- decreases excitability in ischemic tissue and increases excitability in healthy tissue
*Excellent use in post-MI or digoxin-induced tachycardia (especially if PVCs are present)
Pharmacokinetics
- IV dosage only and metabolized through liver. (be careful in patients with cirrhosis of liver since its half live is more than doubled)
Adverse side effects:
- mild CNS effects and hypersensitivity reactions only
Flecainide specifics
Class 1c drug
Effects:
- really blocks sodium channels and then His-Purkinje system strongly.
- widens PR, OT and QRS interval
- shortens the action potential of purkinje fibers
- marked ventricular depression
usually only used for refractory life-threatening ectopic ventricular tachycardia and sometimes paroxysmal reentrant supraventricular tachycardia (since it markedly depresses the cardiac conduction to a dangerous level)
Pharmacokinetics: P.O only
ADRs:
- pro-dysrhythmic (this is why it is a last resort)
- hypersensitivity
- GI and CNS side effects
Propranolol specifics
Class 2 agent
Effects:
- blocks B1 adrenergic receptors, stopping sympathetic innervation (prevents NE binding)
- induces a1 receptor blockade also
- decrease resting heart rate and CO
- increase sinus cycle length, effective refractory period and sinus node recovery time
used primarily for atrial fibrillation/flutter
Pharmacokinetics:
PO for sustained
IV for acute
ADRs:
- hypotension
- a-systole (causes AV nodal blocking and can occur in IV doses only so be careful)
- Bronchospasm
- rebound withdrawal (must slowly take off, if not produces dysrhythmia and HTN crisis)
Amiodarone and sotalol specifics
Class 3 agent
MOA:
- blocks K+ channels and therefore disrupts all cardiac phase 3 (Broad spectrum)
- increases ERP and APD
- decreases automaticity of SA/AV nodes
- slows conduction within His-Purkinje system
Used for refractory life threatening ventricular dysrhythmia especially in WPW patients (not a 1st line agent)
Pharmacokinetics:
- PO and IV (IV I only immediate, not long term)
ADRs:
- Pulmonary toxicity
- liver enzymes elevated
- photosensativity
- increases incidence of thyroid tumors and hypothyroidism
- SLE effects if slow acetylators
- prolonged QT (sotalol only)
Verapamil specifics
Class 4 agent
MOA:
- blocks calcium channels and therefore effects phase 0 in AV/SA nodal tissues
- decreases heart rate
- prolongs PR intervals
- decreases AV conduction
- causes overall cardiac depression
used primarily for supraventricular dysrhythmia (tachycardia) and atrial fibrillation over digoxin
Pharmacokinetics:
IV immediately and PO if needed long term treatment for recurrent SVT
- highly lipophilic with hemodialysis being ineffective to clear the drug (High half life so be careful with dosing)
ADRs:
- constipation (usually orally)
- hypotension
- exacerbates congestive heart failure
- can exacerbate heart blocking if used with BBs
- sexual dysfunction
Adenosine effects
Class 5 agent
MOA:
- endogenous purine nucleosides
- binds to A1 in the AV nodes (not alpha 1) causing mass potassium release (elongates phase 3 (hyper polarizes)
- produces asystole (complete AV nodal block momentarily)
used as first line in acute supraventricular tachycardia and other atrial dysrhythmias (atrial flutter, fibrillation or ectopic foci)
Pharmacokinetics:
IV use: however half life is stupid low (15 sec) so complete heart block for 15 sec isn’t completely life threatening
* will show a rapid bolus within the brachial vein*
ADRs: less toxic than verapamil
- hypotension
- flushing
- complete heart block
- dyspena
- GI congestion
Digoxin specifics
Cardiac glycoside that has 2 primarily MOAs
1) positive inotropic effect by inhibiting Na+/K+ ATPase membrane pumps. This leads to increase intracellular calcium since it cant get out as easily through Na+/Ca+ channels
- decreases conduction through the AV node, prolonging the ERP
2) Increases vagal stimulation which results in a negative dromotropic effect on the AV node resulting in prolonged refraction periods.
- used in treatment for
- MOA 1) is atrial flutter/ fibrilation
- MOA 2) is in CHF
- note digoxin is 1st line in CHF, but NOT in atrial flutter/fibrilation*
Pharmacokinetics:
- PO or IV (usually PO)
- lipid soluble
- sympathetic stimulation overrides its effects
ADRs
- highly dysrhytmogenic due to causing hypokalemia (why its not a first line therapy and requires magnesium sulfide douses with it)
Other possible Tx’s for Bradycardia and sinus tachycardia
Bradycardia:
-Atropine: produces vagal block which increases HR
- Isoproterenol: B1- stimulation to increase HR
- Pacemaker: morphologic AV nodal block
Tachycardia:
- vagal stimulation via carotid sinus massage or valsalva maneuver
What are non drug manipulations to generate sinus tachycardia?
Carotid sinus massage
Valsalva maneuver
can only be used in acute non-life threatening cases
Areas of the human body that regulate blood pressure through the barometric reflex
Carotid sinus
Glossopharyngeal and vagus nerves
Medulla and its centers
these centers all act to counter drugs that regulate BP
Types of HTN
Non-essential/2nd: (10%)
- caused directly by a medical condition/pathology such as tumors or renal/ heart disease
- requires surgery
Essential/1st: (90%)
- idiopathic and is genetic most of the time
- no surgery
Consequences of HTN
Accelerates atherosclerosis, coronary artery disease, MI, CHF, strokes and renal disease chances
Non-pharmological treatments of HTN (lifestyle choices)
Sodium restriction
Maintain healthy potassium, calcium and magnesium levels
Weight reduction
Aerobic Exercise (30-45 min a day)
Mediation/relaxation
OMM
Limit alcohol
Stop mocking
Baroreceptors reflex review
Chronic HTN usually rests the baroreflex point to make the increased pressure be considered normal
- examples of how the baroreflex combats HTN drugs are
1) increasing fluid and sodium retention by the kidney (increasing preload and after load) - use diuretics
2) increasing sympathetic activation increases peripheral resistance and cardiac output
- use B-adrenergics
- because the baroreflex has “reset” it reverse any treatment to try and lower HTN (since the reflex assumes the higher BP is normal)*
Mean arterial pressure in HTN patients
MAP = CO x TPR
- most HTN patients have a normal CO, but a higher TPR (total peripheral resistance)*
Diuretics specifics
includes thiazides, chlorthalidone, metolazone, indapamide, furosemide, bumetanide, spironolactone, triamterene, amiloride
Excitability, automaticity and conductivity definitions
Excitability: ability for a cell to respond to external electrical stimuli
Automaticity: ability of a cell or cells to initiate an action potential
Conductivity: ability of a cell or cells to receive and transmit the action potential
What does an increase/decrease in both ERP and APD do?
Increase them causes a decrease in excitability
Decreasing them causes an increase in excitability
Consequences of dysrhythmia (why treat it?)
Decreases efficiency by lowering Stroke volume and cardiac output
Converts bad issues of the heart into worse issues
Increases chances of thrombigenesis (especially atrial flutter/fibrillation)
Differences between a 1st 2nd and 3rd degree heart block
1st degree: slow conduction through the AV node, but all impulses do reach the ventricles
- shows long PR interval (>200ms) but every P wave has a QRS complex
2nd degree: slower conduction through the AV node where most impulses do reach the ventricle, but some do not
- shows long PR interval (>200ms) but every p wave does not have a QRS complex
3rd degree: complete block of all impulses through the AV node
- Long PR interval (> 200ms) with most P waves not having an associated QRS complex
How do you reverse torsades in patients taking class 1a agents?
Give magnesium sulfate
How to diagnosis hypertension
Above 140/90 BP based on two or more readings at least 2 weeks apart from each other.
HTN does not have many clinical symptoms, but must be treated since it can be pathological and have dire consequences.
What factors go into determining he treatment of HTN?
Age, ethnicity, body type, obesity, willingness to adhere to Tx
- African Americans respond better to different Tx
- obesity responds better to different Tx
Lifestyle (busy, sedentary, athletic)
Etiology of the HTN
Severity and time to onset of HTN
- other risk factors for CV disease are present or not
3 ways to lower Blood pressure
Lower heart rate
Lower blood volume (stroke volume)
Lowering vascular resistance
Class 4 dysrhythmic drugs
verapamil, diltiazem, bepridil
Are all calcium channel blockers, targets nodal tissue and slows phase 0.
Effects:
- ERP/APD ratio is increased (increases AV node refractory period)
- prolongs PR
- reduces HR
- negative inotropic (decreases CO)
most used in A fibrilation and PSVTs (AVRNT and AVRTs)
ADRs:
- causes overall cardiac depression
- hypotension
- GI constipation
- exacerbates CHF and Heart blocks
- will block heart if used with BB in coadminstration
- overdosing a patient will induce ventricular tachycardia
Diuretics
thiazides, spironolactone, indapamide
MOA: unknown but its effects are
- reduces blood volume, CO and TPR
- no effect on HR
- increased renin
- (indapamide also has direct vasodilation effects)
Efficacy in HTN treatment: (20/10) as
- taken PO w/ 2-4 weeks to notice effects
Indications:
- edema
- HTN (especially in renal failure patients)
- heart failure complications
- especially useful in blacks and old people.
ADRs:
- hypokalemia and hyperuricemia
- cant use in diabetics (increases glucose levels in blood to dangerous levels)
- cant use in hyperlipidemia patients (elevate LDL to dangerous levels
Clonidine
MOA: centrally acting sympatholytic that stimulates postsynaptic a2 receptors in baroreflex and presynaptic a2 in vascular smooth muscle.
- inhibts sympathetic outflow and prevents baroreflex counter
- vasodilation (lowers SVR and BP)
- induces Bradycardia (lowers HR)
- reduces renin (lowers Blood volume and sodium retention)
Efficacy in HTN: (35/20)
- taken PO and takes 2-4 hrs to notice
ADRs
- severe rebound hypertension (if suddenly discontinued
- AV block
A-methyldopa
MOA: inhibits presynaptic a2 receptors
- reduces SVR and Blood pressure
- decreases release of NE
- lowers renin levels
Efficacy for HTN: (20/10)
- VERY indicated in pregnant patients with HTN (even more so if they have preeclampsia)
ADRs:
- erectile dysfunction
- frank-hemolytic anemia (positive Coombs test indicates this, stop immediately if so)
Azosins
MOA: selective antagonist at ONLY vascular smooth muscle a1 receptors
- reduces SVR and BP (prevents vasoconstriction)
- does not induce NE release (since it doesn’t touch a2 receptors) lowers chance of reflex tachycardia
- also decreases total cholesterol, LDL and triglycerides
Efficacy for HTN: (15/10) as monotherapy (25/15) w/ diuretic
ADRs
- reflex tachycardia
- erectile dysfunction
Verapamil/diltiazem effects on HTN specifically
MOA: direct vasodilator by inhibiting both Calcium entry and release from SR
- decreases TPR via vasodilation
- decreases afterload and BP
Efficacy of the drugs for HTN:
- verapamil (30/20)
- diltiazem (20/15)
ADRs
- cardio depression (can be used to counter reflex tachycardia w/ other drugs)
Nifedipine
MOA: special class 4 CBB which physically plugs the calcium channels on vascular smooth muscle.
- induces vasodilation (decreases SVR)
- also sequesters already present calcium
- significantly less cardio depressant activity (since it targets vascular muscle over cardiac tissue)
Efficacy of HTN: (30/20)
ADRs:
- prominent reflex tachycardia
Hydralazine
MOA: direct vasodilation of smooth muscle by stimulating cGMP production, which in turn, promotes calcium sequestration and blocks calcium release from SR
- lowers SVR (specifically arterioles, NOT veins)
- note this drug is VERY susceptible to developing baroreflex tolerance (baroreflex ignores drug and further increases HTN)*
- increases heart rate
- increases cardiac output
- increases renin (sodium and water retention)
- Because of this, this MUST ALWAYS BE USED W/ BB AND/OR DIURETIC*
Efficacy in HTN: (25/25)
ADRs:
- tolerance
- tachycardia/palpation
- SLE like for slow acetylators (contraindicated)
Minoxidil
MOA: K+ agonist on vascular smooth muscle (inducing widespread repolarization and in turn vasodilation)
- decreases SVR and BP
- note this drug is VERY susceptible to developing baroreflex tolerance (baroreflex ignores drug and further increases HTN)*
- increases heart rate
- increases cardiac output
- increases renin (sodium and water retention)
- Because of this, this MUST ALWAYS BE USED W/ BB AND/OR DIURETIC*
Efficacy in HTN (25/25)
ADRs:
- tolerance (tachyphylaxis)
Loniten
Very potent minoxidil that is only used in severe refractory HTN
Sodium nitroprusside
MOA: donates Nitric oxide groups to vascular smooth muscle to mass generate cGMP
- decreases both arteriole and venous tone (vasodilation of all vessels)
- decreases BP, SVR, CO, dramatically
ONLY used in emergency HTN or rapid management of CHF
ADRs: (only present if prolonged use)
- methemoglobin
- cyanide poisoning
- hypoxia necrosis
PRILs
MOA: directly inhibit angiotensin converting enzyme (ACE) which prevents angiotensin 1 -> 2 conversion
- prevents sodium and water retention
- prevent NE release mildly
- prevents vasoconstriction ( keeps vasodilation present)
- decreases CO and SVR and BP
- induces bradykinin (BK) build up overtime since it also blocks kininase 2 which breaks down BK
Efficacy in HTN:
ADRs:
- potent ever present cough (due to BK buildup, is contraindicated if present)
- contraindicated in pregnancy
- very poor efficacy in African Americans
- nephrotoxicity
- angina
- hypersensitivity
SARTANs
MOA: block AT1 receptors (indirectly stops ACE inhibitors)
- similar effects to ACEIs
often used as replacement if BK-induced cough is present
SAME ADRs w/ slightly lowered efficacy
