Contraction/conduction and cardiac glycosides Flashcards
1
Q
Contractility
A
- Force of contraction
- Increase preload=Increase contractility
- Decrease afterload=Increase contractility
- Contractility is independent of loading
2
Q
SV factors
A
- Contractility
- Preload
- Afterload
3
Q
Fast AP
A
- aka muscle/Long AP
- Ventricular Myocyte
- His-Purkinje System, Atrial and ventricular muscle
- Mediated by Na+ influx
- Resting membrane potential is lower than nodal
- prevents hyperexcitabilty
- wont spontaneously fire
- wait for signal from nodal tissue
- Phase 0,1,2=QRS
- Phase 3=T wave
- Phase:
- Phase 0=depolariation
- Na+ Channel opens, Na+ influx
- Upstroke; Increase permeability of Na+
- Phase 1: partial repolarization
- Na+ Channel closes, K+ channel opens
- K+ eflux
- Phase 2: Plateau phase=K+-mediated
- Ca2+ Channel opens, (Fast K+ Channel close)
- Ca2+ Influx (K+ efflux)
- Phase 3: Ca2+ Channel close, Slow K+ channel open
- K+ efflux
- Phase 4: Resting potential
- stable potential; K+ eflux
- Phase 0=depolariation
- Class I and III antiarrhythmics
4
Q
Fast AP:Absolute refractory period
A
- aka effective refractory period
- Under no circumstance will heart fire/depolarize
- phase 0-2 of Fast AP
5
Q
Fast AP: Relative Refractory Period:
A
- Mostly refractory but if you come in w/a strong enough stimulus=you can trigger a resopnse
- PHASE 3
- Problem: Long QT Syndromes
- arrival of T wave is delayed (repolarization delayed)
- common source for dangerous arrhythmias
- occurs due to dysfunctional K+ channels
6
Q
Cardiac Glycosides: Pharmocological effects:
A
- Improves contractility
- Increase CO
- Increase Renal BF
- Decrease Blood Volume and edema
- Decrease preload
- Sensitize the carotide sinus (Both causes Decrease HR)
- Decrease Sympathetic tone
- Increase Vagus tone
- Vasodilation
7
Q
Cardiac Glycosides: MOA:
A
- Inhibition of Na+/K+ ATPase causes Increase in intracellular Na+
- 2 possible mechanisms
- Inhibits Ca2+/Na+ exchange–>Less Ca2+ extrusion–> Increase Ca2+ intracellular
- Stimulates Ca2+/Na+ exchanger–> Na+ eflux, Ca2+ influx
- Both Cause Increase of Ca2+ intracellular–>Stimulates Contractile proteins
- Increase Force of contraction (contractility)
8
Q
Cardiac Glycosides: Electrical effects
A
- Inhibition of pump redistributes Na+, Ca2+, and K+
- Depolarizes Cells
- Increase ectopic automaticityin heart
- due to Ca2+ Loading
- Increase refractory period early
- Decrease conduction velocity due to increase vagal tone
9
Q
Effects of Digoxin on electrical properties of cardiac tissue: SA Node etc:
Therapeutic dose vs toxic doses
A
- SA Node
- Therapeutic: Decrease rate
- Toxic: Decrease rate
- Atrial Muscle
- Therapeutic:
- Decrease refractory period
- Toxic:
- Decrease refractory period
- arrhythmias
- Therapeutic:
- AV node:
- Therapeutic:
- Decrease conduction velocity
- Increase refractory period
- Toxic:
- Decrease refractory period
- Therapeutic:
- His-purkinje/ Ventricles:
- Therapeutic:
- Slight decrease refractory period
- Toxic:
- extrasystoles
- tachycardia
- Fibrillation
- Therapeutic:
- ECG:
- Therapeutic:
- Increase PR interval
- Decrease QT interval
- Toxic:
- Tachycardia
- Fibrillation
- Cardiac arrest with really high doses
- Therapeutic:
10
Q
Digoxin: Pharmokinetics:
Onset, optimal serum levels, GI Absorption, Plasma half life, Daily excretion, Plasma protein, excretion
A
- Onset of action: 10-30 mins
- Optimal serum levels:
- 0.5-2.5ng/mL
- GI Absorption:
- Tablets: 60-80%
- Lanoxicaps: 90-100%
- Plasma Half Life
- 35-40 hours
- Load dose
- 35-40 hours
- Daily excretion:
- 30%
- kidney disease=modify dose
- Plasma protein Binding:
- 20-40% excreted out
- Excretion:
- kidney
- CCR=Creatine clearance level: Assess in elderly to determine if you need to modify dose
11
Q
Digoxin: Toxicities:
A
- High Risk of Toxicity:
- 20-25% hospitalized patients
- Greater risk in advanced heart disease
- Antidote for Overdose:
- Digoxin immune fab
- Cardiac Toxicities:
- Primary toxic effect is arrythmias
- can be sinus block, AV block, AV junctional arrythmias
- casues:
- premature ventricular contractions (most common)
- Tachycardia
- Ventricular Fibrillation
- Primary toxic effect is arrythmias
- Non-cardiac toxicities
- Fatigue, muscles weakness
- GI
- Anorexia
- Nausea-cenrally mediated
- common early sign
- CNS:
- difficulty walking
- confusion
- halucinations
- restlessness
- insomnia
- drowsiness
- Psychoses
- Vision:
- blurred
- photophobia
- alterations in color=objects appear green or yellow
- some make pats develop gynectomastia
- due to androgenic effect
12
Q
Digoxin: Factors that increase conc.
A
- High dose (received wrong dose)
- Reduced renal fxn
- decreased excretion
- Altered distribution
- elderly-lean body mass
13
Q
Digoxin: DDIs
A
- Diuretics–>produce hypokalemia
- decrease Plasma K+ and Mg2+
- Increase serum Ca2+
- Increase Toxicity
- Antacids: Decrease absorption
- Decrease K+
- Corticosteroids:
- decrease serum K+
- Increase toxicity
14
Q
What maintains Resting membrane potential in fast action potentials?
A
- K+ Leak channels
- Na+/K+ ATPase
15
Q
Mechanism of Fast APs
A
- Nodal AP enters from adjacent cell
- Voltage gaded Ca2+ channels open, Ca2+ enters
- Ca2+ induces Ca2+ release through ryanodine receptor channels (RYR) from sarcoplasmic reticulum
- Local release causes Ca2+ spark
- Summed Ca2+ spark creates a Ca2+ signal
- Ca2+ ions bind to troponin to initiate contraction
- Relaxation occurs when Ca2+ Unbinds from Troponin
- Ca2+ is pumped back into sacroplasmic reticulum to storage
- Ca2+ is exchanged with Na+
- Na+ gradient is mainted by the Na+/K+ ATPase