Exam 2 Review Flashcards
Afterload
Resistance to flow in the aorta and arteries (peripheral vascular resistance)
Also, the work required to opn the aortic valve
Preload
Venous return from the upper and lower body to the right atrium
Blood volume/ventricular filling
Where is angiotensinogen produced/released from?
Liver
Where is renin produced/release from?
Kidney
Which drug class for hypertension did we learn about that has a sideffect of a slight cough? Why? What would you substitute?
ACE inhibitors (-prils)
-Because there is decreased bradykinin breakdown (more of them present)
Substitute with ARBs
Which drug is the cornerstone of CHF (congestive heart failure)?
ACE inhibitors (-prils)
- Reduced pre- and after-loads
- Inhibits cardiac and vascular remodeling
Angioedema is a rare but lifethreatening side-effect
Contraindicated in pregnancy and K-sparing diurectics (spironolactone) due to decrease in aldosterone secretion
ARBs
- artans
- Reduced pre- and after-loads
- Also inhibit cardiac and vascular remodeling
- valsartan approved for post-MI usage like ACE inhibitors; others aren’t
How do the ARBs and ACE inhibitors reduce pre- and after-loads?
Dilate veins and arteries by down-regulating the amount of Angiotensin II in circulation
What is the Triple Whammy Crisis?
ACE inhibitors, NSAIDs, and Diuretics
Efferent arteriole dilation, block prostaglandin production (afferent arteriole constricted), and decreased plasma volume
Combined, they lead to severe Renal failure crisis
Cardiac Glycosides (digoxin and digitalis)
Inotropic drug
Primary use is for CHF but never the first drug (or only drug) used
Secondary use is for atrial tachycardia, flutter, and fibrillation
MOE is to block Na/K ATPase, leading to a buildup of intracellular Ca++
Pharmacokinetics of digoxin
25% plasma protein bound
36 hour half-life
Antibiotic treatment can lead to a sudden increase in digoxin availability and toxicity!
Digoxin Toxicity
Low therapeutic index (narrow safety margin)
Side-effects: Visual disturbances, disorientation, and confusion; various stages of heart block, ectopic systoles of ventricular origin and arrythmia
What is the best treatment for Digoxin toxicity?
digoxin specific antibodies (Digoxin Immune Fab [Digibind]) has a rapid response in less than a minute
lidocaine is used for ventricular arrhythmias
Digoxin Drug Interactions
Adrenergic agonists (epinephrine)
Antibiotics
Anticholinergics (antisialologues) : via antagonism with vagus nerve cholinergic effect of digoxin
Antacids
Diuretics (K depleting)
Prolonged corticosteroid therapy
Therapy Approaches for CHF
Decreased Preload pressure
Increased contractility
Decreased Afterload pressure
Arrythmia
Any abnormality of firing rate, regularity or site of origin of cardiac impulse or disturbance of conduction that alters normal sequence of activity of atria and ventricles
Definitions:
Flutter
Tachycardia
Bradycardia
Fibrillation
Flutter: very rapid but regular contractions
increased rate
decreased rate
fibrillation: disorganized contractile activity
Atrial Fibrillation increases the risk for what?
Blood clots
Stroke
Heart failure (in the long term)
What is a non-invasive method of treatment for a-fib?
Catheter ablation
Atrioventricular Nodal Reentry Tachycardia (AVNRT)
AVRT
There’s an abnormal electrical pathway involved (ablation can help)
Premature Ventricular Contraction
1 area in the ventricles producing abnormal signals
Ventricular fibrillation
Multiple areas in both ventricles producing abnormal signals
What are 3 principles to keep in mind about anti-arrythmic agents?
- Every antiarrythmic drug can be pro-arrythmic
- Therapeutic range of drug levels is empirically-derived
- Caution needs to be taken, especially with high-risk patients like the elderly, pregnancy, hepatic/renal insufficiency or failure, and patients on multiple drugs
What are the 4 main classes and 3 subclasses of Antiarrythmic drugs?
1: Na+ Channel blockers
1a: Quinidine/Procainamide
1b: Lidocaine
1c: Flecainide/Propafenone
2: Beta blockers (Propanolol)
3: K+ Channel blockers (sotalol and amiodarone)
4: Ca++ Channel blockers (verapamil)
*note sotalol is also a beta blocker
Class 1a Antiarrythmic Drugs
Quinidine
- Actions opposite to digitalis (anti-cholinergic effect leading to increased heart rate)
- Negative inotropic effect and diarrhea side-effect
Procainamide
- More commonly used but short term due to higher incidence of adverse reactions
- Common choice for ventricular arrythmias associated with acute MIs (more effective than lidocaine)
- Increased antinuclear antibody titer with long-term use that resembles Lupus Erythematosus!
Class 1b Antiarrythmic drugs
Lidocaine
-Very low toxicity with good therapeutic index but rarely used today
Little effect on atria function or vagus nerve
-Primary target is ventricular function (treatment of ventricular tachycardia of digoxin toxicity and ventricular ectopic rhythms)
Class 1c Antiarrythmic drugs
Flecainide (Tambocor)
-Associated with significant mortality and use limited to a last resort
Na Channel Blockade Strength
1C > 1A > 1B
Class 1 ERP Ranking
1A > 1C > 1B
1C is a last resort
Class 2 Antiarrythmic drugs
Beta Blockers
- Slow AV conduction
- Prolong AV refractory period
- Suppress automaticity
*Treatment for Pheochromocytoma and Thyroid disorders
Class 2 Antiarrythmic drugs Toxicities
Will worsen congestive heart failure
SA and/or AV block
Sudden withdrawal may worsen angina and arrythmias due to receptor upregulation
-Bronchospasm, sedation, insomnia, and depression
Class 3 Antiarrythmic Drug Action
Primary anti-arrythmic action is through blockade of rapid component of the delayed rectifier outward potassium current; this action prolongs the the ERP (effective refractory period) of mycocardial cells
Class 3 Antiarrythmic Drugs
Sotalol
- Also a beta blocker on top of being a K-blocker
- Atrial flutter and fibrillation
Amiodarone
-High incidence of adverse effects including: potentially fatal pulmonary toxicity (fibrosis) and thyroid dysfunction; many drug-drug interactions due to metabolism by CYP3A4 and CYP2C8
Class 4 Antiarrythmic Drugs
Ca blocking agents
-First choice with adenosine for SVT (supraven. tac.) due to AVNRT
Examples: non-dihydropyridine Ca blockers => verapamil and diltiazem
What are the important considerations for treating arrythmias?
Class 1-3 are used for ventricular conditions while supraventricular is Class 4
Acute: Adenosine (1), Digoxin (cadiac glycoside), Amiodarone (3), Procainamide (1a), Sotalol (2)
Chronic: beta blocker (2), Ca blocker (4), Amiodarone (3), Sotalol (3), Flecainide (1c)
End of Drug Arrythmias and CHF drugs
3 Types of Angina pectoris
- Chronic Stable: classic angina of effort; presence of atheromatous obstruction in coronary arteries; therapeutic goal is to increase myocardium perfusion/decrease O2 demand
- Variant: coronary vasospasm (goal is to prevent vasospasm)
- Unstable: presence of transient thrombi near atherosclerotic plaque (goal is to correct tendency to form thrombi)
Classifications of Drugs Used to Treat Angina Pectoris
- Negative inotropic vasodilators
- Nitrates (nitroglycerine) and nitrites
- dipyridamole - Other
- beta blocker (propranolol)
- Ca channel blocker (nicardipine)
- ACE inhibitor (-pril)
- ARB (-artan)
How do negative inotropic vasodilators treat Angina Pectoris?
Via dilation of nearly all vascular beds
may also relax non-vascular smooth muscles (GI, bronchi)
What is the primary action of Angina Pectoris drugs?
To decrease preload and/or afterload blood pressure
-This leads to increased efficiency in oxygen utilisation by myocardium and decreases oxygen demand
Increased Oxygen Supply/Demand ratio
What is the MOA for Nitrates such as nitroglycerin?
To produce NO (nitric oxide) in vascular smooth muscle
Dephosphorylation of myosin results in relaxation, vasodilation, and hyperpolarization
Which is affected more significantly by nitrates like nitroglycerin: venous dilation or arterial dilation?
Venous dilation is more significantly impacted:
- Decreased venous return, ventricular preload pressue, mechanical work and O2 consumption
- Increased exercise tolerance
What are some other effects of nitrates (nitroglycerin)?
Cardiac muscle: may initiate reflex tachycardia
Relaxation of other smooth muscles: bronchi, GI
Platelet aggregation may decrease
*No direct effect on skeletal muscle
What is the primary route of administration for nitrates (nitroglycerin)?
Sublingual because oral is avoided to circumvent the 1st pass effect (exception is dinitrites)
What are some of the adverse reactions/precautions for nitrates?
Throbbing vascular headaches
Face flushing
Fainting, hypotension, reflex tachycardia (palpitations), methemoglobulinemia
What occurs after long-term nitrate administration?
Decrease in guanylyl cyclase activation
ANS compensatory mechanism
Salt and water retention
*reversed by stopping administration for 8 hours
Beta 1 Blocker Function for Treating Angina Pectoris
Reduces myocardial O2 demands
Negative chronotropism and inotropism
propranolol and metoprolol
Ca Blockers MOA for Angina Pectoris
-Relaxant effect on vascular smooth muscle
-Arterial dilation in coronary and systemic beds
Blockage of L-type Ca channel
nifedipine, amlodipine, and nicardipine
Section: Anticoagulants
Heparin
-Extreme negative charge
Unfractionated heparin has activity on thrombin and factor Xa
Low weight heparin just binds Xa (Lovenox and Arixtra)
Antagonized by protamine sulfate
Adverse Effects: bleeding, thrombocytopenia, headache
warfarin (Coumadin)
past oral anticoagulant of choice (now been replaced by Xarelto, etc.)
-Antagonizes the utilization of Vitamin K (factors 7, 9, and 10 require this as a cofactor)
-Highly bound to plasma protein (99%)
-Metabolized by CYP2C9 and 3A4
-36-72 hour lag in onset
Coumadin Dosing
Pharmacogenetics may explain large response differences in the population
-Polymorphism in CYP2C9 AND VKORC1
Coumadin Adverse Effects
Fatal bleeding (black box warning)
What is the antidote for warfarin (Coumadin)?
phytonadione (Mephyton)
Emergency: fresh plasma transfusion as antidote may take up to 25 hours or longer
warfarin (Coumadin) Drug-Drug Interactions
What are the newer oral anticoagulants?
Direct Factor Xa inhibitors: Xarelto, Eliquis
Direct Thrombin inhinitors: Pradaxa
Antidote for Pradaxa –> Idarucizumab
Antidote for Xarelto/Eliquis –> Andexanet
Anticoagulant Factor Xa Inhibitors
- xaban
- Metabolism by CYP3A4
Rivaroxaban (Xarelto)
Apixaban (Eliquis)
Edoxaban (Savaysa)
Guide to Anticoagulatant use (photo)
*Heparin can be used in pregnancy but is not administered orally
*Warfarin (Coumadin) has a delayed onset
Section: Thrombolytics
What is the primary use of thrombolytic enzymes/drugs? What are 4 examples?
For treatment of post-MI and stroke patients (not hemhorragic strokes though?)
- Tissue Plasminogen Activator (t-PA)
- alteplase (Activase) is most common and binds to fibrin and activates fibrin-bound plasminogen better than free plasminogen to break clots - Tenecteplase (TNKase)
- Urokinase (Abbokinase)
- Streptokinase (Streptase)
How quickly must thrombolytics be administered to be useful in post-MI and stroke patients?
post-MI must occur within 6 hours
Stroke therapy must occur within 3 hours of onset of symptoms
MOA of Thrombolytic Agents
What are the antidotes for the thrombolytic agents?
Amino caproic acid (Amicar)
Tranexamic acid (Cyklokapron)
They act by blocking the binding site of plasminogen to prevent fibrinolysis
Platelet Inhibitors Section
