Week 5 ~ Drugs Affecting CVS/Renal/Electrolytes Flashcards
2 Kinds of Positive Inotropic Drugs?
- Cardiac Glycosides: Digoxin
~ Obtained from Digitalis Plant Foxglove - Phosphodiesterase Inhibitors: Milrinone
Cardiac Glycosides Mechanism of Action
~ Used for heart failure
~ Control ventricular response to arterial fibrillation and flutter
~ Increase myocardial contractility
~ Change electrical conduction properties of the heart
- Decrease rate of electrical conduction - Prolong the refractory period, between SA node and AV node
~ Reduces heart rate and improves cardiac efficiency
Cardiac Glycosides Drug Effects
- Increases stroke volume
- Decrease venous blood pressure
- Increase in coronary circulation
- Promotion of diuretics due to improved blood circulation
- Positive Inotropic effect
- Negative chronotropic effect
- Negative dromotropic effect
- Palliative of exertion all and paroxysmal nocturnal dyspnea, cough,
Cyanosis
What’s a Positive Inotropic Effect?
Increase in force of the heart
What’s a Negative Chronotropic Effect?
Reduced heart rate
What’s a Negative Dromotropic Effect?
Decreases the automaticity at SA node, decreases AV node conduction
Cardiac Glycosides Indications
Heart Failure
Supra ventricular Dysrhythmias
- Atrial Fibrillation and atrial flutter
Cardiac Glycosides Contraindications
Drug allergy
2nd or 3rd degree heart block
Ventricular tachycardia or fibrillation
Sub-aortic stenosis
Digoxin Adverse Effects
Very narrow Therapeutic window
Drug levels and electrolyte levels must be monitored
Low potassium levels increase its toxicity
Dysrthmias: Tachycardia or bradycardia
Headaches, fatigue, confusion, convulsions
Coloured vision (green, yellow, purple), halo
Anorexia, nausea, vomiting, diarrhea
Digoxin Toxicity Therapy
Hyperkalemia K> 5mmol/L can cause life threatening
Dysrhythmia
Digoxin immune Fab (antibodies) therapy
Phosphodiesterase Inhibitors Mechanism of Action
Work by inhibiting the enzyme phosphodiesterase
Results in a Positive Inotropic Response and Vasodilation
What’s the name of the only Phosphodiesterase Inhibitor in Canada?
Milrinone
Indications for Phosphodiesterase Inhibitors
Used for short term management of heart failure
Given when the patient hasn’t responded to treatment with digoxin, diuretics or vasodilators
Given as weekly 6 hour infusions
Phosphodiesterase Inhibitors Contraindications
Drug Allergy
Severe aortic or pulmonary valscular disease
Milrinone Adverse Effects
Dysthymia, mainly ventricular
Hypotension, angina, hypo kalmia, tremor, thrombocytopenia
Milrinone Drug Interactions
With Diuretics:
Hypovolemia
Reduced cardiac filling pressure
Digoxin Adverse Effects
Potentiates Inotropic Effects
What’s a Dysrhythmia?
Any deviation from the normal rhythm of the heart which can be seen on ECG
What are AntiDysrhythmic Drugs?
Drugs used for the treatment and prevention of disturbances in cardiac rhythm
3 Common Dysrhthmias
- Supra Ventricular Dysrhythmias
- Ventricular Dysrhythmias
- Conduction Blocks
Vaughan Williams Classification
- Class 1: Block Na Channels
- class 1a
- class 1b
- class 1c
- Class 2: decrease spontaneous depolarization
- Class 3: prolong action potential duration
- Class 4: blocks Ca channels
What do Vaughan Williams Class 1 drugs do?
- Membrane stabilizing drugs
- Fast sodium channel blockers
- Increase the action potential duration (APD)
~Divided into 3 different classes
Class 1a Drugs
Procainamide
Quinidine
Disopyramide
Class 1b Drugs
Phenytoin
Lidocaine
Mexiletine
Class 1c Drugs
Propafenone
Flecainide
Class 1 Drugs Mechanism of Action and Indications
Atrial/Ventricular fibrillation
Premature atrial/ventricular contractions
Ventricular Tachycardia
Wolff Parkinson White Syndrome
What is Wolff Parkinson White Syndrome?
A condition in which there is an extra electrical pathway of the heart. The condition can lead to tachycardia.
Class 2 Drugs Mechanism of Action and Indications
B-Blockers
Reduce or block sympathetic nerve system
Used as antianginal and anti hypertensive drugs
Class 2 B-Blocker drugs
- Acebutolol
- Esmolol
- Propranolol
Class 3 Drugs Mechanism of Action and Indications
Increase action potential duration
Used for Dysrhythmias that are difficult to treat
Class 3 drugs
- Amiodarone
2. Sotalol (Also exhibits class 2 properties)
Class 4 Drugs
- Verapamil
2. Diltiazem
Class 4 Drugs Mechanism of Action and Indications
~ Calcium Channel blockers
~ Inhibit slow channel (calcium dependant) pathways
~ Reduce AV node conduction
- used for paroxysmal Supra Ventricular tachycardia, rate control for atrial fibrillation and flutter
What are Unclassified AntiDysrhythmic Drugs?
Have properties of several classes and are not placed into one particular class
What’s the name of an Unclassified AntiDysrhythmic drug?
Adenosine
What does Adenosine do?
Slows conduction through the AV node
Has a very short half life - less then 10 sec
Ad instead only as intravenous push
AntiDysrhythmic Drug Adverse Effects
ALL can cause Dysrhythmias!
Hypersensitivity reactions
Nausea, vomiting, diarrhea
Dizziness, blurred vision, headache
AntiDysrhythmic Drug Interactions
Commonly potentiates anticoagulant activity of warfarin (Coumadin)
What is Acute Coronary Syndrome?
Group of clinical symptoms compatible with acute myocardial Ischemia
What’s Angina?
When the supply of oxygen and nutrients in the blood is insufficient to meet the demands of the heart and the heart muscle “aches”
Drugs for Angina
- Nitrates and Nitrites
- B-blockers
- Calcium Channel Blockers
2 Nitrate/Nitrite Drugs
- Isosorbide Dinitrate
2. Nitroglycerin
Nitrate/Nitrite Mechanism of Action
Potent vasodilator, mainly affecting the venous vascular bed
Dose dependant effect atrial vasodilator effect
What’s the Prototypical Nitrate?
Nitroglycerin
Has large first pass effects with oral forms
Nitrate Indications
- Stable, unstable angina and vasospasm
- Rapid acting forms are used to treat acute anginal attacks
- Hypertensive emergencies
* Long acting Nitrates are used to prevent anginal episodes in Hypertensive emergencies*
Nitrate/Nitrite Contraindications
Drug Allergy
Severe anemia
Closed Angle Glaucoma
Hypotension
Severe head injury
Nitrate/Nitrite Adverse Effects
Headaches
Tachycardia, postural hypotension
Tolerance
What is Tolerance?
Occurs in patients taking long acting formulations or taking them continuously
How to prevent Nitrate Tolerance…
Transdermal forms
Remove patch at bedtime for 8hours and apply a new patch in the morning
Nitrate/Nitrite Drug Interactions
Addictive hypotensive effects when taken with:
- alcohol - B-blockers - Calcium Channel Blockers - Phenothiazines - Sildenafil
B-Blocker Drugs
Atenolol
Metoprolol
Propranolol
Nadolol
What is CardioProtective?
After MI, high level of circulating Catecholamines can be blocked by B-Blockers
3 Calcium Channel Blocker Drugs
- Benzodiazepines
- Diltiazem Hydrochloride
- Dihydropyridines
- Nifedipine
- Amlodipine Besylate
- Nimodipine
- Felodipine
- Phenylalkylamines
- Verapamil Hydrochloride
Calcium Channel Blockers Mechanism of Action
Cause coronary artery vasodilation
Cause peripheral arterial vasodilation, decreasing systemic vascular resistance
Reduce the workload of the heart, decrease myocardial oxygen demand
Calcium Channel Blockers Indications
Angina, hypertension and supraventricular tachycardia (first line)
Treat coronary artery spasms (Prinzmetal’s Angina)
Short term management of atrial fibrillation and flutter
Calcium Channel Blockers Adverse Effects
Hypotension
Tachycardia
Bradycardia
Constipation
Nausea
Dyspnea
Calcium Channel Blockers Drug Interactions
~ Diltiazem interferes with metabolism and elimination of cyclosporine
~ Grapefruit juice can reduce the metabolism of Calcium Channel Blockers
Antihypertensive Drug Ethnocultural Considerations
B-Blockers and Angiotension-converting enzyme (ACE) inhibitors are more effective in White patients over Black patients
Calcium Channel Blockers (CCBs) and diuretics are more effect in Black patients then White patients
What’s the Canadian Hypertension Education Program?
Endorses:
- Home blood pressure monitoring
- Annual Bp assessment for pre hypertension
- Ongoing routine assessment
LifeStyle Modifications:
- Regular exercise
- Stress reduction
- Moderation in alcohol
- Healthy diet and reduction in sodium
Treat to Target:
- Less then 140/90 mm Hg
- Less then 130/80 mm Hg in those with diabetes/chronic kid disease
What are Positive Inotropic Drugs?
Drugs that increase the force of myocardial contraction.
These drugs are used to treat heart muscle failure
6 Antihypertensive Drugs
- Adrenergic Drugs
- Angiotensin - converting enzyme inhibitor
- Diuretics
- Vasodilators
- Angiotensin 2 receptor blockers (ARBs)
- Calcium Channel Blockers
4 ACE Inhibitors
- Benazepril Hydrochloride
- Captopril (Can be used in liver dysfunction)
- short half life
- Enalapril
- oral/Parenteral forms
- Lisinopril and Quinapril
- newer drug, long half life, once a day dosing
ACE Inhibitor Mechanism of Action
Block the angiotensin converting enzyme thus preventing the formation of angiotensin 2
Prevent the breakdown of Bradykinin
- result in vasodilation, decreased systemic vascular
ACE Inhibitor Indications:
Hypertension
Heart Failure
Drugs of choice for diabetic patients
ACE Inhibitor Contraindications
Drug Allergy
Lactating women and children
Bilateral rental artery stenosis or hyperkalemia
ACE Inhibitor Adverse Effects
Fatigue
Headache
Impaired Taste
Dry Cough
Dizziness
Mood Changes
ACE Inhibitor Drug Interactions
Lithium can result in lithium toxicity
No steroidal anti-inflammatory drugs can reduce the effect
Potassium supplements and potassium sparing diuretics may result in hyperkalemia
Angiotensin 2 Receptor Blockers Mechanism of Action
Newer class, well tolerated and doesn’t cause a dry cough!
Allow angiotensin 1 to be converted to angiotensin 2 but block the receptors that receive angiotensin 2
Block vasoconstriction and release of aldosterone
2 Angiotension 2 Receptor Blocker Drugs
- Losartan Potassium
2. Valsartan
Angiotension 2 Receptor Blocker Indications
Used primarily in patients who can’t tolerate ACE inhibitors
Diuretics
Hypertension
Adjunctive drugs from the treatment of heart failure
Angiotension 2 Receptor Blocker Contraindications
Drug Allergy
Pregnancy
Lactation
Angiotension 2 Receptor Blocker Adverse Effects
Upper respiratory infections
Headache
Dizziness
Inability to sleep
Diarrhea
Dyspnea
Heartburn
Nasal Congestion
Back pain
Fatigue
Angiotension 2 Receptor Blocker Drug Interactions
Cimetidine
Phenobarbital
Rifampin
Calcium Channel Blockers Mechanism of Action
Cause smooth muscle relaxation by blocking the binding of calcium to its receptors and preventing muscle contraction
This causes decreased peripheral smooth muscle tone and decreased systemic vascular resistance
Decreased blood pressure results
Calcium Channel Blocker Indications
Angina
Hypertension
Dysrhthmias
Migraines
Raynaud’s Disease
Diuretics ~ Thiazide Mechanism of Action
Most commonly used and first line Anti-Hypertensives in the CHEP guidelines
Decrease the plasma and extra cellular fluid volumes
Decreased pre-load
Decreased total peripheral resistance
Decreased workload of the heart and decreased blood pressure
3 Types of Vasodilators
- Hydralazine Hydrochloride
- Minoxidil
- Sodium Niitroprusside
Vasodilator Mechanism of Action
Directly relax arteriolar and venous smooth muscle
Result in decreased systemic vascular response, decreased after load and peripheral vasodilation
Vasodilator Indications
Hypertension
Sodium Nitroprusside is reserved for the management of hypertensive emergencies
Vasodilator Contraindications
- Drug Allergy
- Hypotension
- Cerebral Edema
- Head injury
- Acute myocardial infarction (MI)
- Coronary Artery Disease
Vasodilator Hydralazine Adverse Effects
Dizziness Headache Anxiety Tachycardia Nausea/Vomiting Dyspnea Edema Anemia Diarrhea Nasal Congestion
Vasodilator Sodium Nitroprusside Adverse Effects
Bradycardia
Hypotension
How much of the human body is water (TBW)?
60%
3 main compartments that TBW is distributed?
- Intracellular Fluid (ICF)
- Interstitial Fluid (ISF)
- Plasma Volume (PV)
What is Crystalloids?
IV fluids that supply water and Na to maintain osmotic gradient between extravascular and intravascular compartments
Types of Crystalloids?
- Normal Saline (0.9% Sodium Chloride)
- Hypertonic Saline (3% Sodium Chloride)
- Lactated Ringer’s
- D5W
- Plasma-Lyte
Crystalloids Indications
Dehydration Acute Liver Failure Acute Nephrosis Burns Adult Respiratory Distress Syndrome Shock Kidney Dialysis Reduction of the risk of deep vein thrombosis Hypotroteinemia
Crystalloids Contraindications
Drug Allergy
Hypervolemia
Severe electrolyte disturbance
Drug interactions are rare!
Crystalloids Adverse Effects
Edema, especially peripheral and pulmonary
May dilute plasma proteins
May have sort lived effects
What are Colloids?
Increase Colloid Oncotic Pressure
Protein substance that move fluid from interstitial compartment to plasma compartment
3 Types of Colloids
- Albumin + Na + Cl
- Dextran + Na + Cl
- Hetastarch + Na + Cl
Colloid Indications
Superior to Crystalloids in plasma volume expansive but more expensive
Colloid Contraindications
Drug Allergy
Severe electrolyte disturbance
Usually safe adverse effects
What are Blood Products?
Blood products pull fluid from extravascular space into intravascular space
RBC products carry oxygen
Blood products increase the body’s supply of various products such as clotting factors and hemoglobin
3 Types of Blood Products and their Indications
- Cryoprecipitate and Plasma Protein Fractions
- Manage acute bleeding
- Fresh Frozen Plasma
- Increase clotting factor levels
- Packed red cells and Whole Blood
- Loss of blood
Blood Products Adverse Effects
Anaphylaxis
Incompatibility with recipients immune system
Transmission of pathogens such as hep, Hiv
Types of Electrolytes
Potassium
Sodium Cations
Chloride Cations
Calcium
Magnesium
Phosphorus
What is Hypokalemia?
Serum Potassium levels less than 3.5 mmol/L
Causes of Hypokalemia?
Digoxin Therapy
Corticosteroids
Loop Diuretics
Vomiting/Diarrhea
Ketoacidosis
Potassium Contraindications
Drug allergy
Severe Kidney Disease
Acute Dehydration
Severe hemolytic disease
Potassium Adverse Effects
Diarrhea
Nausea/Vomiting
GI bleeding
Ulcerations
Potassium Drug Interactions
ACE inhibitors
With diuretics and amphotericin B
Sodium Adverse Effects
Nausea/Vomiting
Cramps
Can cause phlebitis with IV route administration
What is a normal Sodium concentration?
135 - 145 mmol/L
What is Hyponatremia?
When sodium serum levels are below 135 mmol/L
Same causes as Hypokalemia
What is Sodium responsible for?
~ Control of fluid and electrolyte balance
~ Participate in Acid-Base balance
How is Sodium administered?
Available as intravenous normal saline or lactated Ringer’s solution
3 Types of Fluids given in hospital?
- Crystalloids
- Colloids
- Blood Products
3 Types of Hydralazine?
- Adrenergics
- Antihypertensive
- Monoamine oxidase inhibitors
Type of Minoxidil?
Antihypertensives/ Thiazides
Monoamine oxidase inhibitor mechanism and result?
M –> Altered Biotransformation
R –> Increased Hypotensive Effect
Antihypertensives/Thiazides Mechanism and Result?
M –> Additive Effects
R –> Increased hypotensive effect
Antihypertensives Mechanism and Result?
M –> Additive Effects
R –> Increased Hypotensive effect
Adrenergics Mechanism and Result?
M –>Antagonism
R –> Decreased Hypotensive effect
What’s the only drug that has a Decreased Hypotensive Effect?
Hydralazine –> Adrenergics