EXAMS 2 Flashcards
functional unit of the kidney
The nephron
5 mains regions of the nephron
- Glomerulus
- Proximal convoluted tubule
- Loop of Henle
- Distal convoluted tubule
- Collecting duct
three basic function of the renal
- Cleansing of extracellular fluid (ECF) and maintenance of ECF volume and composition
- Maintenance of acid-base balance
- Excretion of metabolic wastes (drugs/toxins)
renal filtration
- Occurs at the glomerulus
- All small molecules get filtered
renal absorption
- 99% of water, electrolytes and nutrients undergo reabsorption via active transport
renal active tubular secretions
- Located in proximal convoluted tubule
- Excrete products into lumen of nephron
where in the regions of the nephron does filtration occur
glomerus
where in the regions of the nephron does active tubular secretion occur
- Located in proximal convoluted tubule
- Excrete products into lumen of nephron
what are the most abundant electrolytes in filtrate
sodium and chloride.
SODIUM AND CHLORIDE ARE ABSORBED IN DIFFERENT AMOUNTS based on the location in the nephron
how does diuretics work?
Diuretics work by disrupting reabsorption of electrolytes (Na and Cl)
proximal convoluted tubule (PCT)
- High reabsorptive capacity
= 65% of filtered Na+ and Cl- reabsorbed here
= 100% of filtered K+ and bicarbonate reabsorbed here
- Water flows freely
what percentage of filtered sodium and chlorine are rebasorbed in the proximal convoluted tubule
65%
what percentage of filtered potassium and bicarbonate are rebasorbed in the proximal convoluted tubule
100%
where does water flow freely in the nephron?
proximal convoluted tubule
which of the limbs of the loop of henle is freely permeable to water
descending limb
which of the limbs of the loop of henle IS NOT permeable to water
ascending limb
which of the limbs of the loop of henle does filtrate become VERY concentrated
descending limb
which of the limbs of the loop of henle does filtrate become LESS concentrated
ascending limbs
what does not leave the descending limb
sodium and chloride
….% of sodium and chloride are rebasorbed in the ………. whereas …..% of sodium and chloride are rebabsorbed in the ……..
65% of sodium and chloride are reabsorbed in the proximal convoluted tube, whereas the 20% of Na and Cl rebasorbed in the ascending limb
early segment of distal convulated tubule (DCT)
- Freely permeable to water
- 10% of Na and Cl reabsorbed here
late segment of distal convulated tubule (DCT)
- Na can be exchanged for K
- Process stimulated by hormone called aldosterone
- Part of Renin-angiotensin-aldosterone system
where can sodium be exchanged for potassium
late segment of distal convoluted tubule (DCT)
THIS PROCESS IS STIMULATED BY ALDOSTERONE HORMONE which is part of the renin-angiotensin-aldosterone system
what are direutics
drugs that increase urine output
what diurectics are more effective
Diuretics that work EARLIER in the nephron are more effective
Increases in urine are directly related to??
Increases in urine are directly related to how much reabsorption of Na and Cl are blocked
most diuretics work by….
Most work by blocking reabsorption of Na and Cl at some point in the nephron. Remember, water follows salt!
Applications of diurectics
- Treatment of hypertension
- Edema associated with heart failure, kidney failure, and cirrhosis
classes of diuretic
- loop diuretics
- thiazide diuretics
- potassium-sparing diuretics
- osmotic diuretics
what are the potassium-sparing diuretics
- Aldosterone antagonists
- Non-aldosterone antagonists
Most effective class of diuretics
- loop diuretics
mechanism of action of loop diuretics
- Block sodium and chloride reabsorption in the ascending Loop of Henle
- 20% of Na and Cl typically reabsorbed here, inhibition leads to profound diuresis
loop diuretics drugs
- Furosemide
- Torsemide
- Bumetanide
- Ethacrynic acid
Oral= 60 mins IV= 5 minutes
indication of loop diuretics
- Congestive heart failure
Pulmonary edema
Peripheral edema - Hypertension
adverse effects of loop diuretics
- Hypovolemia/dehydration
- Electrolyte abnormalities
Hyponatremia, hypochloremia, hypokalemia, hypomagnesemia, hypocalcemia - Hypotension
- Ototoxicity
- Hyperuricemia
drug interactions of loop diuretics
- Digoxin
- Ototoxic drugs
- Potassium-sparing diuretics
- Lithium
- Anti-hypertensive drugs
- NSAIDs
monitoring points for loop diuretics
- Avoid taking before bedtime
- Monitor urine output
- Watch for signs of dehydration
- Give IV doses SLOWLY to avoid ototoxicity
- Caution in patients with a sulfa allergy
- Monitor urine output
- Can be given safely to patients with a sulfa allergy
Thiazide Diuretics
Lesser diuretic effect than loop diuretics
mechanism of actions of thiazide diuretics
- Block reabsorption of Na+ and Cl- at the early segment of the distal convoluted tubule (DCT)
- 10% of Na and Cl reabsorbed from DCT; inhibition leads to diuresis
drugs of thiazide diuretics
- Hydrochlorothiazide (HCTZ)
- Chlorothiazide
- Chlorthalidone
- Metolazone
indication of thiazide diuretics
- Hypertension (first-line)
- Edema
- Diabetes insipidus
drugs interactions of thiazide diuretics
- Digoxin
- Potassium-sparing diuretics
- Lithium
- Anti-hypertensive drugs
- NSAIDs
adverse effects of thiazide diuretics
- Electrolyte abnormalities Hyponatremia, hypochloremia, hypokalemia, hypomagnesemia - Dehydration - Hyperglycemia - Hyperuricemia
route for thiazide diuretics
oral EXCEPT chlorothiazide
chlorothiazide = IV
monitoring points for thiazide diuretics
- Avoid dosing before bedtime
- All agents equally effective
- Monitor for ADEs especially related to electrolyte abnormalities
- Caution in patients with a sulfa allergy
therapeutic effects of potassium-sparing diuretics
- Small amount of diuresis
- DECREASE potassium excretion
- Reduce cardiac remodeling
Aldosterone Antagonists drug of potassium-sparing diuretic
Spironolactone
Non-aldosterone Antagonists drug of potassium-sparing diuretic
- Amiloride
- Triamterene
mechanism of spironolactone
Blocks aldosterone in the distal convoluted tubule
- Aldosterone typically causes sodium retention and potassium excretion.
- Increased excretion of sodium and retention of potassium
indications of spironolactone (PO)
- Hypertension and edema
- Heart failure
- Acne
- Polycystic ovarian syndrome
adverse effects of spironolactone
- Hyperkalemia
- Endocrine effects
drug interaction of spironolactone
- Thiazide and loop diuretics
- Agents that raise potassium
mechanism of action of amiloride and triamterene (PO)
- Direct inhibitor of the Na/K ion exchange transporter
- Increased excretion of sodium and retention of potassium
indications of amiloride and triamterene
- hypertension
- Edema
adverse effect of amiloride and triamterene
hyperkalemia
drug interactions of amiloride and triamterene
- Thiazide and loop diuretics
- Agents that raise potassium
same as spironolactone
implications with mannitol
ONLY GIVEN BY IV
- Inspect the product prior to administration
- Mannitol can crystalize
- Must be administered through a 0.22 micron filter to remove microcrystals
what is mannitol
Osmotic diuretic made of a 6-carbon sugar
mechanism of action of mannitol
- Filtered by the glomerulus
- Does NOT undergo reabsorption and remains in the lumen
- Increased osmotic pressure keeps water from being reabsorbed
indications of mannitol
- Reduce elevated intracranial pressure
- Reduce elevated intraocular pressure
adverse effect of mannitol
- Edema
- Electrolyte imbalances
Drugs Impacting the Renin-Angiotensin-Aldosterone-System (RAAS)
- Angiotensin converting enzyme inhibitors (ACE-i)
- Angiotensin II receptor blockers (ARB)
- Direct renin inhibitors (DRI)
- Aldosterone antagonists
role of the RAAS system
- The RAAS system plays critical role in regulating blood pressure, blood volume and fluids and electrolytes
key compounds of the RAAS
- Angiotensin
- Aldosterone
- Renin
what is renin of the RAAS
Enzyme that starts the whole RAAS pathway
renin are produced by the kidney in response to?
- Low blood pressure
- Low blood volume
- Low blood sodium content
renin release is suppressed when……
- Low blood pressure, volume and sodium content return to normal
three subtypes of angiotensin
angiotensin I, II, III
Angiotensin I:
inactive; converted into angiotensin II by angiotensin-converting enzyme (ACE)
Angiotensin II:
- Powerful vasoconstrictor (increases blood pressure)
- Stimulates release of aldosterone (increases blood pressure)
- Causes remodeling and hypertrophy of the myocardium
Angiotensin III
effects incompletely understood
function of aldosterone
- Stimulates Na+ retention and K+ excretion in the distal convoluted tubule
- Na+ retention leads to water retention which increases blood pressure
- Causes pathologic remodeling and hypertrophy of the myocardium
what does Na+ leads to? and causes what?
Na+ retention leads to water retention which increases blood pressure
Angiotensin Converting Enzyme Inhibitors (ACE-i) drugs
- Lisinopril (PO)
- Enalapril (PO)
- Enalaprilat (IV)
- Captopril (PO)
- Benazepril (PO)
- Generally well-tolerated
- All agents are equally efficacious
Angiotensin Converting Enzyme Inhibitors (ACE-i) are very effective for treating?
- Hypertension
- Heart failure
- Diabetic nephropathy
mechanism of action Angiotensin Converting Enzyme Inhibitors (ACE-i)
- inhibit angiotensin converting enzyme (ACE) from converting angiotensin I to angiotensin II
- Inhibit kinase II from converting bradykinin to an inactive form
increase in bradykin results in
- vasodilation
- cough
- angioedema (RARELY)
decrease in angiotensin II results in
- vasodilation
- decrease blood volume
- decrease cardiac and vascular remodeling
- potassium retension
fetal injury
pharmacokinetics of ACE- inhibitors
- All administered orally (EXCEPTION: enalaprilat is IV)
- Long half-lives (EXCEPTION: captopril)
- Renally excreted
adverse effects of ACE-inhibitors
- First-dose hypotension
- Dry cough
- Hyperkalemia (high potassium levels)
- Renal failure in patients with bilateral renal artery stenosis
- Fetal injury
- Angioedema
ACE-Inhibitors indication
- hypertension
- heart failure
- myocardial infarction
- diabetic nephropathy
- Prevention of MI, stroke and death in patients at high risk for CV disease
Angiotensin II Receptor Blockers mechanism of actions
block angiotensin II from binding to its receptor
Angiotensin II Receptor Blockers physiologic effects
- Vasodilation
- Decrease production of aldosterone
- Reduce cardiac remodeling
- Dilation of renal blood vessels
Angiotensin II Receptor Blockers drugs
- Losartan
- Valsartan
- Telmisartan
- Olmesartan
all PO
Angiotensin II Receptor Blockers (ARB) therapeutic uses
- Hypertension
- Heart failure
- Diabetic nephropathy
- Myocardial infarction
- Prevention of MI, stroke and death in high risk patients
adverse effects of Angiotensin II Receptor Blockers (ARB)
- Angioedema
- Fetal harm
- Renal failure
Direct Renin Inhibitors (DRI) drug
Aliskiren (PO)
Direct Renin Inhibitors (DRI) mechanism of action
binds to renin and prevents it from cleaving angiotensinogen to angiotensin I
Direct Renin Inhibitors (DRI) physiologic actions
- Vasodilation
- Decrease production of aldosterone
- Reduce cardiac remodeling
- Dilation of renal blood vessels
same as Angiotensin II Receptor Blockers
adverse effects of Direct Renin Inhibitors (DRI)
- Angioedema
- Dry cough
- Diarrhea
- Hyperkalemia
- Fetal injury
indications of Direct Renin Inhibitors (DRI)
Hypertension
Aldosterone Antagonists mechanism of action
blocks aldosterone from binding to receptors in kidney
Aldosterone Antagonists physiologic effects
- Decrease Na+ reabsorption and increase reabsorption of K
- Decrease blood pressure and blood volume
- Reduce pathologic remodeling of the heart
drugs of Aldosterone Antagonists
Eplerenone (PO) =
Selective for aldosterone receptors
Spironolactone (PO) = NON-selective
Aldosterone Antagonists indications
Hypertension
Heart failure
Aldosterone Antagonists adverse effects
Hyperkalemia
Diarrhea
Gynecomastia
Physiology of Calcium Channels
Calcium channels are gated pores in the cytoplasmic membrane
locations of calcium channels
- Vascular smooth muscle (stimulates contraction)
- Heart
Myocardium = increase force of contraction
SA node = increase heart rate
AV node = increase conduction velocity which increases heart rate
Classification of Calcium Channel Blockers (CCBs)
- Dihydropyridines
- several drugs
- works only on vascular smooth muscle - Non-dihydropyridines
- two drugs
- Work on heart and vascular smooth muscle
Dihydropyridine Calcium Channel Blockers drugs
- Amlodipine (PO)
- Nifedipine (PO)
- Felodipine (PO)
- Nimodipine (PO)
- Nicardipine (IV)
- Clevidipine (IV)
IV 5 to 10 mins
PO= 12 to 24 hours
Dihydropyridine Calcium Channel Blockers mechanism of action
block calcium channels in the vascular smooth muscle
MINIMAL effects on the heart
indications of Dihydropyridine Calcium Channel Blockers
Angina pectoris
Hypertension
hemodynamic effects if Dihydropyridine Calcium Channel Blockers
- Vasodilation of the arteries and arterioles which decreases blood pressure
- Vasodilation cardiac vasculature which increases myocardial perfusion
- Reflex tachycardia
first line iv medications for hypertension
Nicardipine
Clevidipine
monitoring points for Dihydropyridine Calcium Channel Blockers
- DDI with beta-blockers
- Toxic doses can affect the myocardium
- Nimodipine is ONLY indicated for SAH
- Nicardipine and clevidipine are first-line IV medications for hypertension
Non-dihydropyridine Calcium Channel Blockers drugs
- verapamil ( both mouth and IV )
- diltiazem ( both mouth and IV)
oral 1-2 hours
IV - 5 minutes
Mechanism of action of Non-dihydropyridine Calcium Channel Blockers
block of calcium channels in the vascular smooth muscle AND heart
Hemodynamic effects: of non-dihydropydrine calcium channel blockers
- Vasodilation of the arteries and arterioles which decreases blood pressure
- Vasodilation cardiac vasculature which increases myocardial perfusion
- Blockade of the SA and AV node which decreases heart rate
- Decreased force of myocardial contraction
indications of non-dihydropydrine calcium channel blockers
- Angina pectoris
- Hypertension
- Cardiac dysrhythmias
monitoring points for non-dihydropydrine calcium channel blockers
- DDI with digoxin and beta-blockers
- Possible interaction with grapefruit juice
- Monitor BP, ECG and heart rate
- Do not crush or chew ER products
adverse effects of non-dihydropydrine calcium channel blockers
Constipation (verapamil) Dizziness Flushing Headache Bradycardia AV nodal block Peripheral edema
Classification of Hypertension (HTN)
- primary/essential = NO IDENTIFIABLE
- secondary = IDENTIFIABLE CAUSE
Why is hypertension so dangerous?
- Increases risk of heart disease and stroke
- Increases risk of irreversible kidney damage
- Often asymptomatic (the “silent killer”)
overall management of hypertension
- Diagnose (Primary vs Secondary)
- Evaluate for factors that increase CV risk and target organ damage
- Treatment Goals
- Therapeutic Management
drug therapy of hypertension
- Many different options
Treatment algorithms to guide decisions - Different mechanisms of action can be combined to have stronger effect or synergistic effect
- Combine with lifestyle changes
hypertensive emergency
- end organ damage
Need to rapidly decrease BP over one hour
- Requires IV medications
- Sodium nitroprusside, labetalol, clevidipine, nicardipine
hypertensive urgency
- no end organ damage
Decrease BP gradually over 24 hours
- Can use IV or PO medications
chronic hypertension
- Discontinue all category X drugs ACE-i ARBs DRI Preferred drugs: labetalol, methyldopa
Preeclampsia and Eclampsia
- Disorder characterized by HTN and proteinuria after 20 weeks gestation
- Presence of seizures = eclampsia
- Serious risks to the mother and fetus
- Treatment
Labetalol
Magnesium(anticonvulsant)
Deliver baby (if possible)
pathophysiology of heart failure
Step 1: Myocardial dysfunction
Step 2: Activation of the RAAS system
Step 3: Activation of the neurohormonal system
Step 4: Remodeling of ventricular myocardium
The normal compensatory systems of the body make the issue worse:
- RAAS system → fluid accumulation
* Neurohormonal system → cardiac remodeling
Angiotensin Receptor Neprilysin Inhibitor drugs
- Valsartan/sacubitril
Valsartan -> ARB
Sacubitril -> neprilysin inhibitor
what is neprilysin
Enzymes that break down natriuretic peptides
ONLY 3 FDA-approved for HF
Bisoprolol
Carvedilol
Metoprolol
inotropes
Added in very severe heart failure
three agents of inotropes
Digoxin ( PO or IV)
Dobutamine (IV)
Milrinone (IV)
- All inotropes are given IV
EXCEPTION digoxin which can be given PO or IV
digoxin mechanism of action
- Inhibition of the Na/K/ATPase pump
↑ intracellular Ca concentrations
↑ force of contraction
role of potassium digoxin
- Competes with digoxin for binding to Na/K/ATPase
- If K levels low = ↑ digoxin binding
- If K levels high = ↓ digoxin binding
low potassium levels impact on digoxin
↑ digoxin binding
high potassium levels impact on digoxin
↓ digoxin binding
digoxin physiologic effects
- Increased cardiac output
- Suppresses renin release in the kidneys → ↓ activation of the RAAS pathway
- Alters electrical activity in the heart → ↑ vagal responses
pharmakokinetics of digoxin
- Well absorbed and distributed into tissues
- High levels reached in cardiac tissues
- Long half-life
dosing of digoxin
Loading dose
Maintenance dose
Monitoring points for digoxin
digoxin = last line defense
Narrow therapeutic index DRUG LEVELS (0.5-0.8 mcg/mL)
adverse effects of digoxin
- Cardiac dysrhythmias
- GI symptoms
- Fatigue
- Visual disturbances
dobutamine mechanism of action
- Beta-1 & beta-2 activation
↑ force of contraction
↑ heart rate - Place in therapy =
Acute decompensated heart failure
Adverse effects/ Monitoring parameters of dobutamine
Arrythmias
BP and HR monitoring
Milrinone mechanism of action
- Phosphodiesterase-3 inhibitor
↑ cyclic AMP → ↑ myocardial contractility
Vasodilation
place in therapy = Acute decompensated heart failure
Adverse effects/ Monitoring parameters of milrinone
Arrythmias
Hypotension
two types of dysrhythmia
- Tachydysrhythmia = Dysrhythmia where rate is increasing
- bradydysrhythmia
Dysrhythmia where rate is decreasing
Drugs are used to treat dysrhythmias BUT can also predispose patients to dysrhythmias
SA node
pacemaker of the heart
AV node
getaway for impulse to reach the ventricles; delays impulse travel
His-Purkinje System
conduct electrical impulse to the ventricles
Properties that Generate an Impulse
AUTOMATICITY
- Heart’s ability to generate an electrical impulse
- SA node has the fastest rate of automaticity
CONDUCTIVITY
- Ability of cardiac tissue to transmit electrical impulses
- Orderly, rhythmic transmission of impulses needed to generate effective contractions
4 classifications of antidysrhythmic drugs
Class I: Sodium Channel Blockers Class II: Beta-blockers Class III: Potassium Channel Blockers Class IV: Calcium Channel Blockers Other: digoxin and adenosine
Class I; Sodium Channel Blockers
Class IA
- Disopyramide
- Quinidine
- Procainamide
Class IB
- Lidocaine
- Mexiletine
Class IC
- Flecainide
- Propafenone
- ↓ conduction velocity in the atria, ventricles and His-Purkinje system
- Similar in action and structure to local anesthetics
- Effects are secondary to sodium channel blockade
adverse effect of quinidine
Diarrhea (33%)
Cinchonism = hearing loss, tinnitus, dizziness, flushing, and blurry vision
Procainamide( CLASS IA) adverse effect
- Systemic Lupus Erythematosus reaction
- Blood dyscrasias
- Arterial embolism
adverse effect of lidocaine (CLASS IB)
- CNS effects
- Toxic doses:
Seizure
Respiratory arrest
monitoring points of lidocaine (CLASS IB)
- Narrow therapeutic index
- Monitor: drug levels
- Make sure you’re using the correct product!
monitoring points for Flecainide (CLASS IC)
↑ mortality in post-MI patients with asymptomatic Vtach
Class II: Beta-blockers DRUGS
Propranolol Acebutolol Esmolol Sotalol = 4 approved
Metoprolol
Labetalol
Bisoprolol
Carvedilol
physiological effects of Class II: beta-blockers
Physiologic effects:
↓ automaticity in SA node
↓ conduction velocity through AV node
↓ myocardial contractility
indications of Class II: beta-blockers
Sinus tachycardia
Atrial fibrillation/flutter
Propranolol adverse effect
- AV block
- Sinus arrest
- Hypotension
- Bradycardia
monitoring points for Propranolol
- Give IV SLOWLY to avoid hypotension
- Monitor: HR, BP, ECG
adverse effect of esmolol
- AV block
- Sinus arrest
- Hypotension
- Bradycardia
monitoring points for esmolol
- VERY fast acting
- Short half-life
- Monitor: HR, BP, ECG
monitoring points for sotalol
- Also causes blockade of K channels; can be considered
- Class III
- Monitor: HR, BP, ECG
Class III: Potassium Channel Blockers
- amiodarone (PO/IV)
- dronedarone (PO)
- sotalol (PO)
- Ibutilide
- Dofetilide
adverse effects of Amiodarone (CLASS III)
- Toxicity – lungs, liver, eyes, thyroid
- Photosensitivity
monitoring points for amiodarone (CLASS III)
- Hypotension
- Give through 0.22 micron filter
adverse effects of dronedarone (CLASS III)
- Photosensitivity
- Hepatotoxicity
monitoring points for dronedarone (CLASS III)
Contraindicated in pregnancy
monitoring points for dofetilde (CLASS III)
Initiated therapy in the hospital
Monitoring points for Sotalol (CLASS III)
Class II and III agent – do NOT use like a typical beta-blocker
Adenosine mechanism of action
- ↓ automaticity of SA node
- ↓ conduction through the AV node
- Prolonged PR interval
indication of adenosine
- Termination of supraventricular tachycardia (SVT)
- NOT for treatment of afib or aflutter
pharmacokinetics of adenosine
- EXTREMELY short half-life (2 to 10 seconds)
- Must be given IV push
adverse effects of adenosine
- Momentary asystole
- Chest discomfort
Drug interactions of adenosine
- Methylxanthines (E.g. theophylline) – block adenosine receptors
Types of Angina
- chronic stable
- variant (prinzmetal’s)
- unstable
what is chronic stable angina
- Caused by coronary artery disease (CAD), in which PLAQUES cause PARTIAL occlusion of the vessel
what are chronic stable angina triggered by
- Increase in physical activity (most common)
- Emotional excitement
- Large meals
- Cold exposure
treatment approach for chronic stable angina
- Decrease myocardial oxygen demand
- Increase myocardial oxygen supply
non-drug interventions of chronic stable angina
- Avoid precipitating factors
- Smoking cessation
- Exercise
- Healthy diet
Therapeutic agents: chronic stable angina
All medications work by decreasing myocardial oxygen demand
- Organic nitrates
- Beta-blockers
- Calcium channel blockers
-/+ ranolazine
what is variant angina
Caused by coronary artery SPASM (VASOSPASM) which decreases blood flow resulting in decreased oxygen supply
variant angina precipitating factors
NO precipitating factors
- Can occur at rest, while sleeping, or during normal activity
treatment approach for variant angina
- Decrease Incidence and severity of attacks with drug therapy that increase oxygen supply
therapeutic agents variant angina
- Calcium channel blockers
- Organic nitrates
- Beta-blockers and ranolazine are INEFFECTIVE
INEFFECTIVE Beta-blockers and ranolazine is part of what angina
variant angina
what is unstable angina
CAD complicated by vasospasm.
- a plaque ruptures causing a clot that partially occludes the vessel
- Medical emergency with higher risk of death than stable angina
Presentation of unstable angina
- Symptoms at rest
- New-onset exertional angina
- Intensification of existing angina
therapeutic approach unstable angina
- Maintain oxygen supply
- Decrease oxygen demand
Therapeutic Options unstable angina
- Anti-ischemic therapy: Organic nitrates Beta-blocker Oxygen IV morphine - Anti-platelet therapy: Aspirin Clopidogrel, ticagrelor or prasugrel
Nitrates mechanism of actions
- Converted to nitric oxide using sulfhydryl group
- Acts primarily on cells of vascular smooth muscle (VSM)
nitrates physiologic effects
- Vasodilation
GREATER EFFECTS ON VEIN than arteries
- Nitroglycerin is the oldest and most commonly used
nitroglycerin Mechanism of action in STABLE angina:
- Vasodilates veins which REDUCES VENOUS RETURN to the heart and REDUCES preload leading to decreased oxygen demand
nitroglycerin Mechanism of action in VARIANT angina:
- Relaxes spasms in the coronary arteries which helps increase oxygen supply
pharmacokinetics of nitroglycerin
- Extremely lipid soluble Allows it be administered by uncommon routes (ie. transdermal, ointments, sprays, sublingual) - Rapidly metabolized by the liver Large first-pass effect - Short half-life (5-7 minutes)
adverse effect of nitroglycerin
- Headache
- Orthostatic hypotension
- Reflex tachycardia
drug interactions of nitroglycerin
- Anti-hypertensive agents
- Phosphodiesterase-5 (PDE5) inhibitors
Sildenafil (Viagra), Tadalafil (Cialis) and Vardenafil (Levitra) - Beta-blockers
- Non-dihydropyridine calcium channel blockers
Isosorbide mononitrate (ER)
given twice daily
Isosorbide dinitrate (IR)
given three times daily
what are Ranolazine
first-line or add-on therapy to beta-blockers, CCBs or nitrates
adverse effects of ranolazine
- QT prolongation
- Elevation in BP
- Constipation, dizziness, nausea, headache
drug interactions ranolazine
- CYP3A4 inhibitors
- QT prolonging drugs
- CCB - can inhibit CYP 3A4 - ecept amlodipine
myocardial infarction complete block
STEMI
myocardial infarction incomplete block
NSTEMI
routine therapy of STEMI
M = morphine O = oxygen N = nitroglycerin A = aspirin B = beta- blockers
Adjuncts to Reperfusion Therapy ANTICOAGULANTS
- heparin
- fondaparinux
- bivalirudin
Adjuncts to Reperfusion Therapy ANTIPLATELETS
- thienopyridines
- glycoprotein IIb/IIa inhibitors
- Aspirin
lipoprotein class
VLDL = probably contribute to atherosclerois LDL = bad cholesterol = contribute to atherosclerosis HDL = protect against atherosclerosis
VLDL is triglyceride
LDL AND HDL are cholesterol
HMG-CoA Reductase Inhibitors drugs
- Atorvastatin
- Rosuvastatin
- Lovastatin
- Pravastatin
- Simvastatin
HMG-CoA Reductase Inhibitors pharmacokinetics
- Administered orally
- Metabolized by the liver (CYP3A4
drug-drug interaction HMG-CoA Reductase Inhibitors
- other lipid-lowering drugs
- Drugs that inhibit CYP3A4
CONTRAINDICATED IN PREGNANCY
counseling points for HMG-CoA Reductase Inhibitors
- Take medication in the evening at bedtime
- Maximal effects seen in 4 to 6 weeks
- Continue treatment lifelong
adverse effects of HMG-CoA Reductase
Mild headache, rash, GI disturbances Myopathy and rhabdomyolysis Possible with ALL statins Measure CK at baseline and repeat if patient complains of muscle pain and weakness Hepatotoxicity Rare Measure LFTs at baseline Memory Loss Transient True incidence and correlation unclear Cataracts
Bile Acid Sequestrants mechanism of action
- Bile acids are needed for re-uptake of cholesterol into the blood stream
- BAS binds to bile acids and prevent their physiologic action
Bile Acid Sequestrants
- Decrease LDL (15-30%)
- Increase HDL
- Possible transient increase in TG
Ezetimibe mechanism of action
- Decrease reabsorption of cholesterol in the small intestines
Ezetimibe effects on lipids
- Decrease Total cholesterol
- Decrease LDL (19%)
- Decrease TG (5-10%)
- Possible modest increase in LDL
indication of Ezetimibe
- Adjunct therapy for decrease LDL
adverse effects of ezetimibe
- well tolerated
- rare - myopathy and rhabdomyolis, hepatitis
drug to drug interactions of ezetimide
- Statins
- Fibrates - increase risk of gallstones
- Bile acid sequestrants
drugs of bile acid sequenstants
- Colesevelam
- Cholestyramine
- Colestipol
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9 Inhibitors)
- Alirocumab
- Evolocumab
Mechanism of action: Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9 Inhibitors)
- PCSK9-inhibitors PREVENT the binding of PCSK9 to LDLRand enhances clearance of LDL
adverse effects of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9 Inhibitors)
- Hypersensitivity reactions
- Immunogenicity = Body may develop antibodies to the drug itself
Niacin
- B2 vitamin, also called nicotinic acid
- As a vitamin, products are not regulated by the FDA
- Thought to it may help decrease LDL and TG levels
- Niacin has not been shown to improve CV outcomes in patients, thus no longer recommended for use
niacin adverse effects
flushing
DDI fibric acid derivatives
increase risk of myopathy when combined with a statin
fibric acid derivatives drugs
Gemfibrozil
Fenofibrate
Fenofibric acid
Most effective drugs for lowering TG levels
Also known as ‘fibrates’
No proven mortality benefit
Third-line agents for lowering lipid levels
fish oil drugs
- Lovaza
- Vascepa
Goal to have 1 gram/day minimum beneficial oils to maintain a healthy heart:
Docosahexaenoic acid (DHA)
Eicosapentaenoic acid (EPA)
Effective for lowering TGs (20-50%)
Used as adjunct therapy for lowering TGs
Counseling points:
Can cause fishy burps, can freeze capsules to help prevent this
Stage C heart failure
Symptoms AND structural heart damage
drugs of stage C and D heart failure
ACE-i/ ARB/ARNI drugs
- Beta-blocker diuretics
- /+ digoxin or aldosterone antagonist
stage D heart failure
Refractory HF requiring specialized intervention
