Day 1 Flashcards
Epidemiology
Affects 76.4 million Americans
1 in 3 adults has HTN
Lifetime risk is 90%
Risk Factors for HTN
Cigarette smoking Obesity (BMI ≥ 30) Physical inactivity Dyslipidemia Diabetes mellitus Renal dysfunction Age: men > 55 years, women > 65 years family history of premature cardiovascular disease (age: men < 55, women < 65)
Etiology for 2 types of HTN
Essential Hypertension:
> 90% of cases
Hereditary component
Secondary Hypertension:
< 10% of cases
Common causes: chronic kidney disease, renovascular disease
Total Peripheral Resistance (TPR)
Sum of peripheral resistance in peripheral vasculature (represents DBP)
Cardiac Output
Amount of blood pumped out by the ventricles (represent the SBP)
Systolic and Diastolic BP
Systolic BP (SBP): Number that represents the cardiac contraction
Diastolic BP (DBP): Number that represents nadir (lowest point)…filling of the heart
JNC 8 New BP Goals
Patients older than 60 = less than 150/90
Patients younger than 60= less than 140/ 90
Patients with DM and CKD= less than 140/90
Mechanism of Pathogenesis for HTN
Increase Peripheral Resistance:
Functional Vascular Constriction/Structural Vascular Hypertrophy:
Over activity of sympathetic nervous system
Genetic components
Increased cardiac output (CO): Increased Preload: Increased fluid volume Excess sodium intake Renal sodium retention
Venous Constriction:
Excess RAAS stimulation
Sympathetic nervous system over activity
Non-Pharmacological Therapy for HTN
Smoking Cessation Weight loss in overweight and obese DASH diet Dietary sodium reduction Increased physical activity limit alcohol intake to no more than 1-2 drinks/day
First Line Treatment Approaches for HTN
First line options:
Thiazides, CCB’s, ACE-I, ARB’s (all equal in choice)
Note: not the best choice to use ACE-I or ARB’s in a black patient
DM or chronic kidney disease:
ACE-I or ARB’s
JNC 8 states do not use them together
Cardiac history:
Beta-blocker
3 Options for Treating HTN
1st option:
Start with 1 drug and max the dose and then add on a 2nd agent if still not at goal, and then add on a 3rd agent once the 2nd drug is maxed out if pt. still not at goal.
2nd option:
Start with 1 drug and if not at goal add a 2nd drug prior to maxing out the dose on the first. Then max the dose on both drugs and if not at goal add a 3rd agent
3rd option:
Start with 2 drugs from the beginning if the SBP >160 and/or the DBP >100. Max out the drug doses and add on a 3rd agent if needed.
Thiazide Diuretics MOA
Drugs: Hydrochlorothiazide (HCTZ), chlorthalidone, metolzaone
MOA: Inhibits sodium reabsorption in the distal tubule.
Precautions for Thiazide Diuretics
Caution in sulfa allergic patients
Ineffective in patients with severe renal disease
Avoid in patients taking lithium– may increase serum lithium concentrations
Avoid in patients with GOUT
Adverse Effects for Thiazide Diuretics
Orthostatic Hypotension
Electrolyte abnormalities: ↓ K, ↓ Na, ↑ Ca, ↑ uric acid, ↑ glucose
Photosensitivity
Increase urination (initially)
Place in Therapy and Dose for Thiazide Diuretics
One of the first line drug classes used to treat HTN
Dose: Typically 25mg (can start at 12.5mg)
Loop Diuretics
Drugs:
Furosemide (Lasix™)
Bumetanide (Bumex™)
Torsemide (Demadex™)
Mechanism of action:
Inhibits active transport of sodium, chloride and potassium in thick ascending limb of Loop of Henle, causing excretion of these ions
Collecting duct excretes more water in response
Place in Therapy for Loop Diuretics
NOT 1st LINE TREATMENT
CHF (preferred diuretic)
Edema (both peripheral and pulmonary)
HTN
Adverse Effects for Loop Diuretics
Electrolytes abnormalities: ↓ K, ↓Na, ↓ Ca, ↓ Mg, ↑ uric acid
Dehydration
Ototoxicity
Increase in SCr
Precautions for Loop Diuretics
Caution in sulfa allergic patients
Nephrotoxicity
Avoid in patients with GOUT
Potassium Sparing Diuretics—Aldosterone Receptor Blockers MOA
Aldosterone Receptor Blockers:
Spironolactone (Aldactone™)
Eplerenone (Inspra)
Mechanism of Action: Competes with aldosterone, prevents sodium reabsorption and potassium excretion
Potassium Sparing Drugs
Triamterene
Amiloride
Mechanism of action: blocks sodium reabsorption and potassium excretion, effect independent of aldosterone
Potassium Sparing Diuretics Place in Therapy
Hypertension, often in combination with thiazide
Spironolactone – Class IV heart failure
Adverse Effect for Potassium Sparing Diuretics
General: Hyperkalemia (caution in patients with renal failure)
Spironolactone: Gynecomastia, menstrual irregularities
Eplerenone: More selective thus less side effects
10 ACE- Inhibitor Drugs
Benazepril (Lotensin) Captopril (Capoten) Enalapril (Vasotec) Fosinopril (Monopril) Lisinopril (Zestril, Prinivil) Moexipril (Univasc) Perindopril (Aceon) Quinapril (Accupril) Ramipril (Altace) Trandolapril (Mavik)
MOA of ACE- Inhibitors
Inhibits ACE to block production of AT II
Inhibits breakdown of bradykinin (vasodilator)
Benefit: lowers blood pressure
Disadvantage: inflammatory mediator, probably some common adverse effect of ACE-I
Dilate the efferent arteriole of kidney
ACE- Inhibitor Place in Therapy
One of the first line drug classes in HTN
First line option for CKD
Used in CHF
What is the Dose and what do you have to monitor with ACE inhibitors
Dose: Often once a day, sometimes twice daily
Monitor:
Serum K+ & SCr within 4 weeks of initiation or dose increase. You will likely see a benign increase in Scr (<30% from baseline)
Angioedemia
Adverse Effects of ACE Inhibitors
Cough
Up to 20% of patients
Due to increased bradykinin
Angioedema (rare)
Hyperkalemia: particularly in patients with CKD or DM
Other: Neutropenia, agranulocytosis, proteinuria, glomerulonephritis, acute renal failure
Contraindications for ACE inhibitors
Pregnancy category C/D- contraindicated
Angioedema with other ACE-inhibitors
Renal artery stenosis (increased risk of renal toxicity)
Drug Interactions for ACE inhibitors
Potassium supplements
Potassium-sparing diuretics
NSAIDs
ACE-I Clinical Differences
All can be dosed once daily except captopril
Captopril is dosed twice to three times daily
Most may be dosed more than once a day for efficacy
Enalapril is a prodrug of enalaprilat (only one that is available IV)
Most commonly used ACE-I: lisinopril
Dose is 10-40 mg daily
Captopril absorption decreased by 30-40% when given with food
Angiotensin II Receptor Blockers (ARB) 7 Drugs
Candesartan (Atacand) Eprosartan (Teveten) Irbesartan (Avapro) Losartan (Cozaar) Olmesartan (Benicar) Telmisartan (Micardis) Valsartan (Diovan)
ARB MOA
Inhibits angiotensin II at its receptor sites
Does NOT inhibit the breakdown of bradykinin
ARB Place in Therapy
Place in Therapy: One of the first line drug classes in HTN First line option for CKD Used in CHF Dose: Often once daily
Adverse Effects of ARB
Hypotension/orthostatic hypotension Angioedema Hyperkalemia Dizziness Cough (only case reports)
What needs to be monitored with PT taking ARB’s
Potassium
Angioedema
Contraindications for ARB’s
Pregnancy category C/D- should not be used
“Caution” in pts with renal artery stenosis
ARBs CAN be used in patients who have experienced angioedema when taking an ACE inhibitor- but use caution.
Drug indications for ARB’s
Potassium supplements
Potassium-sparing diuretics
NSAIDs
Renin inhibitor- Aliskiren
First oral agent that directly inhibits renin
Role in treatment of hypertension is unclear as it is a new agent
Can be used as monotherapy or in combination
ADRs are similar to ACE inhibitors; and similar to ACE inhibitors, this drug should not be used in pregnancy
MC Beta Blockers
Most common: Atenolol: once a day Metoprolol Succinate: Once a day Metoprolol Tartrate: Twice a day Sotalol (Betapace) Class III anti-arrhythmic agent
Dose: Depends on the beta-blocker
Beta Blockers Place in Therapy
Place in Therapy: Not a first line Reserved for patients that have significant cardiac history Heart failure Post-MI High coronary artery disease CKD
MOA for Beta Blockers
Beta-1 receptors; located in heart and beta-2 receptors are located in the lungs
Beta-blockers block beta-1 receptors thus decreasing the effects of epinephrine, and nor-epinephrine which therefore decrease BP and HR
Beta Blocker Differences
Cardioselectivity (dose-dependent)
AMEBBA: Atenolol, metoprolol, esmolol, bioprolol, betaxaolol, acebutolol
Mixed α and β blockers
Carvedilol and labetalol
ISA (intrinsic sympathomimetic activity)
CAPP: (Carteolol, acebutolol, penbutolol, and pindolol)
Non-Specific
Nadolol, propranolol, timolol
Common Adverse Effects for Beta Blockers
Initial: “Beta-blocker blues”: tired, fatigued, depressed, and their chest might feel “different” due to change in heart beat
Other: Sexual dysfunction, rebound HTN if suddenly discontinued
Relative Contraindications for Beta Blockers
Asthma and COPD (bronchospasm)
Diabetes (masks hypoglycemic response except sweating)
Severe peripheral vascular disease (decreased output can worsen symptoms)
Heart block
Severe acute heart failure
Pregnancy category C
