What is the ratio of adults who have HTN?
1 in 3
What is HTN a risk factor for?
Development of heart disease, stroke, heart failure, renal disease
What are Risk Factors for hypertension?
Smoking Obesity (BMI > 30) Physical inactivity Dyslipidemia DM Renal dysfunction Age: Men > 55yo, Women > 65 yo Fam hx.
What percentage of HTN cases are essential HTN?
Greater than 90%
What is essential HTN?
Hereditary/idiopathic
What percentage of HTN cases are secondary HTN?
Less than 10%
What are common causes of secondary HTN?
Chronic kidney disease, renovascular disease
What does systolic BP represent?
Cardiac contraction
What does Diastolic BP represent?
Filling of the heart
TPR
Total peripheral resistance : sum of total peripheral resistance in peripheral vasculature (represents DBP)
What medication should be used for HTN in a pt with a cardiac hx?
Beta-Blocker
What does systolic BP represent?
Cardiac contraction
Majority of pt’s will require ________ to reach goal?
a. Monotherapy
b. At least 2
c. At least 3
d. No therapy just lifestyle change
B-At least 2
What are some lifestyle modifications that can be used in non-pharmacological tx of HTN?
Smoking cessation Wt. loss-in overweight and obese DASH diet Dietary sodium reduction Increased physical activity Limit alcohol to no more than 1-2 daily
What is the most effective non-pharmacologic tx for HTN?
Wt. Loss
What are the firs line options for tx of HTN?
Thiazides
CCB’s
ACE-I
ARB’s
What is the best choice to use in a black pt with HTN?
Thiazides or CCB’s
What first line meds should be avoided in a black pt?
ACE-I
ARB’s
What medications are best for use in a pt w/ HTN who has chronic kidney disease?
ACE-I
ARB’s
*regardless of race.
Would you use both ACE and ARB together according to JNC 8?
NO - JNC 8 says not to use together because of increased risk of renal dz/
What medication should be used for HTN in a pt with a cardiac hx?
Beta-Blocker
Describe option 1 for tx. pt with HTN?
- start drug 1 and max the dose
- add 2nd agent if still not at goal-max dose
- add 3rd agent
Describe option 2 for tx. pt w/ HTN?
- Start drug 1 and if not at goal add drug 2 prior to maxing out drug 1 dose.
- Max the dose on both drugs
- If not at goal add drug 3
Describe option 3 for tx. pt w/ HTN?
- Start w/ 2 drugs right from the beginning. Max these out.
- Start drug 3 if needed
When would you use option 3 for tx. of a pt . w/ HTN?
When SBP>160 and/or DBP>100
What is MOA for Thiazide Diuretics?
Inhibit sodium reabsorption in the DISTAL TUBULE.
What is the result of the inhibition of sodium reabsorption on water in the distal tubule?
Less H20 is retained-Pee it out!!
What medications are in the class Thiazide Diuretics?
HCTZ
Chlorthalidone
Metolazone
Which thiazide diuretic is not typically used daily because it is very potent?
Metalozone
T/F Thiazides can be used as first line therapy for pt’s with DM who have HTN.
True!
What electrolyte abnormalities are assoc. with Thiazide diuretics.
Decreased K
Decreased Na
Increased Ca
Increased Uric Acid
Increased Glucose
Other than electrolyte imbalances what are ADE’s of thiazides?
Orthostatic Hypotension Photosensitivity Increased Urination (blocking reabsorption on Na)
What medication is a look like for Thiazide Diuretics in the body and therefore should be cautioned if pt. is allergic?
Sulfa
OK to use if not an anaphylaxis reaction but caution
T/F Thiazide diuretics are a good choice for pt’s with renal disease
False!
In pt’s with severe renal disease the kidney is working really hard to get to the Distal tubule to begin with so Thiazide diuretics are a bad choice because they will be ineffective.
What other medication should be avoided when taking thiazide diuretics due to the fact that it will increase the concentrations?
Avoid with Lithium. May increase Lithium conc.
Are loop diuretics considered first line?
No. The thiazide diuretics are the only first line diuretic choice.
What drugs are in the class of loop diuretics?
Furosemide
Bumetanide
Torsemide
Which loop diuretic is the most potent?
Torsemide
Which loop diuretic is the least potent and most used?
Furosemide (Lasix)
What are loop diuretics more commonly used for (as opposed to Thiazides)
Heart failure and cardiac history. Especially helpful with Edema
What is the Mechanism of action for loop diuretics?
Inhibits active transport of sodium, chloride, and potassium in the thick ascending limb of the LOOP OF HENLE causing excretion of these ions. This means the collecting duct excretes more water!!!
What is significant about the location of where the loop diuretics work?
Earlier removal of fluid means that more fluid is removed and the kidney does not have to work as hard to get to the site of action of the drug.
What are the electrolyte abnormalities associated with loop diuretics?
Decreased K
Decreased Na
Decreased Ca
Decreased Mg
Increased Uric Acid
What other adverse effects are related to loop diuretics?
Dehydration
Ototoxicity
Increased SCr (esp if pt is dehydrated)
Is a loop diuretic a good choice for a pt with renal disease?
NO-Nephrotoxicity may occur, you have to watch the kidney when giving this med to begin with.
What medication do Loop Diuretics mimic in the body and therefore if there is an allergy you must take caution when taking.
Sulfa
What is the MOA of Aldosterone receptor blockers?
blocks the aldosterone receptors which normally would tell mRNA to produce Na and K channels preventing Na reabsorption and K excretion. A buildup of Na in the tubule causes water to flow into the tubule from the blood.
What is the common trend of diuretics so far?
They all cause sodium to hang around for longer in the Tubular lumen.
H20 follows Na and is excreted.
Difference between Loop Diuretics and Thiazide Diuretics?
Thiazide diuretics work to hold on to ~5% Na, and Loops hold on to ~25% Na. Loops are found earlier in the schematic and therefore excrete more since they are stronger at diuresing.
Difference between the potassium sparing diuretics?
Aldosterone receptor blockers-block aldosterone, and inhibit production of Na K channels
K+ sparing diuretics-Block Na+ channels that would typically facilitate indirectly the opening of K+ channels.
What are medications in the class Aldosterone Receptor Blockers?
Spironolactone
Eplerenone
What is the MOA for Potassium sparing drugs?
(NO effect on Aldosterone!!) Block Sodium reabsorption and potassium excretion.
When are potassium sparing diuretics used?
Often in combination with a thiazide for HTN.
What additional use other than HTN can Spironolactone (a potassium sparing diuretic) be used for?
Class 4 heart failure
What are the adverse effects of potassium sparing diuretics?
Hyperkalemia (caution in pts with renal failure)
Gynecomastia, menstrual irregularities
Eplerenone (not used as much as spironolactone)-More selective thus less side effects.
What is the PRIMARY function of ACE?
ACE hooks up with Angiotensin I to produce Angiotensin II. It can then act on AT1 and AT2 receptors to produce vasoconstriction which increases BP.
Other than the conversion of Angio I to Angio II what does ACE do?
breaks down Bradykinin which is a vasodilator
What is the MOA of ACE-I?
inhibits ACE and blocks production of ATII
Inhibits breakdown of Bradykinin (vasodilator)
-this lowers BP but also adversely effects inflammatory mediation.
Dilates efferent arteriole of the kidney
What is the first line option for pt’s with CKD???
ACE-I
When are ACE inhibitors used?
First line drug class in HTN
First line in CKD
Used in CHF
How often are ACE-I dosed?
Often once daily, sometimes BID
What levels should be monitored when giving ACE-I?
Serum K+ and SCr within 4 weeks of dose
What will likely occur when giving an ACE-I?
Benign increase in SCr (
What side effect is a risk when giving ACE-I d/t increase in Bradykinin?
Cough
Angioedema (rare)
Hyperkalemia (esp. with DM /CKD pt’s)
Renal failure
What are contraindications for ACE-I?
Pregnancy (C/D)
Angioedema w/ other ACE-I
Renal artery stenosis
DI’s of ACE-I?
Potassium supplements
Potassium sparing diuretics
NSAIDs
Can Lisinopril be given with Triamterene?
No. Triamterene is a potassium sparing diuretic and Lisinopril is an ACE-I and DI may occur
Can Triamterene and HCTZ be given together?
HCTZ is a thiazide and Triamterene is a potassium sparing diuretic so they should be dosed together!!! :)
What suffix do ACE-I end with?
PRIL
What is the most commonly used ACE-I?
Lisinopril
What other ACE-I exist?
Lisinopril
Benazepril Enalapril Fosinopril Moexipril Perindopril Quinapril Ramipril Trandolapril
What can occur when giving an ACE-I with an NSAID
NSAIDs can increase BP and work on afferent nephrons. Prostaglandins significantly effect the kidney and can cause significant kidney problems
Which ACE-I is available in IV?
Enalapril
What is the dosing for Lisinopril?
10-40mg daily
Which ACE-I is used is both decreased by 30-40% when given with food AND is dosed BID-TID making it unusual for use?
Captopril
What is the Suffix for ARB’s?
Sartan
What are the MC ARB’s?
Valsartan
Olmesartan
Losartan
Irbesartan
What is the MOA of ARBs?
Inhibit Angio II at receptor site. Does NOT inhibit breakdown of bradykinin!!
When are ARB’s used?
First line in HTN
First line for CKD
used in CHF.
How often are ARB’s dosed?
QD
What must be monitored for with ARB’s
Potassium
Angioedema
What are ADE’s of ARB’s?
Hypotension/orthostatic Angioedema (less likely than with ACE-I) Hyperkalemia Dizziness Cough (less likely than with ACE-I)
What are contraindications for Angio II receptor blockers?
Pregnancy (C/D)
Renal artery stenosis
DI’s of ARB’s
Potassium supplements
Potassium-sparing diuretics
NSAIDs
What is the first oral agent that directly inhibits renin?
Aliskiren
What drug class has ADR’s that are similar to Aliskiren?
ACE-I (don’t use this drug in pregnancy)
What are the two categories of CCB’s (calcium Channel Blockers)
Non-dihydropyridines
Dihydropyridines
What are the drugs in the class Non-dihydropyridines?
Verapamil
Diltiazem
What is important to know about the different brands of diltiazem?
The brands are not interchangeable
What drugs are in the class of dihydropyridines?
-Pines Amlodipine Felodipine Isradipine Nifedipine
What occurs in the body when calcium channels are open?
Calcium influxes into the smooth muscle specifically
Cardiac smooth muscle and
Vascular smooth muscle
What does activation of intracellular calcium (by influx of calcium into the smooth muscle) cause?
Muscle contraction
What is the MOA of Calcium Channel Blockers (CCB’s)
Inhibits calcium influx (prevents muscle contraction)
at CARDIAC smooth muscle-Decreases Inotropy and Chronotropy
at VASCULAR smooth muscle-causes vasodilation
What comorbidity receives no benefit and can in fact worsen from CCB’s?
CHF
Where do Dihydropyridines work?
on VASCULAR smooth muscle
resulting in peripheral vasodilation
Where do NON-dihydropyridines work?
on CARDIAC smooth muscle
decreases rate and force of contraction
Which CCB can be sued to tx for migraine prophylaxis?
Verapamil
What other dx can CCB’s be used to tx?
Diltiazem and verapmil-supraventricular tachy, and AFIB
Verapamil-migraine prophylaxis
ADE’s of all CCB’s?
Hypotension
ADE’s of Non-dihydropyridines?
CONSTIPATION (very common) Bradycardia Exacerbation of CHF Heart block Gingival hyperplasia (remember this one works directly on cardiac muscle)
ADE’s of dihydropyridines?
Peripheral edema (most common)
Reflex tachy (body trying to get blood back from ext)
Flushing
Headache
(remember dihydropyridines work on the peripheral)
which CCB is peripheral edema worst with?
dihydropyridine-Nifedipine
Which HTN medication is useful for pt’s with isolated systolic HTN (esp. elderly)?
CCB-dihydropyridines
Which CCB is contraindictated in soy/egg allergy?
Clevidipine I (IV only)
Which of the following is NOT a potential ADE associated with furosemide therapy? a - Hypokalemia b - Hyperuricemia c - Hyperglycemia d - Hypercalcemia e - Ototoxicity
D - Hypercalcemia
*should by hypocalcemia
Furosemide is a loop diuretic. For loops everything goes down except for Uric acid
Which of the following is a direct renin inhibitor? a - Aliskiren b - Perindopril c - Eprosartan d - Enalapril
a - Aliskiren
*Perindopril-ACE-I
Eprosartan-ARB
Enalapril - ACE-I
This is an important counseling point for lisiniprol?
a - This medication will increase urination
b - If you have diabetes, you may need to monitor your blood glucose more frquently
c - Take extra medicine if you miss a dose
d - Don’t use salt substitutes which taking this mediacation
D - Don't take salt substitutes when taking this medication Lisinopril is in the class ACE-I
- a - Meds that increase urination are in the diuretics (esp thiazides)
b - ACE-I are first line for DM so you wouldn’t need to closely monitor
c - Never take extra meds if you miss a dose
Are Beta Blockers considered first line?
NO
When are beta blockers used in HTN?
Pt's with significant cardiac hx- Heart failure Post-MI High coronary artery disease CKD
Where are Beta 1 receptors located?
In the heart
Where are Beta 2 receptors located?
In the lungs
What do Beta blockers do?
They block the Beta-1 receptors which decreases the effects of epinephrine and NE and therefore decrease BP and HR.
What medications are considered Cardioselective (dose-dependent) Beta blockers?
AMEBBA- Atenolol Metoprolol Esmolol bioprolol betaxaolol acebutalol
What is the suffix for all beta blockers?
-Olol
What medications are Mixed a and B blockers?
Carvedilol
Labetalol
What is true about ISA’s?
a - They cause the most HR lowering effects
b - Lower heart rate minimally relative to other B blockers
c - Are POTENT sympathomimetics
d - should be dosed at night due to orthostatic hypotension
B - ISA’s give protection of a B-Blocker without the bradycardia effects like the others-however is not as strong in HR lowering as other B-blockers
What medications are ISA’s?
CAPP: Carteolol acebutolol penbutolol pindolol
What 3 meds B-Blocker meds are used in HF?
Bisoprolol
Metoprolol
Carvedilol
What are the non-specific B-Blockers?
Nadolol
Propanolol
timolol
What medication is very lipophilic and is used in stage fright?
Non-specific B-blocker-Propanolol
What 2 meds are safe for HTN tx of pregnant women?
Labetalol (B-Blocker)
Methyldopa (alpha 2 agonist)
What is the MC ADE of B-Blockers?
“Beta-blocker blues” when they first start the med
tired, fatigue, depression, funny chest (non-painful)
What meds cannot be stopped suddenly because of risk of rebound HTN?
B-Blockers
Alpha 2 agonists
Contraindications of B-blockers?
Asthma and COPD (avoid non-selective agents that can block B2) DM (mask hypoglycemia) PVD (worsened by decrease CO) Heart bloack Severe ACUTE HF Pregnancy cat. C. (exception-Labetalol)
When are Alpha 1 blockers used?
As adjunct therapy-more often in males but not often in general.
What is the MOA of A-1 blockers?
Inhibits A1 recptors in the periphery which causes vasodilation
What additional diagonsis are Alpha 1 blockers useful for treating?
BPH - justification for why more common in older males
also not generally used as mono therapy
What is the most significant side effect of Alpha 1 blockers?
orthostatic hypotension
What medication causes the the worse example of orthostatic hypotension?
Alpha 1 blockers
Because of the risk of reflex tachycardia, and orthostatic hypotension what is suggested as far as dosing for pt’s who are starting an A-1 blocker?
slowly titrate dose up.
What is MOA of Alpha 2 agonists?
Stims Alpha 2 rec in the brain. It tells the brains “we have so much A2 which causes the brain to shut off the sympathetic outflow (forces the negative feedback loop). This results in lowered BP and PVR.
What drugs are part of class Alpha 2 agonists?
Methyldopa
Clonidine
When is clonidine used?
resistant HTN
Opiate withdrawal and avoidance
Adjust pain management
ADD
When is Methyldopa used?
Pregnancy
ADE’s of Alpha 2 agonists?
Orthostatic Hypotension, dizziness
fatigue, sedation, depression
Sodium and water retention
rebound tacky and HTN if stopped abrputily
What medication can elicit a rash with a patch, “anticholinergic-like” side effects (dry mouth, sedation, constipation, urinary retention)?
Clonidine
What drug may cause liver toxicities, hemolytic anemia?
Methyldopa
Who often does a clonidine patch need to be reapplied?
every 7 days
What medication are direct Vasodilators?
Hydralazine
Minoxidil
What is the MOA of vasodilators?
direct vasodilation, especially in arterial side-leads to decreased systemic vascular resistance
What may it be smart to start a pt on a vasodilator with??
Beta-Blocker and a diuretic
Why might it be a good idea to start a pt on a vasodilator with a Beta Blocker?
Because of reflex tachycardia (which occurs because vasodilation tells the heart that there is more blood to push through more quickly-the heart speeds up to accommodate but the beta-blocker will work to tell the sympathetic system to slow down resulting in lower HR>
t/f headaches are common with Vasodilators?
T
Why might it be a good idea to start a pt on a vasodilator with a diuretic?
When vasodilation occurs renin increases as a response-co-administration with diuretic is advised.
What medication has a ADE of Hirsituism, a side effect that has been advantageous by using it in rogain tx.?
Minoxidil
What medication may cause a lupus-like syndrome, dermatitis, drug fever, peripheral neuropathy, and hepatitis?
Hydralazine
What are most common drugs to cause HTN?
NSAIDS
Appetite suppressants
Caffeine
Pseudophedrine
According to JNC8 what are the HTN guidelines for a person over 60yo
Less than 150/90
According to JNC8 what are the HTN guidelines for a person under 60yo?
Less than 140/90
According to JNCi what are the HTN guidelines for a person of any age who has DM or CKD?
Less than 140/90