1. Rapid stenosis = Thrombus/embolism

2. Gradual stenosis = Atheroslerosis

Brain = stroke

Heart = Myocardial ischemia or infarction

1. Endothelial cells

2. Smooth muscles cells

3. Extracellular matrix eg. elastin, collagen and glycosoaminoglycans

decreases;

Increases

(1) large or elastic arteries, including the aorta, its large branches (particularly the innominate, subclavian, common carotid, and iliac), and pulmonary arteries;

(2) medium-sized or muscular arteries, comprising other branches of the aorta (e.g., coronary and renal arteries); and

(3) small arteries (less than approximately 2 mm in diameter) and arterioles (20 to 100 μm in diameter), within the substance of tissues and organs.

16-fold increase in resistance to flow (vasocontriction);

Arterioles  = principle points of physiologic resistance to blood flow

Atherosclerosis = elastic and muscular arteries

Hypertension = small muscular arteries and arterioles

Vasculitis = vascular segments

1. Vasculogenesis -de novo formation of blood vessels during embryogenesis

 2. Angiogenesis - process of new vessel formation in the mature organism.

3. Andarteriogenesis - remodeling of existing arteries in response to chronic changes in pressure or flow, and results from an interplay of endothelial cell–and smooth muscle cell–derived factors.

Important functions of endothelium are:

1. Maintain homeostasis and circulation

2.Non-thrombogenic blood-tissue 

3. Modulate vascular resistance

4. Metabolize hormones

5. Regulate inflammation, and affect the growth of other cell types, particularly smooth muscle cells.

Promoters include:

1. PDGF

2. Endothelin-1

3. Thrombin

4. Fibroblast growth factor (FGF)

5. Interferon-γ (IFN-γ)

6. Interleukin-1(IL-1).

Growth Inhibitors include:

1. Heparan sulfates

2. Nitric oxide

3. TGF-β. 

1. Blood pressure (BP) = Q * PR (Q or PR is increased = increased BP)

2. Cardiac output (Q -- 100ml/s) = BV * Heart Function

3. Blood volume (BV) = fluid intake * fluid secretion (loss)

4. Heart function (HF) = Heart rate (HR) * Stroke Volume (SV)

5. Pressure gradient (change in BP) / PR = Flow = Q

6. Peripheral resistance = or < metabolic needs and nervous system.

7. Conductance (Q/change in BP) = 1/PR i.e as conductance increases, peripheral resistance decreases or vice-versa.

8. Increase in hematocrit = increase in PR

1. Bloo pressure is down = Stroke volume increases, large venous reservoirs contract to push more blood and peripheral resistance increases.

2. Nervous system = has fast/immediate action during low BP.

3. Kidneys = delayed action 

Name the 4 major factors that influence blood pressure.

1. Age

2. Gender

3. BMI 

4. Diet (salt intake)

1. Increased Nitric oxide

2. Increased Prostacyclin

3. Increased Kinins

4. Increased Atrial natriuetic peptide (decreases blood volume)

5. Decreased neural factors (beta-adrenergics)

1. Decreased blood volume (increased ANP)

2. Decreased heart rate

3. Decreased contractility

1. Increased heart rate

2. Increased contractility

3. Increased blood volume (aldosterone)

1. Increased Catecholamines (sympathetic NS--> epinephrine)

2. Increased Angiotensin II (from liver; needs renin from kidney)

3. Increased thromboxane

4. Increased endothelin

5. Increased neural factor

Increased blood pressure= Norepinephrine binds and stimulates alpha-1 and epinephrine on beta-1 receptor in the smooth muscle (vasoconstriction occurs).

Decreased blood pressure (Vasodilation) =  Norepinephrine binds to alpha-2 receptor and Epinephrine binds and beta-2 receptors on the muscle muscle.

Note: Epinephrine binds the Beta-1 and 2, while Norepinephrine binds alpha-1 and 2

Beta-1 stimulation by epinephrine = increased renin from kidney = increased angiotensin II and aldosterone = increase cardiac output

Sustained systolic pressure greater than 139 mm Hg and diastolic of 89 mm Hg.

Normal = less than 140/90 mmHg

1. Also known as Accelerated hypertension

2. Has to be 200/120 mm Hg sustained for a long time + renal failure + Retinal hemorrhage and Exudate +/- Papilledema.

1. Atherosclerosis

2. Hyaline Arteriolosclerosis - when plasma components leak into the walls of the artery.

3. Hyperplastic arteriolosclerosis - occurs in kidney and is cause of Malignant hypertension.

NADPH oxidase and IL-17

Also note: this occurs when T-cells enters the adventitia of the blood vessel

1. Lifestyle modification and dietary regimen change

2. Vaccines against angiotensin II

3. Renal denervation in those with refractory hypertension

Afferent brings blood in 

Efferent removes the filtered blood

Proximal tubule = highest reabsorption

Collecting duct = lowest reabsorption

Majority of the sodium is reabsorbed at the ___, which is also highly permeable of H2O.

Water is absorbed but not Na+ or urea 

[image]

Main segment of the loop of Henle for Na+ reabsorption.

- No water reabsorption, only Na+

1. Fine control of ultrafiltrate composition

2. Volume control

Direct inhibition of Na+/K/Cl symporter/reabsorption.

Indirect inhibition of Ca2+ and Mg2+ reabsorption

1. Very high increase in urine flow (output)

a. increase in Na/Cl/K/Ca2+/Mg2+ excretion 

b. Increase in uric acid excretion (if used acutely) and decrease in uric acid excretion if used chronically.

2. Reduced blood volume and blood pressure (initially) followed by renin release and SNS activity.

1. Hypertension and Heart failure

2. Acute pulmonary edema

3. Edemas and Ascites (fluid accumulation in peritoneal cavity)

4. Drug overdose (induce diuresis - excessive urin production)

5. Hypercalcemia (in combi with isotonic saline to prevent vol. depletion)

1. Electrolyte imbalance

a. Hypokalemia, Hyponatremia, hypomagnesemia, hypocalcemia and hypochloremic alkalosis

2. Ototoxicity - common with Ethacrynic acid

3. Hyperuricemia and hypoglycemia (rarely precipitating gout or diabetes mellitus)

4. May increase LDL cholesterol & decrease HDL cholesterol levels.

Ethacrynic Acid (Edecrin) = 100% oral biovailable

then 

Bumetanide (Bumex) = Torsemide (Demedex) = at 80%

Least orally bioavailable = Furosemide (Lasix)

Bumetanide (Bumex) = most potent  

Ethacrynic Acid (Edecrin) = least potent

Longest half-life = Torsemide (Demedex)

Shortest half-life = Bumetanide (Bumex) - also the most potent.

1. Indapamide - Lozol

2.Hyrochlorothiazide - Microzide

3. Chlorthalidone - Hygroton

4. Metolozone - Zaroxolyn

1. Moderate increase in urine flow (output)

a. increased Na and Cl excretion

b. Indirect increase in excretion of K+ 

c. Chronic use = decrease excretion of Ca2+ and uric acid

2. Lower blood pressure in result of increase Na+ excretion

1. Hypertension

2. Edema-associated heart failure, cirrhosis of liver and kidney failure.

3. Nephrogenic diabetes insipidus

4. Ca2+ nephrolithiasis (kidney stones) 

5. Osteoporosis

Altered if GFR <35 ml/min

Exception: Metolozome (Zaroxolyln)  &  Indapamide (Lozol)

1. Fluid and electrolyte imbalance

a. decrease in extracellular fluid volume = hypotension

b. Hyponatremia, hypokalemia (arrhythmia risk), hypochloremia (metabolic alkalosis), hypocalcemia and hypomagnesemia. Hyperuricemia (high risk for gout)

2. Reduce glucose tolerance - may unmask latent diabetes (reduced insulin secretion - type 1)

3. Increase risk of sexual potency

4. Increase LDL cholesterol, total cholesterol and triglycerides.

1. Na+ channel inhibitors:

a. Amiloride - Midamor

b. Triamterene - Dyrenium

2. Aldosterone antagonists:

a. Eplerenone - Inspra

b. Spironolactone - Aldactone

Slight increase in urine flow due to"

1. slight excretion of Na+ and Cl

2. decrease excretion of K+

1. Hyperkalemia - since they reduce K+ excretion

2. Nausea, vomitting, diarrhea and headache

3. Triamterene (Dyrenium) can cause reduce glucose tolerance and photosensitivity.

1. Both classes are used to spare K+ from excretion (reduces heart arrhythmia)

2. Aldosterone antagonist used for Heart failure 

3. Spironolactone (Aldactone) is useful in primary and secondary hyperaldosteronism.

4. Spironolactone (Aldactone) is used for hepatic cirrhosis

1. Hyperkalemia

2. Spironolactone can cause gynecomastia, secual impotency, decreased libido.

3. Spironolactone may alter clearance of digitalis glycosides

Which K+-sparing diuretic:

1. has the longest t1/2? Shortest?

2. Which is most orally bioavailable? Least?

3. All of them are equally potent, but which is the least potent?

1. Longest t1/2 = Amiloride (Midamor); shortest t1/2 = Spironolactone (Aldactone)

2. Most oral bioavail = Eplerenone (Inspra); least oral bioavail = Amiloride (Midamor)

3. Least potent = Triamterene (Dyrenium)

Angiotensin I --(NEP)-> Angiotensin 1-7

Angiotensin II --(ACE-2)-> Angiotensin 1-7

It is a peptide made by when NEP converts angiotensin I to Angiotensin 1-7 or when ACE-2 converts Angiotensin II to angiotensin 1-7.

It has opposite effects of angiotensin II.

Uses Mas receptor

1. Short-loop negative feedback: stimulating angiotensin receptors (AT1 or AT2) on juxtaglomerular cells decreases renin release

2. Long-loop negative feedback: 

a. Macula densa pathway = increased filtration causes more Na in the filtrate.

b. Intrarenal baroreceptor pathway: increased blood pressure on afferent arterioles causes decreased renin released.

c. Beta-adrenergic receptors on juxtaglomerular: decreased norepinephrine from sympathetic NS causes decreased activation of Beta receptors and decreased renin.

1. Brain: increases release of vasopressin and regulation of thirst & salt appetite, and increase sympathic NS outflow

2. Heart: stimulate myocardial hypertrophy and collagen synthesis.

3. Kidney: contraction of the efferent and afferent (to lesser decree) arterioles; increase Na reabsorption in proximal tubule; and inhibit renin release from JG cell.

4. Adrenal cortex: aldosterone secretion

5. Adrenal medulla: Epinephrine release

6. Vasculature: vasocontrictio on vascular system; and smooth muscle hypertrophy.

1. Decrease angiotensin II 

2. Indirectly increases Angiotens 1-7 

3. Increase bradykinin levels --> reduction in blood pressure

4. Increase renin activity because negative feedback by angiotensin II is not function.

In other words, ACE inhibitors increase bradykinin (role of dilation of blood vessels) and Angiotensin 1-7 (opposite role of angiotensin I - reduce peripheral resistance)

Overall reduction in systemic blood pressure:

1. Decrease vascular resistance and blood pressure

2. Decrease glomerular filtration rate and/or filtration fraction

3. Increased compliance of large arteries (reduction in systolic pressure)

4. Aldosterone is slightly decreased = less K excretion and less Na reabsorption - increase risk of arrhythmia

5. Cardiac function is usually unchanged

1. Hypertension

2. Left ventricular systolic dysfunction

3. Acute myocardial infarction

4. Prevention of CAD and stroke

5. Chronic renal failure

1. Vasodilation and reduction of peripheral resistance

2. Reduction of aldosterone

3. Inhibits sympathetic activity

4. Increase renin secretion and activity (inhibits feedback inhibition of Angiotensin II on renin)

5. Increase angiotensin level

6. Improves hemodynamic profile in heart and kidney

1.  Azilsartan - Edarbi

2. Candesartan - Atacand

3. Eprosartan - Teveten

4. Irbesartan - Avapro

5. Losartan - Cozaar

6. Olmesartan - Benicar

7. Telmisartan - Micardis

8. Valsartan - Diovan

1. Olmesartan (Benicar)

2. Candesartan (Atacand)

1. Losartan (Cozaar)

2. Valsartan (Diovan)

3. Telmisartan (Micardis)

1. ACE increases renin levels, while ARB increase both renin and Angiotensin II levels.

2. ARB reduces AT1 receptor activities better than ACE inhibitors (duh, ARB inhibit AT1-r directly)

3. ACE inhibitors increases Angiotens 1-7 and bradykinin more than ARBs.

4. In ARBs, the increased Angiotensin II can bind to AT2-r causing opposite effect of AT1 = more reduction in blood pressure.

Intracellular Ca2+ is low during resting

while extracellular Ca2+ is 10,000 fold higher

Dihydropyridines CCB:

Amlodipine (Norvasc)

Clevidipine (Cleviprex)

Felodipine (Plendil)

Isradipine (DynaCirc)

Nisoldipine (Sular)

Nifedipine (Procardia XL, Adalat CC)

Nicardipine (Cardene SR)

Non-dihydropyridines CCB:

Verapamil (Calan, Covera, Isoptin, Verelan)

Diltiazem (Cardiaxem, Cartia, Dilacor, Tiazac)

Dihydropyridine CCBs access the close-channel state and stabilizes it, and act mainly on arterial muscle cells by causing vasodilation.

Non-hydropyridine CCBs access the open-state Ca2+ and inactivates it, by slowing down recovery of Ca2+. Has more profound effect on heart,

Non-dihydropyridines = heart = open channels

hydropyridines = arterial muscle = closed channels

Give the effects (increase, decrease or no effect) of dihyro-and non-dihyropyridines on:

a. Coronary vessel tone

b. coronary blood flow

c. peripheral vasodilation

d. heart rate

e. heart contractility

f. AV conduction

a. Coronary vessel tone  = dihydro (decrease more),

non-dihydro (decreases but less)

b. coronary blood flow = dihydro (increases more),

non-dihydro (increases but less)

c. peripheral vasodilation = dihydro (increases more),

non-dihydro (increases less)

d. heart rate = dihydro (decrease less),

non-dihydro (decreases more)

e. heart contractility = dihydro (slight increase) ,

non-dihydro (slight decreases )

f. AV conduction = dihydro (no effect),

non-dihydro (decreases)

1. Increase contraction of smooth muscles and Vasodilation of arteries leading to:

a. decreased peripheral resistance

b. decreased coronary vascular resistance

c. Increased blood flow

d. Decreased cardiac output and decreased heart rate

2. Contraction of cardiac myocytes:

a. decreased inotropic effects and decreased oxygen demand

3. Regulates Pacemaker rate in SA node and conduction velocity in AV node - decrease chronotropic effects and decreased oxygen demand

1. Hypertension

2. Migraines

3. Angina Pectoris - chest pains due to ischemia of heart vessels

4. Superventricular arrhythmia

Main: Cardiodepression

Moderate: hypotension, peripheral edema, AV node blockage, increase liver enzymes

Mild: constipation (mainly verapamil), headache, flushing of face.

Caution: moderate CYP3A4 inhibition

1. Doxazosin (Cadura) - longest t.5

2. Terazosin (Hytrin)

3. Prazosin (Minipress) - shortest t.5

1. Decreased peripheral resistance

2. decreased venous return (decreased cardiac preload)

3. Suppression of sympathetic outflow

4. Decreases LDL and trilycerides, and increases HDL

1. Clonidine (Catapress)

2. Methyldopa (Aldomet)

3. Guanfacine (Tenex)
4. Guanebenz (Wytensin)

- sedation & dry mouth (>50% of patients, maybe a reason for discontinuation)

- sexual dysfunction (because of hyperprolactinemia)

- bradycardia

- withdrawal reactions upon abrupt discontinuation

1. 100% bioavailability

2. 50% eliminated via kidney as urine (so watch if renal disease/failure)

3. Half life of 12 hours

Aldomet (Methyldopa) is

1. a prodrug

2. Recommended for preemclampsia (HTN in pregnant women) 

3. Can cause hemolytic anemia and hepatoxicity (all similar to Clonidine, except clonidine can exacerbate renal problems)

4. Effect is delayed for 6 hours, so do not give if emergency.

1. Clonidine (Catapress)

2. Methyldopa (Aldomet)

3. Guafacine (Tenex)

4. Guanebenz (Wytensin)

Riserpine - a sympatholytic

1. Increase retention of Na+ & water

2. Sedation & inability to concentrate

3. Depression & suicidal thoughts (~ dose related)

  caution: drug should be discontinued at the first sign of depression   (may last several months after discontinuation!)

Hydralazine (Apresoline)

Minoxidil  (Loniten)

direct vasodilation (mechanism is not clear, some connection with intracellular Ca2+ levels)

1. Effective decrease in peripheral resistance (with powerful stimulation of SNS → is usually combined with other drugs!)

 2. Minimal effect on veins (vsa-blockers) → no postural (orthostatic) hypotension

1. Drug-induced lupus syndrome (immune reactions)

2. Increase retention of Na+ & water

3. Headache, flushing, hypotension, tachycardia, angina pectoris

4. caution: aggravation of myocardial ischemia

activates ATP-depedent K+ channels in smooth muscles leading to efflux of K+ from cells, which causes

hyperpolarization resulting in the relaxation of smooth

muscle.

Loniten (Minoxidil)

1. Hypertrichosis (hairy-ness)

2. Angina pectoris, myocardial ishemia and tachycardia

3. Na and water retension (like Hydralazine (Apresoline) and Riserpine)

Norepinephrine (NE): is synthesized in ___nerve terminals & CNS as a ____

Epinephrine (Epi): is synthesized in the ___ by ___as a ___ and in CNS as a _____(adrenergic neurons in the brainstem)

adrenal medulla; Chromaffin cells; hormone

CNS as a neurotransmitter 

alpha-2 receptor  = decreased Norepinephrine

Beta-2 receptor = increase norepinephrine

Give facts about these adrenoreceptors

1. alpha-1

2. alpha-2

3. beta-1

4. beta-2

5. beta-3

1. alpha-1 = post synaptic

2. alpha-2 = presynaptic

3. beta-1 = found in juxtaglomerular cells (kidney) and myocardium

4. beta-2 = can be post or pre-synaptic, found in smooth muscles 

5. beta-3 = adipose tissue

1. Epinephrine - Beta-1 = Beta-2 > alpha-1 & 2

2. Norepinephrine -  alpha-1 & 2 > beta-1 >> beta-2

G protein-coupled receptors:

  a1is coupled to Gq→ Ýinositoltriphosphate, diacylglycerol & iCa2+

  a2is coupled to Gi → ßadenylylcyclase → ßcAMP

  all b subtypes are coupled to Gs→ Ýadenylylcyclase→ ÝcAMP

Give main effects seen when epinephrine or norepinephrine binds to these G protein-coupled receptors.

1.alpha-1

2. beta-1

3. beta-2

4. beta-3

alpha-1 = vasoconstriction in blood vessels and increased Na reabsorption in kidney

beta-1 = increased chrono-, domo- and inotropic effects in heart and renin release JG cells of kidney

beta 2 - vasodilation of arterioles, relaxation and increase intraocular pressure in eye

Beta-3 = lipolysis in adipose tissue

Give info about selectivity of these beta-blocker:

1st generation

2nd gen

3rd gen

1st gen: non-selective Beta-1 and beta-2 antagonist

2nd gen: selective beta-1 antagonists

3rd gen: non-selective and selective beta antagonists

short term effects of non-selective (1st gen) = decreased cardiac out put leading to decreased  BP, which causes reflector sympathetic activation causing increased NE/Epi release. NE binds to alpha receptor causing a temporary increased peripheral resistance (Beta-2 are blocked = no vasodilation)

Long term of non-selective (1st gen) = peripheral resistance returns to normal level and cardiac output is lowered further.

1. Labile diabetics - hypoglycemic reaction

2. Asthma and COPD patients - causes bronchoconstriction

1. Glaucoma

2. Migraines prophylaxis

3. angina pectoris

4. hypertension

5. cardiac arrhythmias

6. Myocardial infarction

  blockade of βadrenoceptors& prevention

of NE (Epi)-mediated effects

1. heart failure

2. arrhythmias 

3. bronchospasm - nonselectives (1st gen and 3rd gens) = could worsen asthma and COPD

4. Hypertriglyceridemia

5. Sexual dysfunction

6. Sedation, sleep issues and depression

7. Worsen peripheral vascular disease

8. Can cause hypoglycemia and can mask hypoglycemia -induced tachycardia

a)    24-hr monitoring documents BP at frequent intervals throughout day

b)    Helpful in drug resistance, hypotensive symptoms on Tx, episodic HTN, and autonomic dysfunction.

c)     Indicated for “white coat” HTN

d)    ≥130/85 abnormal

Define these terms:

1. Essential/primary HTN

2. Secondary HTN

3. White coat HTN

4. Pseudo-hypertension

5. Isolated systolic HTN 

6. Resistant HTN 

7. Hypertensive HTN

8. HTN Urgency

1. Essential/primary HTN = No known etiology. occurs due to older age

2. Secondary HTN = due to underlying disease (Cushings and hyperaldosteronism), Drugs (NSAIDS and birth controls),  alpha-1 agonist (decongestants) and B1-agonists.

3. White coat HTN: false increase in BP in clinical settings

4. Pseudo-hypertension: falsely elevated BP due to brachial artery calcification - use Osler maneuver to test

5. Isolated systolic HTN = common in elderly. decrease elasticity and compliance of arteries.

6. Resistant HTN  = blood pressure fails to be controlled after patient is on at least 3 drugs

7. Hypertensive Emergency= BP is greater than stage 2 (>180/120) with organ damage. Treat immediately in minutes to hours with IV drugs. Goal is to reduce diastolic to <100.

8. HTN Urgency = BP is greater than stage 2 (>180/120) but with NO organ damage.Treat in hours to days with oral agents. Goal is to reduce to stage 1 levels.

Give the classifications levels for hypertension: 

Normal

Pre-HTN

Stage I

Stage II

Normal = <120/80

Pre-HTN = 121-139/80-90

Stage I = 140-159/90-99

Stage II = > 160/100

Microalbuminuria = 30-300 mg/daily from spot urine

Scr = >1.5 for men and >1.4 for women

GFR = <60ml/min/m2

Goal for diabetes + chronic kidney disease :

JNC 7 : 130/80

ADA guideline: 130/80 (but if just diabetes, then 140/80)

What is the SBP reduction range for:

1. Weight reduction

2. DASH diet 

3. Physical activity

4. Restriction of dietary intake

5. Moderate alcohol consumption

1. Weight reduction = 5-20mmHg

2. DASH diet = 8-14 mmHg

3. Physical activity = 4-9mmHg

4. Restriction of dietary Na = 2-8mmHg

5. Moderate alcohol consumption = 2-4 mmHg

<140/90; 

treat with any anti-hypertensive drug or combination if Stage II

<130/80

Treat with ACEI or ARB or CCB or Thiazide diuretic or combine if Stage II

<130/80

Treat with beta-blocker + ACEI or ARB

If beta-blocker is contraindicated, then use non-DHP such as Verapamil (80-120mg) or Diltiazem (30-120mg), or DHP CCB. Give thiazide for BP control

<130/80;

Beta-blocker (if hemodynamically stable) + ACEI or ARB

If beta-blocker is contraindicated, then substitute with

non-DHP or DHP CCB. Give thiazide for BP control

130/80;

Beta-blockers (if hemodynamically stable) + ACEI or ARB; give non-DHP or DGP CCBs if beta-blockers are contraindicated. Add thiazide for BP control

<120/80;

Beta-blocker + Aldosterone antagonist + ACEI or ARB + thiazide or loop diuretic.

Add Hydralazine/Isosorbide dinitrate for blacks

If any contraindication: add Verapmail or Diltiazem, Clonidine (alpha-2 agonist), Moxonidine, and alpha-1 blockers.

Clinical pearls:

1. Aim for ___ goal for most patients.

2. Consider ___ goal for DM and CKD patients

3. T/F: data supports AHA recommendation

4. T/F: Always push for normal BP with medication.

1. Most patients = 140/90

2. DM or CKD = 130/80mmHg

3. False: AHA sucks

4. False: never push for normal with meds due to side effects

1. Stage II or >20mmHg above goal or >10mmHg DBP

2. Thiazide is included as the addition therapy

Beta-blockers

  alpha blockers

Central alpha-2 agonists

vasodilators

Adrenergic inhibitors

direct renin inhibitor (Aliskeren)

Chlorthalidone (Hygroton)

Amlodipine (Norvasc)

Lisinopril (Prinivil, Zestril)

Doxazosin

1.       No difference in primary outcome.

2.        Clorthalidone decreased secondary compared to lisinopril

3.       Chlorthalidone (diuretics) were cheaper and were of equal benefit

4. Most patients needed more than one agent.

Give the recommended doses for:

1st gen thiazides

2nd gen thiazides`

1st gen: Chlorthalidone and HCTZ = 12.5-25mg daily

2nd gen: Indapamide(1.25-2.5mg daily) and Metolazone 2.5-10 mg daily

a. Diuretic effects of thiazides decrease with time.

b.    Takes 2 to 3 weeks to see maximum blood pressure drop

c.     Chlorthalidone is about 1.5X as potents as HCTZ and has longer t1/2.

d. As you increase dose of thiazide, you increase electrolyte problems; typically 

Amiloride/HCTZ

Triamterene/HCTZ

Spironolactone/HCTZ

Amiloride/HCTZ = Moduretic

Triamterene/HCTZ = Maxide or Dyazide

Spironolactone/HCTZ = Aldactazide

ONTARGET - looked at Ramipril (Altace) and Telimisartan (Micardis) in patients with vascular disease or diabetes.

Found no difference in death from stroke, MI, hospitalization for HR between ACEI and ARBs

Conclusion: do not combine ACEI and ARBs

ALTITUDE = compared Aliskeren to ACEI and ARB

Stopped prematurely due to increase adverse effects. 

Conclusion: do not combine ACEI and ARBs

1. Diuretics - thiazide

2. ARBs

3. CCB - only without any compelling indications

4. ACEI - only if without compelling indications (but is 2nd line per JNC-7)

5. Beta-blockers

Dihydropyridines CCB

Direct vasodilators - reflex tachycardia only

1. Myocardial infarction

2. Angina

3. Heart failure

Alpha-1 blockers

 Reserpine

Direct arterial vasidilators: Hydralazine and Minoxidil

Diuretic + RAAS inhibitors

or 

CCB + RAAS Inhibitor (Aliskeren, ACEI, aldosterone antagonists)

Diuretic + Beta-blockers

or 

Beta-blocker + DHP CCB

or

DHP + non-DHP CCB

Diuretics + DHP CCB

or

Beta blocker + ACEI/ARB - combination only used in MI or CAD

1. Methyldopa

2. Labetolol - alpha/beta blocker

3. Beta-blockers

4. CCB
5. Diuretics - use if all else fails 

1. ACEI

2. ARBs

3. Aliskeren

CBC

Urine analysis

CMP

EKG

cardiac enzymes

Imaging

echocardiogram

1. Use IV meds to lower SBP by 20 (25%) in 1 hour and diastolic by 10-15% over 30 mins to 1 hour.

2. Stabilize blood pressure to <160/110 over 2-6 hrs.

3. Assess volume status and gently hydrate with NS to restore fluid/Na.

4. Continuous cardiac monitoring, assess volume and 

Give 2 facts about these treatment regimen for HTN emergencies.

1. Nitroprusside

2. Nitroglycerin

3. Labetalol (Normodyne or Trandate)

4. Enalaprilat

5. Esmolol

6. Fenoldapam

7. Hydralazine

8. Phentolamine

9. Nicardipine

10. Clevidipine

1. Nitroprusside - arterial and venous vasodilator. For emergency HTN + acute pulmonary edema. Contraindication: MI and renal impairment.

2. Nitroglycerin - more venous dilation than arterial. Adjunct use (not 1st line) for coronary ischemia or acute pulmonary edema.

3. Labetalol (Normodyne or Trandate) - nonselective a-1 and beta blocker. Contraindicated in COPD, Heart failure and heart block.

4. Enalaprilat - For heart failure. CI: MI, eclampsia, bilateral RAS.

5. Esmolol - CI: if already on B-blocker, bradycardiac, or decompensated heart failure.

6. Fenoldapam - Dopamine agonist, conatins sulfite. CI: angina, glaucoma, and high intracranial pressure.

7. Hydralazine - vasodilator (pre-and afterload reducer) for Eclampsia. CI: use as last option due to prolonged effects and unpredictibility.

8. Phentolamine - alpha blocker for sympathetic crisis or catecholamine toxicity, cocaine and amphetamine intoxication , clonidine withdrawal, MOA inhibitor interactions.

9. Nicardipine - Dihydropyridine CCB. CI: Heart failure and coronary ischemia.

10. Clevidipine - short-acting DHP CCB. For all hypertensive emergencies.

Give the monitoring parameter for these classes:

1. Diuretics

2. Aldosterone antagonists

3. Beta-blockers

4. ACEI/ARBS/Renin inhibitors

5. CCBs

1. Diuretics = BP, BUN/Scr, electrolytes, uric acid

2. Aldosterone/ACEI/ARBs/Renin inhibitors = BP/BUN/SCr/K

3. Beta-blockers/CCB = BP and HR

1. Synergistic (RAAS inhibitors + diuretic OR RAAS inhibitor + CCB) or Additive ( Beta blocker + diuretic OR beta-blocker + DHP CCB OR nonDHP + DHP)

2. Add loop diuretics (Bumex or Lasix)

3. Add Aldactone

4. Combine alpha-beta blockers

5. Central-acting agents (alpha-2 agonists)