Hypertension

Question 1

essential hypertension

Answer 1

-Systolic BP > 140 mmHg or diastolic BP > 90mmHg with no underlying or specific identifiable cause
-1. increasing age
-2. men
-3. African-Americans- LOW RAAS -> use CCB
-genetics
-asymptomatic
-men(55)>females(65)

Question 2

Secondary Hypertension

Answer 2

-HTN caused by an underlying or primary disease
-1. Renal disease
-2. Endocrine (thyroid, pheochromocytoma, hyperaldosteronism, Cushing’s syndrome)
-3. Sleep Apnea
-4. Drug-Induced HTN: NSAIDs, COX-2 inhibitors, OCs, steroids, sympathomimetics; antidepressants, erythropoietin; cyclosporine; tacrolimus; licorice, herbal preps, Illicit drugs (cocaine)
-5. Social factors: Increased sodium intake, alcohol

Question 3

BP categories

Answer 3

Question 4

physiological regulation of BP

Answer 4

-bp regulated by SNS, RAAS system & kidneys through influence on CO and peripheral vascular resistance (PVR)
-physiologic control of BP and MOAs of antihypertensives (BP=COxPVR)
-1. CO- volume, HR, contractility, RAAS
-2. peripheral vascular resistance- endothelin, vasopressor, angiotensin 2
-muscle tone of vasculature prostaglandins, serotonin, endothelin
-3. baroreceptor reflex

Question 5

baroreceptor reflex

Answer 5

-ACE- angiotensin 1
-ARB- angiotensin 2

Question 6

non-pharmacological tx

Answer 6

-“Lifestyle modifications” initiated in pts w/ prehypertension and stage 1 HTN
-A. weight reduction, diet – low Na, rich in potassium and calcium, exercise and moderation of alcohol intake.
-B. Refer to 2017 AHA/ACC Lifestyle Management Guidelines

Question 7

initiating drug therapy

Answer 7

-1. Start immediately if diastolic BP >90mmHg
-2. If BP still > 150/90mmHg after 3-6 months of lifestyle modifications (or if BP > 140/90mmHg in pts w/ DM or chronic kidney disease)
-3. Thiazide diuretics usually 1st line tx (except if another class is specifically indicated or if absolute contraindication to thiazides, ie pts with CKD) -> Other 1st line agents include beta blockers, ACE inhibitors/ARBs and CCBs
-4. See tx algorithm below from JNC 8 report – guidelines, tx must be individualized based on pt factors

Question 8

BP management chart

Answer 8

-dont memorize charts
-important to know when to start tx
-130/80 is goal

Question 9

diuretics

Answer 9

-hydrochlorothiazide -> no real change from 25 to 50 dose -> better off switching to chlorthalidone

Question 10

diuretics: in general

Answer 10

-All types of diuretics cause an increase in renal sodium excretion -> “natriuresis”
-blocks reabsorption of water and enhances its excretion -> decrease blood volume -> decrease stroke volume -> decrease CO -> decrease BP
-cell membrane alteration: decrease Na + -> decrease Na+ influx into smooth muscle cell -> decrease contractility -> decrease PVR -? decrease BP (primarily for thiazides only)

-Indications: Also used to treat edema associated w/ CHF and renal disease

Question 11

thiazide diuretics (pregnancy B/D)

Answer 11

-1st line
-association in response b/w thiazide diuretics and CCBs – mainly due to similar effects on cell membrane alteration
-MOA: blocks reabsorption of NaCl at distal convoluted tubule (decrease Ca excretion in urine) -> cell-membrane alteration
-Indications: Good as single drug therapy in mild HTN; tx of edema in CHF and nephrotic syndrome
-Precautions: ineffective in severe renal disease
-Contraindications: hypreuricemia, gout, sulfa allergy (sulfonamide-like structure) -> DM is not contraindicated but monitor glucose
-ADRs:
-Electrolyte abnormalities (hyponatremia, hypokalemia, hypomagnesaemia)
-Metabolic effects: hyperglycemia* (early on), hyperuricemia, increase cholesterol and triglycerides
-Sexual dysfunction
-DDIs: diuretic effect may be decreased by NSAIDS, increase lithium levels
-JNC-8 Recommendations:
-1st line in most cases (except if another class is indicated or if absolute contraindication to thiazides)
-Increased efficacy as monotherapy over ACE-Is/ARBs in African-Americans
-Useful for ISH in elderly
-Potential favorable effects in osteoporosis
-DO NOT use in pts w/ gout, hyperuricemia or Hx of severe hyponatremia
-ex. hydrochlorothiazide (HCTZ), chlorthalidone, chlorthiazide, indapamide, metolazone

Question 12

loop diuretics (pregnancy cat C)

Answer 12

-2nd line
-MOA: blocks reabsorption of Na+ in ascending loop of Henle
-More powerful natriuresis than other diuretics
-Indications: edema associated with CHF and hepatic or renal disease; HTN
-Precautions: Causes profound diuresis -> Monitor fluid status, renal function and electrolyte status closely -> Adjust doses to avoid dehydration
-Contraindications: sulfa allergy (sulfonamide-like structure)

-ADRs:
-Electrolyte abnormalities: hypokalemia, hypocalcemia,
-Renal effects: increase BUN/Cr, oliguria, azotemia (2○ to diuretic effect – adjust dose downward)
-Metabolic effects: hyperglycemia, hyperuricemia
-GI effects: pancreatitis, hepatic damage
-Other: sexual dysfunction, ototoxicity (vertigo, ear pain)**

-DDI – NSAIDS, increase lithium levels (as with thiazides), AMGs
-JNC-8 recommendations:
-Not first line – Final option
-Examples: Furosemide (Lasix)*, Torsemide (Demadex), Bumetanide (Bumex), Ethacrynic Acid (Edecrin – used if severe sulfa allergy)

Question 13

potassium sparing diuretics (pregnancy B/D)

Answer 13

-2nd line
-MOA: block reabsorption of Na+ via Na+ channels in collecting duct but reduce K+ secretion into urine
-Indications: edema due to CHF; HTN
-Precautions: can cause hyperkalemia esp in combination w/ ACE inhibitors and K+ supplements
-Contraindications: hyperkalemia (K+ > 5 mEq/L prior to treatment)
-ADRs: hyponatremia, increase BUN/Cr, jaundice, H/A, N,V, D.
-DDIs: hyperkalemia w/ ACE-I and K+ supplements, NSAIDs, Lithium
-JNC-8 recommendations- Not first line – Final option

-Examples:
-amiloride (Midamor), triamterene (Dyrenium)
-spironolactone* (Aldactone) and eplerenone (Inspra):
-1.Dual MOA – K+ sparing diuretic & aldosterone antagonist
-2. Uses: HTN, CHF, primary hyperaldosteronism, polycystic ovary disease and hirsuitism;
-3. Unique ADRs - gynecomastica, ED, amenorrhea*

Question 14

angiotensin converting enzyme inhibitors (ACE inhibitors)

Answer 14

-All are pregnancy category C in 1st trimester, but cat. D in 2-3rd trimester -> However labeled as CONTRAINDICTED in pregnancy
-association in response b/w ACE inhibitors and beta-blockers -> mainly due to similar effects on RAAS
-Indications: HTN; CHF, post MI
-Precautions: Can cause renal failure in pts w/ bilateral renal artery stenosis
-Contraindications: angioedema, bilateral renal artery stenosis*, pregnancy
-ADRs - !nonproductive cough (10-20%), rash, angioedema, hyperkalemia, decreased renal function!, dizziness, abnormal taste!!
-Little or NO sexual dysfunction
-DDI – antihypertensive effects increased with thiazide and loop diuretics, hyperkalemia w/ K+ sparing diuretics, lithium (increase Li levels), NSAIDS (decrease effect of ACE-I)
-JNC-8 recommendations:
-Compelling indications: DM, chronic kidney disease (excluding bilateral renal artery stenosis), heart failure and post-MI
-Neutral effects on lipid profile
-Neutral effect in bronchospastic disease
-CI in pregnancy, bilateral renal artery stenosis, angioedema
-ex: Enalapril (Vasotec), Quinapril (Accupril), Benazapril (Lotensin), All drugs end in “PRIL”

Question 15

angiotensin converting enzyme inhibitors (ACE inhibitor): MOA

Answer 15

-MOA – acts at the renin-angiotensin-aldosterone axis to block the conversion of Angiotensin I to Angiotensin II (potent vasoconstrictor), also blocks degradation of bradykinin (potent vasodilator), thereby reducing PVR -> decrease BP

Question 16

angiotensin receptor blockers (ARB)

Answer 16

-MOA
-block the binding of angiotensin II to its receptors in vascular smooth muscle -> vasodilation -> decrease PVR -> decrease BP
-blocks the binding of angiotensin II to its receptors in the adrenal cortex -> decrease aldosterone secretion -> decrease blood volume -> decrease stroke volume -> decrease CO -> decrease BP
-Same indications, precautions, contraindications, JNC-8 recommendations, and pregnancy categories as ACE-Inhibitors
-ADRs: same as ACE-I, but less effect on kidney and less incidence of cough and angioedema, BUT increased incidence of URI
-ex. Losartan (Cozaar); Valsartan (Diovan). All drugs end in “SARTAN”

Question 17

calcium channel blockers (pregnancy category C)

Answer 17

-association in response b/w thiazide diuretics and CCBs -> due to similar effects on cell membrane alteration
-MOA- blocks Ca ion channels in plasma membrane of smooth muscle -> relax vascular smooth muscle -> vasodilation -> decrease PVR -> decrease BP
-verapamil and diltiazem exert effects in myocardium, reducing HR and slowing nodal conduction -> Useful for arrhythmias
-Indications: HTN, angina, specific agents for arrhythmias; migraine, Raynaud’s disease
-Precautions: peripheral edema and reflex tachycardia are common –> slowly titrate dose; concurrent use of verapamil and diltiazem w/ beta-blockers;
-Contraindications: Verapamil and Diltiazem -> hypotension (SBP<90), cardiogenic shock, sick sinus syndrome, 2nd or 3rd degree heart block
-ADRs – !constipation, bradycardia, flushing!, fatigue, headache, dizziness, peripheral edema, !reflex tachycardia! (compensation if too much vasodilation), !CHF, heart block and hypotension! (w/ diltiazem and verapamil)
-Nifedipine – short acting form has been associated w/ serious adverse events – (syncope, heart block, sinus arrest, acute MI, EKG changes and fetal distress) when used in Tx of hypertensive emergencies
-DDI – several, esp. w/ verapamil and diltiazem – digoxin, amiodarone, azoles, etc
-JNC-8 recommendations:
-Preferred in: atrial tachyarrhythmias (non-DHP type); angina, Raynaud’s syndrome
-Avoid non-DHP type in second and third degree heart block
-Examples:
-Dihydropyridine class (DHP): amlodipine; felodipine, israpidine, nicardipine, nisoldipine -> All end in “PINE” – this sub-class have very little effect on the cardiac tissue
-Non-dihydropyridines (non-DHP): diltiazem (Cardizem); verapamil (Calan)

Question 18

second line anti HTN: beta blocker

Answer 18

-Pregnancy Category C -> however category D in 2nd and 3rd trimester based on analysis
-association in response b/w ACE inhibitors and beta-blockers -> due to similar effects on RAAS
-Indications: HTN, angina, post MI, specific agents for arrhythmias, migraine, glaucoma, CHF (specifically carvedilol and metoprolol succinate XL)
-Precautions: Avoid abrupt withdrawal; concurrent use w/ verapamil and diltiazem; bronchospastic disease, DM, PVD; Use beta1 specific agents (cardioselective) in bronchospastic disease and DM
-Contraindications: sinus bradycardia, greater than 1st degree heart block, uncompensated cardiac failure, cardiogenic shock, sick-sinus syndrome, severe peripheral arterial disease, Asthma with active bronchospasm
-ADRs – bradycardia, CHF, hypotension, bronchoconstriction, sexual dysfunction, fatigue, dizziness, cold extremities (reflex peripheral vasoconstriction), hypercholesterolemia, mask Sx of hypoglycemia (tachycardia & nervousness), CNS side effects like confusion, nightmares (w/ lipid soluble BB)
-DDI – digoxin & BB (increas bradycardia), NSAIDS (decrease hypotensive effect of BB)
-JNC-8 Recommendations:
-Not first line – Final options
-Compelling indication: post-MI
-Preferred in: angina/ischemic heart disease; atrial tachyarrhythmias; essential tremor; heart failure (specific agents listed above); migraine (propranolol); thyrotoxicosis;
-Avoid in second or third degree heart block
-Avoid non-selective agents in bronchospastic disease

Question 19

beta blockers MOA

Answer 19

-blocks beta receptors in heart and other tissues -> decrease HR and contractility -> decrease CO -> decrease BP
-Inhibits renin secretion from renal juxtaglomerular cells -> decrease formation of angiotensin II -> decrease aldosterone secretion -> decrease blood volume -> decrease stroke volume -> decrease CO -> decrease blood pressure
-Reduce sympathetic outflow from CNS
-Some BBs have Intrinsic sympathomimetic activity (ISA) – weak agonist activity on beta receptors (smaller reduction in heart rate), less ADR on lipid profile

Question 20

beta blockers examples

Answer 20

-All drugs end in ”OLOL, ILOL, ALOL”
-Selected BBs with unique properties:
-Nonselective: Propranolol, nadolol , timolol
-Cardioselective (B1 specific) – atenolol, metoprolol, betaxolol, bisoprolol, nebivolol
-BBs with ISA activity: Advantage: causing less bradycardia than other BBS -> ex are acebutolol, penbutolol, pindolol,
-Carvedilol (Coreg) – alpha/beta blocker – mostly used for CHF
-Labetalol (Trandate) - alpha/beta blocker – can be used in pregnancy*
-Nebivolol (Bystolic) – Newest cardioselective beta blocker with additional vasodilating properties b/c it stimulates nitric oxide

Question 21

alpha 1 blockers

Answer 21

-block VC of peripheral vascular smooth muscle, -> vasodilation -> decrease PVR -> decrease BP
-May cause some activation of SNS -> increase HR and contractility
-activate renin system and may cause fluid retention so often combined with diuretics
-Indications: HTN, BPH
-Precautions: Causes significant orthostatic hypotension and syncope (mostly after 1st dose and especially with diuretics) - so give HS; concurrent use with PDE-5 inhibitors
-Contraindications: Some products labeled as CI with PDE-5 inhibitors
-ADRs - orthostatic hypotension, sexual dysfunction, reflex tachycardia, dizziness, N, V, D, headache, drowsiness, epistaxis, dry mouth, nasal congestion, edema
-JNC – 8 recommendations:
-Preferred in BPH
-May have positive effects on lipids (decrease LDL, increase HDL)
-Ex: doxazosin (Cardura); terazosin (Hytrin), prazosin (Minipress). All end in “AZOSIN”

Question 22

beta blockers 3 main jobs

Answer 22

-ionotropic- contraction
-chromotropic- rate
-dromotropic- speed of electrical signal

Question 23

centrally acting agents (alpha 2)

Answer 23

-MOA – reduce SNS outflow from brainstem to the heart, blood vessels and other tissues -> decrease PVR -> decrease BP
-HR and CO are either reduced or remain unchanged
-Indications: In general, reserved for refractory HTN after other agents fail
-Precautions: AVOID rapid withdrawal – must taper off slowly to avoid rebound HTN; caution in elderly; Tricyclic antidepressants can block the effects of centrally acting drugs, avoid concurrent use; CNS depression
-Contraindications: Vary amongst agents
-ADRs – bradycardia, heart block, impotence, dry mouth, sedation, depression and other CNS side effects b/c centrally acting

Question 24

centrally acting agents: examples

Answer 24

-Clonidine (Catapres) (C), PO, transdermal patch.
-MOA – alpha 2 agonist. Also binds to imidazoline receptor (research to dvp drugs which bind specifically to these receptors and avoid the other CNS effects)
-Lots of non-FDA uses: heroin and nicotine withdrawal; sever pain; ADHD
-Patch form may contain metal – remove prior to MRI

-Methyldopa (Aldomet) (B)
-JNC-8: Preferred antihypertensive for pregnancy.
-Unique MOA in that it interferes with dopamine’s conversion to Norepinephrine. Instead it is converted to methylnorepinephrine (20 X less active than NE).
-Has immunologic side effects and may cause Coomb’s positive hemolytic anemia

-Guanethidine and reserpine – neuronal blockers -> RARELY used anymore

Question 25

direct vasodilators

Answer 25

-MOA -directly dilates arteriolar smooth muscle
-Indications: In general, reserved for refractory HTN after other agents fail
-Precautions/Contraindications: see individual agents below
-ADRs - reflex tachycardia, angina, myocardial ischemia, nausea, flushing, edema
-Ex:
-1. hydralazine (Apresoline)
-Other indications: HTN secondary to eclampsia and pre-eclampsia, CHF, and primary pulmonary HTN
-JNC-8: Preferred agent in pregnancy
-Unique ADR: lupus-like syndrome*
-2. minoxidil (Loniten) (Rogaine – topical for baldness*)
-3. sodium nitroprusside (Nipride) hypertensive crisis -> cyanide anecdote kit MUST be present when administering
-4. diazoxide (Hyperstat) hypertensive crisis

Question 26

direct renin inhibitors

Answer 26

-MOA – inhibits renin-angiotensin-aldosterone system earlier in cascade that ACE inhibitors or ARBs
-Indications –approved for HTN, but will be studied for heart failure and nephropathy as well
-Same pregnancy Category as ACE-Is and ARBs
-ADRs – diarrhea, cough and angioedema

Question 27

combination products

Answer 27

-classes with major diff pharm effects are combined for greatest synergistic effect possible
-Ex:
-1. Ace Inhibitors + CCBs (AC combo) or diuretic (AD combo):
-Benazepril and amlodipine (Lotrel)
-Benazepril and HCTZ (Lotensin HCT)

-2. Beta blockers and diuretics (BD combo):
-Bisoprolol and HCTZ (Ziac)

Question 28

pregnant pt with HTN

Answer 28

-methyldopa
-labetalol *

Question 29

goals of tx

Answer 29

-Reduce Target Organ Damage
1. Cardiac: LVH, angina, MI, HF
2. Cerebrovascular: stroke, TIA
3. Peripheral vascular: absence of 1 or more major pulses in the extremities, w/ or w/o intermittent claudication; aneurysm
4. Renal: Serum creatinine > 1.5 mg/dl; proteinuria; microalbuminuria
5. Retinopathy: Hemorrhage or exudates, with or without papilledema

-Reduction of blood pressure (Target or Goal BP ≠ BP Stage)

Question 30

choice of drug

Answer 30

-Consider concomitant diseases:
1. Recommendations:
-Compelling indications
-Concomitant drug benefit
-ADRs on other disease states

-Consider Pathophysiology and MOA
1. drug classes w/ similar response
2. Pathophysiology based on demographics:
-African-American: low RAAS; high Na/H20 retention - thiazides/CCBs
-Whites: high RAAS; high SNS output – BBs/ACE-Is/ARBs
-Elderly: ISH (isolated systolci hypertension)– diuretics
-Pregnancy: Chronic HTN vs. eclampsia vs. preeclampsia
-Men w/ BPH: alpha 1 blockers

-ADRs

-Cost of Therapy

Question 31

dosing

Answer 31

-Initial doses: start at lowest dose
-Titration: Increase after several weeks of therapy
-Assessment of blood pressure control
-Is patient at goal:
-Poor response:

Question 32

hypertensive crisis, emergency, urgency

Answer 32

-Hypertensive crisis: SBP > 180mmHg / or DBP > 120 mmHg

-Hypertensive emergency: Severe increase in BP with evidence of target organ damage
-Treatment should be over minutes to hours
-Treat inpatient with IV meds*
-GOAL: Reduce pressure by < 25% within first hour (less for HTN associated w/ stroke)

-Hypertensive urgency: Severe increase in BP without evidence of target organ damage.
-Tx should be over several hours to days
-May be treated as an outpatient with follow-up with PO meds*
-GOAL: Reduce DBP < 100 over 24-48 hours

Question 33

IV therapeutic options for hypertensive emergency

Answer 33

-1. Beta-blockers: (Esmolol and Labetalol)
-2. Nitrovasodilators [Sodium Nitroprusside (SNP) and Nitroglycerin (NTG)]
-NTG preferred if AMI or HF -> NTG: headache; hypotension, reflex tachycardia; tolerance
-SNP preferred if heart failure with increased SVR (peripheral vascular resistance) -> SNP contains 44% cyanide. Need good kidney and liver fn for removal. Need access to cyanide antidote kit in case of overdose

-3. Vasodilators (Hydralazine)
-4. dopamine receptor agonist (Fenoldopam)- Good choice in pts w/ renal dysfunction
-5. CCBs (Nicardipine) and Clevidipine
-Nicardipine has strong cerebral vasodilation so good choice in hypertensive encephalopathy and stroke
-Clevidipine: Lipid emulsion. CI in soybean, soy or egg allergy. Ultra-short acting. Good choice perioperatively (CABG).
-6. ACE inhibitor - Enalaprilat -> Good choice in hypertensive crisis associated w/ HF

Question 34

questions

Answer 34

-a. dilitiazem + b. HCTZ
-d.
-ACE
-C OR D OR C+D
-E