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581 - Pharmacology I > Exam 7 - Antihypertensives & Renal Pharm > Flashcards

Exam 7 - Antihypertensives & Renal Pharm Flashcards

1
Q

Hypertension

A
  • Systolic > 140 mmHg
  • Diastolic > 90 mmHg
  • 30% incidence
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2
Q

Prehypertension

A

120-139 / 80-89

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3
Q

Stage I HTN

A

140-159 / 90-99

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4
Q

Stage II HTN

A

> 160 / >100

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5
Q

Primary HTN

A
  • Essential HTN
  • Idiopathic
  • Most common
  • 90%
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6
Q

Secondary HTN

A
  • caused by specific disease

- valve disease / coarcation of aorta / pregnancy

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7
Q

Diagnosis of HTN

A
  • Repeated and reproducible measurements

- at least 3 over several weeks / organ damage

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8
Q

HTN risk factors

A
  • Advanced age
  • DM
  • Obesity
  • Family history
  • Stress
  • Smoking
  • Poor diet
  • Lack of activity
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9
Q

HTN complications

A
  • Stroke/Ischemic heart heart disease (leading causes of death)
  • LV hypertrophy
  • Aortic aneurysm
  • Arrhythmias
  • End organ damage
    • especially kidneys / eyes
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10
Q

Blood Pressure

A

BP = CO x PVR

  • so antihypertensives either drop CO and/or PVR
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11
Q

Four ways of controlling BP

A
  • Arterioles resistance
  • Venule capacitance
  • Cardiac output
  • Volume via kidneys
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12
Q

CO and PVR control

A
  • Barroreceptor reflex

- Renin-Angiotensin-Aldosterone system

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13
Q

Barroreceptors

A
  • rapid, moment to moment changes

- in aortic arch and carotid sinuses

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14
Q

Renin-angiotensin-aldosterone system

A
  • baroreceptors release renin if BP drops
  • renin converts angiotensinogen to angiotensin I
  • Angiotensin I to Angio II via ACE
  • Angio II constricts..drops GFR…increases aldosterone
  • aldosterone increases Na absorption…more volume
  • BP goes up
    (Look at chart in slides)
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15
Q

Combo therapy

A
  • more than one drug used to treat HTN
  • minimize side effects
  • monotherapy can be used if mild HTN
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16
Q

Recommended HTN treatment strategy

A

Start with:

  • Thiazide diuretic
  • ACE inhibitor
  • Angiotensin receptor blocker (ARB)
  • Ca channel blocker
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17
Q

Diuretics

A
  • lower BP by reducing volume
  • safe
  • inexpensive
  • first line drug choice
  • used in combo therapy
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18
Q

Thiazide diuretic drugs

A
  • Hydrochlorothiazide
  • Chlorthalidone
  • Indapamide
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19
Q

Thiazide diuretic mechanism

A
  • inhibit Na/Cl cotransporter in distal tubule
  • increase Na/H2O excretion…drops volume
  • increase NaCl excretion
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20
Q

Thiazide diuretic uses

A
  • useful in combo therapy
  • Not effective in renal failure…metabolized by kidney
  • not recommended in pregnancy
    Can cause:
  • hypokalemia
  • hyperuricemia
  • hyperglycemia
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21
Q

Loop diuretic drugs

A
  • Furosemide (LASIX)

- Bumetanide (BUMEX)

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22
Q

Loop diuretic mechanism

A
  • inhibit Na/K/2Cl transporter in ascending limb
    • blocks reabsorption
  • decrease RVR
  • increase RBF
  • fast acting
  • increase Na excretion
  • increase K excretion
  • increase Cl excretion
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23
Q

Loop diuretic uses

A
  • Works well in renal failure
    Causes:
  • hypokalemia
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24
Q

K sparing diuretic drugs

A
  • Spironolactone

- Eplerenone

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25
Q

K sparing diuretics mechanism

A
  • Aldosterone receptor antagonist
    • more Na/H2O into collecting duct
  • reduces K loss in urine
  • used in combo therapy w/ thiazides to reduce K loss
  • increase Na excretion
  • increase K retention
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26
Q

B blockers

A
  • block B1/B2 receptors
  • decrease sympathetic outflow
  • drop CO / HR / contractility
  • inhibit renin release from kidney
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27
Q

B1 selective drugs

A
  • Acebutolol
  • Atenolol…for HTN
  • Bisoprolol
  • Esmolol (BREVIBLOCK)….use in OR….short acting
  • Metoprolol…for HTN
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28
Q

Nonselective B blockers

A
  • Propanolol
  • Nadolol
  • don’t use w/ COPD
  • ALL B blockers Nonselective at high doses
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29
Q

A/B blockers

A
  • Carvedilol… for heart failure

- Labetalol….OK for pregnancy HTN

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30
Q

B blocker adverse effects

A
  • Bradycardia
  • Hypotension
  • Fatigue
  • Insomnia
  • Sexual dysfunction
  • Altered lipid panel…high LDL…low LDL…high triglycerides
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31
Q

B blocker cautions

A
  • do not stop abruptly ….angina / MI / death

- tapered off over weeks

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32
Q

B blockers in IV form

A
  • Esmolol
  • Metropolol
  • Propanolol
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33
Q

ACE inhibitor drugs

A
  • Benazepril
  • Captopril
  • Enalpril
  • Lisinopril
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34
Q

ACE inhibitor mechanism

A
  • blocks ACE
  • No Angio I to Angio II
  • drops Angio II levels
  • causes vasodilation
  • increases bradykinin
  • reduces aldosterone…decrease in Na/H2O retention
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35
Q

ACE and bradykinin

A
  • ACE breaks down bradykinin
  • bradykinin increase NO / prostacyclin
    • both vasoconstrictors
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36
Q

ACE inhibitor uses

A
  • good for patients with diabetic nephropathy
    • decrease progression and albuminuria
  • common following MI
    Chronic use can:
  • drop in BP
  • LV hypertrophy regression
  • better LV healing after MI
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37
Q

ACE inhibitor adverse effects

A
  • dry cough…main reason to get off
  • rash
  • fever
  • altered taste
  • hypotension
  • hyperkalemia
  • fetal malformations
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38
Q

Angiotensin II Recepter Blockers (ARBs)

A
  • Candesartan
  • Eprosartan
  • Irbesartan
  • Losartan
  • Telmisartan
  • Valsartan
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39
Q

ARB mechanism

A
  • Block angio II receptors
  • produce vasodilation
  • block aldosterone secretion…lowers BP and Na/H2O retention
  • DOES NOT increase bradykinin
40
Q

ARB uses

A
  • good for DM / HF / Chronic kidney disease
  • adverse effects like ACE inhibitors…but less cough
    • put on ARB if ACE inhibitors don’t work
  • DO NOT combine with ACE inhibitors
  • Teratogenic…fetal malformations
41
Q

Renin inhibitors

A
  • Aliskiren
42
Q

Renin inhibitor mechanism

A
  • directly inhibits renin
  • drops Na/H2O retention
  • as effective as other methods
  • NO NOT combine worth ACEi or ARB
43
Q

Renin inhibitor adverse effects

A
  • diarrhea
  • cough
  • DO NOT use in pregnancy
44
Q

Ca channel blockers

A
  • blocks Ca into heart cells / smooth muscle cells
  • smooth muscle relaxation
  • dilates MAINLY arterioles
  • initial or add on therapy
45
Q

Alpha 1 blocker drugs

A
  • Doxazosin
  • Prazosin
  • Terazosin
46
Q

Alpha 1 blocker mechanism

A
  • decrease PVR
  • decrease BP
  • relaxes venous and smooth muscle
  • causes reflex tachycardia / orthopedic hypotension
  • Na/H2O retention increases….so used with diuretic
  • NOT used as initial treatment
47
Q

Clonidine

A
  • Alpha 2 agonist
  • drops sympathetic outflow…drops PVR and BP
  • relaxation of venules
48
Q

Clonidine adverse effects

A
  • dry mouth
  • sedation
  • constipation
  • rebound HTN if stopped abruptly
49
Q

Methydopa

A
  • Alpha 2 agonist
  • similar to clonidine
  • HTN during pregnancy
    • also Labetol OK for pregnancy
50
Q

Vasodilator drugs

A
  • Hydralazine
  • Minoxidil
  • Nitroprusside
  • Nitroglycerin
51
Q

Hydralazine

A
  • releases NO from endothelium
  • mainly on arteries
  • reflex stimulation of heart… causes angina / MI / HF
  • increases renin…Na/H2O retention
    • must be used w/ beta blocker AND diuretic
  • OK for pregnancy
  • Can cause Lupus at high doses…autoimmune disease
52
Q

Minoxidil

A
  • Hyper-polarization of smooth muscle…contraction less likely
  • Mainly in arteries
53
Q

Minoxidil side effects

A
  • severe tachycardia…dose dependent
  • palpitations
  • angina
  • headache
  • sweating
  • hypertrichosis…hair growth
  • used w/ beta blocker and diuretic
54
Q

Nitroprusside

A
  • dilates arteries/veins by releaseing NO
  • drops PVR and venous return
  • rapid onset/offset…IV infusion…used in emergencies
    • lasts 5 min
55
Q

Nitroprusside side effects

A
  • Accumulation of cyanide
    • only use 3 days
  • arrhythmias
  • excessive hypotension
56
Q

Nitroglycerin

A
  • common in OR / on CPB / after CPB
  • bolus or IV drip
  • decreases BP and SVR
  • dilates coronary vasculature
    • good for coronary spasm / air in coronaries
57
Q

HTN on pump

A
  • adjust flow
  • check anesthetic depth
    • increase isofluorene
  • drugs
58
Q

Proximal convoluted tubule

A

Reabsorbed:

  • 100% of glucose, proteins, metabolites
  • 65% Na, H2O, Cl, K, bicarb

Secreted:

  • H
  • organic acids/bases
  • catecholamines
  • drugs/toxins
59
Q

Descending loop

A

Reabsorbed:

- 20% H2O

60
Q

Ascending loop

A
  • impermeable to H2O

Reabsorbed:

  • 25% Na, Cl, K
  • Ca, bicarb, Mg

Secreted:
- H

61
Q

Early distal

A
  • impermeable to H2O

Reabsorb:
- 5% Na, Cl, K

62
Q

Late distal / Collecting tubule

A

Reabsorb:
- H2O if there is ADH

Principal cells:

  • reabsorb Na
  • secrete K

Intercalated cells:
- reabsorb/secrete K, bicarb, H

63
Q

Collecting duct

A

Reabsorb:

  • 10% Na, H2O (if ADH)
  • urea

Secrete:
- H

64
Q

Common uses for diuretics

A
  • HTN
  • Edema from:
    • CHF / liver cirrhosis / corticosteroid therapy / bad renal
65
Q

Ascites

A

Swelling in abdomen

66
Q

Thiazide diuretics characteristics

A
  • most widely used
  • acts on distal tubule
  • all have same Emax….but different potencies
    • low ceiling diuretics
  • effective orally
  • 1-3 weeks for BP drop
67
Q

Thiazide diuretics mechanism

A
  • blocks Na/Cl transporter
  • enter lumen via proximal tubule…act on distal
  • compete with organic acids to enter proximal
68
Q

Thiazide diuretics actions

A
  • Increased excretion of Na and Cl
    • hyperosmolar urine…UNIQUE to thiazides…don’t change pH
  • Loss of K
    • high Na = more K secretion later in tubule…continual loss
  • Loss of Mg
    • supplementation required
  • Ca retention
    • due to increased PTH in distal…good for bones
  • Reduced PVR
    • less volume = less CO…overtime volume comes up but PVR stays low
69
Q

Thiazide therapeutic uses

A
  • HTN: drug of choice / minor diuretic effect / PVR low
  • HF: loops are drug of choice / thiazide is supplement
  • Hypercalciuria: idiopathic / good for kidney stones
  • Diabetes Insipidus: substitute for ADH
70
Q

Thiazide diuretics adverse effects

A
  • K depletion
  • Hyponatremia
  • Hyperuricemia…caution with gout
  • Volume depletion…orthostatic hypotension
  • Hypercalcemia
  • Hyperglycemia…impaired release of insulin/tissue glucose uptake
71
Q

Thiazide diuretic drugs

A
  • Hydrochlorothiazide (HCTZ) (Microzide)

- Chlorothiazide (Diuril)…not oral…ok for pregnancy

72
Q

Thiazide-like diuretics

A
  • Chlorothalidone (Thalitone)
  • Metolazone (Zaroxolyn)….more potent than others
  • Indapamide
  • different structure / same functions / same effects
73
Q

Loop diuretics characteristics

A
  • act on ascending loop
  • high ceiling diuretics…higher doses…higher urine output
  • Oral or IV
  • Rapid onset, short duration…2-4 HOURS
  • Limiting step: how much gets into lumen via proximal tubule
  • good at removing Na and Cl from body
74
Q

Loop diuretics mechanism

A
  • blocks Na/K/2Cl transporter on luminal membrane
  • downstream sites can’t compensate for increase in Na
  • greatest diuretic effect
  • increase RBF via prostaglandin synthesis
    • this effect blocked by NSAIDS…they block loop diuretics
  • increase secretion of Na / K / Ca
75
Q

Loops diuretic uses

A
  • Peripheral/pulmonary edema
  • Emergency…acute pulmonary edema
  • Hypercalcemia (1.2-1.4 is normal)
  • Hyperkalemia (3.5-5 is normal)
  • Diuretic of choice in renal failure
76
Q

Loop diuretic perfusion uses

A
  • remove extra fluid on pump
  • treat hyperkalemia
  • maintain urine production / renal function
77
Q

Loop diuretic dose

A

20-40 mg bolus…lasts 2 hours in pump

78
Q

Loop diuretic adverse effects

A
  • Ototoxicity…hearing loss
  • Hyperuricemia…compete with uric acid for secretion
  • Acute hypovolemia
  • K depletion…more exchange of Na for K in tubule
  • Hypomagnesemia….on chronic use
79
Q

Loop diuretic drugs

A
  • Furosemide (Lasix)
  • Bumetanide (Bumex)
  • Ethacrinic acid
80
Q

K sparing diuretic characteristics

A
  • act in collecting tubule
  • aldosterone antagonists… stops Na reabsorption/K secretion
  • Na channel blockers
81
Q

Aldosterone

A
  • from adrenal cortex…zone glomerulosa cells
    • principal cells of collecting tubule
  • increase Na/K ATPase activity AND permeability of membrane Na
  • increase Na reabsorption and K secretion
  • important regulator of K
82
Q

K sparing diuretic uses (aldosterone antagonists)

A
  • Diuresis…given with loops or thiazides
  • Secondary hyperaldosteronism
    • like hepatic cirrhosis or nephrotic syndrome
  • HF…prevent remodeling / decrease mortality / UNIQUE effect
  • Resistant HTN…use of 3+ medications w/o BP drop
  • Ascites…like with hepatic cirrhosis
  • Polycystic ovary syndrome…high androgen levels
    • off label use…stop steroid synthesis
83
Q

K sparing adverse effects (aldosterone antagonists)

A
  • Gynecomastia in males
  • Menstrual irregularities
  • Hyperkalemia…careful if on high K diet
  • confusion
84
Q

K sparing drugs (aldosterone antagonists)

A
  • Sprinolactone (aldactone)

- Eplerenone (Inspra)…less endocrine effects

85
Q

K sparing diuretics (Na channel blockers)

A
  • not very effective
  • in combo w/ other diuretics for k sparing effects
  • increase Na secretion
  • increase K reabsorption
86
Q

K sparing diuretics (Na channel blockers) adverse effects

A
  • Increase uric acid
  • renal stones
  • K retention
87
Q

K sparing diuretics (Na channel blockers) drugs

A
  • Triamterene (dyrenium)

- Amiloride

88
Q

Carbonic anhydrase inhibitors

A
  • much less effective than loops and thiazides

- 1st diuretic developed

89
Q

Carbonic anhydrase inhibitors mechanism

A
  • acts in proximal tubule
  • drops Na uptake by dropping H levels in tubule cells
    • less effective Na/H exchange
  • urine pH increase
  • metabolic acidosis after several days
  • increase excretion of Na / K / bicarb
90
Q

Carbonic anhydrase inhibitors uses

A
  • glaucoma: less aqueous humor / pressure
  • correction of metabolic alkalosis (gets rid of bicarb)
  • mountain sickness
    • prophylaxis…counters respiratory alkalosis
    • drops pulmonary edema
91
Q

Carbonic anhydrase inhibitors drug

A
  • Acetazolamide (Diamox)
92
Q

Osmotic diuretics drug

A
  • Mannitol (osmitrol)

- IV only

93
Q

Osmotic diuretics mechanism

A
  • elevates blood osmolality…pulls in water
  • elevates tubular filtrate osmolality
    • filtered but not reabsorbed
    • causes water excretion
    • inhibits reabsorption of Na / Cl / solute
94
Q

Osmotic diuretic uses

A
  • reduce intracranial pressure
  • acute renal failure…shock/drug toxicity/trauma
  • will give on bypass
95
Q

Mannitol dose

A

CPB: 0.5-1.0 g/kg
In prime: 12.5g/50ml vials in prime

  • check for crystals
  • use filtered needle
  • may cause transient hypotension if given too fast

581 - Pharmacology I (6 decks)

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