Pharmacology Renal Drugs Year 2 Winter

Front 1

What 2 types of drugs decrease venous pressure?

Back 1

diuretics and venodilators

Front 2

How do diuretics decrease venous pressure?

Back 2

by decreasing volume

Front 3

how do venodilators decrease venous pressure?

Back 3

increasing lumen

Front 4

How do diuretics increase the rate of urine flow?

Back 4

most by decreasing reabsorption of sodium (water follows Na+)

Front 5

What effect do diuretics have on GFR?

Back 5

most have no effect

exception is osmotic diuretics

Front 6

major indication for diuretics?

Back 6

need to decrease extracellular fluid volume

treatment of edema and effusions

Front 7

how do diuretics decrease extracellular fluid volume?

Back 7

decreasing body NaCl content -> water follows -> achieves new steady state

Front 8

where is Na+ reabsorbed in the nephron?

Back 8

proximal tubule

thick ascending loop of Henle

distal tubule

Front 9

what are the important targets of diuretics?

Back 9

NaK2Cl symport in thick ascending loop of Henle

NaCl symport and mineralocorticoid receptor in distal tubule

Front 10

What is the traditional classification of diuretics?

Back 10

inconsistent:

osmotic (MOA)

loop diuretics (site of action)

thiazides (chemistry)

K+ sparing (effect on K+)

Front 11

Where do osmotic diuretics act?

Back 11

Loop of henle

Front 12

Examples of osmotic diuretics

Back 12

mannitol - used most often b/c more predictable

glucose

urea

Front 13

characteristics of osmotic diuretics

Back 13

freely filtered in glomerulus

limited reabsorption

relatively inert pharmacologically

Front 14

MOA of osmotic diuretics

Back 14

osmotic --> pulls water into vessels --> increase GFR

decreased prox tubule reabsorption

increased osmolality in thick ascending loop of Henle --> less Na reabsorped (decreased reabsorption in Loop of Henle)

Front 15

T/F Excretion of water is greater than electrolytes with osmotic diuretics

Back 15

true

Front 16

Theraputic uses for osmotics diuretics

Back 16

Anuric/Oliguric renal failure (emergency!)

nephroprotection

control intraocular pressure (acute glaucoma)

decrease cerebral edema

Front 17

Why are osmotic diuretics NOT used to treat heart failure?

Back 17

b/c osmotic diuretics draw fluid into the vessels which would create more work for a heart that cannot pump

Front 18

Toxicity and Adverse effects of Osmotic diuretics

Back 18

patients that cannot tolerate increased ECF volume (heart disease)

hyponatremia (main electrolyte excreted)

Front 19

What is the MOA of "loop diuretics?"

Back 19

inhibitor of Na+-K+-2Cl- symport in thick ascending loop of henle --> blocks Na reabsorption and water stays with Na

Front 20

examples of inhibitors of Na+-K+-2Cl- symport

Back 20

Furosemide (Approved for vet use)

Bumetamide

Torsemide

Front 21

why are Na-K-2Cl symport inhibitors highly efficacious?

Back 21

b/c 25% of Na+ is reabsorbed in the loop of Henle where loop diuretics act

distal segments have limited reabsorptive ability (salt transport virtually stops at this site)

Front 22

T/F Na-K-2Cl symport inhibitors excrete more water than electrolytes

Back 22

false water and electrolyte excretion is about equal

Front 23

theraputic uses for Na-K-2Cl symport inhibitors

Back 23

anuric/oliguric renal failure (emergency use)

acute pulmonary edema

edematous states

ascites

congestive heart failure

Front 24

Toxicity and adverse effects of Na-K-2Cl symport inhibitors

Back 24

diuretic related:

dehydration and hypotension

hyponatremia, hypochloremia, hypokalemia

(metabolic alkalosis - classic for excessive loop diuretic use)

Front 25

Na-K-2Cl symport inhibitor drug interactions

Back 25

Aminoglycosides (compete for same transport increases nephrotoxicity)

Digitalis (increases toxicity)

Propanolol (increases plasma levels of propanolol)

thiazides (synergistic effect on diuresis [increased urine])

Front 26

Why is the use of sequential diuretics necessary?

Back 26

kidneys can upregulate resorption at distal nephron with continued diuretic (Na-K-2Cl symport inhibitor) use; thiazides (Na-Cl symport inhibitor) use is synergistic

Front 27

MOA of thiazides

Back 27

inhibit Na+-Cl- symport in the distal convoluted tubule

Front 28

why are thiazides less potent that loop diuretics?

Back 28

>90% of Na+ is reabsorbed before reaching the distal tubule

max 5% of filtered load of Na+ is excreted in distal tubule

Front 29

What is a positive aspect of thiazides being less potent than loop diuretics (Na-K-2Cl symport inhibitors)?

Back 29

dehydration and hypokalemia are less pronounced

Front 30

examples of thiazides (Na-Cl symport inhibitors)

Back 30

chlorothiazide

hydrochlorothiazide (used most)

metolazone

Front 31

T/F inhibitors of Na-Cl symport excrete less water than electrolytes

Back 31

false Na-Cl symport inhibitors (thiazides) excrete approx equal amounts of water and electrolytes

Front 32

therapeutic uses of Na-Cl symport inhibitors (thiazides)

Back 32

edematous states

congestive heart failure (second diuretic after loop diuretic [furosemide])

ascites (drug of choice in dogs b/c safer than loop diuretic [furosemide] for chronic use]

calcium oxalate stones (adjuvant therapy)

nephrogenic diabetes insipidus

Front 33

toxicity and adverse effects of Na-Cl symport inhibitors

Back 33

diuretic related:

dehydration and hypotension

hyponatremia, hypochloremia, hypokalemia

*less pronounced than with loop diuretics*

Front 34

What is the MOA of K sparing diuretics?

Back 34

aldosterone antagonists or mineralocorticoid receptor antagonists = competitive inhibitor more effect is seen if aldosterone is increased

late distal tubule/collecting dut

do not alter renal response to hydropenia

Front 35

examples of mineralocorticoid receptor antagonists

Back 35

spironolactone

eplerenone (expensive but more efficacious in humans)

Front 36

T/F mineralocorticoid receptor antagonists excrete equal amounts of water and electrolytes

Back 36

true

Front 37

theraputic uses of mineralocorticoid receptor antagonists

Back 37

second diuretic for edematous states, CHF*, ascites

primary hyperaldosteronism

proteinuria and hypertension

*may prolong survival with CHF

Front 38

toxic and adverse effects of mineralocorticoid receptor antagonists

Back 38

hyperkalemia

severe facial ulcerative dermatitis

Front 39

Nitrates are used for ___________________

Back 39

venodilation - decrease venous pressure by increasing vessel lumen size

Front 40

MOA of nitrates

Back 40

nitrates form Nitric oxide in smooth muscle cells which stimulate relaxation

Front 41

Examples of venodilators and how administered

Back 41

nitroglycerin (transcutaneous - wear gloves!)

isosorbide (oral)

Front 42

examples of mixed dilators and how administered

Back 42

nitroprusside (IV)

Front 43

why are nitrates used intermittently and primarily for emergencies? can anything else be given to help with this?

Back 43

tolerance develops in 24 hours (after depletion of sulfur?)

ACE inhibitors and hydralazine can be used to decrease tolerance

Front 44

uses for venodilators?

Back 44

pulmonary edema from heart failure (systemic venodilation)

Front 45

indications for use for Nitroglycerine? Isosorbide?

Back 45

Nitroglycerine - emergency heart failure

Isosorbide - chronic use in refractory heart failure

Front 46

indication for use of nitroprusside?

Back 46

short-term management of severe, fulminant heart failure or hypertensive crisis (>200mmHg)

Front 47

why is nitroprusside IV use only?

Back 47

effect lasts only 5 minutes after drug is stopped; tolerance is not issue

Front 48

side effects and special consideration of nitroprusside?

Back 48

hypotension

cyanogen toxicity with prolonged high dose IV use

considerations - sensitive to light, heat, moisture

Front 49

examples of arterial vasodilators?

Back 49

hydralazine

calcium-channel blockers

alpha1-adrenoreceptor blockers

Front 50

What factors create vessel pressure?

Back 50

flow x resistance

flow = cardiac output

resistance = degree of vasocontriction

Front 51

Uses for arterial dilators?

Back 51

decrease blood pressure - systemic hypertension

increase cardiac output - heart failure

Front 52

examples of calcium channel blockers

Back 52

amlodipine

hydralazine

prazosin

Front 53

MOA of amlodipine

Back 53

blocks calcium channels in systemic arteriolar smooth muscle (almost no effect on heart)

Front 54

clinical use of amlodipine

Back 54

hypertension - drug of choice in cats (most predictable of chronic use Ca-channel blockers)

mitral regurgitation in dogs - rarely used

Front 55

Amlodipine PK

oral bioavailibility:

time to peak plasma conc:

half life:

protein binding:

Back 55

90% bioavailability

6 hrs to peak plasma conc

30h plasma half-life

95% protein bound

Front 56

adverse effects of amlodipine

Back 56

hypotension

Front 57

MOA of hydralazine

Back 57

direct vasodilator - likely increases prostacyclin concentration

Front 58

clinical uses of hydralazine

Back 58

hypertension - IV for hypertensive crisis, 3rd drug for refractory hypertension

mitral regurgitation in dogs (refractory failure)

Front 59

hydralazine PK

metabolism:

oral absorption:

time to peak plasma conc:

effect in:

stable for:

lasts:

Back 59

dogs:

first pass hepatic metabolism

good oral absorption

3 hr to peak plasma conc

effect begins in 20-60 min

stable for 8-10 hrs

lasts 12 hrs

dose must be titrated

Front 60

adverse effects of hydralazine

Back 60

hypotension

anorexia, vomitting

reflex tachycardia

Front 61

Prazosin rarely used in _____, NOT used in _____

Back 61

dogs, cats

other safer drugs available

Front 62

clinical uses of Prazosin

Back 62

(mixed arterial and venodilator)

arterial hypertension (refractory)

urethral relaxation (other safer drugs available)

Front 63

What are ACE inhibitors and common uses?

Back 63

mixed arteriolar and venodilators

used to prolong survival in heart failure and renal failure via neuroendocrine and local effects

Front 64

how does local angiotensinII contribute to progression of renal failure?

Back 64

1. increased glomerular pressure -> glom sclerosis and increased Angiotensin II

2. mesangial hypertrophy -> glom sclerosis and fibrosis

3. increased TGF-B -> mesangial hypertrophy, glom sclerosis and fibrosis

4. increased NF-kappaB -> inflammation

Front 65

What are ACE inhibitors?

Back 65

special vasodilators

not very potent

weak hemodynamic effects

Front 66

MOA of ACE inhibitors

Back 66

angiotensin converting enzyme inhibition (systemic and local)

Front 67

examples of ACE inhibitors

Back 67

Enalapril

Benazepril

Ramipril

Lisinopril

(Captopril)

Front 68

clinical uses of ACE inhibitors

Back 68

systemic hypertension

first drug for patients with proteinuria, renal failure d/t nephroprotection

second drug for other patients

heart failure - vasodilator of choice, neuroendocrine modulation prolongs survival

renal failure - proteinuria, increased survival

Front 69

Adverse effects of ACE inhibitors

Back 69

hypotension (rare)

anorexia and vomiting

renal disease (failure?) in patients that are volume depleted (in heart disease, kidney interprets body as volume depleted --> nephrtoxic)

Front 70

how do ACE inhibitors work differently in cats than dogs?

Back 70

won't reduce hypertension in cats

in 20% of dogs, BP reduced by 20 mmHg

does not resolve proteinuria in cats but does prevent progression

Front 71

what's the difference between Enalapril and Benazepril?

Back 71

different manufacturers that funded studies

Front 72

What do urinary incontinence drugs target?

Back 72

2 sphincters (1 striated, 1 smooth muscle)

if weak -> increased contraction

if too strong -> decrease contraction

Front 73

What is hypotonic urethra? Signalment?

Back 73

sphincter incompetence

adult female dogs

Front 74

What classes of drugs increase urethral tone?

Back 74

alpha-adrenergic agonists

reproductive hormones

Front 75

Examples of alpha-adrenergic agonists

Back 75

phenylpropanolamine (PPA)

phenylephrine

Front 76

MOA of Phenylpropanolamine

Back 76

direct stimulation of alpha adrenergic receptors

Front 77

how efficacious if phenylpropanolamine? phenylephrine?

Back 77

PPA:

excellent results in >85% of cases

can be used in males and females

should be dosed TID so if giving BID and not effective, try TID

Phenylephrine:

effect is less predictable

also BID-TID

Front 78

adverse effects of alpha-adrenergic agonists

Back 78

anorexia

weight loss

hyperexcitability

tachycardia

hypertension - common, measure BP

Front 79

Reproductive hormones used for hypotonic urethra?

Back 79

Diethylstilbestrol (DES)

Testosterone

Front 80

MOA of DES?

Back 80

sensitization and up-regulation of alpha receptors

Front 81

efficacy of DES? administration?

Back 81

success rate of 60-70%

can be used in females, also males but not seen

starting dose and maintenance dose- use as least often as efficacious

Front 82

adverse effects of DES?

Back 82

alopecia

estrus signs

bone marrow suppression (reversible but may become irreversible)

Front 83

Testosterone use for hypotonic ureter

Back 83

can be used in males but rarely needed

can only be given IM

has side effects

Front 84

What is hypertonic urethra?

Back 84

sphincter contraction is too strong all the time or contracted at inappropriate times

Front 85

what class of drugs are used for hypertonic urethra? examples?

Back 85

alpha adrenergic antagonists

Phenoxybenzamine

Diazepam

Front 86

MOA of phenoxybenzamine

Back 86

irreversibly inactivates alpha receptors - decreases smooth muscle tone

Front 87

which species is phenoxybenzamine less effective?

Back 87

cats - less predictable b/c striated muscle predominates in feline urethra

Front 88

adverse effects of phenoxybenzamine

Back 88

hypotension

reflex tachycardia

GI upset

Front 89

MOA of diazepam?

administration?

Back 89

decreases striated muscle tone

give 15-330 minutes prior to micturtion (take potty)

higher doses lead to sedation

Front 90

adverse effects of diazepam

Back 90

sedation

weakness

paradoxical excitement

hepatotoxicity (cats)

Front 91

causes of hypotonic bladder

Back 91

neurologic diseases

overdistension of bladder

Front 92

general category of drugs used to treat hypotonic bladder? examples?

Back 92

cholinergic agents

bethanechol

Front 93

efficacy of Bethanechol? adverse effects?

Back 93

unreliable

full effect in 1-2 days, voiding w/in 2 hrs

may increase urethral tone (start alpha blocker like phenoxybenzimine first)

SLUD (salivation, defecation) b/c activating PS tone

GI - abdominal cramps, vomiting, diarrhea