Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Systemic pharma Week 1 > Diuretics > Flashcards

Diuretics Flashcards

1
Q

DIURETICS MoA

A

•Crucial for the management of CV risk
and renal disease

● Increase the excretion of Na+ and water
-Decrease re-absorption of Na+ from the filtrate - Increased water loss is secondary

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Diuretics Types

A
  1. Carbonic anhydrase inhibitors
  2. Loop diuretics
  3. Thiazide diuretics
  4. Potassium sparing diuretics
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

LOOP DIURETICS
Examples

A

Most powerful diuretics
Capable of causing excretion of 15–25% Na+

Examples: furosemide; bumetanide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

LOOP DIURETICS

MOA

A

MOA: Act on the thick ascending limb
Inhibit the Na+/K+/2Cl− carrier (Cl− binding site)

Incompletely understood vasodilator effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Sulfonamide loop diuretics examples

A

Furosemide, bumetanide, torsemide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Non-sulfonamide loop diuretic
Example

A

Ethacrynic acid
Used for diuresis in patients allergic to sulfa drugs
(more ototoxic)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

LOOP DIURETICS
Urine levels

A

Increase delivery of Na+ to distal nephron
>Increase excretion of K+, H+, Ca2+ and Mg2+ >Decrease excretion of uric acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

LOOP DIURETICS
Clinical uses

A

1) Tx of HTN complicated by renal impairment (thiazides preferred if renal works fine.)
2) hypercalcaemia tx after replacement of plasma volume w/ iv NaCl soln.
3) They’re used with dietary salt retention AND with other diuretic classes, in tx of salt + water overload ass. W/ :
- acute pulmonary oedema
- chronic heart failure
- liver cirrhosis complicated by ascites(to treat ascites which are from fluid retention)
-nephrotic syndrome
- renal failure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

ADVERSE EFFECTS of loop diuretics

A

Hypovolaemia and hypotension
Hyponatraemia
Hypokalaemia
Metabolic alkalosis
Hypomagnesaemia
Hypocalcaemia
Hyperuricaemia
Renal impairment

•Unwanted effects unrelated to the renal actions of the drugs are infrequent
-Dose-related hearing loss
-Idiosyncratic allergic reactions (e.g. rashes, bone marrow depression) are uncommon
-Sulfa allergy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Contraindications of loop diuretics

A

•Severe hypovolemia •Dehydration •Hypokalaemia •Hyponatraemia •Hepatic encephalopathy •Gout

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

THIAZIDE DIURETICS Examples

A

bendroflumethiazide, hydrochlorothiazide

Other drugs acting on the distal tubule:
Chlortalidone, indapamide, metolazone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

THIAZIDE DIURETICS

A

-Less powerful than loop diuretics
-Preferred in uncomplicated hypertension
-Better tolerated than loop diuretics
-Reduce risk of stroke and heart attack associated with hypertension

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

THIAZIDE DIURETICS: MOA
,

A

Inhibit the distal tubular Na+/Cl − co-transport system by binding to the Cl− site
Natriuresis with loss of sodium and chloride ions in the urine
Decreased blood volume leads to fall in BP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

THIAZIDE DIURETICS
Pk/PD

A

● Contraction in blood volume stimulates
renin secretion
-Limits anti-hypertensive effects of the diuretic on blood pressure
-Combination with ACEI’s/ARB’s is beneficial
-May also balance potassium levels
● Thiazides also have a vasodilator effect
-May contribute to BP reduction in later stages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

THIAZIDE DIURETICS urinary levels

A

● Increased excretion of Na+, K+, H+ and
Mg2+ balance (qualitatively similar to loop diuretics)
● In contrast to loop diuretics, thiazides
reduce Ca2+ excretion
-May be advantageous in older patients at
risk of osteoporosis
● Synergistic effect with loop diuretics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

CLINICAL USES of THIAZIDE DIURETICS

A

-HTN
- mild ❤️ failure (loop diuretics preferred)
-severe resistant oedema (metolazone, used w/ loop diuretics)
- to prevent recurrent tone formation in idiopathic hypercalciuria
- nephrogenic diabetes insipidus (malfxn of ADH, therefore we get dilute urine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

ADVERSE EFFECTS of thiazide diuretics

A

•Increase in urinary frequency
•Hyponatraemia - Warning
•Hypokalaemia (drug interactions) - Contraindication
•Hypomagnesemia
•Excretion of uric acid is decreased
-PK interaction: compete with uric acid for the
organic anion transporter (OAT) -> Warning
• Alkalosis
● Impaired glucose tolerance
-Hyperglycemia
● Hyperlipidemia (except indapamide)
● Erectile dysfunction
● Encephalopathy in severe liver disease
● Idiosyncratic reactions are rare
-Thiazides are also sulfa drugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

POTASSIUM SPARING DIURETICS ALDOSTERONE ANTAGONISTS MOA

A

Aldosterone (you retain Na, you lose K+)

•Enhances Na+ reabsorption and promotes K+
excretion
•Stimulates Na+ channels and induces their
synthesis
•Induces synthesis of Na+ /K +- ATPase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

ALDOSTERONE ANTAGONISTS

Examples

A

spironolactone, eplerenone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

ALDOSTERONE ANTAGONISTS
PK/PD

A

● Limited diuretic action when used singly
● Combined with loop diuretics or thiazides
●Marked antihypertensive effects
●May prevent hypokalaemia
● Prolong survival in heart failure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

CLINICAL USES of K+ sparing diuretics

A
22
Q

ADVERSE EFFECTS
POTASSIUM SPARING DIURETICS

A

•Hyperkalaemia, which is potentially fatal -> Contraindication
● Monitoring may be needed -> Be aware of drug interactions
● Gastrointestinal upset
● Gynaecomastia, menstrual disorders and
testicular atrophy
-May be used in female hirsutism
-Eplerenone has less anti-androgen effects

23
Q

OTHER POTASSIUM SPARING DIURETICS
Examples
MoA
Adverse effects

A

Examples: triamterene and amiloride
•Limited diuretic efficacy
•MoA: They act on the collecting tubules and collecting ducts
-Inhibit Na+ reabsorption by blocking lumenal sodium channels
•May be given with loop diuretics or thiazides to maintain potassium balance

Adverse effects: •Hyperkalemia: contraindication
•Triamterene has been identified in kidney stones
Its etiological role is uncertain

24
Q

CARBONIC ANHYDRASE INHIBITORS MOA

A

-Decrease H+ formation in proximal convoluted tubule cell
-Decrease Na+/H+ anti-port
-Increase Na+ and HCO3- in lumen
-Increase diuresis

25
Q

CARBONIC ANHYDRASE INHIBITORS
Examples

A

acetazolamide, dorlozamide

26
Q

CARBONIC ANHYDRASE INHIBITORS
Urine levels

A

Increase excretion of bicarbonate with accompanying Na+, K+ and water
Increased flow of alkaline urine (metabolic acidosis)

27
Q

CARBONIC ANHYDRASE INHIBITORS
Clinical uses

A

Not used as a diuretic
Glaucoma: reduce the formation of aqueous humor
Idiopathic intracranial hypertension
Metabolic alkalosis

28
Q

CARBONIC ANHYDRASE INHIBITORS
ADVERSE EFFECTS

A

Bicarbonaturia and acidosis
Hypokalemia
Hyperchloremia
Paresthesias
Renal stones (calcium precipitation in alkaline urine) NH3 toxicity (alkaline urine)
Acetazolamide is a sulfonamide
-Rashes, blood dyscrasias and interstitial nephritis can occur
-Cross-allergenicity with: all loop diuretics (except ethacrynic acid), thiazides, sulfa antibiotics,
celecoxib

29
Q

HYDRALAZINE MoA

A

-Acts on arteries and arterioles predominantly
-Interferes with action of IP3 on Ca2+ release from SR
-Increases cGMP levels
•Decrease in BP
-Accompanied by reflex tachycardia and increased CO

30
Q

HYDRALAZINE Clinical Uses

A

Short-term treatment of severe hypertension in
pregnancy
Heart failure (with nitrate)
Severe hypertension

31
Q

ADVERSE EFFECTS of Hydralazine

A

Edema
Headache
Systemic lupus erythematosus-like symptoms
Reflex tachycardia
Can be co-administered with a beta-blocker to prevent reflex tachycardia
Contraindicated in angina and coronary artery disease (CAD)

32
Q

BETA-BLOCKERS: MOA

A

SNS stimulation increases CO

Ventricle:
● Increased force of contraction cAMP
● Increased stroke volume

SA and AV node:
● Increased heart rate

Beta blockers reduce CO and BP

33
Q

BETA-BLOCKERS

A

Less well-tolerated
Evidence supporting use in hypertension is weak Recommended for hypertensive patients with other indications for beta-blockers: angina, heart failure, post-MI
Labetalol: Also has α-1 adrenergic receptor blockade properties.
Safe and licensed to use in pregnancy

34
Q

α1-BLOCKERS
MoA

A

Norepinephrine acting on α-1 adrenergic receptors on vascular smooth muscle cells leads to constriction

35
Q

α1-BLOCKERS
Examples

A

-Doxazosin, prazosin, terazosin
Also improve symptoms of benign prostatic
hyperplasia (BPH): improve urine outflow

36
Q

α1-BLOCKERS

Adverse effects

A

Postural hypotension
-Avoid in pre-existing postural hypotension (warning)
Reflex tachycardia
Urinary incontinence
Impotence

37
Q

CENTRALLY-ACTING ANTIHYPERTENSIVES
Methyldopa

A

Methyldopa used for hypertension during pregnancy
Lack of documented side effects on baby
Centrally acting α2 agonist

Decreases sympathetic outflow: decreased TPR and HR

38
Q

Methyldopa
Troublesome side effects

A

Sedation, depression, dry mouth, diminished libido,
parkinsonian symptoms, hyperprolactinemia, bradycardia, sinus arrest

Less common: hepatotoxicity, drug-induced lupus
Not as commonly used anymore
Also positive Coombs test
-May cause hemolytic anemia

39
Q

HYPERTENSIVE EMERGENCY

A

● Clevidipine/Nicardipine ● Hydralazine ● Labetalol ● Nitroprusside ● Fenoldopam

40
Q

NITROPRUSSIDE MoA

A

-Acts equally on arterial and venous smooth muscle
.-Acts by releasing nitric oxide (NO)
-Has to be administered IV
Little clinical usefulness except in hypertensive
emergencies
-Continuous monitoring for hypotension

41
Q

NITROPRUSSIDE

A

-Prolonged use may cause thiocyanate accumulation and toxicity
-Weakness, nausea, inhibition of thyroid function -Hydrolyzes to cyanide in solution, especially in light

42
Q

FENOLDOPAM

A

Selective dopamine (D1) agonist
Coronary, peripheral, renal, splanchnic vasodilation
Increases natriuresis
Decreased BP: can cause hypotension and tachycardia

Short-term management of severe hypertension in hospital > Improves renal perfusion

Its effect is similar in magnitude to IV nitroprusside
Lacks thiocyanate toxicity
Slower in onset/offset

43
Q

PULMONARY ARTERIAL HYPERTENSION (PAH)

A

May be idiopathic or associated with other disease Increased pulmonary pressure can result from
Increased cardiac output
Vasoconstriction
Structural narrowing of pulmonary resistance arteries
Occlusion of pulmonary arteries by recurrent pulmonary
emboli Cellular proliferation and hypertrophy may follow Can progress to right heart failure

44
Q

PA H D R U G S

A

•Treatment approach
-Calcium channel blockers (e.g. nifedipine)
-May benefit a small number of patients
•Drugs that antagonize endothelin
-Endothelin-1 receptors mediate pulmonary
smooth muscle constriction and proliferation
•Drugs that potentiate NO
•Prostanoids

45
Q

ENDOTHELIN RECEPTOR ANTAGONISTS
Examples

A

Endothelin receptor antagonists (e.g. bosentan,  ambrisentan, sitaxentan) 

46
Q

ENDOTHELIN RECEPTOR ANTAGONISTS

Clinical Use + MoA

A

Clinical Use: Orally for less severe stages of disease MOA: Antagonize effects on endothelin receptors (vasodilation, proliferation inhibition)

47
Q

ENDOTHELIN RECEPTOR ANTAGONISTS
Adverse effects:

A

headache, flushing, hypotension
Hepatotoxic (monitor liver function tests)
Endothelins may affect development of the
cardiorespiratory system
Antagonists are teratogenic (contraindication)

48
Q

SILDENAFIL
MoA+ clinical uses

A

MOA: PDE V inhibitor
Inhibits breakdown of cGMP
Pulmonary artery relaxation

Clinical Uses:
Erectile dysfunction
PAH

49
Q

SILDENAFIL Adverse effects:

A

Adverse effects: headache, flushing, dyspepsia, cyanopia
Risk of life-threatening hypotension in patients taking
nitrates
Should not be taken if high risk of hypotension (recent stroke, recent acute coronary syndrome)

50
Q

PROSTANOID AND ANALOGUES
Examples

A

Epoprostenol
● Prostacyclin (PGI2)
● Given as long-term IV infusion
● Improves survival

51
Q

Prostanoid analogues

A

● Examples: iloprost, treprostinil, beraprost 
● Parenteral routes of administration e.g. intravenous, subcutaneous or inhaled
● Used in more severe stages of disease

Adverse effects: flushing, jaw pain, cough, bronchoconstriction

Systemic pharma Week 1 (2 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions