PHARM: Diuretics and Anti-Hypertensives Flashcards

1
Q

Summarise RAAS Physiology

A
  • Decreased perfusion leads to juxtaglomerular apparatus in macula densa (senses the decreased NaCl in the DCT which means the GFR is too slow) and causes rening secretion
  • Renin converts angiotensinogen to Angiotensin I
  • Angiotensin I is converted to ATII in lungs by Angiotensin Converting Enzyme (ACE)
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2
Q

What does ATII do?

A

Most powerful Na+ retaining hormone!!!

  • Directly stimulates Na+ reabsorption in the PCT and excretion of K+
  • Increases reabsorption by peritubular capillaries
  • Arteriolar vasoconstriction
  • Increased sympathetic activity
  • Stimulates aldosterone secretion from adrenal cortex (increases Na and H2O reabsorption
  • Stimulations ADH secretion from posterior pituitary (increases H2O reabsorption in the CD)
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3
Q

What does aldosterone do?

A
  • Stimulates the basolateral NaKATPase in the DCT and CD
  • Causes Na+ reabsorption and K+ excretion
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4
Q

What does ADH do?

A

Increases aquaporin activity in the DCT, CD

So H2O is reabsorbed which increases BP but Na+ is still being secreted so you end up with dilution of the ECF solutes

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5
Q

What drugs are -pril

A

ACEI

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6
Q

Name some ACEI

A

Ramipril
Perindopril

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7
Q

What is the MOA of ACEI

A

ACEI = angiotensin converting enzyme inhibitors

Inhibits the action of ACE so you have less ATII which:
- Reduces Na and H20 reabsorption
- Vasodilates
- Reduces aldosterone and ADH secretion
- Net decrease in BP which reduces myocardial workload

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8
Q

What are some indications for ACEI

A

HTN= 1st line med
HF
Oedema

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9
Q

What are the side effects of ACEI

A

CAPTOPRIL

Cough (angiotensin induced)
Angioedema (bradykinins also need ACE for breakdown)
Pregnancy no no
Taste changes
Other: rash, fatigue, achy legs
Proteinuria
Renal insufficiency
Increased potassium: achy legs (aldosterone also causes K secretion so it can build up)
Low blood pressure

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10
Q

What are ACEI contraindications

A

Pregnancy
Hyperkalaemia
Renal artery stenosis
Caution in abnormal renal function

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11
Q

What drugs are -sartan

A

ARBs

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12
Q

What are some examples of ARBs

A

Candesartan
Irbesartan

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13
Q

What is the MOA of ARBs?

A

Angiotensin Receptor Blockers

Directly bind to and block AT receptor so it can’t be activated by ATII which decreases the RAAS system causing:
- Vasodilation
- Decreased Na+ and H20 reabsorption
- Reduced Aldosterone
- Net decrease in BP –> reduced myocardial workload

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14
Q

What are the indications of ARBs?

A

HTN
HF
Oedema

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15
Q

What are the SEs of ARBs?

A

Hypotension
Hyperkalemia (ATII and aldosterone both cause K excretion)
Renal failure (less glomerular perfusion pressure)
Cough
Angioedema

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16
Q

What are the contraindications of ARBs?

A

Pregnancy
Angioedema
Hyperkalemia
Renal artery stenosis
Caution on renal impairment

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17
Q

What drugs are -olol

A

B blockers

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18
Q

What are some examples of B blockers

A

Metoprolol
Propanolol
Atenolol
Bisoprolol

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19
Q

What do B1 adrenergic receptors do?

A

Kidneys + Heart, activated by adrenaline. Overall increase CO and cause renin release

  • Chronotropic effect: increases HR at the SA node
  • Inotropic effect: increase cardiac muscle contractility
  • Dromotropic effect: increased automaticity of the AV node
  • Renin release at JGC
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20
Q

What do B2 adrenergic receptors do?

A

Smooth muscle relaxation: lungs, BV, GI tract, bladder, uterus, liver

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21
Q

What do B3 adrenergic receptors do?

A

Lipolysis in adipose tissues
Relaxation of urinary bladder

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22
Q

What B blockers are cardioselective?

A

/B1 selective

Metoprolol
Atenolol
Bisoprolol

23
Q

What B blockers are non-selective?

A

/B1 + B2

Propanolol
Carvedilol

24
Q

What is the MOA of B blockers?

A

Lower BP by:
- Reducing HR
- Reducing heart contractility
- Results in decreased CO

25
Q

What are some indications for B blockers?

A

HTN: not first line unless post-MI
Post AMI
Angina
Tachyarrhythmias
Heart Failure

26
Q

What are some adverse effects of B blockers?

A

Hypotension
Bradycardia
Lethargy
Dyspnoea/bronchoconstriction
Impotence

27
Q

What are contraindications of B blockers?

A

Asthma (relative)
Bradycardia
AV block 2 or 3

28
Q

What are some names of calcium channel blockers?

A

Verapamil = cardioselective
Amlodipine= vascular SM selective
Diltiazem = both

29
Q

What is the MOA of calcium channel blockers?

A

Leaky calcium channels allow pacemaker cells to reach threshold and depolarise –> if the Ca channels are blocked then the rate of automaticity will be reduced

  • Vasodilation
  • Negative inotropic: decreased force of contraction
  • Negative chronotropic: decreased HR
30
Q

What is verapamil indicated for?

A

HTN
Angina
SVTs (AF, AVNRT)

31
Q

What is amlodipine indicated for?

A

HTN
Angina

32
Q

What is diltiazem indicated for?

A

Angina

33
Q

What are the side effects of calcium channel blockers?

A

Hypotension
Headache, flushing
Peripheral oedema
Constipation

34
Q

What are some names of thiazide diuretics?

A

Hydrochlorothiazide
Indapamide

35
Q

What is the MOA of thiazide diuretics?

A

Inhibit the Na+/Cl- transporter in the DCT
- Less NA and Cl reabsorption, therefore less H2O reabsorption
- Increases the action of the Na+/K+ transporter –> causes K+ excretion
- Ca reabsorption
- Causes diuresis and natriuresis

*Less efficacious than loop diuretics as this transporter only reabsorbs 5% of Na

36
Q

What are the indications of thiazide diuretics?

A

HTN
Oedema

37
Q

What are the side effects of thiazide diuretics?

A

Hypokalaemia
Hypercalcaemia
Gout (hyperuricaemia)
Metabolic syndrome
Erectile dysfunction

38
Q

What is the name of a loop diuretic?

A

Frusemide

39
Q

What is the MOA of loop diuretics?

A

Inhibition of the Na/K/Cl co-transporter in the thick ascending loop
- Less Na+ reabsorbed (less H2O absorbed also)
- Less K+ reabsorbed
- Less Ca and Mg

*This transporter reabsorbed 25% of Na so inhibition can cause significant Na and H2O excretion!!

40
Q

What are the indications for loop diuretics?

A

Oedema
HTN
Renal failure
HF

41
Q

What are some side effects of loop diuretics?

A

Hypokalaemia
Excessive diuresis

42
Q

What is a contraindication of loop diuretics?

A

Anuria

43
Q

What are two potassium sparing diuretics?

A

Spironolactone
Amiloride

44
Q

What is the MOA of spironolactone?

A

Aldosterone antagonist: binds to the aldosterone receptors in the DCT and CD
- Does not induce NaKATPase activation
- Less Na is reabsorbed
- Less K is excreted

Remember: aldosterone MOA is to activate the Na/K/ATPase which makes you retain Na and excrete K so spiro does the opposite

45
Q

What are the indications for spironolactone?

A

HTN
CCF
Oedema
Primary hyperaldosteronism

46
Q

What are some side effects of spironolactone?

A

Hyperkalaemia
Hyponatraemia
Anti-androgen effects (gynaecomastia, sexual dysfunction)

47
Q

What is the MOA of amiloride?

A

Directly inhibits eNaC in the DCT (epithelial sodium channels)
- Less Na is interstitial to drive the NaK pump so K is spared whilst Na is left in the tubules/urine
- Diuresis with K sparing

48
Q

What are the indications for amiloride?

A

HTN
Oedema

49
Q

What are some side effects of amiloride?

A

GI upset
Hyperkalaemia

50
Q

What is the name of an alpha adrenoreceptor blocker?

A

Prazosin

51
Q

What is the MOA of prazosin?

A

It’s an alpha adrenoreceptor blocker and the function of the a receptor is that it triggers smooth muscle contraction

So the receptors are peripherally active in BVs and the blockers cause vasodilation and decrease PVR

52
Q

What is the indication for prazosin?

A

Uncontrolled HTN

53
Q

What are some side effects of prazosin?

A

Reflex tachycardia
Peripheral oedema (increased capillary bed pressure)