Drugs used for treatment of Hypertension 4

Question 1

List the indications for loop diuretics

Answer 1

Oedema, pulmonary oedema
* Oedema secondary to heart failure, liver cirrhosis, etc.
* Reserved for use in hypertension for patient with poor renal function
(CrCL<30ml/min)
* Despite greater natriuretic effect than thiazides, usually less effective
that thiazides to control blood pressure in patients with normal renal
function
* Hypercalcaemia

Question 2

explain the pharmacokinectics for Loop diuretics

Answer 2

• Route of administration: oral or IV
• Partly metabolised before excreted in the urine

Question 3

List 6 adverse effects for loop diuretics

Answer 3

• Hypokalaemia, hypomagnesaemia, hypocalcaemia, hyponatraemia,
• Hyperuricaemia (gout), hypochloraemic alkalosis
• Dehydration, hypotension, hypovolaemia
• Endocrine abnormalities like thiazides
• Hearing loss
• Hypersensitivity (sulphonamide structure)

Question 4

Based on the potassium sparing diuretics: MoA
Explain the role of sodium

Answer 4

Sodium enters the principal cells through
sodium channels. Sodium is then
transferred into the interstitial fluid by the
sodium pump, while potassium is pumped
in the opposite direction and then moves
through potassium channels into the
tubular fluid.

Question 5

Based on the potassium sparing diuretics: MoA.
Explain the role of Aldosterone

Answer 5

Aldosterone stimulates these processes
by increasing the synthesis of messenger
RNA that encodes for sodium channel and
sodium pump proteins.

Question 6

Based on the potassium sparing diuretics: MoA
explain the role of potassium-sparing diuretics

Answer 6

The potassium-sparing diuretics exert
their effects via two mechanisms:
amiloride and triamterene inhibit the
entrance of sodium into the principal
cells, whereas spironolactone blocks the
mineralocorticoid (aldosterone) receptor
and thereby inhibits sodium reabsorption
and potassium secretion.

Question 7

explain the MOA od spironolactone

Answer 7

• Structural analogue of aldosterone, blocks aldosterone binding to the
  mineralocorticoid (aldosterone) receptor in epithelial cells of the
  distal tubule and collecting duct.
• Mineralocorticoid receptors (when stimulated) interact with DNA to
  promote expression of genes for sodium channels and the sodium
  pump that enable sodium reabsorption and reduce renal potassium
  excretion – i.e. sodium excretion and decreased potassium excretion

Question 8

List 4 adverse effects for spironolactone

Answer 8

Prevent hypokaleamia
* Primary hyperaldosteronism
* Reduce mortality in people with heart failure
* Antiandrogenic effects: polycystic ovary disease and hirsutism in
women

Question 9

Adverse effects for spironolactone

Answer 9

Adverse effects
* Antiandrogenic effects: Gynecomastia & impotence in men
* Hyperkalaemia

Question 10

Contraindications for spironolactone

Answer 10

Contraindications:
* Kidney impairment (eGFR <30ml/min)
* Pregnancy

Question 11

List the centrally acting antiadrenergic drugs

Answer 11

• Reserpine,
• Methyldopa*,
• Moxonidine

Question 12

False transmitter precursor for noradrenaline synthesis

Answer 12

Methyldopa

Question 13

how does methyldopa produces adverse effects

Answer 13

• It produces side effects typical of centrally acting antiadrenergic drugs (e.g. sedation), as well as
  carrying ‘off-target’ risks of immune haemolytic reactions and liver toxicity, so it is now little
  used, except for hypertension in the second half of pregnancy where there is considerable
  experience of its use and no suggestion of harm to the unborn baby.

Question 14

Methyldopa is taken up by which neurons and converted to what?

Answer 14

Methyldopa , is taken up by noradrenergic neurons, where it is converted to the false transmitter
α-methylnoradrenaline.

Question 15

explain how α-Methylnoradrenaline is released

Answer 15

α-Methylnoradrenaline is released in the same way as noradrenaline but is less active than
noradrenaline on α 1 receptors and thus is less effective in causing vasoconstriction.

Question 16

α-Methylnoradrenaline is not deaminated within the neuron by MoA so it accumulates and ?

Answer 16

This substance is not deaminated within the neuron by MAO, so it accumulates and displaces
noradrenaline from the synaptic vesicles

Question 17

explain when is alpha-methylnoradrenaline is more active

Answer 17

However, it is more active on presynaptic (α 2 ) receptors, so the autoinhibitory feedback
mechanism operates more strongly than normal, thus reducing transmitter release.
* Both of these effects (as well as a central effect, probably caused by the same cellular
mechanism) contribute to the hypotensive action.

Question 18

Methyldopa is recommended treatment for hypertension in?

Answer 18

Pregnancy

Question 19

explain the dosing of methyldopa

Answer 19

require multiple daily dosing

Question 20

explain the pks of methyldopa

Answer 20

Absorbed slowly by mouth
* Excreted unchanged or as conjugate
* Plasma half-life 6 hours