Antihypertensives III

Question 1

Examples of Centrally acting antiadrenergic drugs

Answer 1

Reserpine,
* Methyldopa*,
* Moxonidine

Question 2

What is methyldopa?

Answer 2

It is a false transmitter precursor for noradrenaline synthesis.

Question 3

Explain the uptake of methyldopa in the body

Answer 3

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

Question 4

What happens to methyldopa after it has been converted to alpha methylnoradrenaline?

Answer 4

this substance is not deaminated within the neuron by MAO, so it accumulates and displaces
noradrenaline from the synaptic vesicles.
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 5

alpha methylnoradrenaline is effective on which receptors?

Answer 5

However, it is more active on presynaptic (α 2 ) receptors, so the autoinhibitory feedback
mechanism operates more strongly than normal, thus reducing transmitter release.

Question 6

Side effects of methyldopa

Answer 6

antiadrenergic side effects e.g. sedation
also immune hemolytic rxns
liver toxicity

Question 7

In which circumstance can methyldopa be prescribed?

Answer 7

Recommended treatment for hypertension in pregnancy

Question 8

Methyldopa absorption, excretion and half life

Answer 8

Absorption slowly by mouth
Excreted unchanged or as conjugate
Plasma half-life of 6 hours

Question 9

Adverse effects of methyldopa (5)

Answer 9

hypotension, drowsiness, diarrhoea, impotence,
hypersensitivity reactions

Question 10

State the 7 steps of hypertension treatment

Answer 10

1. Lifestyle modification
2. Add 1st agent: Hydrochlorothiazide
3. Add second agent: Enalapril or amlodipine
4. Increase dose of second agent
5. Add third agent: Enalapril or amlodipine
   6.Increase dose of 3rd agent
6. Increase dose of hydrochlorothiazide and add spironolactone

Question 11

Explain the beta blocker mechanism in hypertension

Answer 11

Block B1 receptors in the heart leading to decreased HR and force of contractiliy, leading to reduced cardiac output and reduced Bp.

Also blocks B1 receptors in the juxtaglomerular cells of the kidney, leading to reduced renin release and decreased RAAS activation, leading to lowered Bp.

Question 12

Doxazosin indication

Answer 12

Consider 4th/5th
line for use in hypertension, if BPH is a co-morbidity.

Question 13

Explain alpha 1 blocker mechanism in hypertension

Answer 13

Antagonism of alpha 1 receptors —-»» vasodilation, reduced PVR ——»»> lower Bp

Question 14

Explain problems associated with alpha 1 antagonists

Answer 14

• Orthostatic hypotension
• Reflex sympathetic stimulation:
• ↑ HR, contractility, and circulating NA levels leads to ↑
  myocardial O2
  requirements
• Activation of RAAS and fluid retention

Question 15

What is hypertensive urgency?

Answer 15

SBP >180mmHg and/or DBP >110mmHg

Question 17

Symptoms of hypertensive urgency

Answer 17

headache, shortness of breath (SOB), oedema without neurological or cardiac complications

Question 18

Mx of hypertensive urgency

Answer 18

Commence treatment with amlodipine AND furosemide/hydrochlorothiazide if renal insufficiency or pulmonary congestion
* Goal of treatment: lower DBP to 100mmHg over 24-48 hours
* Refer to hospital

Question 19

What is hypertensive emergency?

Answer 19

A markedly elevated BP: systolic BP > 180 mmHg and/or a diastolic BP > 130 mmHg associated
with ≥ one of the following:
* unstable angina/chest pain
* neurological signs, e.g. severe headache, visual disturbances, confusion, coma or seizures
* pulmonary oedema
* renal failure

Question 20

What is the medical tx for hypertensive emergency

Answer 20

Amlodipine, oral, 10 mg immediately as a single dose.
* If pulmonary oedema:
* Furosemide, IV, 40 mg as a single dose