L13 Anti-hypertensive drugs

Question 1

At what BP do we decide to treat for hypertension with drugs. When to start lifestyle changes

Answer 1

Persistently >160/100
or
>140/90 + target organ damage/ comorbidities: (high CVS risk
eg. HF, DM, Proteinuria,

For lifestyle: Hypertension arbitrarily starts at 140/90 in EU but lower in US. Depends on the age - the target depends on risk and age

Question 2

What does Hypertension increase the risk of

and what is the relationship between Blood pressure (mmHg) and CVS risk

Answer 2

Hypertension increases risk of

• Stroke
• Coronary artery disease
• MI
• Renal disease

For every 20mmHg sys rise or 10mmHg dia rise there is a 2x increase in CVS death.

There is a log linear relationship between BP and CVS risk such that a small increase in BP leads to marked increase in CVS risk.

Question 3

What are the benefits of a 10mmHg systolic BP fall - and does age or starting BP affect it

Answer 3

20% reduction in CVA
40% reduction in MI
25% less CVS death.

Age starting (old age), 1’ or 2’ prevention or starting BP doesn’t affect the benefit conferred - always reduction in risk gained.

Question 4

What are problems with treatment and diagnosis of hypertension (4)

• in future may have multidrug w synergistic effect and little dose to increase adherence/reduce SE

Answer 4

1. Hypertension is generally asymptomatic - poorly diagnosed
2. Some people don’t want to treat bc of concurrent diseases, perceived benefits of treatment
3. Often polypharmacy to treat leading to SE and adherence issues
4. Still 75% of patients on treatment don’t reach goal BP.

Question 5

What are the lifestyle changes for BP treatment (4)

Answer 5

1. Salt restriction 5g NaCl per day
2. Weight loss : 5-10kg can get 10-20 mmHg drop
3. Exercise: long term benefits
4. Reduce alcohol: binge leads to BP spikes

Question 6

What are the lines of therapy for prescribing drugs hypertension - which types for 2 groups: renin high activity / low activity

Answer 6

1. a) Younger (<55 and caucasian): High Renin activity
   - Acei (or BB)

b) Older 55+ and african): Low renin activity
- Ca2+ B, Thzd Diuretic

2. Add a group from the other side: (A or B) + (C or D)
3. Acei + ca2 (vasodilator) + Diuretic = most common/effective drug combo
4. Add an a-blocker or spironolactone or other diuretic

Question 7

What are the mechanism of Thiazide diuretics over time, (4) where do they act

Answer 7

Action over time

1. Inhibits Na+/Cl- channel in Distal convoluted tubule therefore reducing Na+ resorption leading to natriuresis
   - -> SE; hyponatremia
2. Losing Na+ leads to Na+/K+ channel in collecting duct to get more activated to keep the Na+, but ends up in losing lots of K+
   - -> SE: hypokalaemia
3. So initially there is a drop in plasma volume and therefore cardiac output, however over time activation of RAAS overcomes this and gets normal plasma volume and CO
4. However BP remains reduced because it causes opening of vascular K+ channels which has vasodilation effect in resistance vessels.

Question 8

What are the mechanism of Loop diuretics over time, where does it act, give example,

Answer 8

eg. Frusemide
Action
1. Potent diuretic inhibits the Na/K/Cl co transporter on the luminal side in ascending LoH causing large Na+ and K+ loss and fluid.

2. As monotherapy will not maintain lower BP effect due to RAAs activation therefore better given with Acei or A2 blocker

Question 9

What are the mechanism of K+ sparing diuretics over time, examples, where do they act and what are the SE

Answer 9

eg. Spironolactone
Action
1. Aldosterone antagonist: inhibits distal Na/K exchange as a mild diuretic = natriuresis and water loss , + pro-inflam, vasoconstriction effects

SE:

• Gynaecomastia (due to E2 like structure)
• Hyperkalemia
• Dehydration

Question 10

What are effects of hypertension on mother and fetus in pregnancy, what is considered hypertension in pregnancy- what time usually

Answer 10

Maternal

• Abruption
• CVA, organ dysfunction, coagulopathy

Fetal

• Intra-uterine growth restriction / death
• Prematurity

140/90 - generally treated after 20 wk when it can start rising after 1st trimester

Question 11

What are anti-hypertensive drugs you cannot use in pregnancy and what is the safe alternative: action

Answer 11

Can’t use

• Acei or Ang 2 antagonist
• Atenolol can cause IUGR
• Diuretics can cause reduced placental blood flow

Safe to use
-Central agents: Methyl dopa : converted to neurotransmitter which acts to decrease symp outflow from vasomotor centre in medulla, but has lots of SE (drowsy, depression, hepatitis, haemolytic anaemia)

• Beta blockers : labetalol
• Ca antagonist: nifedipine
• Vasodilator: Hydralazine

Question 12

what do Loop Diuretics best treat, and what are the SE (4)

Answer 12

Best treats fluid overloading diseases (HF) and in cases of severe/ resistant hypertension, need to be given in higher doses for renal impairment bc needs to be secreted into proximal tubule.

SE:

• Dehydration/ polyuria
• Metabolic hypo Na, K, Mg : needs to be monitored

Question 13

Give 2 examples of thiazide diuretics, and what are the SE (5)

Answer 13

Eg. Bendrofluazide, Chlorthalidone
SE
-hypo Na+, K+, Mg
- increase blood glucose, bc of impairing insulin sensitivity
- increase urate (inhibit uric acid secretion but can still be used if patient is on allopurinol (other gout med)
- Mild diuresis
-erectile dysfunction