Cardio L16 Drug therapy 2 Hypertension

Question 1

Secondary Hypertension

aetiology

Answer 1

1. Renal or renovascular disease
2. Endocrine disease e.g.
   • Phaechomocytoma (tumour of arterial medulla)
   • Cushings syndrome (excess cortisol)
   • Conn’s Syndrome (excess aldosterone)
   • Acromegaly (excess growth hormone)
   • Hypo/hyper thyroidism
   • Pregnancy
3. Co-arctation of the aorta
4. Iatrogenic
   • Hormonal/ oral contraceptive
   • NSAIDs

Question 2

Typical feature of hypertensive heart disease

Answer 2

Left ventricle thickening

Question 3

Treatment: 7 example

Answer 3

1. Thiazides
2. Ca2+ channel blockers
3. ACE inhibitors
4. α 1-adrenoceptor blockers:
5. Ang II receptor blockers:
6. K+ channel activators:
7. α –methyldopa:

Question 4

Thiazides

Answer 4

Class of diuretics control hypertension (in part) by blocking the Na+ - Cl_ symporter in first part of DCT.

Question 5

Thiazides function

Answer 5

• Diuresis follows the increased NA load at CD
• This increases K loss due to increased tubule Na and aldosterone – dependent Na+-K+ exchange.
• Reduced Uric acid, Ma2+, Ca2+ excretion.
• Note “thiazide” can also be used for drugs with similar action but not thiazide structure (e.g. chlorthalidone and metolazone).

Question 6

Thiazides Additional action

Answer 6

• Vasodilator action

Question 7

Thiazides Side effects

Answer 7

• Electrolyte disturbances
• Decrease glucose tolerance
• Can reduce efficacy of anticoagulants and uriosurics
• Can increase LDL and cholesterol

Question 8

Thiazides Examples

Answer 8

• Hydrochlorothiazide

* Bendroflumethazide

Question 9

Ca2+ channel blockers function

Answer 9

Want to dilate periphery to:

1. Reduce peripheral resistance
2. Reduce filling pressure

Question 10

Ca2+ channel blockers examples

Answer 10

1. Dihydropyridines →
   • Nifedipine
   • Amlodipine

Question 11

Ca2+ channel blockers side effects

Answer 11

2. Peripheral oedema, dizziness

3. Generally contraindicated in HF, but non-DHP may be useful (e.g. verapamil) in such cases.

Question 12

ACE inhibitors: function

Answer 12

Long-term control of BP involves renin-angiotensin system.

Question 13

Angiotensin is

Answer 13

A vasoconstrictor

Question 14

Examples of prototypic drugs

Answer 14

Captopril

Enalapril

Question 15

Effects in 2 phases ACE inhibitors

Answer 15

1. Rapid due to direct anti- ANG II effect

2. Slower due to blood volume effect and control of thirst.

Question 16

Side effects ACE inhibitors

Answer 16

• Related to bradykinin (cough in 15%)
• Hyperkalaemia
• Taste disturbances
• First dose hypotension

Question 17

α 1-adrenoceptor blockers:

Answer 17

Beta2 receptors dilate and alpha1 receptors constrict vascular smooth muscle

Question 18

α 1-adrenoceptor blockers: example

Answer 18

Prazosin
Doxazosin
Function → antagonise noradrenaline

Question 19

α 1-adrenoceptor blockers: side effects

Answer 19

Headache
Nausea
Hypotension
Auto-immune problems

Question 20

Alpha 1 receptor

Answer 20

Noradrenaline >adrenaline

Question 21

Beta 2 receptor

Answer 21

Adrenaline&raquo_space; noradrenaline

Question 22

Alpha1 adrenoceptors work via

Answer 22

G alpha induces 
PLC which induces
IP3 and DAG leads to
SR Ca release
CaM
MLCK
Muscle contraction

Question 23

Angiotensin II leads to:

Answer 23

1. Na, water retention

2. Thirst

Question 24

Angiotensin II antagonists function

Answer 24

Block the AT1 receptor and are the most modern approach to limit blood volume expansion (good for CHF and hypertension)

Question 25

Protective in (Angiotensin II blcokers)

Answer 25

Diabetic nephropathy

Question 26

Ang II receptor blockers: Side effects

Answer 26

Hyperkalaemia Diarrhea Dizziness Tiredness

Question 27

Ang II receptor blockers: Example

Answer 27

Losartan

Question 28

K+ channel activators: Act to

Answer 28

Calcium entry into SM cells depends on Vm | • Both L-type channels and NCX Ca entry inhibited by hyperpolarization.

Question 29

K+ channel activators: Example and function

Answer 29

Minoxidil Pinacidil → Increase permeability to K+ thereby hyperpolarizing SM cell

Question 30

K+ channel activators: Side effects

Answer 30

Generally well tolerated Fluid retention May worsen angina Hirsuitism

Question 31

α –methyldopa: action

Answer 31

This pro-drug is converted to methyl-noradrenaline 1. Not metabolized by MAO 2. Displaces noradrenaline in synaptic vesicles 3. Reduces renin secretion (hence ANG II levels)

Question 32

α –methyldopa: used for

Answer 32

Hypertension that does not respond to other (more modern) treatment regimens e.g. severe pre-eclampsia.

Question 33

Ganglion blockers: examples

Answer 33

Guanethidine | Guanadrel

Question 34

Ganglion blockers: function

Answer 34

Target peripheral adrenergic neuron

Question 35

Ganglion blockers: Uptake leads to

Answer 35

Guandrel substituting for noradrenaline in secretory granules reducing sympathetic neurotransmission.

Question 36

Ganglion blockers: used for

Answer 36

Uncontrollable hypertension