Cardio L16 Drug therapy 2 Hypertension Flashcards Preview

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Flashcards in Cardio L16 Drug therapy 2 Hypertension Deck (36):
1

Secondary Hypertension

aetiology

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


2

Typical feature of hypertensive heart disease

Left ventricle thickening

3

Treatment: 7 example

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:

4

Thiazides

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

5

Thiazides function

• 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).

6

Thiazides Additional action

• Vasodilator action

7

Thiazides Side effects

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

8

Thiazides Examples

• Hydrochlorothiazide
• Bendroflumethazide

9

Ca2+ channel blockers function

Want to dilate periphery to:
1. Reduce peripheral resistance
2. Reduce filling pressure

10

Ca2+ channel blockers examples

1. Dihydropyridines →
• Nifedipine
• Amlodipine

11

Ca2+ channel blockers side effects

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

12


ACE inhibitors: function

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

13

Angiotensin is

A vasoconstrictor

14

Examples of prototypic drugs

Captopril
Enalapril

15

Effects in 2 phases ACE inhibitors

1. Rapid due to direct anti- ANG II effect
2. Slower due to blood volume effect and control of thirst.

16

Side effects ACE inhibitors

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

17

α 1-adrenoceptor blockers:

Beta2 receptors dilate and alpha1 receptors constrict vascular smooth muscle

18

α 1-adrenoceptor blockers: example

Prazosin
Doxazosin
Function → antagonise noradrenaline

19

α 1-adrenoceptor blockers: side effects

Headache
Nausea
Hypotension
Auto-immune problems

20

Alpha 1 receptor

Noradrenaline >adrenaline

21

Beta 2 receptor

Adrenaline >> noradrenaline

22

Alpha1 adrenoceptors work via

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

23

Angiotensin II leads to:

1. Na, water retention
2. Thirst

24

Angiotensin II antagonists function

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

25

Protective in (Angiotensin II blcokers)

Diabetic nephropathy

26

Ang II receptor blockers: Side effects

Hyperkalaemia
Diarrhea
Dizziness
Tiredness

27

Ang II receptor blockers: Example

Losartan

28

K+ channel activators: Act to

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

29

K+ channel activators: Example and function

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

30

K+ channel activators: Side effects

Generally well tolerated
Fluid retention
May worsen angina
Hirsuitism

31

α –methyldopa: action

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)

32

α –methyldopa: used for

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

33

Ganglion blockers: examples

Guanethidine
Guanadrel

34

Ganglion blockers: function

Target peripheral adrenergic neuron

35

Ganglion blockers: Uptake leads to

Guandrel substituting for noradrenaline in secretory granules reducing sympathetic neurotransmission.

36

Ganglion blockers: used for

Uncontrollable hypertension

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