Cardio L16 Drug therapy 2 Hypertension Flashcards
Secondary Hypertension
aetiology
- Renal or renovascular disease
- 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 - Co-arctation of the aorta
- Iatrogenic
• Hormonal/ oral contraceptive
• NSAIDs
Typical feature of hypertensive heart disease
Left ventricle thickening
Treatment: 7 example
- Thiazides
- Ca2+ channel blockers
- ACE inhibitors
- α 1-adrenoceptor blockers:
- Ang II receptor blockers:
- K+ channel activators:
- α –methyldopa:
Thiazides
Class of diuretics control hypertension (in part) by blocking the Na+ - Cl_ symporter in first part of DCT.
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).
Thiazides Additional action
• Vasodilator action
Thiazides Side effects
- Electrolyte disturbances
- Decrease glucose tolerance
- Can reduce efficacy of anticoagulants and uriosurics
- Can increase LDL and cholesterol
Thiazides Examples
- Hydrochlorothiazide
* Bendroflumethazide
Ca2+ channel blockers function
Want to dilate periphery to:
- Reduce peripheral resistance
- Reduce filling pressure
Ca2+ channel blockers examples
- Dihydropyridines →
• Nifedipine
• Amlodipine
Ca2+ channel blockers side effects
- Peripheral oedema, dizziness
3. Generally contraindicated in HF, but non-DHP may be useful (e.g. verapamil) in such cases.
ACE inhibitors: function
Long-term control of BP involves renin-angiotensin system.
Angiotensin is
A vasoconstrictor
Examples of prototypic drugs
Captopril
Enalapril
Effects in 2 phases ACE inhibitors
- Rapid due to direct anti- ANG II effect
2. Slower due to blood volume effect and control of thirst.
Side effects ACE inhibitors
- Related to bradykinin (cough in 15%)
- Hyperkalaemia
- Taste disturbances
- First dose hypotension
α 1-adrenoceptor blockers:
Beta2 receptors dilate and alpha1 receptors constrict vascular smooth muscle
α 1-adrenoceptor blockers: example
Prazosin
Doxazosin
Function → antagonise noradrenaline
α 1-adrenoceptor blockers: side effects
Headache
Nausea
Hypotension
Auto-immune problems
Alpha 1 receptor
Noradrenaline >adrenaline
Beta 2 receptor
Adrenaline»_space; noradrenaline
Alpha1 adrenoceptors work via
G alpha induces PLC which induces IP3 and DAG leads to SR Ca release CaM MLCK Muscle contraction
Angiotensin II leads to:
- Na, water retention
2. Thirst
Angiotensin II antagonists function
Block the AT1 receptor and are the most modern approach to limit blood volume expansion (good for CHF and hypertension)
Protective in (Angiotensin II blcokers)
Diabetic nephropathy
Ang II receptor blockers: Side effects
Hyperkalaemia
Diarrhea
Dizziness
Tiredness
Ang II receptor blockers: Example
Losartan
K+ channel activators: Act to
Calcium entry into SM cells depends on Vm
• Both L-type channels and NCX Ca entry inhibited by hyperpolarization.
K+ channel activators: Example and function
Minoxidil
Pinacidil
→ Increase permeability to K+ thereby hyperpolarizing SM cell
K+ channel activators: Side effects
Generally well tolerated
Fluid retention
May worsen angina
Hirsuitism
α –methyldopa: action
This pro-drug is converted to methyl-noradrenaline
- Not metabolized by MAO
- Displaces noradrenaline in synaptic vesicles
- Reduces renin secretion (hence ANG II levels)
α –methyldopa: used for
Hypertension that does not respond to other (more modern) treatment regimens e.g. severe pre-eclampsia.
Ganglion blockers: examples
Guanethidine
Guanadrel
Ganglion blockers: function
Target peripheral adrenergic neuron
Ganglion blockers: Uptake leads to
Guandrel substituting for noradrenaline in secretory granules reducing sympathetic neurotransmission.
Ganglion blockers: used for
Uncontrollable hypertension