Flashcards in Cardio L16 Drug therapy 2 Hypertension Deck (36):
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
3. Co-arctation of the aorta
• Hormonal/ oral contraceptive
Typical feature of hypertensive heart disease
Left ventricle thickening
Treatment: 7 example
2. Ca2+ channel blockers
3. ACE inhibitors
4. α 1-adrenoceptor blockers:
5. Ang II receptor blockers:
6. K+ channel activators:
7. α –methyldopa:
Class of diuretics control hypertension (in part) by blocking the Na+ - Cl_ symporter in first part of DCT.
• 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
Ca2+ channel blockers function
Want to dilate periphery to:
1. Reduce peripheral resistance
2. Reduce filling pressure
Ca2+ channel blockers examples
1. Dihydropyridines →
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.
ACE inhibitors: function
Long-term control of BP involves renin-angiotensin system.
Examples of prototypic drugs
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.
Side effects ACE inhibitors
• Related to bradykinin (cough in 15%)
• Taste disturbances
• First dose hypotension
α 1-adrenoceptor blockers:
Beta2 receptors dilate and alpha1 receptors constrict vascular smooth muscle
α 1-adrenoceptor blockers: example
Function → antagonise noradrenaline
α 1-adrenoceptor blockers: side effects
Alpha 1 receptor
Beta 2 receptor
Adrenaline >> noradrenaline
Alpha1 adrenoceptors work via
G alpha induces
PLC which induces
IP3 and DAG leads to
SR Ca release
Angiotensin II leads to:
1. Na, water retention
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)
Ang II receptor blockers: Side effects
Ang II receptor blockers: Example
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
→ Increase permeability to K+ thereby hyperpolarizing SM cell
K+ channel activators: Side effects
Generally well tolerated
May worsen angina
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)
α –methyldopa: used for
Hypertension that does not respond to other (more modern) treatment regimens e.g. severe pre-eclampsia.
Ganglion blockers: examples
Ganglion blockers: function
Target peripheral adrenergic neuron
Ganglion blockers: Uptake leads to
Guandrel substituting for noradrenaline in secretory granules reducing sympathetic neurotransmission.