Week 1: Pathophysiology and Tx HTN 2 Flashcards
List the classes of drugs to tx. HTN
1) Diuretics
2) Beta Adrenoreceptor blockers
3) Calcium channel blockers
4) ACE inhibitors
Angiotensin 11 receptor blockers (ARBS)
Direct renin inhibitors (DRI)
Alpha adrenoreceptor blockers
How do diuretics reduce BP?
Diuretics act on the renal tubule, promoting the excretion of Na+ and water, therefore reducing blood volume and blood pressure.
Name two thiazide diuretics
Name two thiazide- like diuretics
Thiazide –> Bendroflumethiazide
hydrochlorothiazide
Thiazide- like –> Indapamide
chlortalidone
How do thiazide/ thiazide like diuretics act?
What are two key benefits of thiazide medications?
They act at distal convolted tubule
Inhibit Na+/ Cl- transport from the lumen
increase sodium and water excretion
increase potassium loss
Key benefit: Vasodilate by potassium channel activation (therefore reduce BP)
And proven to reduce heart attack and stroke
Adverse effects: high uric acid and gout; low potassium and low sodium, raised glucose and cholesterol
Name two types potassium sparing diuretics
Name two drugs from each class
What are there uses?
What are their side effects?
- Aldosterone antagonist : Spironalactone, eplerenone
- ENac (Epithelial Na+ channel) blocker: Amiloride, Triamterene
- They are weak diuretics, useful in combo with other drugs
- useful against aldosterone excess
- SE’s:
- High serum potassium
- Low sodium
- Gynaecomastia w spironolactone (Blocks aldosterone by binding MR receptor, but also decreases testosterone production, increases conversion of testosterone to estradiol and displaces estradiol from sex hormone binding globulin.)
What are the effects of beta adrenergic receptor blockers?
- Negative Inotropic effect, decrease contractility
- Negative chronotropic effect, decreases heart rate
- AV nodal conduction –> decreases velocity
- Also promote smooth muscle relaxation –> GI, Vascular, bronchial, ciliary
What are the two types of beta adrenergic receptor?
What are their downstream signalling pw’s?
Beta 1 and Beta 2
Beta 1: coupled to GPCR, activates Adenylyl cyclase, converts ATP –> cAMP, activates protein kinase –> Increase force of contraction, HR and AV nodal conduction velocity
Beta 2: coupled to Gs protein, also activates AC, also increases cAMP–> GI, vascular and brocnial/ ciliary SM relaxation
What are the two types of beta adrenergic blockers?
1) Cardio selective e.g. just beta 1, atenolol
2) non selective beta 1 and beta 2, e,g, propanolol –> careful w non selective as they can precipitate asthma by blocking bronchial SM relaxation
What is the main use of beta blockers?
Indications of beta blockers?
Beta blockers prevent both heart attack and strokes by reducing blood pressure.
Indications: tachycardia, hypertension, myocardial infarction, congestive heart failure, cardiac arrhythmias, +(coronary artery disease, hyperthyroidism, essential tremor, aortic dissection, portal hypertension, glaucoma, migraine prophylaxis)
What are the SE’s of Beta blockers?
Beta BLockers Have Really Extreme Ramifications
Bronchospasm
Bad Dreams
Lethargy
Heart Failure
Raynaud’s
Explosive diarrhoea
Reduced HDL cholesterol
Blockade of calcium channels: Where do Ca2+ channel blockers act?
Act on:
Vascular SM –> vasodilate, reduction in peripheral resistance
Cardiac myocytes and SAN/AVN –> decreased force of contraction, decreased HR
Renal tubules –> mild natriuretic and diuretic effect
Regulate influx of Ca2+ into cells
Stimulate smooth muscle and cardiac myocyte contraction
Contribute to pacemaker currents and AP’s
By blocking Calcium entry CCB’s cause??
- Vascular SM relaxation
- Decreased myocardial force generation
- Decreased HR
- Natriuresis and diuresis
What are the 3 types of CCB?
Dihydropyridines
Diltiazem
Verapamil
Compare and contrast the three types of calcium channel blockers
Dihydropyridines: Powerful vasodilators, mild natriuretic effect, tachycardic due to vasodilation (therefore increase preload and HR) increase Sodium/ Water excretion, can work with BB
Diltiazem: Long acting used for BP, vasodilator moderate, no effect on Na+/H2O balance, mild bradycardic effects, good in combination when there is intolerance to others, can work with BB
Verapamil: bradycardic (like beta blocker), cannot be used with beta blocker (contraindication), precipitates Heart block
Verapamil: , class, Two main effects, SE’s
Verapamil Class: Type 4 antiarrhythmic agent, Ca2+ channel blocker
Effects: 1) Arterial dilator 2) major cardiac inhibitory effects
Side effects:
Heart failure, Heart block (especially with beta blocker)
Peripheral oedema
constipation
Facial flushing
Headaches