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Define Hypertension
Persistently high blood pressure
MOA of Diuretics
Depletes body sodium stores which increases water loss from
body, resulting in decreasing blood volume and lowered cardiac output
resulting in lower BP. In short, diuretics ‘dehydrate’ the body
Side effects of Diuretics
1.Hypokalemia (low K) except for potassium-sparing diuretics
2. Hyponatremia (low Na)
3. Impaired glucose tolerance
4. Increase serum lipids
5. Hyperuricemia (may precipitate gout)
MOA of Beta-Blockers
Initially when therapy is first started , ↓HR leading to ↓CO.
- But reflex peripheral vasoconstriction kicks in to counter the above effects so Systemic vascular resistance (SVR) up , no ↓ in BP
Within a few days, inhibition of release of Noradrenaline leading to SVR ↓; BP ↓
Side effects of BB
- Bradycardia (slow heart rate)
- Fatigue, reduced exercise capacity
- Smooth muscle spasm (Bronchospasm, Cold
Extremities) - Increase insulin resistance (hyperglycemia)
- Insomnia, vivid dreams, depression
Calcium Channel Blocker (CCB)
2 Categories
- Dihydropyridines (DHP)
- Non-dihydropyridines (Non-DHP)
MOA of Calcium Channel Blockers (CCB)
Peripheral arterial dilation : Lowers SVR hence lowers BP
Mild diuretic effect (especially DHPs)
* Inhibit aldosterone
* Na+ reabsorption decrease
* Overall fluid retention decrease
Side effects of CCB
Minor Side Effects
1. Bilateral ankle oedema
2. Headache
3. Flushing
4. Constipation
Severe & Rare Side Effects
1. Excess hypotension, resulting in organ under-perfusion
2. Myocardial ischemia
3. Renal failure
MOA of Angiotensin-Converting Enzyme Inhibitor (ACE-I)
Inhibits Angiotensin Converting Enzyme (ACE) to inhibit the formation of Angiotensin II (AT2) which:
Decrease aldosterone secretion for a diuretic effect
and Vasodilation leading to SVR decrease
Side effects of ACE-I
- Dry cough (due to accumulation of bradykinin)
- Angioedema (higher risk in African American)
- Acute kidney injury (AKI)
- Hyperkalaemia (especially with K-retaining diuretics)
Almost no contraindications (except for bilateral renal artery stenosis)
MOA of Angiotensin-II Receptor Blocker (ARB)
Blocks AT-2 receptors which decreases aldosterone
secretion leading to diuretic effect
also leads to vasodilation that results in SVR decrease
MOA of Renin Antagonist and Example
Inhibits renin to inhibit formation of AT2
Aliskiren
MOA of Alpha Blocker
Blocks alpha-receptor to reduce stimulation by adrenaline or noradrenaline
leading to vasodilation, SVR decrease
May also improve lipid profile
Example of Alpha Blockers (3)
- Prazosin
- Terazosin
- Clonidine
Loop Diuretics examples (3)
Frusemide
Bumetanide
Torsemide
Loop diuretic MOA
Loop diuretics inhibit Na + /K+ /2Cl - cotransporter at ascending limb of Loop of Henle
Chloride, sodium and potassium ions remain intra-luminally and will be lost in urine
Advantages of loop diuretics
Advantages :
* Superior fluid clearance for the same degree of natriuresis
* Works even in presence of renal impairment
* Increasing diuretic response with increasing dose
Side effects of loop diuretics
Ototoxicity
Hypokalemia (very common !)
hyponatremia
Metabolic alkalosis
Hyperuricemia – acute kidney injury (AKI)
Hypomagnesemia
Hypocalcemia
Examples of Thiazide Diuretics
Hydrochlorothiazide
Chlorthialidone
Metalazone
Indapamide
MOA of thiazide diuretics
Thiazides inhibit reabsorption of sodium and chloride in distal part of nephron
More sodium reaches distal tubules
Stimulate exchange with potassium, particularly in presence of renin-angiotensin- aldosterone system
Difference between Loop and Thiazide diuretics
Longer duration of action
Different site of action (ascending loop of Henle vs early distal tubule)
Thiazides have decreased capacity to work in presence of renal failure
Side effects of thiazide diuretics
Hypercalcemia due to proximal tubular reabsorption of calcium increase
Ototoxicity
Examples of potassium sparing agents
Amiloride
Triamterene
Spironolactone
Eplerenone
MOA of Amiloride and Triamterene
A & T inhibit sodium-proton exchanger which is concerned with sodium reabsorption in distal tubules
Since K+ secretion is coupled with Na+ entry, the decrease in Na+ entry helps to reduce K+ exit which leads to potassium-sparing
Effects of angiotensin 2
Efferent arterioles of glomerulus -> Vasoconstriction increase in Glomerular Pressure
Adrenal Gland releases Aldosterone, increase Na+ reabsorption, increases H2O retention, which increases BP
Adrenal Gland release Adrenaline & Noradrenaline which increases BP
MOA of aldosterone antagonists
Spironolactone is a synthetic steroid that acts as competitive antagonist to
aldosterone. Eplerenone is an analogue of spironolactone with greater affinity to aldosterone receptor
Aldosterone is a hormone that stimulates the reabsorption of sodium ions and secretion of potassium ions along the DCT and the collection duct
ACE-Is: Examples of Prodrugs
Enalapril (prototype)
Perindopril
Fosinopril
Quinapril
Delapril
Ramipril
What is Class 1 of ACE-Is
Captopril
Example of Class 3 ACE-I
Lisinopril (Water Soluble)
Side Effects of ACE-Is
Side Effects
* Cough – common
* Hypotension
* Hyperkalemia
* Deterioration of renal function – related to hypotension
* Angioedema – rare
* Neutropenia - captopril
Why is there cough when taking ACE-Is
Due to increased formation of bradykinin
Increased sensitivity of cough reflex leads to dry Irritating nonproductive cough
MOA of ARBs
Direct blocking of angiotensin II receptors
- Similar effects of ACE inhibition
* However it avoids bradykinin-related side effects of ACE
inhibitors
* E.g. cough and angioedema
Examples of ARBs
Losartan
Candesartan
Irbesartan
Valsartan
Telmisartan
Olmesartan
Eprosartan
Side effects of ARBs
- Cough – uncommon
- Hypotension
- Hyperkalemia
- Deterioration of renal function – related to hypotension
- Angioedema – rare
