CVS Drugs Flashcards
Give two examples of ACEi ?
Lisinopril
Ramipril
Describe the MoA of ACEi
ACE inhibitors act by binding to ACE and therefore decrease production of AngII.
Normal effects of AngII:
- activates sympathetic NS –> vasoconstriction
- acts on adrenal medulla to release aldosterone. Aldosterone acts on basolateral membrane of DCT and CT –> taken up into the principal cell where it causes nuclear transcription of ENaC. ENaC then displayed on apical membrane and results in increased Na+ uptake and therefore H20 retention.
- acts on posterior pituitary to release ADH –> increases AQP2 channels in apical membrane of CD –> increased water reuptake.
- acts directly on the kidney –> constriction of afferent arteriole, increases activity of NHE and NaK ATPase in PCT to increase Na+ reabsorption
- stimulates thirst centre
Therefore by inhibiting ACE:
- can cause decrease in BP
- can decrease glomerular pressure as ACEi induces glomerular efferent arteriolar vasodilatation and therefore reduces renal filtration pressure(this actually may be damaging especially in case of renal artery stenosis)
What are the indications for use of ACEi?
- First line treatment for HTN in white patients under 55 years old. 2nd line for all HTN patients with CCB.
- HF - reduces mortality and improves symptoms
What are the contraindications and cautions for ACEi use?
Cardiac: severe aortic stenosis (risk of hypotension), postural hypotension (Especially first dose)
Renal and electrolyte: risk of renal impairment!!! And hyperkalaemia!!
Bilateral renal artery stenosis is contraindicated.
Should not really be used in conjunction with NSAIDs as these act on afferent arterioles –> constriction.
Why should ACEi be given with caution in patients with renovascular disease?
ACEi cause efferent arteriole vasodilation and consequently reduces renal filtration pressures
Any additional reduction in pre-glomerular pressures may lead to significant reduced renal filtration and result in renal failure
Caution therefore required with hypovolemia and diuretic use, renal artery stenosis (bilateral renal artery stenosis contraindicated) and concomitant NSAID use (reduced PG mediated afferent arteriolar constriction)
When there is bilateral renal artery stenosis - the effective renal bf is not significantly reduced but maintained at the cost of increasing the efferent arteriolar constrictor tone. This helps maintain intraglomerular pressure.
When ACEi use - efferent arteriolar tone is removed -> triggers intraglomerular pressure to drop suddenly and filtration pressure reduces.
ADRs of ACEis?
Angioedema - due to accumulation of bradykinin
Dry cough - due to accumulation of bradykinin as ACE is a kininase and without it –> increased bradykinin
Renal failure - due to efferent arteriolar dilation –> decreases renal perfusion pressure
Hyperkalaemia
Orthostatic hypotension
How do ACEis cause hyperkalaemia?
As AngII acts directly on the kidney to cause Na+ reabsorption via aldosterone and thus K+ excretion, without AngII effects –> less K+ excretion and more K+ retention –> hyperkalaemia
Aldosterone –> increased ENaC which creates negative lumen which allows loss of K+ in urine. Also, increased Na+K+ ATPase needed which also promotes K+ loss
Give an example of an Angiotension Receptor Blocker?
Losartan
Candersartan
Why is the first dose of an ACEi given at night?
To avoid symptomatic postural hypotension
What is the drug treatment of HTN?
Step 1: if <55 and white: ACEi / ARB. If >55 or black give CCB
Step 2: ACEi (or ARB) + CCB
Step 3: ACEi/ARB + CCB + Thiazide diuretic
What type of diuretic is most commonly used in the treatment of HTN?
Thiazide diuretic
Give two examples of a thiazide diuretic?
Indapamide
Bendroflumethiazide
What are the indications for use of thiazide diuretics?
HTN
Oedema (use with loop diuretic)
Prevent of renal calculi (ca2+ reabsorption increased therefore decresed in urine)
Contraindications of thiazide diuretics?
Gout (as causes hyperuricaemia)
Long standing hypokalaemia or hyponatraemia
Hypercalcaemia
What are some ADRs of thiazide diuretics?
Postural hypotension (especially when used in conjunction with ACEi or ARB)
Hypomagnesiumaemia, hyponatraemia, hypokalaemia
Hypercalcaemia
Hyperuraemia –> gout
Interaction between NSAIDs and thiazides?
NSAIDs decrease diuretic effect
What class of Calcium channel blockers are used in hypertension? Give two examples.
Dihydropyridines
E.g. Nifedipine and amlodopine
Dihydropyridines better for HTN as more selective for SM receptors
What is the MoA for CCBs?
CCBs block L-type Calcium channels (present in cardiac and SM tissue) which results in decreased influx of Ca2+ –> relaxation of muscle i.e. Vasodilation.
Acts in SM to vasodilate
In heart : negative inotrophy (force of contraction) and chrontropy (HR)
ADRs of amlodopine/nifedipine?
Amlodopine is a dihydropyridine - acts selective of L-type Calcium Channels in SM
Vasodilatory effects: palpitations, flushing,
Peripheral oedema - common
Orthostatic hypertension
Give two examples of loop diuretics?
Indapamide and Furosemide
How do loop diuretics work?
Act on TAL on LoH and inhibit Na+ K+ 2 Cl- cotransporter. Therefore decreased Na+ reuptake. Water follows.
Significant effect on diuresis.
When should loop diuretics be used?
Heart failure (decrease preload and afterload)
Acute pulmonary oedema (IV furosemide for quick fix)
Oedema due to other causes: nephrotic syndrome, renal failure, cirrhosis
Common ADRs of furosemide?
Hyponatraemia, hypocalcaemia, hypokalaemia
Ototoxicity (usually reversible)
Hyperuricaema –> gout
N+V
What risk is associated with taking ACEi/ARBs with loop diuretics or thiazide diuretics?
1st dose hypotension
Why should NSAIDs be avoided when taking loop diuretics?
NSAIDs inhibit PG production which therefore inhibits diuretic effect which partially relies on stimulating PG production for its vaso/venodilatory effects
Give two examples of potassium sparing diuretics and state how each works.
Amiloride - directly blocks ENaC. Inhibits uptake of Na+.
Spironolactone - Aldosterone antagonist.Inhibits aldosterone binding –> decreased transcription of ENaC –> decreased Na+ reabsorption. No change to luminal charge therefore results in no loss of K+.
Both act in late DCT/CD
ADRs of spironolactone?
Has anti-androgen effects (antagonism of DHT i.e. Testosterone at its binding site): irregular menstruation, painful gynaecomastia, impotence, hirsuitism
Hyperkalaemia
Indications for use of spironolactone?
Liver cirrhosis: ascites
HF - congestive
Nephrotic syndrome
Primary hyperaldosteronism
When is mannitol used and how does it work?
Mannitol works on the PCT
IV mannitol used to treat cerebral oedema
Why must you give spironolactone for ascites related to liver cirrhosis?
Hypokalaemia can precipitate hepatic encephalopathy!
Spironolactone is potassium sparing whereas most other diuretics cause hypokalaemia
