anithypertensives

Question 1

When is antihypertensive treatment indicated?

Answer 1

• > 2 measurements > 140mmHg SAP or
• 1 measurement > 180mmHg SAP

Question 2

Name 5 classes of antihypertensive medications.

Answer 2

1. ACEi
2. angiotensin-receptor blockers
3. calcium channel blockers
4. adrenergic antagonists
5. aldosterone antagonists
6. Arteriolar vasodilators
7. fenoldapam

Question 3

What is the MOA of ACEi, what is the effect on the afferent and efferent renal arteriole, how are they metabolised and excreted and what are adverse effects?

Answer 3

MOA: inhibition of angiotensin-converting enzyme –> no conversion of ATI to ATII –> RAAS inhibition
effects:
* arteriolar vasodilation (efferent > afferent) –> reduced GFR + improved renal perfusion –> decreased proteinuria
* reduction of Na+ and water reabsorption
* reduction in ECV
* reduced degradation of bradykinin by ACE –> vasodilation

metabolism: liver
excretion: renal

adverse effects:
* worseninig of GFR (especially in dehydrated or azotemic patients and patients receiving diuretics): >30% increase in creatinin in 24% of cats with CKD
* hyperkalemia

Question 4

What is the MOA of angiotensin receptor blockers, what is the effect on the afferent and efferent renal arteriole, how are they metabolised and what are adverse effects?

Answer 4

MOA: block the ability of ATII to activate its receptor
effects:
* arteriolar vasodilation (efferent > afferent) –> reduced GFR + improved renal perfusion –> decreased proteinuria
* reduction of Na+ and water reabsorption
* reduction in ECV

metabolism: liver (glucuronidation - cat’s genetic defect does not affect this)

adverse effects:
* worsening GFR
* GI effects (Vx, Dx)
* anaemai (cats)
* raised liver enzymes (cats)

Studies:
* PLE: Telmisartan + ACEi –> significant reduction in BP + proteinuria (better than single)
* telmisartan –> decrease in SAP to <160mmHg in 60% of dogs
* telmisartan –> effective at reducing SAP by 24mmHG at 14 + 28d

Question 5

What is the MOA of aldosterone antagonists, how are they metabolised and excreted and what are adverse effects?

Answer 5

MOA: selective competitive aldosterone antagonist –> blocks its effects on principal + intercallated cells of DCT
effects:
* reduction of Na+ and water reabsorption
* reduction in ECV
* reduction in glomerular remodeling + inflammation induced by chornic aldosterone exposure

metabolism: liver
excretion: feaces (70§), urine (20%)

adverse effects:
* hyperkalemia (unlikely unless used with ACEi, ARB, b-blockers)
* facial dermatitis (cats)
* hyponatreima
* dehydration
* CNS effects (ataxia, lethargy)

Question 6

What is the MOA of calcium channel blockers, what is the effect on the afferent and efferent renal arteriole, how are they metabolised and what are adverse effects?

Answer 6

MOA: dihydropyridine L-type calcium channel blocker –> inhibits voltage-gated calcium channels in cardiac and vascular smooth muscle
–> amlodipine + nicardipine: relative selectivity for vascular smooth muscle L-type calcium channels –> primarily found in afferent arterioles

effects:
* increased glomerular filtration pressure –> worsen proteinuria
* vasodilation
* reduced SVR

metabolism: liver

adverse effects:
* gingival hyperplasia
* hypotension
* anorexia
* lethargy
* weakness
* worsening of proteinuria
* RAAS stimulation with chronic use

Question 7

What is the MOA of adrenergic antagonists, what is the effect on the afferent and efferent renal arteriole, how are they metabolised and what are adverse effects?

Answer 7

reduction of SNS activity via:

effects:
1. a1-receptor blocker (prazosin: selective, competitive; phenoxybenzamine: noncompetitive, nonselective, acepromazine): vasodilation - phaeos
2. b1-receptor blocker (atenolol = relatively selective, propanolol = non-selective): negative inotropy + chronotropy - phaeos add on (should not be used without a1-blockage –> can cauase excessive vasoconstriction!)
3. mixed a1 and b1-receptor blocker (labetolol): vasodilation without reflex tachycardia - used in craniotomy + adrenalectomy
+ Na+ and water retention

metabolism: liver
excretion: biliary (+ urine for phenoxy + atenolol), faeces (atenolol)

adverse effects:
* GI upset
* hypotension
* excessive bradycardia (b-blockers)

Question 8

What drugs might be used to manage a hypertensive crisis? What is their MOA + adverse effects?

Answer 8

Hydralazine: semicarbazide-sensitive amine oxidase inhibitor (SSAO) –> alters cellular Ca2+ metabolism in smooth muscle cells; rapid onset of action, IV
adverse effects: reflex tachycardia, GI upset, irreversible excessive hypotension, Na+ and water retention

Sodium nitroprusside: causes NO release –> diffuses to vascular smooth muscle cells –> decreases intracellular Ca2+ influx –> relaxation
adverse effects: cyanide and thiocyanate toxicity (high + prolonged doses)
Alternative: nitroglycerine IV (does not cause cyanide toxicity)

Question 9

What is the MOA of fenoldapam? What are adverse effects?

Answer 9

= selective postsynaptic D1- receptor agonist –> peripheral + renal vasodilation
–> + antagonizes alpha-receptors (a2 > a1) at higher doses –> vasodilation
effect:
* natriuresis
* increased GFR