Chapter 159 - Antihypertensives

Question 1

reading above what SAP/MAP/DAP x 3 consistent with hypertension in dogs?

Answer 1

150/115/95 mm Hg

Question 2

reading above what SAP.MAP/DAP x 3 consistent with hypertension in cats?

Answer 2

135/115/100 mm Hg

Question 3

single reading above what SAP/MAP/DAP consistent with treatment being required, and in what condition?

Answer 3

150/115/95 mm Hg if target organ damage

Question 4

emergency treatment required if SAP/MAP/DAP over?

Answer 4

> 180/140/120 mm Hg

Question 5

two non-vasoactive drugs associated with hypertension

Answer 5

glucocorticoids, erythropoietin

Question 6

how does glucocorticoid excess exaggerate RAAS activation? result?

Answer 6

induces hepatic production of angiotensinogen –> hypertension

Question 7

how does hyperthyroidism cause hypertension?

Answer 7

increased cardiac output - thyroid hormone effect on cardiac muscle

Question 8

list endogenous vasoconstrictors and (lack of) vasodilators that contribute to hypertension

Answer 8

vasoconstrictors: endothelin, thromboxane, vasopressin, catecholamines, angiotensin II
vasodilators: nitric oxide, prostacyclin

Question 9

3-4 mechanisms of hypertension with type II DM?

Answer 9

1. hyperinsulinemia: sodium & water retention = increased blood volume
   2: hyperinsulinemia: increased sympathetic activity; vasoconstriction; increased peripheral resistance
2. hyperinsulinemia ; mitogenic effects; hypertrophy of vascular smooth muscle; increased peripheral resistance
3. hyperinsulinemia: increased levels of intracellular Ca; hyperresponsive vascular smooth m; increased peripheral resistance

Question 10

1 mechanism of hypertension with type I DM?

Answer 10

humans = diabetic nephropathy w/ nephritic syndrome, glomerulosclerosis

Question 11

nephritic syndrome v nephrotic syndrome

Answer 11

nephritic: small pores in podocytes, thin glomerular membrane = proteinuria, hematuria
nephrotic: small pores in podocytes, increased permeability of glomerular capillary walls = proteinuria only

Question 12

how does treatment of chronic anaemia potentially induce hypertension?

Answer 12

chronic anemia > chronically dilated capillary beds > w/ resolution of anaemia, capillary constriction occurs > increased peripheral vascular resistance

Question 13

Ace inhibitors - example, MOA, side effects

Answer 13

Benazepril, Enalapril, Lisinopril (Enalaprilat can be given IV, can be used in emergencies)
Competitively inhibits conversion of angiotensin I to angiotensin II, a powerful endogenous vasoconstrictor – inhibition results in systemic vasodilation resulting in loss of arterial & venous peripheral resistance and decreased systemic blood pressure. Inhibits bradykinin degradation. Also reduces proteinuria by maintaining heparan sulfate layer of glomerular basement membrane
Side effects: weakness, lethargy, reversible azotemia/dec GFR, hyperkalemia dt aldosterone inhibition, dry cough induced by bradykinin

Question 14

Angiotensin II receptor blockers (ARBs) - example, MOA, side effects

Answer 14

Losarten
May work by inhibition of angiotensin type I receptors and dopamine D1 receptors, both of which regulate renal Na excretion and arterial blood pressure. Angiotensin type 1 receptor blockade antagonizes angiotensin II effects (vasoconstriction, sympathetic activation, aldosterone release, renal sodium resorption)
Side effects: GI upset, azotemia

Question 15

a-Adrenergic receptor antagonists- example, MOA, side effects

Answer 15

prazosin
Antagonizes a1-receptors in vessels; decreased peripheral resistance, preserves CO
Side effects: v low BP unresponsive to a1-agonists – care w/ GA

Question 16

b-Adrenergic receptor antagonists- example, MOA, side effects

Answer 16

b1,2: propranolol; b1: atenolol
Decreases sympathetic inotropic and chronotropic effects, blockade of renin release, decreased peripheral vascular resistance and decreased central adrenergic drive
Side effects: bronchospasm (not for asthmatics!), hyperK, insulin resistance, bradycardia

Question 17

Aldosterone blockers- example, MOA, side effects

Answer 17

Spironolactone, Eplerenone (latter is selective)
Nonselective blockade of aldosterone receptors at renal distal convoluted tubule & collecting duct, decreases Na reabsorption, K excretion.
Epleronone is as above but doesn’t also bind to progesterone & androgen receptors, decreases renal inflam.
Side effects: Hyperkalemia, esp when given with ACE inhib, b-blockers, ARB or w/ CKD, Eplerone assoc w/ severe hyperkalemia

Question 18

Ca channel blockers (vascular selective – dihydropyridines) - example, MOA, side effects

Answer 18

Amlodipine, nicardipine
Inhibit slow transmembrane calcium influx into vascular smooth muscle cells via voltage-gated L-type calcium channels, reducing smooth muscle contraction (arteries, arterioles & coronary arteries) and reducing systemic vascular resistance.
Side effects: reflex tachycardia, nausea, weakness, dec GFR

Question 19

Arterial vasodilators - example, MOA, side effects

Answer 19

Hydrazine, Na nitroprusside
Causes relaxation of arteriolar smooth muscle by incompletely understood mechanisms. One proposed mechanism is the inhibition of oxidation of endogenous nitric oxide, leading to prolonged/increased vasodilation.
Side effects: Reflex tachycardia, Na retention, proteinuria, GI upset. Reflex sympathetic activation, lupus-like reactions, GI upset and muscle tremors seen in people.

Question 20

Dopamine-1 agonist - example, MOA, side effects

Answer 20

Fenoldopam
Blocks dopamine 1 receptors, maintains/ increases renal perfusion while lowering BP, maintains efficacy for ~48h by CRI w/o rebound hypertension on d/c
Side effects: Reflex tachycardia, increased IOP (v. $$$)