Pharmacology II Flashcards
EDRF
Endothelial-Derived Relaxing Factor
(now presumed to be nitric oxide)
Normal Blood Pressure range
90-120 / 60-80
Stage I Hypertension range
140-160 / 90-100
Angiotensin Converting Enzyme Inhibitors
treatment for Hypertension
- no bronchospasm, bradycardia, or CHF
- no electrolyte abnormalities
- no rebound hypertension
Describe the Renin-Angiotensin-Aldosterone system
a decrease in renal perfusion triggers:
- liver to secrete angiotensinogen
- kidney secretes renin to convert angiotensinogen into angiotensin I
- endothelium secretes ACE to convert angiotensin I to angiotensin II
Effects of Renin-Angiotensin-Aldosterone system
- increase sympathetic activity
- Na and Cl reabsorption and K excretion
- aldosterone secretion
- arteriolar vasoconstriction and increased blood pressure
- Water absorption and retention
(4) ACE inhibitor examples
- Captopril (capoten)
- Enalapril (vasotec)
- Lisinopril (prinivil)
- Ramipril (altace)
Side effects of ACE inhibitors
- cough
- hypotension with induction/spinal/epidural
(4) Angiotensin Receptor Blockers
- Candesartan (atacand)
- Losartan (cozaar)
- Valsartan (diovan)
- Telmisartan (micardis)
Effects of Angiotensin Receptor Blockers
- block vasoconstrictive action of Angiotensin II
- does NOT inhibit breakdown of bradykinin
- no cough or allergy symptoms
- Hypotension with induction/spinal/epidural
(1) Direct Renin Inhibitor
Aliskiren (teckturna)
Side effects of Beta Blockers
- bradycardia and heart block
- congestive heart failure
- bronchospasm
- masking of hypoglycemia
- sedation
- impotence
Where and how is Nitric Oxide synthesized?
endothelial cells from L-arginine
Half-life of Nitric Oxide
5 seconds
(binds to the iron of heme-based proteins)
Nitric Oxide as a Pulmonary Dilator
administered by inhalation to treat primary pulmonary hypertension
- improves ventilation-perfusion mismatching
- only approved for pediatric lung injury
- Not effective if given IV because it is bound too quickly by iron
Complications of Nitric Oxide
- methemoglobinemia
- withdrawal symptoms
- rebound hypoxemia
- rebound pulmonary hypertension
- NO oxidizes to NO2
- pulmonary toxin (“silo-filler’s disease”)
Silo-Filler’s Disease
caused by inhalation of nitrogen dioxide
- symptoms similar to acute respiratory distress syndrome
Sodium Nitroprusside
direct-acting, nonselective peripheral vasodilator
- relaxes arterial and venous smooth muscle
- immediate onset and short duration
- releases cyanide and NO
Dose and Administration of SNP
0.3 mcg/kg/min
- protect from light
- must have art-line in place
- cyanide toxicity at 2 mcg/kg/min
Cardiovascular side effects of SNP
- baroreceptor mediated tachycardia
- increased contractility from afterload reduction
- decreased SVR, PVR, right atrial pressure
- dilates coronary arteries
- may cause coronary “steal”
Diagnosis of Cyanide Toxicity
tachyphylaxis, metabolic acidosis, and increased mixed venous PO2
Treatment of Cyanide Toxicity due to SNP
- 100% oxygen
- sodium thiosulfate 150 mg/kg IV
- sodium nitrate 5 mg/kg IV
- methylene blue 1-2 mg/kg over 5 niutes
Nitroglycerin
venodilator and large coronary artery dilator
- used in cardiac ischemia, CHF, and controled hypotension
- large doses cause arterial and pulmonary artery dilation
- IV, SL, TC, and oral
Nicardipine
cerebral and coronary vasodilator
- IV infusion for control of blood pressure
Hydralazine
direct arterial vasodilator
- reflex increases heart rate and contractility
- helpful in CHF
- useful in pre-existing slow heart rate
Fenoldopam
Dopamine-1 Agonist
- increases renal blood flow
- increases urine output
- reflex tachycardia and increases IOP
- increases splanchnic blood flow
Diuretics and their site of action
(picture)
(1) Carbonic Anhydrase Inhibitor example
Acetazolamide
(diamox)
Carbonic Anhydrase Inhibitor
diuretic acting on proximal tubules and collecting duct
- Treats glaucoma, pseudotumor cerebri, and altitde sickness
- sulfonamide drug
- causes metabolic acidosis
(2) Loop Diuretic examples
Flurosemide and Bumetanide
Loop Diuretics
inhibit Na+, K+, and Cl- in the thick ascending loop of Henle
- most potent diuretic
- first line therapy in CHF
- decreases CSF production
Furosemide
Loop diuretic
- oral or IV
- rapid onset
- less potent than Bumetanide
Side effects of Loop Diuretics
- Hypokalemia
- Nephrotoxicity
- aminoglycoside antiniotics and Cephalosporn
- increases Lithium levels
- Ototoxicity
(2) Thiazide diuretic examples
Hydrochlorthiazide and Chlorthalidone
Thiazide Diuretics
used for long-term treatment of hypertension
- inhibits Na+ reabsorption
- vasodilatory effect
- long half-life
Side effects of Thiazide diuretics
- hypokalemia
- hypochloremia
- metabolic alkalosis
(4) Osmotic Diuretic examples
mannitol, urea, isosorbide, and glycerin
Osmotic Diuretics
inert substances that do not undergo metabolism
- filtered by golmerulus
- effects proximal tubules and Loop of Henle
- increase plasma and renal fluid osmolality