Midterm Review Flashcards
What are the different categories of HTN?
- Normal (SBP/DBP, below 120/below 80)
- Prehypertension (SBP/DBP, 120-139/80-89)
- Stage 1 HTN (SBP/DBP, 140-159/90-99) [often controlled with a single drug]
- Stage 2 HTN (SBP/DBP, over 160/over 100) [often requires multiple drugs]
What are the compensatory reflexes to HTN treatment?
HTN → treatment → decreased BP →
(1) increased sympathetic outflow → tachycardia → increased blood pressure
(2) increased renin release → salt and retention → increased blood pressure
ACE inhibitors?
Lisinopril, Captopril, Enalapril
ACE inhibitors prevent the conversion of angiotensin I to angiotensin II. Therefore the vasoconstriction from angiotensin II cannot be performed (esp effect of effect renal artery causing decreased peritubular hydrostatic pressure and increased sodium and water reabsorption) as well as release of aldosterone.
ACE inhibitors are used for pts wtih HTN (esp diabetic/non-diabetics who need renal function preserved), chronic HF, and post MI.
Bradykinin (vasodilator) is usually broken down by ACE and when it is inhibited there is an increase in bradykinin levels leading to even more vasodilation (causing angioedema) as well as a dry cough.
Other side effects include: hypotension, hyperkalemia, acute renal failure in pts with bilateral renal artery stenosis
**do not use in patients who are pregnant as it may cause fetal hypotension, anuria or renal failure or patients with bilateral renal artery stenosis
ARB blockers?
Losartan (“-artan”)
ARBs block the type 1 receptors of angiotensin-2 causing a decreased sodium and water retention but increased arteriolar and venous dilation. These drugs are alternatives to patients who cannot handle the bradykinin induced cough with ACE inhibitors. [These pts have increased angiotensin II levels as their receptors are being blocked.]
Decreased risk of angioedema due to break down of bradykinin and there is a lack of a dry cough.
other side effects include hypotension, hyperkalemia, acute renal failure
**do not use in pts who are pregnant or have bilateral renal artery stenosis
Aliskiren?
Aliskiren is an renin inhibitor used to treat HTN preventing the conversion of angiotensinogen to angiotensin I. The end result is a decreased in aldosterone production therefore decreased absorption of sodium and water.
Side effects include: hyperkalemia, hypotension, low risk of angioedema, acute renal failure, and altered taste (same as ACEIs and ARBs)
What Ca2+ chanbel blockers can be used to treat HTN?
Block L-type calcium channels allowing for relaxation of myofibril and vascular SM. Used to control HTN in black or elderly opts, or pts with diabetes or asthma.
- Verapamil [non-dihydropyridine] - side effects include constipation and negative inotropic effects so don’t take if pt is on B-blocker, has 2nd or 3rd deg block or LV failure
- Diltiazem [non-dihydropyrdine]
- Nifedipine [dihydropyrdine] (1st generation)
- Amlodipine [dihydropyrdine] (2nd generation)
Non-dihydropyridine - not selective, binds vSM as well as cardiac muscle therefore can treat HTN as well as arrhythmias
Dihydropyridine - selective for vSM – high doses can increase risk of MI because it causes massive reflex cardiac stimulation post hypotension - can cause gingival hyperplasia
What B-blockers can be used to treat HTN?
- Propranolol → non-selective B1 and B2 receptor antagonist
- Metoprolol and Atenolol [most common] → selective B1 receptor antagonists
- Pindolol → non-selective B1 and B2 partial agonist with intrinsic sympathomimetic activity [preferred B-blocker in pregnancy]
B-blockers decrease renin release as well as CO, HR and contractility - there may be sympathetic reflex with exercise
Adverse effects include:
- bradycardia
- CNS effects – fatigue, lethargy, insomnia, hallucinations
- Hypotension
- Decreased libido and impotence
- Disturbed lipid metabolism → increased TAGs and decreased HDL
- Hypoglycemia (B2 blockers)
- Drug withdrawal → therefore there is a need to taper off dose in pts
- Propranolol is contraindicated in asthmatics and COPD pts
a1 blocker tx of HTN?
Prazosin and Doxazosin are competitive a1-adrenoceptor blockers. They decrease peripheral vascular resistance and arterial BP by relaxing BOTH arterial and venous smooth muscle. Unlike thiazides and furosemides, there is sodium and water retention to decrease bp and decreased perfusion to kidneys so with chronic use Na+ and water retention needs to be managed. These drugs have more side effects than other antihypertensives, therefore are no recommended as first line treatments.
Because of a1 selective effect, the NE in the synapse is able to create a negative feedback mechanism on the a2 receptors thereby decreasing amt of NE released - this can help decrease the risk of reflex tachycardia.
Tx: HTN, BPH, HF
Adverse effects
- orthostatic hypotension upon first dose or large increases in dose
- concomitant use of B-blockers may be necessary to blunt reflex tachycardia
- dizziness, drowsiness, headache, lack of energy, nausea, palpitations
- Doxazosin is shown to increase rate of congestive HF on its own
- Na+ and water retention - with chronic administration therefore you should administer with diuretic to minimize potential for edema
What is Labetalol? (HTN)
This is a mixed a- and B-blocker that can be administered orally and parenterally. It is used in the management of HTN (even with pregnant women). It is generally given IV for a RAPID REDUCTION in BP during HYPERTENSIVE EMERGENCIES. An advantage of Labetalol is that there is a decrease in BP associated with a1-blockade WITHOUT the reflex tachycardia.
-orthostatic Hypotension may be seen upon 1st use
Clonidine and methyldopa (HTN)
central a2-agonist used in emergencies. They decrease sympathetic output and BP but not renal blood flow or CO. Clonidine may cause reflex tachycardia upon withdrawal.
Methyldopa associated with positive Coombs test and depression.
Which drugs are direct vasodilators?
Hydralazine and Minoxidil – these are NOT used as first-line anti-hypertensives. They act directly on vascular SM as relaxants. The vascular relaxation produces reflex tachycardia and increases plasma renin causing sodium and water retention. Major side effects can be prevented if combined with diuretic and B-blockers.
Hydralazine AE:
- fluid retention
- reflex tachycardia
- reversible lupus-like syndrome
- headache, nausea, sweating, flushing
- usually administered with B-blocker and thiazide
Minoxidil AE:
- reflex tachycardia
- fluid retention
- Hypertrichosis → causes excessive hair growth
What are the treatments for pulmonary HTN?
- prostaglandins [epoprostenol] - Synthetic PGI2 that lower peripheral pulmonary and coronary resistance via a vasodilatory effect. It is given via continuous infusion. Adverse effects include flushing, headache, jaw pain, diarrhea and arthralgias.
- inhibitors of endothelin synthesis and action [bosentan] - Nonselective endothelin receptor blocker that blocks both the initial transient depressor (ETA) and the prolonged pressor (ETB) responses to endothelin. This medication falls into pregnancy category X [aka DO NOT USE!].
- vasodilators [Sildenafil] - Inhibitor of phosphodiesterase 5 (PDE5). It increase the amt of cGMP leading to smooth muscle relaxation. Adverse effects include headache, flushing, dyspepsia and cyanopsia (BLUE VISION). Contraindications include individuals on nitrates b/c they also give an increase in cGMP leading to a possible hypotensive crisis.
Discuss what occurs at the proximal tubule, thick ascending limb, distal convoluted tubule and collecting duct.
proximal
Proximal tubule → reabsorbs 65% filtered Na, 85% NAHCO3, 65% K+, 60% water, all glucose and AA. The most important ions in regards to diuretic actions are NaHCO3 (sodium bicarb) and NaCl (sodium choride). The Na+-H+ antiporter movement from lumen then into blood via Na+-K+ transporter is the main driving force for water reabsorption. HCO3- wants to be reabsorbed as well but has poor permeability so via the carbonic anhydrase enzyme it is converted to H2CO3 → OH- + CO2. CO2 quickly diffuses into cell and OH- turns to water with the addition of a proton. CO2 in the cell quickly turns back to H2CO3 then intracellular carbonic anhydrase dissociates it to H+ (for the antiporter) and HCO3-.
Thick ascending
The thick ascending loop of henle receives hypertonic filtrate and allows for reabsorption of NaCl without water. Na+ is reabsorbed via Na+/K+/2Cl- cotransporter (NKCC2). Cl- exits basolateral side of cell, Na+ exits via Na+/K+ ATPase on basolateral side and K+ is recycled back to the lumen for the NKCC2 function. There is also additional reabsorption of Na+, Ca2+ and Mg2+ from lumen to the interstitium driven by K+ recycling.
Distal convoluted
Distal convoluted tubule activity reabsorbs4-8% of filtered NaCl. Na+ enters via Na+/Cl- cotransporter (NCCT) and Na+ exits on basolateral side via Na+/K+ ATPase. Ca2+ is reabsorbed via Na+/Ca2+ exhcnagers.
Collecting duct
The collecting duct is the final site of NaCl reabsorption and this determines the final Na+ concentration in the urine. Luminal Na+ enters cell via ENaC and exits basolateral side via Na+/K+ ATPase. K+ is secreted into the lumen. ENaC and K+ movement is under the control of aldosterone. Collecting duct also expresses vasopressin (ADH) channels that controls the permeability of the collecting tubule to water. (without ADH the urine is dilute)
Loop diuretics
Furosemide - blocks NKCC transport preventing K+ recycling leading to hypocalcemia (increasing kidney stones), hypomagnesemia, hypokalemia (due to increased na+ reabsorption in CD), hyperuricemia, increased COX-2 production. May result in gout and ototoxicity.
All together by decreasing sodium and water reabsorption there is a decrease in renal vascular resistance and an increase in renal blood flow.
Thiazide diuretics
hydrochlorothiazide, chlorothalidone, metalazone - block NCCT transporter, increases Ca2+ reabsorption decreases calcium stone risk.
AE: hyponatremia and hyperGLUC, hypokalemia (increased absorption in CD)
K+ sparing diuretics
Spirnolactone, eplernone - blocks aldosterone receptors [aldosterone dependent]
Spirnolactone AE - galactorrhea (progesterone and androgen receptors activated), hyperkalemia, peptic ulcers, hyperchoremic metabolic acidosis
Amiloride, Triamterene - ENaC blockers, not dependent on aldosterone
AE - hyperkalemia, hyponatremia, Triamterene (photosensitivity, interstitial nephritis, renal stones, reduced glucose tolerance)
carbonic anhydrase inhibitors?
Carbonic anhydrase inhibitors [ACETAZOLAMIDE] inhibit intracellular and extracellular forms of carbonic anhydrase resulting in a reduction of bicarb reabsorption in the proximal convoluted tubules and decrease production of H+ inside the cell therefore decreasing Na+/H+ antiporter activity. This decreases Na+ reabsorption. This drug only has a mild diuretic action b/t bicarb depletion enhances NaCl reabsorption by remainder of nephron.
Used to treat…
- Glaucoma → decreases formation of aqueous humor and thereby decrease intraocular pressure, pre-op management of angle-closure glaucoma and tx for open-angle glaucoma
- Mountain sickness → excrete bicarb, acidify blood, increase ventilation, increase amt of O2 in blood
- Metabolic alkalosis → increased H+ in blood
- Epilepsy
* medication is given orally and is excreted unchanged in proximal renal tubule – therefore, dose must be reduced if there is renal insufficiency
AE
- metabolic acidosis → reduction in bicarb stores
- hyponatremia
- hypokalemia
- renal stones (Crystalluria) → phosphaturia and hypercalciuria during bicarbonaturic response
- malaise, fatigue, depression, drowsiness, paresthesias (with large doses)
- hypersensitivity allergic reactions
Mannitol?
Osmotic diuretics - increase osmotic pressure of the plasma thus draws water out of the body tissue and produces osmotic diuresis. Osmotic diuresis expands the extracellular fluid volume, decreases blood viscosity and inhibits renin release. There is an increased urine excretion of nearly all ions/electrolytes: Na+, K+, Ca2+, Mg2+, Cl-, bicarb, phosphate. There is no effect on sodium excretion directly only that it increases urine volume. Administered via IV b/c low oral bioavailability
Used for..
- reduction of increased intracranial pressure associated with cerebral edema
- reduction of increased intraocular pressure
- promotion of urinary excretion of toxic substances
- genitourinary irrigant in transurethral prostatic resection
- other transurethral surgical procedures
AE
- extracellular volume expansion and hyponatremia
- tissue dehydration
Contraindicated for
Active cranial bleeding, CHF, pulmonary edema
Conivaptan
ADH antagonist - activates and inhibits CYPT3A4, administered via IV in people with hypervolemia hyponatremia, SIADH, and heart failure
AE
- nephrogenic diabetes insipidus
- infusion site reactions
- atrial fibrillation, GI and electrolyte disturbances
Contraindicated for patients
- kidney failure
- hypovolemia hyponatremia
What drugs are used in hypertensive crisis?
- sodium nitroprusside - may cause cyanide toxicity that is fixed with sodium thiosulfate – best drug b/c it releases NO from its structure
- Labetalol - a,b antagonists therefore doesn’t cause reflex tachy - do not use with pts with asthma or cardiac conditions (2nd or 3rd deg block)
- Fenoldopam - D1 agonist that causes arteriolar dilation but maintains kidney perfusion, promotes naturesis, contraindicated for pts with renal insufficiency and glaucoma
- Nicardipine (Ca2+ blocker)
- nitroglycerin (venodilator)
- Diazoside (stablizes membrane by allowing K+ channel to remain open, also decreases insulin release so can be used to treat hypoglycemia)
- Phentolamine - catecholamine emergency
- Esmolol - aortic dissection or post op Hypertension
- Hydralazine - arterial dilator
What are the different classifications of heart failure described by the AHA? What treatments should be used at each stage?
Stage A → high risk for developing heart failure (HTN, diabetes, CAD, hx of cardiomyopathy)
Stage B → asymptomatic heart failure (previous MI, LV dysfunction, valvular disease)
Stage C → symptomatic heart failure (structural heart disease, dyspnea, fatigue, impaired exercise tolerance)
Stage D → refractory end-stage heart failure (marked symptoms at rest despite maximal medical therapy)
Stage A → ACEI, ARB
Stage B → ACEI, ARB, B-blockers
Stage C → diuretics, ACEI, B-blocker [routine drugs], aldosterone antag, ARB, digoxin or hydralazine/isosorbide dintrate [if symptoms do not improve]
Stage D → specialized therapies, continuous support, continuous IV positive inotropic therapy, cardiac transplantation or hospice care
What are the neurohumoral compensatory responses to HF?
- Sympathetic nervous system activation – low bp is detected by the baroreceptors leading to B1-activation increasing both HR and contractility. A1 receptors are also activated causing increased peripheral resistance.
- RAA activation – decreased CO, decreased blood flow to kidneys stimulating renin release therefore increasing peripheral bp
- Increased release of ADH and ANP
What is the basis behind long term treatment of HF?
- RAA inhibition
- SNS activation
* These decrease amt of cardiac remodeling. Remodeling is irreversible so surgical intervention is the only tx when drugs stop working.
* *reduce preload, reduce afterload, enhance inotropic state
ARBs used for HF?
Candesartan
Valsartan