Diuretics and Anti-hypertensives Flashcards
What is mannitol?
A non metabolized and non reabsorbed sugar that acts in the proximal tubule. It is considered an osmotic diuretic. It draws free water out of the tissue and into the circulation where it is excreted by the kidneys.
It is not used as an antihypertensive drug. It’s used to maintain hydration (mostly in surgical situations). It makes sure that there is maintained perfusion during transplants.
It can also be used to manage elevated intracranial pressure.
What is acetazolamide?
It is a carbonic anhydrase inhibitor that acts in the proximal tubule which results in an elimination of bicarbonate to induce metabolic acidosis.
It is used for glaucoma to decrease intraoccular pressure.
It is used to prevent acute mountain sickness (to counteract respiratory alkalosis).
Where do loop diuretics act?
They act on the Na/K/2Cl cotransporter in the thick ascending limb of the loop of henle.
What are loop diuretics used for? (4)
- Volume overload
- heart failure
- BP reduciton
- pulmonary edema
What are side effects of loop diuretics? (4)
- Decreased K/Mg
- Hypocalcemia
- Precipitate gout attack
- Metabolic alkalosis (Because loop and thiazide diuretics increase sodium delivery to the distal segment of the distal tubule, this increases potassium loss (potentially causing hypokalemia) because the increase in distal tubular sodium concentration stimulates the aldosterone-sensitive sodium pump to increase sodium reabsorption in exchange for potassium and hydrogen ion, which are lost to the urine. The increased hydrogen ion loss can lead to metabolic alkalosis.)
What is the duration of action for furosemide?
4-6 hours.
Furosemide is also called Lasix so remember la “SIX”.
Do not give before going to bed because the patient will have to wake up to urinate. It’s best to give once in the morning and another time early in the afternoon.
True or False: Torsemide has longer duration of action and greater bioavailability than furosemide
True.
Furosemide is 4-6 hours with 40-70% bioavailability.
Torsemide is 12-16 hours with 80-90% bioavailability.
Which loop diuretic would you give for a patient with sulfa allergies? Would a patient who is allergic to sulfonamide antibiotics have a reaction to loop diuretics?
Ethacrynic acid. It is the only non-sulfa containing loop or thiazide.
Patients who have allergies to sulfonamide antibiotics are not necessarily allergic to the sulfa loop diuretics. They are different.
What is the most potent loop diuretic?
Bumetanide. 1 mg of bumetanide is equal to about 20 mg of other loop diuretics.
Where do thiazide diuretics act? Do they cause much diuresis?
They act in the distal convoluted tubule at the Na/Cl cotransporter.
They don’t cause much diuresis. They are effective at achieving their antihypertensive effect without producing much urine. Typically, when a patient is started on thiazide diuretics, they will transiently have more urine production but this side effect decreases.
What are side effects of thiazide diuretics?
- Hypokalemia
- Can precipitate gout attacks
- Can cause dehydration
- Hypercalcemia (opposite of loop diuretics)
- Hyperglycemia (in patients who are at high risk of developing hyperglycemia or diabetes)
What is the most common thiazide diuretic? What might you consider if you want to have a drug with a longer half life?
Hydrochlorothiazide (very inexpensive)
Consider chlorthalidone if you want a longer halflife. It has a halflife of 40-60 hours compared to HCTZ which has 2.5. It’s more expensive though.
Which diuretic is considered “first line”?
Thiazides
What is a situation that causes thiazide diuretics to lose their efficacy?
When GFR falls below 30.
Thiazide diuretics lose efficacy in later stages of CKD as less drug reaches the site of action as the kidney fails.
More efficacious loop diuretic use is necessary when GFR is below 30 and the loop diuretics are often paired with metalozone (a thiazide that is the exception to this rule. It is very potent and can work with CKD in conjunction with loop diuretics)
What 2 thiazide diuretics are still shown to have efficacy below the 30 gfr cutoff in patients with CKD?
Chlorthalidone and metalozone
Where do potassium sparing diuretics act?
They act at the collecting tubule binding to aldosterone dependent Na/K exchangers.
Spironolactone and eplerenone competitively inhibit the mineralocorticoid receptors (with eplerenone being more specific so it has less side effects).
What are potassium sparing diuretics usually used in combination with and why?
Thiazide and loop diuretics. They are used to counter the potassium wasting (hypokalemia) effect of thiazides and loop diuretics.
What is a side effect of spironolactone?
gynecomastia (enlargement of male breasts)
True or False: ACE inhibitors and ARBs are contraindicated for pregnancy
True. Also, much of the damage is done in the first trimester before people know they are pregnant so it’s a good idea to take them off their ACE inhibitors or ARBs if they are planning on getting pregnant.
What is an allergic reaction that can happen with ace inhibitors?
Angioedema.
Risk is low but is a severe complication and even life threatening if it occurs.
If their mouth and throats starts to swell up, they need to go to the ED immediately.
In this case, you wouldn’t try ARBs either.
What are side effects of ACE inhibitors? (4)
- Cough (secondary to increase of bradykinin and substance P)
- Hyperkalemia
- Rise in serum creatinine (transient)
- Angioedema (Allergic reaction)
What are side effects of ARBs? (3)
- Hyperkalemia
- Rise in serum creatinine (transient)
- angioedema (allergic reaction)
ACE Inhibitors and ARBs are first line therapy for what? (4)
- Hypertension
- CKD
- HF
- DM nephropathy
True or False: ACE inhibitors and ARBs work better on african americans
False.
They don’t work as well. The reduction in BP is less.
What are the 2 classes of L-type Calcium Channel Blockers and what’s the difference between them?
L-type Calcium Channel blockers cause arterial vasodilation and decrease PVR.
- Dihydropyridines (amlodipine, felodipine, -pine)
- Potent vasodilators with no effect on cardiac contractility
- Non-dihydropyridines (verapamil, diltiazem)
- Less potent vasodilators with greater depressive effect on cardiac conduction (can be used in patients with arrhythmias)
- Know that the non-dihydropyridines have drug-drug interactions because they are metabolized by the CYP450 enzyme.
- Can lead to toxic concentrations of other drugs (like statins)
What is a benefit to using calcium channel blockers?
They have long half-lives and are dosed once a day. So, if a patient misses a day, they aren’t that bad off.
What are adverse effects for dihydropyridines? (4)
- Reflex tachycardia
- Peripheral edema due to vasodilation (not due to Na and water retention)
- Gingival hyperplasia
- Increased HR
What are adverse effects for non dihydropyridines?
- Negative inotropic activity
- Constipation
- Bradycardia
- Nausea
Non dihydropyridines are inhibitors of the cytochrome P450 system (3A4 isoenzyme). What should you be cautious about taking in conjunction? (8)
- Statins
- immunosuppressants
- warfarin
- protease inhibitors
- macrolides
- amiodarone
- antiepileptics
- grapefruit juice
What’s the mechanism of action for beta blockers?
They block peripheral adrenergic receptors and decrease CO by slowing heart rate (decrease sympathetic output)
What are side effects of beta blockers? (4)
- Decreased libido
- Bradycardia
- Bronchospasm
- Glucose/lipid changes
Why are labetalol and carvedilol used for antihypertension?
They have alpha and beta blocking effect providing extra antihypertensive effect
Are beta blockers often used for controlling HTN?
Not often. They are more used for cardiovascular problems but not for isolated HTN that much.
Name 2 arterial vasodilators that are used to control HTN and explain their mechanism of action
Hydralazine
Minoxidil
Increase intracellular cGMP which causes relaxation of arterial smooth muscle resulting in a decrease in systemic pressure and contractility.
What are side effects of hydralazine and minoxidil?
- Edema
- Tachycardia
- Lupus rash (hydralazine)
- neuropathy
- hair growth (minoxidil)
Are hydralazine and minoxidil first line therapies?
They are third/fourth line therapies.
While they are 3rd/4th line, they are still effective.
Why is minoxidil a “3 drug” drug?
It causes arterial dilation which can cause reflex tachycardia and edema. So, these patients are often on beta blockers and diuretics too.
Name 3 alpha-1 receptor blockers and explain when they would be used. What are side effects?
Terazosin, doxazosin, prazosin
They are used as add-on therapy.
Side effects include postural hypotension, dizziness, somnolence, nasal congestion/rhinitis
Name 2 alpha-2 receptor agonists and explain their mechanism of action. What are side effects and when do you use these?
Clonidine, methyldopa
They stimulate presynaptic alpha-2 receptors to decrease sympathetic tone. This decreases PVR and CO.
Side effects include dry mouth, depression, lipid abnormalities, and sedation.
Methyldopa is the drug of choice in pregnancy.
These are 3rd/4th line therapies used as “add-ons”.
What two drugs would you give to African American patients to control HTN?
Thiazides and calcium channel blockers
(Not ACE-I or ARB because those don’t work well in A.A. populations)
What 4 drugs do you consider as 1st line therapy for general population?
Thiazides, ACEI, ARB, CCB
What two drugs do you use to treat CKD patients with HTN?
ACEI, ARBs
Is it okay to use ACE inhibitors and ARBs together?
No. It has been shown to increase mortality.
What’s the difference between HTN urgency and HTN emergency? How do you treat these?
Urgency is severe elevations in BP without progressive target organ damage.
Emergency is severe elevations in BP (greater than 180/120) complicated by evidence of impending or progressive target organ dysfunction.
The goal is to reduce SBP by 10-15% in the first hour and if stable then to 160/100 in 6 hours. If the patient is at rist for aortic dissection, lower SBP to less than 120 within 20 minutes.
What is sodium nitroprusside and how is it used?
It is a nitric oxide donor which activates endovascular guanyl cyclase causing myosin dephosphorylation and vascular smooth muscle relaxation.
This causes both arterial and venous dilation with an onset of action of seconds and duration of 1-2 minutes. This is used for hypertensive crisis.
What are some limitations of sodium nitroprusside?
It requires immediate use and reconstitution because it is reactive to light.
It can cause cerebral and coronary steal. With acute arterial and venous dilation, blood sometimes wont reach smaller vessels.
You also have to watch out for cyanide and thiocyanate toxicity.
Adverse effects include: seizures, cardiac arrest, encephalopathy, and neurological effects.
How can you counteract cyanide and thiocyanate toxicity from sodium nitroprusside?
Co-administer with sodium thiosulfate.
What are parenteral anti-HTN drugs that can be used for HTN crisis?
- Vasodilators
- sodium nitropresside, nitroglycerine, hydralazine
- Dopamine agonists
- Fenoldopam
- Adrenergic-receptor antagonists
- Esmolol, labetalol
- CCBs
- Nicardipine, clevidipine, diltiazem, verapamil
- ACE Is
- Enalaprilat
