46 moments from the Exam 3 lecture recordings where the lecturer said what would be tested, gave a test question, or drew a scope line.
tools/check_pharm_e3_wood.py before this page is written.“They can cause hypercalcemia, but they can reduce calcium stones from forming. I’ll talk about that again in a second, because it’s a little oxymoronic; some students get a little confused by that.”
He flagged this as a point students trip over, so know the contrast: thiazides raise serum calcium slightly yet prevent calcium stones because less calcium stays in the urine (see 17:22 to 18:14).
“Metolazone still retains efficacy even at really low creatinine clearances. He goes, metolazone could make a rock pee… that’s how I know it still retains efficacy, even because rocks don’t even have kidneys, and it makes them pee.”
A nephrologist’s line that he uses as his memory hook for the metolazone exception. The clinical use he described: adding metolazone to a loop diuretic infusion for a volume-overloaded patient whose kidneys are failing.
“One of the big things I told you with ACE inhibitors: you’ve got to know what these medications are doing to your potassium. You need to know whether they’re going to be increasing it or decreasing it, because you can kill somebody very easily with potassium.”
For every drug in this lecture, know whether it raises or lowers potassium. Loops, thiazides and carbonic anhydrase inhibitors lower it; potassium-sparing diuretics, aldosterone antagonists and ACE inhibitors raise it (see the potassium chart).
“If I say something is good for mortality purposes, you know that versus things that are just good for symptomatic care. If it’s good for mortality reasons, that means you want the patient on it no matter what. If it’s just good for symptom management, then they may not need to be on it all the time.”
The organizing rule of the heart failure half. Symptom-only: diuretics, digoxin, milrinone, dobutamine. Survival: ACE inhibitors, the three named beta blockers, aldosterone antagonists (advanced), sacubitril-valsartan, sodium-glucose cotransporter 2 inhibitors.
“ACE inhibitors and/or ARBs absolutely require… they decrease preload and afterload, they decrease sympathetic activation, and biggest thing, they decrease left ventricular remodeling, dilation, hypertrophy… so ACEs or ARBs have to be mandatory for these patients.”
Survival-benefit drugs: the patient is on one irrespective of symptoms. Their problems: acute decrease in renal function, hypotension, high potassium, cough, angioedema (switch to an angiotensin receptor blocker for the cough or angioedema).
“If the patient is complaining about breast development or menstrual problems, then you could utilize eplerenone instead; that’s much less of the androgenic activity, a pretty simple fix, but cost-wise it may be more of a problem.”
A drug-choice shape: a patient on spironolactone develops gynecomastia or menstrual irregularity, so the next step is eplerenone. Eplerenone is the more expensive agent.
“Your main question will be: is the patient hypo- or hypertensive? If they’re hypertensive then milrinone works better; if they’re going to be hypotensive then something like dobutamine or dopamine tends to make more sense.”
A stem about an acutely decompensated heart failure patient can turn on blood pressure: vasodilating milrinone when hypertensive; beta-1 agonist (dobutamine, dopamine) when hypotensive.
“This just reduces the heart rate, it doesn’t affect the contractility… this is for patients who are maxed out on beta blockers but they still have a normal sinus rhythm and heart rate above 70.”
Slide 79: add-on when beta blockers are at their limit, sinus rhythm, heart rate above 70; lowers hospitalization and heart failure death.
“Diuretics are helping to block the reabsorption of sodium and chloride in the renal tubule, which will then cause water to flow with it. This is the general rule I’ll use: wherever salt goes, water wants to follow.”
The one-line mechanism for every diuretic: block sodium and chloride reabsorption somewhere along the nephron and water leaves with it. Where it is blocked sets the strength and the side effects.
“They have this kind of diuretic braking action where you’ll see activation of the renin-angiotensin system, an increase in ADH release… the kidneys don’t like losing all that salt and volume, so they’re going to be fighting you, and that’s why you see synergy between ACE inhibitors and diuretics and calcium channel blockers.”
Volume loss triggers renin-angiotensin, aldosterone and antidiuretic hormone, which limit the diuretic. Drugs that blunt those systems pair well with diuretics. Slides 5, 15 and 26 list the same reflexes.
“On the ascending portion this is where you can see a lot of sodium reabsorption occurring here, so this is going to be a really powerful place where we could block sodium reabsorption… the distal tubule is also an important place for sodium reabsorption here; this is where things like your thiazide diuretics… that’s where these are going to be working… and then you’ll get into the collecting duct, and this is where you’re going to see two major hormones working here, aldosterone and ADH.”
Match the site to the class: loops in the thick ascending limb, thiazides in the distal tubule, potassium-sparing drugs and aldosterone antagonists in the collecting duct. Note: at 3:19 the transcript has him calling the descending limb “only impermeable to water”; that is a slip of the tongue or a transcription error. The descending limb is where water leaves the lumen (slide 9), and the thick ascending limb is the water-impermeable segment.
“We’re going to go in descending order of potency. We’re going to start with the most potent, the most bang for our buck in terms of urine formation… loop diuretics is going to cause the biggest increases in urine outflow.”
Potency order: loops, then thiazides, then the weak classes (potassium-sparing, aldosterone antagonists, carbonic anhydrase inhibitors). The more potent the drug, the more pronounced its side effects.
“You’re going to be seeing calcium and magnesium excretion too. These are important because these are side effects… if I’m increasing potassium excretion, well, I could see hypokalemia, I could see hypocalcemia or hypomagnesemia as a result.”
A loop diuretic wastes potassium, calcium and magnesium; each is a testable adverse effect, and low potassium and low magnesium also raise digoxin toxicity and arrhythmia risk.
“Notably, the loop diuretics still retain efficacy even when patients have really, really poor kidney function. Even though their GFR is less than like 30, the loops will still work… but just because the person’s making urine does not mean their kidneys are functioning all that well.”
Loops work below a creatinine clearance of 30 mL/min (slide 16); thiazides generally do not (metolazone excepted). Making urine is not proof of working kidneys.
“Anytime we need to get fluid off of the patient, loops are great. We use it for pulmonary edema, nephrotic syndrome, cirrhosis, hypercalcemia… heart failure, renal failure. You can use it in hypertension; it’s not going to be good for chronic hypertension, but if it’s related to having too much blood volume it could work.”
Slide 17 lists the loop indications: pulmonary edema, nephrotic syndrome, cirrhosis (ascites), hypercalcemia (with saline), heart failure, renal failure, hypertension (volume-related, not chronic).
“You can see these reflexive mechanisms due to volume depletion, hypokalemia, hyperglycemia, the alkalosis, the gout from the hyperuricemia… even ototoxicity with really high chronic dosing… hearing damage… you can lose too much sodium and cause hyponatremia that can lead to seizures… and an increase in your BUN.”
Slide 18's list: volume depletion, hypokalemia, hyperglycemia, contraction alkalosis, gout, ototoxicity, hyponatremia with seizures, allergic reaction, rise in blood urea nitrogen. Other diuretics share these but milder.
“These are going to be very similar things to what you see with other diuretics, it’s just they’re going to be less pronounced because they’re not going to be as potent at getting rid of salt and water… loops are the biggest players here, they’re going to be the most drastic… one notable exception I will highlight: keep in mind what effects these drugs have on things like potassium, because some will, you’ll find later on, actually increase potassium, some will decrease it.”
Learn the shared adverse-effect set once (loops worst) and then the exceptions, above all potassium and calcium.
“NSAIDs… block our blood pressure response; with an aminoglycoside, which also causes ototoxicity, that could be potentiating; lithium will not be cleared as well, which can lead to toxicities; and with digoxin, arrhythmia risk is going to be the big thing due to the electrolyte disturbances.”
Slide 19: NSAIDs blunt the response, aminoglycosides add ototoxicity, warfarin competes for protein binding, lithium clearance falls, digoxin plus low potassium and magnesium causes arrhythmias.
“It will decrease renal calcium excretion, so it’s able to keep calcium from being excreted into the renal tubules, and that might be useful for patients with a history of kidney stones, nephrolithiasis due to calcium oxalate crystals.”
Thiazides are the opposite of loops on calcium: they reduce urinary calcium (stone prevention) and can raise serum calcium a little.
“Who does this work well in? If you have like elderly patients, obese, African American patients, who they all tend to be more sodium retentive… if you can get rid of that extra sodium you’re going to be able to help to decrease some of this kind of what we call water-logging.”
Best responders: elderly patients, African American patients and sodium-retentive states (slide 25). This site does not key “obese”, which is not an established marker of thiazide response.
“Thiazides have a more long-lasting action than a loop diuretic, so for chronic hypertension you’re going to see far more thiazides than loops. It doesn’t mean they’re first line anymore, but they can be a useful second or third line add-on… well tolerated, cheap, old medications.”
Chronic hypertension: thiazides, not loops. Low-dose thiazides are well tolerated (slide 25). Current hypertension guidelines still list thiazide-type diuretics among the first-line choices; his remark is about their place relative to newer agents.
“It’s going to be causing the patient to suck up more calcium out of the renal tubule so there’s less calcium there available to crystallize out. So yes, it could cause the patient’s serum calcium levels to go up a little bit, but it’s a pretty minor bump… it sounds a little counterintuitive but it actually does work.”
Low urinary calcium, slightly higher serum calcium: the reason thiazides help calcium stones and cause mild hypercalcemia.
“You can find the thiazides actually become ineffective when your creatinine clearance goes down too low. Once you get down below like 30 or 40 most thiazides stop working, with the exception of metolazone, which will still retain the efficacy even at very low creatinine clearances.”
Slide 28 says the same. Key the metolazone exception; the blanket statement about other thiazides is not treated as absolute because newer evidence shows chlorthalidone can work at low clearance.
“Hyperkalemia can be seen here, so that’s one major difference from your other diuretics. If you’re using these with ACE inhibitors or ARBs that could be a problem… or if the patient was on potassium supplements. A little tip: if someone is on a salt substitute, that’s usually potassium chloride… they’ve got to be cautious there.”
Potassium-sparing diuretics plus ACE inhibitors, angiotensin receptor blockers, potassium supplements or potassium-chloride salt substitutes can raise potassium dangerously (slide 33).
“Spironolactone in particular has these weak androgenic effects, and it’s a partial agonist at testosterone receptors… these are very common side effects you’re going to see here… it can both cause masculinizing effects in patients and feminizing effects in patients.”
Slide 38: gynecomastia and testicular atrophy in men, menstrual irregularities and hirsutism in women. His partial-agonist explanation: it pulls both sexes toward the same middle level of androgen activity.
“That’s a diuretic, not very good, right? It works good for glaucoma because it can decrease aqueous humor production… you can use it for altitude sickness, mountain sickness, and also for epilepsy.”
Slide 42 lists glaucoma, epilepsy and mountain sickness as the other uses; the diuretic effect itself is weak and fades.
“You could see a bit of a metabolic acidosis; that’s different than your other diuretics, which typically cause more of a contraction alkalosis… and by hyperpolarizing neurons you may see drowsiness.”
The acid-base contrast is a likely question: loops and thiazides cause alkalosis, carbonic anhydrase inhibitors cause acidosis.
“You’ll see this as a reduced ejection fraction type of heart failure… compare that to diastolic dysfunction, more of an impaired relaxation sort of issue… it’s like thicker and stiffer and will not be able to relax so effectively… even though the ejection fraction may percentage-wise be okay, the total amount of blood you’re pumping is just not the same.”
Systolic failure means reduced contractility and reduced ejection fraction; diastolic failure means impaired relaxation with preserved ejection fraction but less cardiac output (slides 46 and 47).
“Reason for that usually is lack of compliance with either their diet or their medications; arrhythmias can be a big one; fluid overload… holiday heart… emotional stress and chest pain and pulmonary infections can all lead to a decompensation.”
Slide 50's precipitants: non-adherence, uncontrolled hypertension, arrhythmias, inadequate therapy, inappropriate medicines or fluid overload, angina, pulmonary infection, emotional stress.
“Thiazides are not going to be potent enough for our purposes to really reduce that edema, but loops are going to be your best friends here. Loops are kind of the mainstay of therapy for heart failure.”
Slide 52: loops are the mainstay; thiazides are not potent enough for most heart failure patients.
“One thing we can do to monitor how well a heart failure patient is doing is by looking at their weight, day to day, because if they see multiple pounds increase over several days, that’s not actual weight, that’s fluid.”
Daily weights detect worsening fluid overload; some patients take the loop diuretic only as needed when weight rises over several days. This site does not key the pound threshold.
“It’s only like three specific beta blockers: carvedilol, which is that third generation type, metoprolol succinate, the XL formulation, and then bisoprolol. These three in particular have been found to be associated with reducing mortality in these heart failure patients. All the other ones have not been found to do that.”
Name the three: carvedilol, metoprolol succinate (extended release), bisoprolol. His memory hook for succinate: sucking on a hard candy all day long, so it lasts all day.
“You have to be really careful with beta blockers because they can reduce heart rate and contractility; for a heart failure patient that could decompensate them… they probably need to be in the hospital when you start… start low and gradually work them up; it may take six to eight weeks, this is a marathon, not a sprint.”
Start with very low doses in a stable patient and titrate up slowly while watching for worsening heart failure and weight gain (slide 58). This site keys the principle, not the six to eight weeks.
“It inhibits the sodium-potassium ATPase pump… a build-up of sodium within the cell… an increased activity of the sodium-calcium antiporter… more calcium release from the sarcoplasmic reticulum, and you’re going to see a more contractile state.”
The older (inotropic) mechanism, in his sequence: block the pump, sodium rises, calcium enters in exchange, contraction strengthens (slide 62). The neurohormonal effects are the newer mechanism (slides 63 to 65).
“Clinical benefits include improvement of symptoms, better quality of life and exercise tolerance, but no survival benefits. It’s not going to be one of those mandatory ones like beta blockers or ACEs, because they don’t actually provide a survival benefit.”
Digoxin is an add-on for patients still symptomatic on optimal ACE inhibitor, beta blocker and diuretic therapy (slides 66 and 67); also an option when atrial fibrillation accompanies heart failure. This site does not repeat the slide wording “first line” for atrial fibrillation.
“These can be clues that the patient has too much digoxin… xanthopsia; xanth as a prefix means yellow, so they get this yellow-greenish discoloration and they start to see halos around lights… that’s pathognomonic for digoxin, there’s nothing else that does that, and that should really clue you in: we need to check a level right away.”
A stem showing halos around lights and yellow-green vision is digoxin toxicity; the next step is a serum digoxin level (digoxin is one of the few heart failure drugs where levels are checked, 50:44). He calls it pathognomonic; strictly it is the classic sign rather than an exclusive one (ivabradine also causes halos and brightness), but halos with a yellow-green tint point to digoxin.
“Bradycardia is most common, but you can see just about any arrhythmia caused by too much digoxin… advanced heart block can be seen… PVCs kind of give you a clue that the ventricles are a little more sensitive and twitchy, and that can be a bad sign.”
Slides 70 and 71: bradycardia, atrioventricular block, premature ventricular beats and ventricular tachycardia; it can be deadly.
“The big deal to watch for is the electrolytes. The ones more likely to get toxicity… if you have these electrolyte disturbances, toxicity is more likely… they’re on loop diuretics, which can decrease potassium, they’re on ACE inhibitors which are increasing potassium… it gets complicated.”
Note: in the recording he listed “hyperkalemic, hypomagnesemic and hypercalcemic” (as slide 71 also does), but his own point is that loops lower potassium and slides 19 and 29 say hypokalemia. The established risk is LOW potassium, low magnesium and high calcium; this site keys hypokalemia.
“We do have an immune antibody; we hyper-immunized sheep to digoxin and they produce these antibodies… this will rapidly reverse the digoxin toxicity. Be careful though, because it can unmask whatever the digoxin was treating: they may go back into atrial fibrillation or have a heart failure decompensation.”
Slide 72: antibody from immunized sheep, higher affinity for digoxin than the pump has, rapid reversal. After reversal, watch for the return of atrial fibrillation or heart failure.
“This does provide some mortality reduction in later stage heart failure, but they’ll be contraindicated if the potassium is too high or the serum creatinine is too elevated… if you do see feminizing effects in men, you can switch to eplerenone.”
Slide 73: mortality reduction in advanced (class III or IV) heart failure; not eligible with high potassium or creatinine; spironolactone gynecomastia, eplerenone less.
“Milrinone and amrinone inhibit phosphodiesterase 3… they increase cyclic AMP in the heart and cause direct stimulation of myocardial contraction… plus a balanced vasodilation, decreasing afterload and increasing cardiac output… you really just want to use it for short term, because if you leave them on too long, risk for arrhythmia goes up.”
Slides 74 to 76: phosphodiesterase 3 inhibitors for acute decompensated heart failure; long-term use raises mortality; ventricular arrhythmias and thrombocytopenia. He added that patients start in hospital and are later moved to oral therapy.
“Risk for atrial fibrillation… bradycardia… notably this unique side effect, the visual impairment; it affects the photoreceptors in the eye… retinal persistency; that usually resolves on its own… similar contraindications to beta blockers: heart block, pacemakers.”
Slide 80: atrial fibrillation, symptomatic bradycardia, phosphenes; contraindications like beta blockers (hypotension, heart block, pacemaker).
“You would not want to use this with an ACE inhibitor, because this has the angiotensin receptor blocker instead; that’s why you may want to switch them out, with a washout period to avoid that overlap, which would include hypotension, hyperkalemia, cough.”
Slide 81: neprilysin inhibitor plus valsartan; never combine with an ACE inhibitor; 36 hour washout when switching.
“They actually found that by using these medications they also had reductions in heart failure related deaths. So now this is another one of those necessary add-on medications to patients with heart failure, these SGLT2 inhibitors… especially reduced ejection fraction; you see reduction in mortality and hospitalizations… you can see risk for hypotension, mainly because you’re peeing out extra fluid, so your blood volume goes down, and they can also run into fungal UTIs, which is a pretty unique side effect.”
Slide 82: dapagliflozin and empagliflozin reduce mortality and hospitalization in stable chronic heart failure with reduced ejection fraction; hypotension and fungal urinary tract infections are the adverse effects.
“I may need to save whatever I have left for the next lecture… but we should be good, because this is on test three.”
The diuretics and heart failure material is in the Exam 3 block (lectures 9 to 13), not Exam 2. He also said most heart failure drugs had been seen before, and the new part is how they are used in heart failure.
“Digoxin is what we call a very narrow therapeutic index drug… maybe shooting for a level of like 0.5 to one. I’m probably not going to quiz you specifically on the level on the test, but just know that this has a very tight therapeutic index; it is very easy to get too much and end up causing major problems.”
Scope line: know the narrow margin, not the number (slide 65 gives the target). This site does not ask the level.