116 moments from the Exam 2 lecture recordings where the lecturer said what would be tested, gave a test question, or drew a scope line.
tools/check_pharm_e2_wood.py before this page is written.“I do have three which are going to be starred here. These are what we call the soft steroids and these are going to be agents which have lower risk for increasing intraocular pressure. So because of that, they may be preferred for those patients who may have issues with glaucoma or at risk for glaucoma… it could be one big distinction between those versus like a dexamethasone which is just a hardcore steroid.”
The deck marks fluorometholone, loteprednol and rimexolone with three asterisks as the “soft steroids” with lower eye-pressure risk; dexamethasone, prednisolone and difluprednate are the harder-hitting ones. He gave one use case: a patient who has glaucoma or is at risk of it.
“So only the non-DHPs [non-dihydropyridines] work directly on the heart to reduce heart rate and contractility. Only the non-DHPs work on the heart; the dihydropyridines work more so on the blood vessels… I’m repeating this for emphasis because it’s a very important distinction.”
The non-dihydropyridines are only two drugs, diltiazem and verapamil; they slow the heart rate and weaken contraction (and slow atrioventricular conduction) as well as dilating vessels. Dihydropyridines (DHPs) end in -dipine (amlodipine, nifedipine, nicardipine and others) and act on the blood vessels only.
“Anytime you see “cane” on the end of a drug name, you know it’s a local anesthetic, just like cocaine was the first local anesthetic.”
Ophthalmic local anesthetic drops end in -caine. They numb the surface of the eye and are used in the clinic only.
“Again, anytime you see QT prolongation, you always want to make a note of that… anytime you see QT prolongation or cytochrome P450 3A4 (CYP3A4) effects, you always want to make notes of that because it’s easy to ask questions to come up with later on, okay? Why do I make so many test questions about that stuff? Because I think it’s important that you know it because it can lead to really significant drug interactions and potentially lead to, you know, if you get Torsades, like that’s not a life compatible arrhythmia.”
This lecture’s example is systemic ketoconazole: it lengthens the QT interval, injures the liver, and inhibits cytochrome P450 3A4 (CYP3A4), which raises the levels of other CYP3A4 substrates. It is the same standing instruction he gave in the antibiotic lectures, and it keeps coming: the calcium channel blockers diltiazem and verapamil are strong CYP3A4 inhibitors and several statins depend on that enzyme.
“Anytime we say something that’s kidney protective, that’s a really good thing to know because your kidneys are so important for just normal life function… anytime I mention a nephrotoxin or something that’s kidney protective, always highlight that because it’s a very important thing to take note of… preserve kidney function as best you can.”
In this block the kidney-protective drugs are the angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (they lower pressure inside the glomerulus and are preferred in diabetes, slowing diabetic nephropathy); the kidney-harming ones are nonsteroidal anti-inflammatory drugs (NSAIDs), which clamp the afferent arteriole by removing prostaglandins.
“Hyperkalemia — this is going to be the first of many medications which affect potassium, and I want to emphasize this: anytime you have a medication which affects your potassium levels, you have to know that… this is why I’m trying to emphasize this for you now, to highlight this, to start to underline it, because anything that affects your potassium, one, it’s a very easy test question to ask, and then two, you need to know that because it is very easy to kill somebody with potassium, either lack thereof or too much of it.”
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers raise potassium, most often with kidney disease, potassium-sparing diuretics, potassium supplements or salt substitutes. In the nose-and-throat lecture the direction reverses: a diuretic plus dexamethasone lowers potassium, and dexamethasone with digoxin raises the risk of arrhythmia. Diuretics come in a later lecture.
“This will be the first of several medications we’re going to get into, so anytime you see acetylation, make sure to highlight that, because it’ll come up a few times — not common, but it comes up enough and it’s unique enough that I want you to highlight that because of the unique interactions you can see here.”
Hydralazine is acetylated in the liver: fast acetylators clear it quickly and it works less; slow acetylators have a longer half-life and more side effects, including the lupus-like syndrome (butterfly rash), more likely with high doses, long use, women and Caucasians (lower the dose or stop). Like other direct vasodilators it causes reflex tachycardia and fluid retention, and it is contraindicated in coronary artery disease and the elderly.
“This can turn the stools black. Anytime you see a drug that changes the color, or other features, of their stools or urine, let them know ahead of time, because this can really freak someone out, especially if they think black stools are associated with a gastrointestinal (GI) bleed.”
The deck lists “stools may turn black” under hydralazine, and he said it aloud (it is not a well-established hydralazine effect; black stool is classic for iron and bismuth, so a patient with black stool still needs a bleeding check). The rule that carries over to any drug is counseling: tell the patient in advance about an expected color change.
“I will reiterate and reiterate and reiterate that some things are for prophylaxis and some things for acute treatment… I may say a test question, which one of these is best suited for quick relief of symptoms, which would be one class of medications, and then if I were to say which one of these are good for prevention of symptoms, that’s a totally different set of class events.”
Prevention: beta blockers, calcium channel blockers and long-acting nitrates. Quick relief of an attack: short-acting (sublingual) nitroglycerin. Expect a stem that asks for one and offers the other.
“The specific combinations, I don’t care that you memorize, but just know if I was to say, hey, patients on this drug right now, what would be a helpful second line agent to add on? And I might have a drug of a similar category, and you would say, no, I wouldn’t want to add that one because it’s not going to give you any additional benefit.”
Stem shape: a patient is on one glaucoma drug; which drug would you add? Answer: an agent with a different mechanism, never a second drug of the same class (same mechanism gives more side effects and no extra benefit). Two routes to keep straight: raise outflow (prostaglandins, alpha-2 agonists, cholinergic agonists) or lower production (alpha-2 agonists, beta blockers, carbonic anhydrase inhibitors).
“For my purposes, I don’t have you memorize the dosing in particular. I’m more so doing that for context purposes… You’re gonna be looking more so for getting down like first, second line kind of options, right? Or first line’s not good because the patient has an allergy. What are you gonna use as a backup? Or first line failed, patient’s not improving. What do you go to then?”
The three stems to expect for each infection. Ear infection: high-dose amoxicillin, then add clavulanate if it is severe or antibiotics were used in the past month; penicillin allergy gets cefdinir (he preferred it over azithromycin because pneumococcal macrolide resistance is common; cross-reaction from a true penicillin allergy is under one percent); no improvement at three days escalates to amoxicillin-clavulanate, a third-generation cephalosporin, or ceftriaxone injections. Sinus infection: amoxicillin-clavulanate; allergy gets clindamycin plus cefixime, or levofloxacin. Strep throat: amoxicillin, or one benzathine penicillin G injection; allergy gets cephalexin, clindamycin or azithromycin.
“Another key thing here, this is really important, polymyxin B, not recommended for patients with a ruptured TM [tympanic membrane, the eardrum] or tubes in place… That would be what we call an absolute contraindication. Okay, so for example, on a test question, if I were to ask you, patient is coming in, you diagnose them with otitis externa, they have a history of recurrent otitis media cases and they had tubes put in place, which one of these would be contraindicated, you’d be looking for the product that contains that polymyxin B, right? … Alternatively, I could say which one would be most preferred, and so you’d be skipping the one that would contain polymyxin B.”
Answer: the neomycin, polymyxin B and hydrocortisone drops, because polymyxin B can pass through a perforation into the cochlea and damage the hair cells, causing hearing loss. He asked the same fact two ways (which is contraindicated, which is preferred). The other ear notes: neomycin is the most likely to cause a contact allergy, and ciprofloxacin with dexamethasone is expensive, so ofloxacin drops plus ophthalmic dexamethasone is the workaround.
“Consider what your patient’s situation is. I might give you a vignette, and I say a patient’s complaining of seasonal allergies, but they drive a truck for a living, driving a truck 18 hours a day. What antihistamine would you recommend for them, right? Or what would be the most likely to cause sedation and you’d want to avoid, or different permutations of that type of question.”
Answer: a second-generation antihistamine (cetirizine, fexofenadine, loratadine), which barely enters the brain. The sedating, first-generation drugs (chlorpheniramine, dimenhydrinate, diphenhydramine, hydroxyzine, meclizine, promethazine) are the ones to avoid there, but are the right choice for insomnia and motion sickness. Sedation adds up with alcohol, and some children react with excitement instead (a paradoxical reaction).
“Start asking a test question and say, which one of these would you use to reduce heart rate? You would say, okay, it’s either diltiazem or verapamil… this is very easy to ask about test questions. I could ask what contraindications, that’s what side effects, that’s about indications, all stemming from this one table.”
Answer: diltiazem or verapamil. Among the calcium channel blockers only they are used for supraventricular tachycardia and atrial fibrillation or flutter (they slow signals reaching the ventricles; a problem starting in the ventricles is not helped). Dropping vessel resistance can make the dihydropyridines cause reflex (rebound) tachycardia, whereas the non-dihydropyridines cause bradycardia and atrioventricular block.
“I want to be asking questions on the test more like, okay, the patient’s on this, what do you want to go to next, right? Or based off of this comorbidity, what should you start with? Things like that, right? So for example, if the patient has type 2 diabetes, well then something like an angiotensin-converting enzyme (ACE) or an angiotensin receptor blocker (ARB) makes a lot of sense because of the kidney protective actions that it has.”
His order: start an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker, or a dihydropyridine calcium channel blocker (both together if pressure is well above goal; protein in the urine favors the ACE inhibitor or receptor blocker); if still high, combine the two; add a diuretic third (diuretics used to be first, no longer). Beta blockers, non-dihydropyridine calcium channel blockers and alpha blockers show up when there is a compelling indication, not as first or second choices.
“So test question I might ask for you, for your purposes, are something like, hey, the patient’s only issue is they have this familial hypertriglyceridemia, which one of these would be best at reducing those levels? And you’ll be able to identify, okay, it’s either the fibrates or there’s another class I’ll look at here in just a second.”
Answer: a fibrate (gemfibrozil, fenofibrate, bezafibrate) or niacin. Fibrates activate peroxisome proliferator-activated receptor alpha (PPAR-alpha), which burns more fatty acids so the liver secretes less very-low-density lipoprotein, and they raise high-density lipoprotein (HDL); they barely lower low-density lipoprotein (LDL). Their main use is triglycerides over one thousand milligrams per deciliter, or low HDL.
“From a test question perspective, you know, you can say, well, the patient has a triglyceride of 600, which of these would be contraindicated, right? So can I ask a question, say which one would you use to treat the triglycerides, and say, oh, like a fibric acid derivative would be a good option there. But if I said, okay, the triglycerides are high, which would be contraindicated, then you need to identify, oh yeah, it’s a bile acid resin. Okay, so again, slight difference in the question, totally different answer.”
Answer to the contraindicated version: the bile acid resin, because resins can raise triglycerides (absolute contraindication above four hundred milligrams per deciliter, relative above two hundred). The treating version is answered with a fibrate or niacin.
“I would want you to be able to identify those four risk categories, though. So while I wouldn’t have you calculate the 10-year risk for a person, I might say, oh, somebody is, you know, 78, they have diabetes, they had a heart attack last year, right? That’s obviously someone who would definitely benefit from a statin there. I’ll make it pretty clear cut in the question.”
The four groups: clinical atherosclerotic cardiovascular disease (for example a heart attack, angina, stroke or peripheral artery disease; his 78-year-old with a heart attack belongs here); low-density lipoprotein (LDL) above 190 milligrams per deciliter; diabetes, age 40 to 75, LDL 70 to 189, without cardiovascular disease; and no cardiovascular disease or diabetes, LDL 70 to 189, with an estimated 10-year risk above 7.5 percent (the deck's wording; the guideline itself says 7.5 percent or higher). He will not ask you to calculate the risk score.
“How do we sequence these medications, in what order do you use these… that was really easy for test questions where I can say, okay, well, patient’s already on this and they’re not really at goal, what do you want to do next? Or they’re intolerant to this, what do you want to switch to?”
Two stem shapes: add-on (beta blocker, then a dihydropyridine calcium channel blocker, then a long-acting nitrate) and switch (beta blocker not tolerated, so a non-dihydropyridine calcium channel blocker).
“If I told you a patient was coming in, they were started on a beta blocker for anginal symptoms and they are complaining they just can’t tolerate it, they complain about having horrible nightmares, what would you want to switch to? That could be a situation which you can switch out for a non-DHP calcium channel blocker.”
He wrote this question out loud. Beta blocker not tolerated (nightmares is one of the listed adverse reactions): the non-dihydropyridine calcium channel blocker is the swap.
“If you were to say what’s the treatment of choice for a variant angina or Prinzmetal angina, usually it’s going to be a DHP… their problem is not necessarily contractility or heart rate, it’s just that vessel is clamping down.”
Deck wording: calcium channel blockers and nitrates reduce symptoms in variant angina, and beta blockers are avoided because they may worsen it.
“If I say a test question, which one of these is best for quick relief of myocardial… a quick relief of anginal symptoms, this is the answer. Okay, keep that in mind, highlight.”
Short-acting nitroglycerin (sublingual tablet or spray, which skips first-pass metabolism) is the quick-relief answer. Beta blockers and calcium channel blockers prevent attacks.
“This is a really good table for your anti-anginals… come back to this, because this is like a cornucopia of test questions could come from something like this.”
He walked the table row by row: hypertension, prior myocardial infarction and reduced left ventricular function all point to a beta blocker; bradycardia or block points to a dihydropyridine; asthma points to a cardioselective beta blocker or a non-dihydropyridine. Study note: he also read the prior-infarction cell (avoid calcium channel blockers) and the diabetes cell (non-dihydropyridine first line); the course keys both as he read them, and the guide says where current practice differs.
“One thing you might want to be worried about, this is kind of notable here, is if patients have a history of a sulfonamide allergy, it could trigger an allergic reaction… Remember, not just the sulfa allergy, but more specifically, a sulfonamide allergy. They’re not allergic to sulfur, it’s the sulfonamide group is what they’re allergic to.”
Sulfacetamide is a sulfonamide antibiotic that blocks folic acid synthesis (it competes with para-aminobenzoic acid), and the deck says to avoid it in a patient with a sulfonamide allergy because the conjunctivitis can worsen. The allergy is to the sulfonamide chemical group, not to sulfur.
“Notice we talk about conjunctivitis, but also corneal ulcers, that’s an interesting one here. So in some cases, especially with contact lens use, you may see these corneal ulcers that can develop here, and one thing you always want to be thinking about in those instances is Pseudomonas aeruginosa. Fluoroquinolones do tend to have coverage against Pseudomonas.”
The deck prefers a fluoroquinolone drop (ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, gatifloxacin) for corneal ulcers or Pseudomonas, and for conjunctivitis in contact lens wearers once keratitis is ruled out. They are effective but expensive, and resistance is emerging, which is why simpler drugs come first for routine conjunctivitis.
“How do we administer an ophthalmic medication? First step, most important step: wash your hands, so you are not introducing any new bacteria, fungus or virus into the eye itself.”
Hand washing is the first and most important step of putting drops or ointment in the eye.
“Most of you will probably forget this and we’ll get it wrong on the test. But I will tell you, I will ask this question… there’s rebound hyperemia, right? … So a really good counseling point, no more than two weeks because it’s rebound hyperemia… So just keep that, star that, underline it, highlight it. A lot of people still get it wrong every test. I don’t know why because I tell you explicitly, that’s what I’m going to be asking about.”
The drops are tetrahydrozoline, naphazoline, and the combination with the antihistamine pheniramine (Visine-type products). They constrict eye vessels through alpha-1 receptors; used past two weeks the receptors down-regulate, so stopping causes rebound hyperemia (worse redness), patients go back to the drop, and a slow taper is needed. If there is no improvement in 72 hours, stop and see a provider. He said the same idea returns in the nose lecture.
“These products like naphazoline and tetrahydrozoline, they kind of fit into this category of what we call the imidazoline derivatives. And so while locally they work on the alpha-1 receptors, they’re actually alpha-2 agonists as well… you can find pretty significant cardiovascular actions, especially in little kids, where you can see bradycardia, hypotension. So just because something is over the counter does not mean that it is safe.”
Locally these drugs act on alpha-1 receptors, but swallowed they reach alpha-2 receptors, which lower norepinephrine release, so a toddler who drinks the bottle gets a slow heart rate and low blood pressure and needs the hospital. The counseling point is to keep the product out of reach of children.
“So things which will increase aqueous outflow. This will include your prostaglandins, which are generally considered first line agents… Our beta blockers, which are generally considered second line, but we’ll caveat that in a second… carbonic anhydrase inhibitors… our third, fourth line kind of agents… Last line for glaucoma, you could use cholinergic agonists.”
The ladder on the deck: prostaglandin analogs (latanoprost, travoprost, bimatoprost, tafluprost; once daily, no more, and they change eyelash length and iris color) first; beta blockers second, or first if the patient will not accept iris darkening; alpha-2 agonists in between; carbonic anhydrase inhibitors third or fourth; cholinergic agonists (pilocarpine, carbachol) last because they cause small fixed pupils and poor vision. Often more than one drug is needed.
“We have the beta-1 selective agents. This includes betaxolol. And then we have non-selective agents, things like carteolol, timolol, and then levobunolol. These are just ones you kind of have to know… while the non-selective are more efficacious, you do tend to see more side effects.”
Betaxolol is the beta-1 selective eye drop; carteolol, timolol and levobunolol are non-selective. Non-selective agents work better (the eye has more beta-2 receptors) but cause more systemic effects: slow heart rate, heart block, worse heart failure and more airway resistance.
“Selective agents are going to hit mainly beta-1 receptors, so less risk for bronchial constriction. That’ll hold true no matter where we’re using beta blockers. If you have the asthma history, go with a cardioselective beta blocker.”
For an older glaucoma patient with heart failure or heart block he would be hesitant to use a beta blocker and said the prostaglandins look much more attractive; for a patient with an asthma history he said to choose a beta-1 selective (cardioselective) blocker. The deck lists worsening heart failure, slow heart rate, heart block and increased airway resistance as the beta blocker adverse effects. The same rule returns in the antihypertensive lecture.
“We don’t let patients go home with these anesthetic drops, because if they’re having pain or irritation they’re likely to keep treating themselves with the anesthetic, and that can be a problem if they’re not blinking.”
Repeated use removes the blink reflex and the eye’s pain warning, so the cornea can be injured without the patient feeling it. Anesthetic drops are given in the clinic, never sent home.
“However, I will say, please, this is really, really important, please make sure patients use distilled water, some sort of purified clean water they’re using… I would not take water straight out of the tap, for example, pond water, pool water… there have been situations in which people were using contaminated water sources and they actually developed brain-eating amoeba infections.”
Saline irrigation is a useful add-on for a sinus infection, and the education point is the water source: distilled, purified or sterile water, because the sinuses sit close to the brain. He said to document that you educated the patient.
“So one of the best education points for inhaled steroids is actually to tell patients to make sure after they use it to brush their teeth or at least rinse their mouth out with water, and that will get rid of any drug there and prevent any thrush from setting in. But if it does develop, then you would want to utilize something like a nystatin oral suspension.”
Nystatin is a nonabsorbable antifungal that binds sterol in the fungal membrane; it treats oral candidiasis (thrush), which appears with inhaled steroids, advanced human immunodeficiency virus (HIV) infection and chemotherapy. It can be swished and then spit or swallowed, and because it is never absorbed it does nothing for a systemic infection.
“Note this is an irreversible inhibitor in the platelets… But the key difference with this is it’s an irreversible inhibitor… Aspirin is an irreversible inhibitor on your platelets, so it takes time for you to produce whole new platelets to be able to overcome that, so it’s usually seven to ten days, right? … versus something like ibuprofen, give it 24 hours, it’s out of the system.”
Aspirin blocks both cyclooxygenase-1 and cyclooxygenase-2 and, in platelets, cannot be undone until new platelets are made, so stop it seven to ten days before a procedure; ibuprofen and naproxen are reversible, so bleeding risk returns to baseline about a day after the last dose. This is also why aspirin plus an anticoagulant raises bleeding risk.
“You see this children with fever associated with a viral disease, in particular things like chickenpox and influenza. So this is a really notable one. So generally speaking for kids less than like 16, I’d say just avoid aspirin in general… it could induce this thing called Reye’s syndrome, which can be potentially fatal… Pepto-Bismol… bismuth subsalicylate… it’s a subsalicylate component there, so it still can cause a similar sort of Reye’s syndrome.”
Reye syndrome is fatty-liver encephalopathy: vomiting, progressive brain injury, liver injury and low blood sugar, with a rash on the hands and feet early, and it can be fatal. The age cutoff differs by source (the deck says under 15, he said under 16); current public-health advice is to avoid aspirin for viral illness in children and teenagers generally. The one exception he named is Kawasaki disease, under specialist care.
“Nonsteroidal anti-inflammatory drugs (NSAIDs) and the kidneys don’t necessarily play well together… Prostaglandins will open this afferent arteriole and will allow more blood flow to come in… So that is why an NSAID can potentially induce a decrease in your creatinine clearance or a decrease in your GFR [glomerular filtration rate], which could lead to potentially acute renal failure… So those are two big concerns we’re looking for, the gastrointestinal (GI) toxicity and then issues of renal concerns.”
Stomach: cyclooxygenase-1 makes the protective prostaglandin, mucus and bicarbonate layer, so long-term use causes ulcers, perforation and bleeding. Kidney: prostaglandins hold the afferent arteriole open, so a nonsteroidal anti-inflammatory drug (NSAID) cuts filtration and causes fluid retention, worst in chronic kidney disease, critical illness or with a diuretic. They also blunt angiotensin-converting enzyme (ACE) inhibitors and diuretics and raise lithium and methotrexate levels.
“Now, you don’t have to memorize a lot of dosages, but this is one you have to know. Tylenol, no more than four grams in a day… So make sure no more than four grams in 24 hours. Know that number. Star it, highlight it, whatever you got to do.”
Count every source toward the four grams: cold and cough products such as NyQuil, and hydrocodone-acetaminophen or oxycodone-acetaminophen tablets. Lower it to three grams or avoid it in a patient with liver disease or chronic alcohol injury. Too much forms a toxic metabolite that injures the liver, and N-acetylcysteine is the antidote. Acetaminophen has no anti-inflammatory action, which is the key difference from the nonsteroidal anti-inflammatory drugs (NSAIDs).
“And then note here, discontinuation. If patients are going to be on steroids for more than one week, we’ll say five days… that’s time enough for the adrenal glands to start to shut down cortisol production… We do not want them to discontinue it abruptly. No cold turkey. Have them slowly taper off.”
Outside steroid feeds back to the pituitary and hypothalamus and switches off the adrenal glands, which take time to restart, so dexamethasone, prednisone and prednisolone are tapered, over a length that depends on dose and duration. The same drugs also lower resistance to infection (avoid live vaccines), raise blood sugar and blood pressure, and drain potassium.
“And again, I highlight this every year, and I tell students, hey, there’s probably going to be a test question about this, and I still see a significant number of people that miss it… I’m telling you right now, it’ll be somewhere on the test. You do not want to use this for more than three to five days, and if you do, you have to taper off. Otherwise you’re going to get this rebound stuffiness, which is even worse than what they’re probably dealing with in the first place.”
Oxymetazoline is an alpha agonist that constricts nasal vessels; constant use down-regulates the receptors, and stopping causes rebound congestion (rhinitis medicamentosa). Going back to the spray keeps the cycle going, so the fix is a slow taper, and the limit is three to five days. It is the nasal version of the eye-drop rebound hyperemia: in the eye lecture he flagged the same rebound effect for tetrahydrozoline and naphazoline and said it would return for nasal sprays. Use caution with uncontrolled high blood pressure.
“You still see pseudoephedrine on the store shelves, but it’s always “pseudoephedrine PE.” What does PE mean? It means phenylephrine. And so this stuff does not work.”
Oral phenylephrine is not an effective decongestant; the effective oral decongestant is pseudoephedrine.
“This is a good example of a product which will show up on what we call the do-not-chew-or-crush list … if you were to chew this up it could cause local anesthesia within the mouth, and then it’s not really effective for treating the cough.”
Benzonatate capsules are swallowed whole: chewing releases the local anesthetic in the mouth (numbness) and the drug then does not treat the cough.
“It’s a renal function impairment — now that’s interesting, I just said that it preserves kidney function but I’m telling you that it can impair kidney function… yes, acutely you can see a drop in kidney function, but over time… it will be kidney protective in the long run… it can both injure the kidneys and it’s also protected the kidneys, but you have to think about the context of time… for patients who have pre-existing kidney dysfunction we can basically start low dose and gradually work up.”
Angiotensin II constricts the efferent arteriole and holds up filtration pressure; when kidney blood flow depends on it, an angiotensin-converting enzyme (ACE) inhibitor lowers glomerular filtration acutely. Over years the lower pressure reduces wear on the glomerulus. So in kidney disease start low and go slowly.
“These are going to be category X when it comes to pregnancy, so anyone who is capable of becoming pregnant should be checking to make sure they’re not pregnant prior to starting any of these angiotensin-converting enzyme (ACE) inhibitors, because they will have very negative outcomes on the fetus, birth defects, fetal death.”
Answer on the fetal-harm fact: Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers carry a boxed warning for fetal toxicity and are stopped when pregnancy is found. The deck says contraindicated in the second and third trimesters; the letter categories are no longer used, and the old label for these drugs was D rather than X. Check a pregnancy test before prescribing to anyone who could become pregnant.
“Nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce angiotensin-converting enzyme inhibitor effects… you’ll see that as a very frequent interaction, that NSAIDs inhibit the actions of your antihypertensives, and it’s all because of this action here in the kidneys and the response the kidney has to say, well, we need to produce more angiotensin too. [Later, on the prazosin slide:] NSAIDs really impact all of your antihypertensives… if you’re doing one-time dose for an ache or pain, no big deal probably, but if you’re going to be doing it chronically for chronic pain issues, that’s much more of a concern.”
Removing prostaglandins narrows the afferent arteriole, the kidney senses low flow and releases more renin, so angiotensin II rises and fights the blood pressure drug. A single dose for an ache matters little; chronic use matters. The deck also lists it for prazosin, and the ibuprofen slide in the nose lecture says the same for angiotensin-converting enzyme (ACE) inhibitors.
“So for the most part so far ACEs [angiotensin-converting enzyme inhibitors] and ARBs [angiotensin receptor blockers] look pretty similar, right? But what are the key differences here? One, ARBs do not cause the cough because they do not inhibit the breakdown of bradykinin… they have a much lower incidence of angioedema… There are a lot of similarities between them, but those are the key things, and again great for test questions. Great stuff I could ask there potentially.”
Angiotensin-converting enzyme (ACE) inhibitors also block the breakdown of bradykinin, so they cause a dry cough (about 5 to 15 percent of patients, one week to six months in, not dose-related) and rarely angioedema. Angiotensin receptor blockers (ARBs) (drugs ending in -sartan) do not touch bradykinin, so they do not cause the cough and have a much lower (not zero) incidence of angioedema; they are the switch for cough or after ACE-inhibitor angioedema, with monitoring. ACE inhibitors may lower pressure slightly better; both raise potassium, cause first-dose low blood pressure, impair kidney function and harm the fetus, and cost often decides.
“Therapeutic doses, calcium channel blockers decrease afterload but have no effect on preload, meaning they reduce that pressure the heart’s pumping against… but they don’t do anything on the amount of blood flow coming back in, preload. That’s a kind of notable distinction here on how the calcium channel blockers work.”
They relax arteries but do little to veins, and arteries are far more sensitive to them than heart muscle cells are.
“Constipation, this is very common with your calcium channel blockers… constipation is very, very, very common with these medications, and again it’s not unlikely for your patient to be on two or three or four medications that all cause constipation, so this is why I highlight, try to emphasize it for you: ask about your patient’s bowel habits.”
A calcium channel blocker slows the gut as well as the vessels. The rest of the side-effect list: flushing, headache, edema, low blood pressure, gingival hyperplasia, and for the non-dihydropyridines a slow heart rate, first-degree block and worse heart failure.
“This is notable, this is very important: these are strong cytochrome P450 3A4 (CYP3A4) inhibitors, meaning they can affect a ton of other medications, like our statins, which we’re going to talk about later today… so know that it’s a strong CYP3A4 inhibitor, note that down, start underlining… along with that also inhibits P-glycoprotein.”
He called them strong cytochrome P450 3A4 (CYP3A4) inhibitors (standard drug-interaction tables class diltiazem and verapamil as moderate; either way the interaction matters). They raise the levels of atorvastatin, lovastatin, simvastatin, carbamazepine, propranolol, tacrolimus and cyclosporine, all of which CYP3A4 clears, and of digoxin (through P-glycoprotein), and adding a beta blocker or amiodarone slows the heart further. They are also victims: grapefruit juice or another CYP3A4 inhibitor lengthens their half-life. The deck lists no CYP3A4 inhibition for the dihydropyridines (amlodipine and nifedipine have none of note; nicardipine is a real exception).
“How do we distinguish between first versus second versus third gen ones here? There’s not the best rule because there’s exceptions to the rule, which I don’t like, but essentially if it starts with an N as in Nancy through Z, you can pretty well guess that it’s likely to be a first generation non-selective beta blocker… A through M as in Mary is usually your second gen or cardioselective beta blockers.”
N through Z (nadolol, propranolol, sotalol, timolol) is usually non-selective; A through M (acebutolol, atenolol, bisoprolol, esmolol, metoprolol) is usually beta-1 selective. Beta blocker names end in -lol. He called it an imperfect shortcut and gave the exceptions a few minutes later (carvedilol and labetalol are non-selective despite their letters).
“Esmolol is a pretty interesting one: it is an IV product, it has a really short half-life, very short acting, and so it’s very titratable — atrial fibrillation or supraventricular tachycardia, I can put them on a Brevibloc drip.”
Esmolol is the intravenous, very short-acting beta blocker, given as a titratable drip for fast atrial rhythms.
“So yes, these do buck the naming convention… However, these two are going to be exceptions. You just have to know these. So these are, in addition to non-selective beta blockers, they also block alpha-1 receptors, so they have an additional ability to help reduce blood pressure over just blocking beta receptors on their own.”
The two third-generation drugs on the deck with extra alpha-1 blockade are carvedilol and labetalol; carvedilol is also one of the three heart-failure beta blockers. (The recording garbles the two names, so they are taken from the deck.)
“I just know this can be utilized for prophylaxis, so one of your first-line medications for migraine prophylaxis for a lot of people.”
Beta blockers are a first-line option to prevent migraine, one of the uses listed for the class.
“There’s three in particular we’re going to use here: carvedilol, metoprolol succinate, and bisoprolol. These three have been found to be beneficial in heart failure… just know these three are the ones specifically indicated for heart failure… we like to start really, really low dose, kind of gradually work them up.”
Beta blockers were once contraindicated in heart failure; with these three they lower mortality, but they can worsen symptoms at first, hence low dose and slow titration. Metoprolol succinate is the extended-release salt and tartrate is immediate release (his memory hook: you suck on a hard candy and it lasts a while).
“The sudden withdrawal syndrome — this is going to be kind of the first set of medications we’re looking at where you do not want to abruptly discontinue the beta blocker… by chronically blocking those beta receptors you’re going to start to see an up-regulation of them, and then when you remove the beta blocker cold turkey, all of a sudden you’re much more sensitive to the effects of norepinephrine.”
Abrupt withdrawal causes a spike in blood pressure and heart rate that can bring on acute angina, a heart attack or stroke; taper slowly. He gave the same warning for clonidine (severe rebound hypertension), and clonidine given with a beta blocker makes the withdrawal worse.
“Generally speaking, beta blockers and non-dihydropyridine (non-DHP) calcium channel blockers really should not be used together, that’s a very odd combination… chances for things like heart block and bradycardia are just very high. Now you can use a dihydropyridine plus a beta blocker and that’s a great combination, because now you have one working on the heart, you got one working on the blood vessels.”
Diltiazem or verapamil with a beta blocker stacks the effects on rate, contraction and blood pressure (if ever combined, use lower doses of each). A dihydropyridine covers the vessels while the beta blocker covers the heart.
“Same side effects, same precautions, same drug interactions, nothing notable here. Again, your job is to be able to identify these agents into which class they fit into. So if you see a zosin on the end of the name… you can pretty well assure that, yeah, it’s probably an alpha blocker.”
Prazosin, terazosin and doxazosin block alpha-1 receptors: main risks are orthostatic low blood pressure (start at bedtime, especially in the elderly), reflex tachycardia and salt and water retention, so they are add-on drugs used with a beta blocker or diuretic; they also treat benign prostatic hyperplasia. Tamsulosin is the alpha-1A-selective one with little effect on vessels. Nonsteroidal anti-inflammatory drugs (NSAIDs) blunt their effect.
“We give nitroprusside plus this product called sodium thiosulfate … we give you the antidote along with the cyanide itself to help reduce toxicity … if they have renal dysfunction, try to limit its use.”
Nitroprusside is given with sodium thiosulfate to limit cyanide toxicity, used for as short a time as possible, and limited in kidney dysfunction.
“Several of these are going to be cytochrome P450 3A4 (CYP3A4) substrates, so atorvastatin, lovastatin and simvastatin. These are really important because if you were to have an inhibitor come along, like grapefruit juice for example, you will see elevations of these drug levels… So definitely know these… it may come up on a test, who knows… if they need to be on that non-dihydropyridine (non-DHP) calcium channel blocker, I don’t want to use a statin that’s going to interact with that.”
Higher levels, a longer half-life and toxicity follow from cytochrome P450 3A4 (CYP3A4) inhibitors: verapamil and diltiazem, amiodarone, grapefruit juice and erythromycin. The deck also lists niacin and fibrates on this interaction slide; they raise muscle-toxicity risk with statins by other mechanisms rather than by inhibiting CYP3A4, so the point to answer is: avoid statin plus fibrate or niacin where possible. Statins that avoid that enzyme are rosuvastatin (his go-to), pravastatin and pitavastatin; fluvastatin uses a different enzyme, cytochrome P450 2C9 (CYP2C9).
“Definitely one thing to note is going to be the changes in liver enzymes… this is definitely this class of meds where you need to both check a baseline set of LFTs [liver function tests] and you need to follow that… if the patient came back complaining of myalgias without any kind of other obvious cause, definitely I would check something like a creatine kinase level.”
Liver enzyme rises are dose-dependent and managed by lowering the dose or pausing. Muscle effects run from myalgia to myopathy and, rarely, rhabdomyolysis (muscle breakdown floods the kidneys with myoglobin); a rising creatine kinase signals it, and muscle toxicity means stopping the statin. Lower the risk with the lowest effective dose, caution in kidney impairment, and avoiding a statin plus a fibrate.
“Otherwise contraindications would be hepatic disease, pregnancy — this is another one of those category X, like do not use, do not pass go kind of medications… just look at the ACEs [angiotensin-converting enzyme inhibitors], the ARBs [angiotensin receptor blockers] and now the statins are going to be like mega no-no-go for pregnancy kind of medication groups.”
The deck lists hepatic disease and pregnancy as statin contraindications (relative ones: cyclosporine, gemfibrozil, niacin, erythromycin). The old “category X” letter system is retired, and in 2021 the Food and Drug Administration relaxed the statin pregnancy contraindication (statins are still stopped in most pregnancies), so answer on the avoid-in-pregnancy fact. Fibrates are also avoided in pregnancy, while the bile acid resins are the exception.
“Back in the day the goals were more so to shoot for certain low-density lipoprotein (LDL) targets… we’ve now realized through studies and whatnot that it’s not really the number that matters so much, it’s more of like a what’s your risk profile look like and how intense of a statin do you need to be on.”
One slide still lists the older treatment-guideline goals (low-density lipoprotein (LDL) under 100, high-density lipoprotein (HDL) over 60, triglycerides under 150), but the current approach starts a moderate- or high-intensity statin by risk group and does not titrate to an LDL number. Lipids are re-measured mainly to check adherence: a high-intensity statin with no fall in LDL means the patient is probably not taking it.
“So this is where you want to be really careful mixing statins and fibrates, it’s usually not recommended if you can avoid it just because myopathy risk is going to go up pretty significantly there.”
He said it twice, once under statins and again under fibrates. Fibrates with ezetimibe raise the risk of gallstones (cholelithiasis) and myopathy, and fibrates increase the effect of warfarin, so watch for bruising and bleeding.
“The other thing too is it is not specific to binding the bile acids, it will bind to many other things, a lot of other medications, so this is really critical here, it needs to be separated from other meds… take the interacting drug either an hour before the bile acid resin or wait till four hours after.”
Take the resin (cholestyramine, colestipol, colesevelam) within an hour of a meal, when bile acids are released; mix powders in water or a pulpy juice. It binds digoxin, warfarin, thyroid hormone, beta blockers and thiazide diuretics, and it impairs absorption of fat-soluble vitamins (A, D, E, K) and folic acid. It is not absorbed, so it is the safest class and approved in children and pregnancy, but it is the weakest and poorly tolerated.
“If you ever see niacinamide, that’s not going to be the same thing, it’s not really as effective as an antilipemic… look for either niacin or nicotinic acid, basically.”
Niacin (nicotinic acid, a B vitamin) is sold as an over-the-counter supplement and as prescription products; extended release is preferred because immediate release causes more side effects. For a supplement he advised a reputable brand used consistently, since supplements are not held to prescription manufacturing standards.
“That should sound like the fibrates, and in fact niacin and the fibrates, while they have different mechanisms, they do share common features in the fact they both are good at getting triglycerides down and they are good at getting high-density lipoprotein (HDL) up, right? The only one that we’ve seen that’s bad for triglycerides and can elevate them is the bile acid resins… keep in mind these different flavors of effects on lipids as we go through, because those are good for test questions.”
Niacin cuts the release of fatty acids from fat tissue, so the liver makes less triglyceride and very-low-density lipoprotein and high-density lipoprotein (HDL) rises.
“So how do we mitigate this one? You don’t use the immediate release products. Two, you can actually pre-treat with aspirin. Now why does aspirin work? Remember, aspirin inhibits cyclooxygenase and by doing that you inhibit prostaglandin formation. So the goal would be to pre-treat with aspirin and that would prevent that prostaglandin mediated flush.”
The flush is prostaglandin-mediated (hot, red, nauseated skin). Mitigate it by using extended-release rather than immediate-release niacin and by pretreating with aspirin, which blocks prostaglandin formation. At larger doses niacin also raises liver enzymes, blood sugar and uric acid, so gout, diabetes and peptic ulcer disease are relative contraindications and chronic liver disease is an absolute one.
“So again, keep in mind those changes you can see, and think of the kind of test questions I could ask that would have you delineate between these different products, right? That’s kind of a big thing. Otherwise, if you say what’s the gold standard, what’s the first line agent, it’s going to be statins ten times out of ten, but there could be reasons why you might choose another option there.”
The comparison table: statins lower low-density lipoprotein (LDL) the most and modestly lower triglycerides and raise high-density lipoprotein (HDL); the bile acid resins lower LDL but leave triglycerides unchanged or raise them; niacin and the fibrates raise HDL and lower triglycerides most; ezetimibe is modest. The higher the starting triglyceride level, the bigger the drop.
“Really the guidelines have said focus on the statins, but if you can’t use statins, that’s where you’re starting to get into the other agents. So maybe you do switch from a statin because they can’t tolerate it to something like one of those PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitors, right? Or maybe they have like a familial hypertriglyceridemia, I don’t really need a statin for that, but I could use niacin or like a fibrate.”
The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are alirocumab and evolocumab, monoclonal antibodies (the -mab ending) that must be injected and are expensive; by blocking the protein that degrades low-density lipoprotein (LDL) receptors they keep receptors on the liver longer and can drop LDL by roughly half. Hypersensitivity is the most serious adverse reaction.
“How you grade angina is basically off of the degree of physical activity limitation… can you do more stuff before you start to have chest pain, that’s how we’re really going to determine how well our therapy is working.”
Angina is graded by how much activity the patient can do before symptoms, and the same measure, exercise capacity, shows whether an antianginal is working.
“Remember the rule we used was A through M … beta-1 selective. N through Z typically are considered the non-selective agents, and then we’ll just need to know our exception with the third gen, that’s carvedilol and labetalol.”
Selective: metoprolol, atenolol. Non-selective: propranolol, nadolol. Third generation (the exception to the alphabet rule): carvedilol, labetalol.
“We recommend against immediate discontinuation, so don’t quit cold turkey… even MIs have been induced because of the rapid discontinuation of beta blockers.”
Beta blocker education: avoid rapid discontinuation. He tied it to rebound angina and even myocardial infarction.
“Here I want you to notice the major difference between the dihydropyridines and the non-dihydropyridine calcium channel blockers… if a patient could not get a beta blocker for one reason or another, you can basically sub that out for a non-DHP.”
Non-dihydropyridines (verapamil, diltiazem) act like a beta blocker on heart rate and contractility, so they are the substitute. Dihydropyridines (the -dipines) act on the vessels.
“For your typical anginal cases you would not want to use a DHP med by itself because of that increase in heart rate, you’re kind of fighting yourself… you wouldn’t really want to do a beta blocker plus a non-DHP because they’re just doing the same thing… bradycardia, heart block, it’s just more likely to occur.”
A dihydropyridine is added to a beta blocker, which blunts its reflex heart rate rise. A beta blocker plus verapamil or diltiazem is avoided in most cases because of added bradycardia and heart block.
“Keep in mind the LV dysfunction is going to be suppressed or is worsened with the use of a non-DHP calcium channel blocker, so the way I highlight here is DHPs only for that.”
Reduced left ventricular function is a contraindication for the non-dihydropyridines; a dihydropyridine (amlodipine) is the calcium channel blocker that remains.
“Typically we avoid short-acting agents, agents like nifedipine, so if you can stick with something long-acting like amlodipine… you’re not going to get that yo-yo type of effect.”
Avoid short-acting nifedipine; a long-acting dihydropyridine such as amlodipine is the pattern to know.
“If you don’t know any other CYP enzyme, know CYP3A4, please, that’s my only ask… the non-DHPs are both inhibitors of CYP3A4 and substrates… the DHPs like amlodipine are just substrates… a patient on verapamil and then you put them on simvastatin… now all of a sudden you’re jacking your simvastatin levels up.”
Verapamil and diltiazem inhibit and are substrates of CYP3A4; dihydropyridines are only substrates. The worked example: verapamil raises simvastatin levels (muscle and liver toxicity).
“Ask your patients about their bowel habits… what happens when they’re sitting there straining on the toilet… let’s put a little strain on the heart too.”
Calcium channel blocker education from the deck: dizziness and constipation. He added why constipation matters in a cardiac patient.
“The problem comes when you do both of these together… that can lead to profound hypotension… if the answer is yes, you cannot give them a nitrate, because it will synergize, it’ll drop their blood pressure, they could die.”
Sildenafil, tadalafil and vardenafil with any nitrate: contraindicated, with hypotension, myocardial infarction and stroke as the risk. He said the patient should be asked, bluntly if needed.
“That’s why I say after five minutes if you don’t get the relief, call 911, okay, so you get one try and that’s it, but while waiting you can continue taking the doses every five minutes.”
The patient takes the first dose; no relief after five minutes means call emergency services (time is tissue), and further doses can be taken while waiting. The action is the testable point.
“Orthostatic hypotension makes sense… store them in the original packaging, a cool dry place, don’t put them into your pill minder… and then we’ll say after opening it replace every three to six months or so… I say go ahead, yes, do replace it.”
Warn about orthostatic hypotension; keep tablets in the original packaging in a cool, dry place; he teaches replacement every three to six months, which is the course rule (the guide notes that current labeling ties expiry to the original bottle).
“This is usually like the third add-on medication in that list… usually adjunctive therapy, very rarely or not recommended as monotherapy.”
Long-acting nitrates: adjunct after a beta blocker and a calcium channel blocker, not monotherapy unless neither can be used.
“Regardless, all you need to know is do the nitrate-free interval for 12 hours when the patient is least likely to have symptom frequency, usually when they’re asleep.”
Tachyphylaxis (the body becomes resistant after about 12 hours) is handled by 12 hours on and 12 hours off, timed so the off period is when the patient is asleep and least likely to have chest pain.
“For things to avoid, for prior MI, calcium channel blockers kind of in general, we really prefer beta blockers just from the evidence that we have in terms of mortality… be very cautious.”
After a myocardial infarction the beta blocker is first line; he said to avoid or be very cautious with calcium channel blockers, citing the mortality evidence. The course keys this as taught; current practice allows a non-dihydropyridine when a beta blocker cannot be used.
“They do not relieve symptoms of angina, but they will help to prevent the progression of the coronary artery disease… these should be indefinitely in patients for post-MI, LV dysfunction, diabetes.”
Vasculoprotective, not antianginal: continue indefinitely after infarction, with left ventricular dysfunction or with diabetes; angiotensin receptor blockers are largely interchangeable.
“If you see anyone who’s on a beta blocker plus a non-DHP, you’re just kind of begging for trouble with that kind of combination… if you need a third agent you probably need further workup.”
Combination therapy: dihydropyridine plus beta blocker is the sensible pair; a third agent means further workup such as angiography.
“Unless contraindicated, patients with coronary artery disease or ischemic heart disease should be getting aspirin, if they’ve had a previous MI beta blockers for sure, ACEs or ARBs in patients who have diabetes or LV dysfunction, lipid lowering therapy… they will have sublingual nitroglycerin for acute relief.”
Aspirin; a beta blocker after infarction; an ACE inhibitor (or receptor blocker) with diabetes or left ventricular dysfunction; lipid-lowering therapy; sublingual nitroglycerin for acute relief.
“For the variant angina, the Prinzmetal angina, that’s where you get into utilizing your dihydropyridine calcium channel blockers most commonly, you typically avoid beta blockers, they tend to worsen symptoms for the patient.”
The one angina where the beta blocker is avoided; the problem is vessel spasm, a supply problem, not oxygen demand.
“If you only had to know two clotting factors, the two most important ones are 10 and 2… that’s what’s going to cause the activation of fibrin.”
Factor X and factor II (thrombin) sit in the common pathway; thrombin also activates platelets, a positive feedback loop, and turns fibrinogen into fibrin.
“Nitrates only help with symptom relief… they don’t do anything for outcomes.”
In acute coronary syndrome nitrates give pain relief with no mortality benefit (sublingual first, intravenous infusion once in hospital).
“Aspirin contraindications would just be different kind of like GI bleed or intracranial hemorrhage… should be one of the absolute got to use it, if you have an allergy and couldn’t receive aspirin that’s where those ADP blockers like clopidogrel come into play.”
Aspirin is chewed and swallowed at the first signs; contraindications are allergy, gastrointestinal bleeding and intracranial hemorrhage; clopidogrel is the alternative.
“Beta blockers will start IV initially till we get them under control and then we can switch over to PO, just know there’s going to be contraindicated if they’re already hypotensive or bradycardic or if they’re having heart block… and then you know they have severe reactive airway disease, something like a cardioselective beta blocker would make sense.”
He teaches intravenous first, then oral, as the course sequence. Cautions: hypotension, bradycardia, heart block, severe reactive airway disease (cardioselective agent). Flag: current guidelines favor oral therapy in the first day; the course answer is the sequence he taught.
“Morphine is not really shown to have any benefits on outcomes but it does help out with the pain… if they’re having pain unresponsive to nitrates then you would initiate an opioid like morphine… some controversy in using it for unstable angina and [NSTEMI], but for the most part for STEMI is perfectly fine.”
Morphine treats the pain only; reserved for pain that does not respond to nitrates; fine in ST-elevation infarction, controversial in unstable angina and non-ST-elevation infarction.
“The three main ones you’re going to run into include tPA, which is a recombinant tissue plasminogen activator, and then we also have reteplase and tenecteplase… working more specifically on plasminogen that’s bound to fibrin… if it activated plasminogen all over the body you just bleed out and die.”
Alteplase, reteplase and tenecteplase: recombinant, aimed at clot-bound plasminogen. Study note: he describes the fibrin selectivity at the class level; this site does not key the claim that reteplase has increased fibrin affinity, which is not true of reteplase.
“Adverse effects, all these agents, bleeding is the big one… hemorrhagic stroke, GI bleeds, all kinds of bleeds are possible… allergic reactions because these are protein-based medications… and then you could also see ventricular arrhythmias.”
Bleeding (including hemorrhagic stroke and gastrointestinal bleeds), allergic reactions, ventricular arrhythmias.
“This is important, whenever you’re about to decide to give fibrinolytics… you have to go through your contraindications and if they meet any of these you don’t give it… you have to go through this checklist… because once it’s given you can’t take it away.”
He read the whole list aloud (recent surgery, serious gastrointestinal bleeding, severe uncontrolled hypertension, active bleeding, previous cerebrovascular accident or brain tumor, aortic dissection, acute pericarditis, allergy, pregnancy). Study note: the guide lists the firm items and marks the relative ones.
“They work very similar to one another, they’re all going to be expensive, they can all cause allergy and they all cause bleeding… it’s usually just based off provider preference and hospital formulary.”
No agent is the preferred one: choice follows provider preference and hospital formulary; all are expensive and all can cause allergy and bleeding.
“Patients less than 75 years of age, for example, if they’re within 12 hours of symptom onset… outside of that window you tend to find patients have less benefit while still having that bleeding risk… relatively few patients end up getting these big full-blast doses.”
Benefit is greatest early (within 12 hours); the catheterization laboratory is preferred where available, which is why few patients receive systemic fibrinolytics. (This site does not key the age or hour figures.)
“Glycoprotein 2b3a inhibitors… another anti-platelet type of drug along with your ADP receptor blockers, [which] are also called P2Y12… whenever a stent gets placed that’s foreign material… patients who go home on stents will need to be on some kind of anti-platelet therapy sometimes indefinitely.”
Stent placement means antiplatelet therapy afterwards (sometimes indefinitely); P2Y12 receptor antagonists are used before intervention and with stents; heparins accompany fibrinolysis or antiplatelets.
“Treatment for NSTEMI is going to be similar to MI, it’s just less use of fibrinolytics and then more use for things like your 2b3a inhibitors and enoxaparin.”
Early treatment resembles ST-elevation infarction; fibrinolytics are not recommended in non-ST-elevation acute coronary syndrome, and glycoprotein IIb/IIIa inhibitors are used more.
“Don’t worry so much about indications for use… And then formulation-wise, I don’t care that you memorize that necessarily, with some exceptions… [On dosing:] not for memorization sake necessarily, because you can always look up the dosing for a medication if you know which drug you actually want to use in the first place.”
The antibiotic table lists strengths, forms and indications, and he said not to worry about them; he covers the specific use of each agent as he goes. The ones he built up: erythromycin ointment is the most common ophthalmic antibiotic, dirt cheap, and soothing on the inflamed eye even before a bacterial infection is confirmed; azithromycin is a drop given less often at higher cost and used less; and the fluoroquinolones are held for corneal ulcers, Pseudomonas and contact lens wearers.
“Adverse effects, this is gonna be the same with just about any ophthalmic antibiotic. So don’t memorize which ones cause eye irritation or hypersensitivity. Any of these can do that, right?”
Eye irritation and hypersensitivity belong to every ophthalmic antibiotic on the deck, and he called interactions a non-issue for the topical forms because so little reaches the bloodstream. The exceptions he did name: sulfacetamide (sulfonamide allergy) and the aminoglycosides gentamicin and tobramycin, which irritate more and can cause corneal ulceration, so they are kept for special cases.
“Strains this works against, I’m not going to be quizzing on necessarily. I’ll just give you an idea. It’s a fairly broad spectrum antifungal.”
Know that natamycin is the only commercially available ophthalmic antifungal: it binds sterol in the fungal membrane and makes it leak, and mostly causes eye irritation. Serious fungal eye infection usually needs a systemic antifungal such as fluconazole instead.
“Unless you’re working specifically in ophthalmology, you’re probably never going to prescribe these. You might see patients using these and so it’s good to be familiar with what they’re being used for and what some of the downsides are.”
What to carry: they are reserved for refractory or severe inflammation and limited to short courses (under two weeks), and the downsides are cataract formation, raised eye pressure that can become glaucoma, infection from lowered immunity, slow wound healing and corneal ulcers.
“We’re mainly gonna focus on the open angle glaucoma because drugs are mainly gonna be focused there… It’s more of a surgical issue if you’re having a closed angle glaucoma sort of issue.”
Open-angle glaucoma is the chronic, painless form (too much aqueous humor made or too little drained) and is where the drugs work: they either cut aqueous production or raise outflow through the trabecular meshwork. Angle-closure is an acute, very painful blockage that is treated surgically.
“Again, it gets really complicated when you’re looking at the flow of ions… Don’t get lost in the weeds. It’s really easy to drive yourself crazy and try to make heads and tails of all these arrows going back and forth in your ions and all that good stuff.”
What to know instead: dorzolamide and brinzolamide block carbonic anhydrase (which converts carbon dioxide and water to bicarbonate), so less bicarbonate and fluid move, less aqueous humor forms and eye pressure falls. They are add-on drugs because of burning, stinging and a bitter taste; acetazolamide is the same class used in the kidney.
“For my purposes, in terms of like test questions, I’m probably not going to be asking a lot of duration questions either, just like the dosing. You can always look that stuff up, but if you don’t even know what drug to use in the first place, you kind of lost. So I’d rather you know what drug to use.”
The durations on the deck are context: ear infection five to seven days (five may be too short when severe), sinus infection ten to fourteen days in children versus five to seven in adults, strep throat ten days of amoxicillin.
“So looking at kind of the dosing ranges here, and the specific numbers, I don’t care that you memorize, right? What I’m talking about are the relative safety sort of features between salicylates and some of your other nonsteroidal anti-inflammatory drug (NSAID) type of products.”
The table shows the pattern by dose: low doses give the antiplatelet effect and bleeding; mid doses give pain and fever relief with stomach upset; higher doses cause ringing in the ears (tinnitus); the toxic range causes rapid breathing, then metabolic acidosis, shock and death. His point was that an aspirin overdose is far more dangerous than an ibuprofen overdose, which is why he prefers other nonsteroidal anti-inflammatory drugs unless there is a specific reason for aspirin.
“There’s a few exceptions, like captopril and lisinopril — I don’t care necessarily that you know that. But just to give you an example, if we needed an intravenous (IV) ACE [angiotensin-converting enzyme] inhibitor you couldn’t give the prodrug form… if you ever see the drug called enalaprilat, that’s the activated form of a drug called enalapril.”
Most angiotensin-converting enzyme (ACE) inhibitors are prodrugs activated in the liver (captopril and lisinopril are not); enalaprilat is the injectable, already-active form of enalapril. The suffix -pril identifies the class.
“Angiotensin-converting enzyme (ACE) inhibitors are mostly renally eliminated, angiotensin receptor blockers (ARBs) are going to be a little bit more equal between renal and biliary excretion. It’s not really going to be a really key feature for their purposes here, so I’m not going to worry too much about that.”
For the record, the deck says angiotensin-converting enzyme (ACE) inhibitors are cleared by the kidney (fosinopril is the balanced exception) and angiotensin receptor blockers (ARBs) by both kidney and bile, but this is not a distinguishing fact he will test.
“Am I going to have you memorize which one has three pluses versus five pluses? No, I don’t care if you know that, but I do want to get the general flavor of the differences between your non-dihydropyridines (non-DHPs), which will have both vasodilatory action but also suppressing cardiac function, versus the DHPs are mainly focusing on vasodilatory actions.”
The grid rates vasodilation, contraction, sinoatrial node and atrioventricular node effects: the dihydropyridines are strongly vasodilating with little effect on the heart, and verapamil hits the heart harder than diltiazem. Know the direction, not the number of pluses.
“Other things that could differentiate beta blockers, which I’m not going to highlight too much for our purposes here… I’m not going to get in the weeds on that… Do I care that you know if something’s renally eliminated versus how it’s metabolized, or if it has a membrane stabilizing effect or intrinsic sympathomimetic activity? No, I’m not going to worry about that so much. I want you to distinguish between your different groups of beta blockers and what kind of side effects and clinical actions that entails.”
Learn the three groups (non-selective, beta-1 selective, third generation with extra vasodilating actions) and what each causes. The one property he singled out: propranolol is very lipid soluble, so it reaches the brain and is tied to nightmares and worse depression.
“Now on the test question, am I going to get so granular to give you a patient situation to say, hey, what do they need, moderate versus high versus low intensity statin? Probably not, right? But more so is, can you identify what falls into the category of high versus moderate… only two drugs based off their dose get into the high intensity statins, atorvastatin and rosuvastatin, only those two are considered high intensity.”
Only two statins reach high intensity, and only at higher doses: atorvastatin and rosuvastatin. The others are less potent; at the right dose they reach moderate intensity, and lower doses are low intensity. Intensity depends on both the drug and the dose. He will not ask you to pick low versus moderate versus high for a patient.
“The end of the testable material for the exam for Monday ends with this PowerPoint, and then we’ll get started on the first PowerPoint for the third exam right after.”
Myocardial ischemia is the last lecture on Exam 2. The diuretics and heart failure deck he starts straight afterwards, in the same recording, belongs to the next exam.
“Streptokinase, kind of an older one we’ve used in the past, I don’t want you to worry so much about that, but I do want to focus on this picture here… plasminogen coming in with streptokinase to form a complex… a tissue plasminogen activator, which is what we naturally produce, could do this as well.”
Streptokinase the drug is low priority; the mechanism picture (plasminogen converted to plasmin, by a streptokinase complex or by tissue plasminogen activator) is what he wants known.
“I don’t care that you know the difference between which one’s made with E. coli versus hamster cells.”
Skip the cell-line details on slide 64 (hamster ovary cells against Escherichia coli).