Non-sustained VT less than 30 seconds generally only needs treatment if the risk of subsequent sustained VT or arrest is high. For For example, if the LVEF is under 35% or if it's associated with marked QT prolongation, which we'll definitely get into. And one more point, VT with a structurally normal heart, that's rarely life-threatening, even if it's sustained, and typically requires no therapy if it's asymptomatic and non-sustained.

Okay, that distinction based on structural heart disease seems absolutely central.

Now, here's where it gets really interesting, I think, and directly impacts daily pharmacy practice.

Drug induced QT prolongation. It's such a huge safety concern. Let's unpack the QT interval and its connection to arrhythmia risk.

Okay. Yeah. Let's dive into the QT interval. It's an ECG measurement rate from the very start of the QRS complex to the end of the T-wave. Think of it as a crucial surrogate measure for the heart muscle's repolarization time. Basically, how long it takes the heart's electrical system to reset after each beat. Measuring it accurately can be tricky. Sometimes it's affected by heart rate. There's variability across different ECG leads. Sometimes U-waves get in the way,

right? And that's why we use the corrected QT. The QTC.

Exactly. Because the raw QT interval changes dynamically with heart rate, we use a corrected QT or QTC to account for this. The Bazette formula is very commonly used. Though interestingly, it can undercorrect at very fast heart rates. For clinical purposes, the American Heart Association defines a prolonged QTC as 470 milliseconds or more in men and 480 milliseconds or more in women. Those are key numbers to remember.

Okay. 470 for men, 480 for women. Why is this so important. What's the danger?

Well, the danger is that prolongation of this repolarization time significantly increases the likelihood of a very specific dangerous type of ventricular arhythmia called torsads deoint or TDP

to de point right

TDP is a form of polymorphic VT. It often stops on its own but it can cause hemodynamic instability or even degenerate into fatal VF. So it's serious and the risk of TDP directly increases as the QTC gets longer. It becomes a major concern when the QTC goes over 500 milliseconds or increases by more than 60 milliseconds from the patient's baseline QTC.

So QTC over 500 or a jump of over 60 milliseconds. Got it. What causes this QT prolongation?

It can be congenital. There are genetic long QT syndromes. Patients with these conditions absolutely must avoid QT prolonging drugs their whole lives. So that patient history is vital again. But for us as pharmacists, acquired causes are far more common. These include things like bradic cardia, slow heart rate, electrolyte abnormalities, especially low pot. potassium, low calcium, low magnesium hypothermia, myioardial eskemia, and medications. By far the most common culprit, both anti-arithmic drugs and many, many non-cardiac medications can prolong the QT interval. They mainly do this by acting on a specific potassium channel called IKR. This is really where pharmacists are the frontline defenders. For a comprehensive, up-to-date list of QT prolonging drugs, you should always refer to reputable resources like credible meds. It changes frequently.

That's a huge list. I know. For our PBC candidates listening, can you maybe highlight some of the most critical drug classes or specific drugs that pharmacists absolutely need to be watching out for, the high yield ones for TDP risk?

Absolutely. Let's spotlight the really high impact ones for your exams. Among the anti-riythmics themselves, amuterone, sodalol, quinadine, proanomide are key. Amuterone is interesting. It very frequently prolongs the QT interval, but it's actually infrequently associated with TDP, possibly due to its broader antiorythmic effects blocking multiple channels. Sodtool, however, is a different story. It marketkedly prolongs QT. It shows something called reverse use dependence, meaning its effect is more pronounced at slower heart rate.

Reverse use dependence. Okay.

Yeah. And it's actually the drug most often associated with QT prolongation in registry studies. There is a nearlinear relationship between the sodalol dose and QT prolongation. The risk really jumps at doses higher than 320 milligs per day. So, sodtool is a big one.

Okay. Sodalol is key. What about non-cardiac? drugs

right beyond anti-riythmics certain antibiotics are notable think macrolytes like aithramycin chloriththramycin eriththramycin also floricquinolones like cyproloxicin we also see it with some anti-depressants like cyopram especially at higher doses and the older tricyclic anti-depressants antimedics like andatetron some ozole antifungals many typical and atypical antiscychotics even the opioid methadone it's not just cardiac drugs it's a really wide range

wow it really is everywhere

it is is but what's also crucial is understanding the actual risk. The risk of prohibia with most of these non-cardiac QT prolonging drugs is actually quite low. Unless the uncorrected QT interval is already quite long, say over 500 to 520 milliseconds. The probability of TDP significantly depends on the patients individual risk factors. Think of these as compounding effects. Things like female sex, older age, bricardia, low potassium or magnesium, higher drug dosage, using multiple QT prolonging drugs together, and medical conditions. is affecting drug metabolism like heart failure or sepsis. These things multiply the risk.

So it's not just the drug, it's the drug plus the patient context.

Makes sense. Okay. So connecting all this once a patient is diagnosed. What about non-farmacologic interventions both immediate and chronic? What's vital there?

Right. For immediate therapy, if a patient has sustained monomorphic VT and they're unstable, meaning hypotension, angina, heart failure, severe symptoms, then synchronized cardioversion is the way to go. That's a precisely timed electrical shock. But for polymorphic VT or VF, it's different. It's an immediate non-synchronized shock defibrillation. You don't wait to synchronize with the chaotic rhythm. You just shock immediately. Repeat every 2 minutes if needed. Maybe increasing the shock energy if the first attempts fail. This immediate action is absolutely life-saving.

Okay. Shock therapy first for emergencies. What about long-term prevention? Non-drug approaches.

When it comes to chronic therapy, preventing recurrence, the implanted cardioverter defibrillator or ICD is incredibly effective. It detects VT or VF and delivers a shock internally to terminate it. Current guidelines strongly recommend an ICD as the preferred treatment for patients with a history of cardiac arrest, VF, or sustained VT that isn't due to some reversible cause. Studies like the AVID trial showed significant mortality benefits compared to drug therapy alone.

So, ICDS are really the gold standard for prevention in high-risisk patients.

For secondary prevention, yes. However, it's important for pharmacists to understand this distinction. While ICDs terminate events, they don't necessarily prevent the arhythmias from happening again long term. They're a safety net, not a cure for the underlying tendency.

That's a good point. Any other non-drive strategies?

Yes, catheter ablation is another key option. It involves mapping the heart's electrical pathways and using energy, usually radio frequency, to destroy the small area causing the arhythmia. It's often considered first line for patients with structurally normal hearts who have BT, and it's also used for selected patients with eske. cardiammyopathy often combined with beta blockers. Ablation is generally comparable in efficacy to amadronone actually superior to sodtool and often more effective than just escalating drug therapy if VT keeps recurring despite medications. There's also something called stereotactic cardiac radio ablation using focused radiation. It's still investigational really a last resort for truly refractory VT that hasn't responded to anything else.

Okay, ICDS and ablation are major players.

Now let's turn back to the ological toolbox. We've touched on QT issues, but what are the key medications used for immediate and chronic management of VTVF? What should our PBC candidates specifically focus on?

Right, the drugs for immediate therapy and sustained VT or VF, introvenous amodderone is uh moderately effective. It rarely terminates VT immediately, but it's particularly useful in preventing early recurrence, especially in what we call an electrical storm, multiple VTVF episodes close together or in shockresistant VF. F doses typically involve an IVA bololis maybe a second bolus followed by an infusion. As pharmacists you need to watch for hypotension low blood pressure especially with rapid administration.

Okay around the fourth what else?

Procanomide also given introvenously it's mainly for monomorphic VT not polymorphic VT like torsods and again you need careful blood pressure monitoring due to hypotension risk. Magnesium IV magnesium sulfate. This is the treatment of choice for torsodin very important. It can also be useful in myioardial esia but remember it has no benefit in regular monomorphic VT

magnesium for torsods. Got it.

Yes. Then intravenous beta blockers like metoprolol or propranolol. These can prevent VT or VF especially in the setting of an acute MI or electrical storm. Interestingly some evidence suggests propranolol might be superior to metoprolol specifically in electrical storm. Lastly licane. It's only occasionally effective in sustained monomorphic VT maybe less than 20% of cases respond. It might increase the rate of return of spontaneous circulation ROC and shockresistant VF, but watch for CNS side effects like confusion or seizures at higher doses.

Okay, that covers the acute drugs. What about chronic therapy? Preventing recurrence with meds.

For chronic therapy preventing recurrence, it's absolutely paramount for pharmacists to understand this. ICD implantation is superior to drug therapy for preventing sudden death in high-risisk patients both for secondary prevention and for primary prophylaxis in patients with low LVEF drugs are often adjuncts or for patients who aren't ICD candidates.

So drugs are often secondary to ICDs in high-risisk cases.

In many cases, yes, but medications still play a huge role. Beta blockers are a cornerstone. They're recommended for pretty much all patients if tolerated. They suppress arhythmias and they reduce mortality in heart failure or postMI patients. They're excellent for exercise, stress or eskeeia induced VT. Metaprolol, a tennol, bicopolar are common choices there. Emiodarone and sodalol taken orally are effective in preventing VTBF recurrence. But remember they are less effective than ICDs in preventing sudden death and overall mortality in those high-risisk patients. They can however be used as a really important adjunct to ICD therapy to reduce the frequency of painful shocks from the ICD. That improves quality of life significantly.

Using drugs to reduce shocks makes sense. Are there other drug options?

Yes, but they're less common now. Class Agents like meine or sometimes quinadine. These are typically last resort addition. ions maybe for electrical storm that's resistant to beta blockers and amiodorone or if amioderone isn't tolerated or effective used very cautiously quinodine notably is only available in Canada through health Canada's special excess program

okay so mainly beta blockers emioderone sodalol with ICDs being primary for high-risisk prevention now this brings up a critical practical question for pharmacists given everything we've said about drug induced QT prolongation how should we approach patients who need these potentially problematic medications especially if they're already at high risk. What's our framework?

Yeah, this is where your clinical judgment as a pharmacist really shines. It's a balancing act. I recommend a step-wise approach. First, always verify, is this medication actually on a known QT prolonging drug list. Is it associated with TDP? Use resources like credible meds.

Second, clarify the patients history, personal or family history of ventricular arhythmias, congenital long QT syndrome, unexplained syncopy, sudden death. If a patient has known congenital LQT syndrome. It's generally best to avoid QT prolonging medications entirely if possible.

Okay. Verify their drug. Check the history. Then

then review the patients other medications and their medical conditions. Look for those high-risisk features we talked about. Electrolyte imbalances, brady cardia, female sex, older age, interacting drugs, conditions affecting drug metabolism. Are there multiple risk factors present for patients identified as high risk or those already on multiple QT prolonging meds? Really assess the indication for the new drug. Is it absolutely necessary? Can it be safely replaced with a nonQT prolonging alternative? This is your chance to intervene to suggest safer options.

Proposing alternatives. Good point. What if the drug is deemed necessary?

If the medication is truly necessary after that careful risk benefit assessment, then start with the lowest effective dose. Now, ECG monitoring. It's not always mandatory for all QT drugs, but some recommend getting a baseline ECG and maybe a follow-up, especially if the baseline QT interval is already prolonged or if multiple risk factors exist. If you do monitor Repeating the ECG after about five drug half- livives or after any dosage adjustment is reasonable. And remember those crucial thresholds, a QTC interval over 500 milliseconds or a QTC prolongation by more than 60 milliseconds from the patient's baseline. Both of those warrant immediate careful reassessment. Those are your big red flags. Stop and reevaluate.

QTC 500 or increase 60 m.

Exactly.

Also, educate patients. Tell them to report new symptoms like palpitations, dizziness, shortness of breath. Remind them about conditions that can lead to low PAC. ium like gastroenterteritis or starting a new diuretic. And for those on multiple therapies known to affect electrolytes or QT, consistently monitoring serum potassium and magnesium is key. We need to manage those electrolytes actively. Now, here's a really vital insight, something that often causes perhaps undue fear. In practice, using two or more QT prolonging medications, even in high-risisk patients, doesn't automatically mean further QTC prolongation or that arhythmias will happen.

Oh, yeah. Studies have shown pretty inconsistent results. For example, one large study looked at over 3,400 patients and found no cases of TDP, even when multiple QT prolonging drugs were used concurrently, even with hypocalemia present sometimes. So, the takeaway is if a QT prolonging medication is clinically indicated, we shouldn't necessarily withhold it based entirely on fear of QT prolongation, especially if alternatives aren't suitable. It's about careful risk assessment, individualized management, monitoring, and mitigation, not absolute avoidance based on the list alone. That's a very important nuance. Risk assessment, not just avoidance. Okay, great. Now, to bring all this together for our PBC candidates studying, the source material, the CTC reference, provides excellent algorithms and a really comprehensive drug table. How can these tools be best used for practical insights and ultimately exam success?

Oh, these are truly invaluable study aids. The management algorithms like figure 1 for non-sustained VT and figure two for long-term management of sustained VT or VF. They provide a clear visual roadmap for decision making for non-sustained VT. The algorithm nicely guides you based on whether structural heart disease is present or absent and crucially the patients LVF for the long-term management of sustained VT, VF, or resuscitated cardiac arrest. Figure 2 really emphasizes the primary role of an ICD, but it also shows where catheter ablation fits in and where pharmicotherapy comes in. Always guided by the underlying cause like CAD or LV dysfunction, it consistently reinforces that key message.

An ICD is the preferred therapy for for most patients with sustained VT and structural heart disease. That's a major takeaway for exams.

So, the algorithms provide the framework. What about the drug table?

Then there's the comprehensive drug therapy table, table four. This is gold for quick recall on your exam. It summarizes the key classes, beta blockers, class IA like quinadine, class IB like meatine, and class 3 like sodalol and amioderone. For each drug, it hits the critical details you need for PBC. Common dosages, notable adverse effects, especially TDP risk for those QT prolonging ones. Key drug interactions are listed in crucial comments. For instance, for sodalol, it'll remind you about the significant TDP risk, the need for dose adjustment and renal dysfunction, and the fact it has both beta blocking and class 3 anti-arithmic properties. For amuarone, it highlights that extremely long half-life can be months and its wide range of potential non-cardiac toxicities like thyroid or pulmonary issues and those critical drug interactions like needing to reduce warerin or dioxin doses. The table also points out important context like the fact that class AI agents generally have limited long-term benefit in reducing mortality compared to ICDs when structural heart disease is present. Use this table to really drill down on dosages, adverse effects, interactions, and those key clinical pearls. It's high yield stuff.

Excellent. Sounds like focusing on those algorithms at the drug table is key study strategy.

Okay. And now to put all this fantastic knowledge to the test, here's a quick question. Just the kind of thing you might see on your PBC exam. Ready? Which of the following medications is most frequently associated with prolongation in registry studies due to its potassium channel blocking activity and reverse use dependence.

Mhm.

Is it a a zithramycin b amiodarone c sodalol d f fl fleckenine

h okay let's think we talked about several of these aithramy can amiodarone does but tdp is less common fleonide is class I see the one really noted for frequent QT prolongation in registries and that specific reverse use dependence the answer is c sodalol As we discussed, while many drugs prolong QT, sodtool really stands out in registry studies for this risk, especially at higher doses, and that unique reverse use dependence mechanism makes it a key drug to monitor very closely.

See, sodtool is correct. Nicely explained. We really hope this deep dive into ventricular tachy has given you a clear, concise, and maybe confidence boosting summary for your PBC preparations. Remember, understanding these complex interactions, the diagnostic pathways, the treatment strategies, both drugs and devices. It's all key to becoming a well-informed and effective pharmacist. Keep learning, keep questioning, and thanks for joining us on the deep dive.

Absolutely. And until next time, continue to critically evaluate the information you encounter. Apply it to your patient scenarios. Because in pharmacy, there's always more to learn, always more context to consider. Good luck with your studies.

تروبوآمبولی وریدی
Welcome to the deep dive. We're your shortcut to well getting really well informed.

Yeah. We cut through the noise and get straight to what matters

and deliver it right to you. So today we're doing something a bit special actually.

A custom deep dive. It's specifically for you, our Canadian pharmacist PDC candidates.

That's right. We're zeroing in on a really core area of practice.

Venus thrombbo emolism, VTE for short.

Exactly. Which, you know, covers deep vein thrombosis. DVT. and pulmonary embolism or PE.

And this is uh definitely a high yield topic for your exams.

Clarity and accuracy are key here.

Absolutely. And we should mention this deep dive is brought to you by the farmerboard group.

Correct. And all the insights, everything we're discussing, it's drawn straight from the authoritative CTC reference.

So our mission today, it's really to distill down those key details from the VTE chapter in the CTC.

Yeah. We want to focus on um therapeutic choices, those medication algorithms that guide you.

The key tables too. They simplify things so much. they do

and those essential tips that can really make a difference. Basically, we want to give you some peace of mind.

Summarize the critical stuff concisely. Make sure you don't miss anything vital for the exam

or you know, more importantly for your future patients.

Okay, let's get into it then. Let's unpack this and start right at the foundation. What exactly is VTE?

So, like we said, it's DVT and PE

and why is it such a big deal for us?

Well, it's the third most common cardiovascular disorder. That's huge.

Wow. And it affects up to what 5% of the population in their lifetime.

That's the figure. And think about PE specifically. The annual incidence is about 1.29 per 10,000 people.

And you mentioned it climbs sharply with age.

It really does, which makes sense. You know, more risk factors as we get older. It just underscores how common this is.

So, as pharmacists, our radar needs to be up, especially with older patients.

Definitely. And the link between the two is critical. The most common way a PE happens

is from a DVT breaking off and traveling. An embleization.

Exactly. An embleization of a DVT. So stopping DVT or catching it early is paramount for preventing PE.

And the impact isn't just about how common it is. It's severe, too.

Oh, absolutely. VTE is a cause of death for uh up to 10% of hospitalized patients.

10%. That's significant.

It is. Now, there's a bit of difference in the stats for mortality after diagnosis. Some registry studies show up to 17% dying within 3 months. Randomized trials show a lower figure.

Yeah, closing to 2%. Yeah, that's an important distinction. Probably reflects different patient populations or a closer monitoring in trials.

And it's not just about the acute event, is it? There are long-term problems too.

Big time. Post thrombotic syndrome PTS that can affect up to 40% of DVT patients.

And that's chronic swelling pain affects quality of life

hugely. And then after PE about 1 to 4% can develop chronic thrombomolic pulmonary hypertension, CTAP,

which is really serious. is lifelimiting

very much so. So yeah, the stakes are high, short and long-term.

Okay, so given that serious impact, what are we actually aiming for with treatment? What are the goals of therapy?

Right? So for DVT, the goals are pretty clear. First, prevent a major PE. That's number one.

Makes sense.

Then stop the thrombus, the clot from getting bigger. Prevent it extending.

Okay.

Also try to prevent or mitigate that postthrombotic syndrome we just talked about

and reduce the immediate problems, the morbidity of the acute event itself.

Exactly. For PE the goals are even more well critical prevent death

the ultimate goal

prevent it happening a recurrent throbo embolism

and prevent that long-term complication CTEF

those are the core objectives

all right so before we jump into treatments let's quickly touch on initial investigations what does a pharmacist need to know

good point because the signs and symptoms you know the classic swelling or pain for DVT

or shortness of breath chest pain for PE

they're actually quite insensitive and non-specific You really can't hang your hat on symptoms alone.

So if symptoms aren't reliable, what do we rely on?

We use validated clinical prediction rules, things like the well score or the modified Geneva score

applied after the initial history and physical.

Yes, exactly. After the basics, and then if the pre-est probability comes back as low or moderate or unlikely,

that's where D- dimer comes in.

Precisely. The D-dimer test is incredibly useful there. A negative result, especially using an age adjusted threshold. can reliably rule out VTE without needing imaging.

In many cases, yes, it avoids unnecessary imaging, which is great.

But if VTE isn't excluded by DD- dimer,

then imaging is the next step. Absolutely crucial. Usually ultrasound for suspected DVT

like B mode compression or color duplex.

Yep. And for suspected PE, it's usually a CT, pulmonary angography, a CTPa.

Got it. And a quick note, you mentioned on distal DVT, clots in the calf veins.

Right. If symptoms aren't severe, sometimes initial anti coagulation isn't started immediately,

but close monitoring is needed. Repeat imaging

absolutely you need to watch closely to see if it extends proximally further up the leg. If it does, then treatment is definitely needed.

And one last point on investigations screening for thrombophilia.

Yes, important for a specific group. Patients under 40, particularly if they have recurrent VTE or a strong family history.

Identifying those underlying clotting disorders can change long-term management

significantly. Yes. Helps the duration and maybe even the type of therapy.

Okay. Diagnosis and risks covered. Let's pivot to the core therapeutic choices. The pharmacologic heartbeat as you called it,

right? But first, some general measures. These sometimes get overlooked

like the fact that many patients can be treated outpatient.

Yeah. Most DVT patients and even about half of PE patients if their heart and lung function isn't compromised.

That relies on good outpatient support systems, though.

Of course, safe discharge planning is key. And pain management starts simple with a opioids if needed.

Yes. And NSADs. They work for pain, but we have to be cautious

because of the bleeding risk with anti-coagulants. Big counseling point there.

Huge. Definitely flag that interaction.

And for DVT specifically, moving around early. Ambulation is preferred now.

Often, yes. Seems to help resolve pain and swelling faster than strict bed rest used to. And elevating the leg helps with edema, too.

For PE, it's more about supportive care initially. Oxygen, fluids, Exactly. Oxygen if they're hypoxic. 5V fluids if hypotensive or dehydrated. Vasopressors if they're in shock. Stabilize first.

Okay. Now, non-farmacologic choices, elastic stockings, compression bandages.

Right. So, they do help acutely. They improve the edema, the swelling, and the pain.

But, and this is a big butt, isn't it? They don't prevent postroomotic syndrome.

That's the key takeaway from the evidence, particularly the SOX study. A large well done trial.

Placeboc controlled showed no difference in PTS rates. between active and placebo stockings.

Virtually identical around 14% in active versus 13% in placebo. No significant difference.

So we should be careful about promising PTS prevention with stockings long term.

Absolutely. Manage expectations based on the evidence. Acute symptom relief, yes. Long-term prevention, no.

What about IVC filters? Inferior vanava filters?

Very niche. Really reserved for patients where anti-coagulants have failed

despite being on the right dose.

Yes. Or if anti-coagulants are absolutely contraindicated, like an active major bleed, you can't stop.

And retrievable filters are preferred now.

Strongly preferred.

Mhm.

The idea is to remove them once the acute risk period is over or if anti-coagulation becomes possible again.

Avoid long-term filter complications.

Makes sense. All right, let's dive into the main event, pharmacologic choices, the drugs we use. The CTC reference has a great table on this table two.

It does. And the direct oral anticoagulants, the DOAC's are front and center now. A Pixaban, Dabagatran, a Docaban, Riveroxan. working either as direct throbin inhibitors

that's debagran

or factor zats inhibitors

which is the other three a pixabin a doxan river oxiban

and their advantages are pretty clear right quick onset

yeah rapid onset usually within hours

short half- livives relatively speaking

fixed dosing no routine monitoring usually

big plus for patients and fewer drug and food interactions compared to say warerin

represents a major step forward in convenience

definitely but there's a really crucial distinction in how you start Start them. This is vital for the exam.

Okay. What's that?

Aixabiban and riveroxaban can be used as monotherapy. Meaning you start them directly. No need for hepin first.

Just the tablet from day one

essentially. Yes. Though often at a higher initial dose for a short period. But dabagatran andoxiban

they need that leadin period.

Correct.

Yeah.

They require 5 to 10 days of a parental anti-coagulant first like LMW. Then you switch.

So a pixabana river oxiban potentially offer for a simpler start, maybe easier discharge.

That's often the case.

Yeah.

Also, important note on kidney function. Most trials excluded patients with creatinine clearance below 30 millm.

But there's some newer data.

Yeah. Particularly for a Pixaban, there's growing evidence supporting its use down to a CLCR of 15 lmmen, though caution is still needed.

And what about bleeding? Reversal agents exist now.

They do, which is reassuring. The Dard seesmab for Davagatran and Dexanet alpha for the factors A inhibitors

though and Dex is quite expensive still.

It can be yes but having specific reversal agents is a big safety advancement and overall the direct inhibitors show lower risks of major bleeds compared to VKAs.

Good to know okay what about the heperins low molecular weight hepins LMW's

like deltaarin and oxiparin tensiparin key advantage more predictable response than unfractionated hepin

so dosing is simpler weight-based

usually weight adjusted fixed doses given subcutaneously longer Halflife often allows for once or twice daily dosing. Great for outpatient use.

And you mentioned one review suggesting tinsiparin might be better than VKAs for reducing PTS.

Yes, that was an interesting finding in one systematic review. Needs more research, but suggestive

dosing details are in the reference materials. Usually units per kg or milligram per kg,

right? With specified maximum daily doses sometimes. Main side effect is bleeding of course,

but less hit and less osteoporosis than UFH.

Correct. Better facy profile in those aspects, which is a plus for longerterm use if needed. Now unfractionated hepin UFH mostly 4V infusion

most commonly. Yeah. Adjusted based on monitoring usually APTT or sometimes anti levels

aiming for that therapeutic range 1.5 to 2.5 times control for APT.

Exactly. Subcutaneous injection is possible but may be less common for treatment now and depends on concentration availability.

And the big complication to watch for is hit induced thrombocytoenia.

Serious though thankfully rare. If you suspect HIT, stop all hepin immediately. No question.

And you had a clinical pearl about SC Heperin in certain patients.

Ah, yes. Avoid subcutaneous UFH or LMW in patients with massive edema, anarcha or those on vasopressors

because absorption is unreliable.

Very unreliable. Compromised peripheral circulation means you might not get therapeutic levels. IV is safer in those situations.

Got it. Okay. The classic vitamin K antagonists, VKAs, warferin

still very much in use. Requires that careful INR monitoring. targeting two to three.

And the monitoring frequency is intense at first, right? Daily, then every few days.

Yeah.

Then weekly, then eventually maybe every two to four weeks or even up to 12 weeks in some stable patients, but it takes effort to get there.

Sounds like managing warerin is still well a bit of an art form. Needs pharmacist involvement.

It absolutely does. The biggest challenge, the sheer number of drug and food interactions

like ASA and NSA day, they don't change the INR,

but they hammer the stomach lining and platelets, right? So bleeding risk skyrockets.

Critical counsel point and herbals too.

Yes, things like ginko, jinseng, St. John's word can interact significantly. Patients need clear advice on these.

Okay. Lastly, thrombolytics, altiplas used less often.

Much less often less than 10% of VTE patients reserved for the really severe cases

like PE with hypotension, hemodynamic instability.

Exactly. Or maybe patients who are initially stable but then deteriorate rapidly if they have a low bleeding risk.

And for DBT even rare

very rare maybe life or limbthreatening clots like massive ilophemeral DVT with no contraindications

catheter directed lis is sometimes considered

but the bleeding risk is high very high especially intraanial hemorrhage it's always a major risk benefit calculation and remember altois isn't actually health Canada approved for PE it's used off label based on guidelines

good point for the exam okay we have the drugs now the crucial question how long duration of anti-coagulation This depends heavily on recurrence risk. Your reference likely has an algorithm like a figure one to guide this.

So if it's a first VTE clearly caused by something temporary like major surgery.

Typically 3 months of treatment is enough. The provoking factor is gone. Risk drops.

But it's not always that simple. What about minor risk factors?

Right? Other transient things like maybe prolonged travel, immobilization, postpartum period. But even persistent minor risks like IBD, heart failure, obesity

might need longer than 3 months. maybe 6 months or even longer.

It often warrants consideration for extended therapy beyond that initial 3 6 months. It needs individual assessment.

And what about unprovoked VTE? No clear cause.

That's where indefinite or long-term treatment often comes into play. The risk of recurrence is significantly higher and often lifelong.

But you have to balance that against bleeding risk

always. That's the constant equation. There are scoring tools like ET predict or the CH shape score that can help estimate both recurrence and bleeding risk to guide that conversation. And for distal DVT, you mentioned three months is preferred over six weeks.

Yes, guidelines generally suggest three months now for distal DVT as well.

The source mentions males having a higher recurrence risk.

It does statistically, but again, the emphasis is always on the individual patients overall risk profile, not just one factor.

And for long-term therapy choice, DOAC is often preferred.

Generally, yes, for convenience and safety profile. VKAs are an option, especially if CLCR is under 30 or the are interaction issues

and LMW alone

might be used if oral options aren't suitable particularly in some active cancer patients like those with GI cancers where LMW has shown benefit

okay we've covered treatment thoroughly but prevention prophylaxis is just as vital right

absolutely preventing VTE in the first place especially in hospitalized patients is a huge focus risk varies a lot though

and recommendations depend on the situation like type of surgery

exactly high-risisk orthopedic surgery like hip or knee replacement, major general surgery. Those patients usually need prophylaxis details often in tables like table one in your reference.

And it's not just surgical patients. Medically ill patients too.

Yes, acutely ill medical patients think severe infection, heart failure, exacerbation, respiratory failure. They often benefit from prophylaxis too if immobilized.

How long does prophylaxis usually last?

Often 10- 14 days or until mobility improves, but sometimes longer.

Extended prophylaxis is beyond discharge, especially after a hip or knee replacement.

What about CO 19? Any specific recommendations?

Yeah, the guidelines evolved. Critically ill COVID patients generally get standard dose prophylaxis. For moderately ill patients, not in ICU, therapeutic dose heperin might be considered if bleeding risk is low,

but not intermediate doses.

No. Studies didn't really support intermediate dosing.

And the goals of prophylaxis pretty similar to treatment goals

essentially, yes, but focused on prevention. Prevent DVTP, reduce mortality, Prevent PTS. Prevent CEPH. Stop it before it starts.

What about non-farmacologic prophylaxis stockings, compression devices?

Graduated compression stockings, intermittent pneumatic compression, IPC devices, they do reduce risk,

but less effective than drugs

generally. Yes. Pharmacologic prophylaxis is usually more effective. So, these mechanical methods are often reserved for patients at very high risk of bleeding where drugs are just too dangerous. Neurosurgery is a classic example.

Okay, let's talk pharmacologic. is for prophylaxis. Again, your reference probably has a table like table three LMWs.

Yep. LMWs like Daltaparin and Oxiparent Tinsiparin are main stays used at lower fixed daily doses for prophylaxis

and still have that lower risk of hit and osteoporosis compared to UFH. Correct. UFH for prophylaxis

still used usually 5,000 units subcutaneously two or three times a day. Generally considered effective mainly for moderate risk procedures.

Fondiparent arra that's 2.5 milligrams daily subcutaneously. It's specifically approved for high-risisk orthopedic patients. A good option there.

Now, this is interesting. Aspirin, ASA, for prophylaxis.

Yes. Specifically in the context of hip or knee replacement surgery after an initial course of a more potent anticoagulant like LMW or a DOAC.

Switching to lowdose aspirin like 81 milligram daily.

Exactly. Studies have shown is pretty much as effective and safe as continuing the LMW or DOAC for extended prophylaxis in that specific setting. A simple cheaper option for some.

That's a really practical point. And doc's for prophylaxis

definitely used especially after elective hip and knee replacement. A Pixaban 2.5 milligram B riveroxaban 10 milligrams daily. Debbie getran has a specific posttop initiation regimen

and effective

very as effective as LMW and in fact a pixaban riveroxaban have shown superiority over anoxiparin in some major orthopedic trials.

Wow superiority that's significant.

It is it really reinforces their role in orthopedic prophylaxis

in cancer patients. Prophylaxis important there too.

Very important. Cancer itself increases VTE risk significantly. Prophylaxis is often recommended especially for ambulatory patients starting chemotherapy who have a high corona score.

Options include LMW or DOAC's like a Pixaban.

Yes, a Pixaban showed good results in the AVERT trial for ambulatory cancer patients. LMW is also a standard option. Important area for pharmacist intervention.

Okay, loads of great info on treatment and prophylaxis. Let's shift to some special considerations and therapeutic tips. Pregnancy and breastfeeding first. This is critical.

Absolutely critical. VTE is a major cause of maternal morbidity and mortality. The risk just skyrockets during pregnancy and postpartum.

Like 7 10 times higher before birth and 15 35 times higher after.

Those are the numbers. It's a massive increase compared to non-pregant women of the same age.

And it links back to Virgow's triad again

perfectly. You get venous stasis from hormones in the is pressing on veins, you get potential vessel injury during delivery and pregnancy itself creates a hypercoagulable state.

A perfect storm for clots

indeed.

So managing VTE during pregnancy, what's the approach?

LMW is the anti-coagulant of choice. Deltaarin and Noxiparin.

Why LMW?

Crucially, they don't cross the placenta, so they're safe for the baby. UFH also doesn't cross, but LMW is generally preferred.

Less bone loss, too.

You mentioned

Yes. Less risk of heper induced osteoporosis compared to long-term UFH.

And treatment duration, minimum 3 months.

Minimum 3 months total and it must include at least 6 weeks postpartum because the risk stays high after delivery. Full treatment doses initially.

What drugs must be avoided in pregnancy?

Warin is the big one. Terraogenic effects especially first trimester. Avoid

docs

also generally avoided. Not enough safety data. They do cross a placenta and they get into breast milk.

Fond paranex.

Only if you absolutely have no other choice like a severe LMW. ology very limited data

and delivery planning is complex for women on LMW

very needs careful coordination between the obstitrician hematologist anesthesiologist to plan when to hold and restart the LMW around delivery to balance clotting and bleeding risks sometimes a retrievable IVC filter is even considered if anti-coagulation is has to be stopped near term

what about postpartum and breastfeeding management

for that postpartum period up to 6 weeks warrin seuf or LMW are all considered safe options for continued treatment or secondary prevention

and breastfeeding safe with those agents.

Yes, Warin, UFH, LMW safe during breastfeeding. They don't pass into milk in significant amounts or aren't absorbed by the baby.

But DOAC safety in breastfeeding is still unknown,

not established. So generally avoided or used with extreme caution and specialist advice if breastfeeding.

Okay, last key area, therapeutic tips for managing hit. Hepin induced thrombocytoenia. Rare but serious.

Very serious. If it happens, you need to switch anti-coagulants immediately to something non- heepin.

What's approved in Canada for HIT?

Aratrobin, a direct thrombin inhibitor and danapareroid which is a hepoid.

Are there other options used?

Yes, based on evidence though maybe less data are not officially indicated by villerudin phiparinex even riveroxaban have been used successfully

and expert consensus often leans towards

often fondarex is considered a good choice. It's effective seems seems to have low crossreactivity risk with the hit antibbody and has predictable dosing.

Great practical tip. So to wrap up, we've really done a deep dive into VTE today.

We have covered the definition, the serious impact, the treatment strategies, drugs, non-drug options, duration,

prophylaxis measures which are so important

and those critical considerations for pregnancy and managing HIT. We look at DOAC's, hepins, warfin, the whole landscape

and understanding all these choices, the doses the patient factors. It's absolutely essential for the PBC exam.

Paramount, but more than the exam, it's fundamental for safe, effective patient care in your pharmacy practice going forward.

Definitely. Now, for a final provocative thought to leave you with, with DOAC's becoming so widespread, how do you think this will continue to shift VTE management long term, especially around say monitoring needs or the role and cost of reversal agents?

That's a really interesting question. The reduced need for routine monitoring is a huge shift, but maybe complacent. is a risk and access to reversal agents.

Yeah,

it's changing the game, but cost is still a factor. Definitely something to keep thinking about.

Absolutely. Okay, time to test your knowledge with a quick multiple choice question based on our discussion.

Ready? Which of the following direct oral anti-coagulants, DOAC's can be initiated as monotherapy for the treatment of acute venus throboism without requiring an initial parental anti-coagulant?

Is it a dabatran, b docaban, c riverox? man D fondarin

think about which ones don't need that hepin and leadin we'll provide the answer and a brief explanation in the accompanying materials

we really hope this deep dive has given you clarity accuracy and practical insights for VTE

and remember this deep dive was brought to you by the Pharma board group drawing directly from the CTC reference keep learning keep asking questions

and you'll absolutely continue to deepen your expertise thanks for joining us on the deep dive

فشار خون بالا
Are you a Canadian pharmacist examining board candidate, a PBC candidate? Then you definitely know that um unique stress of trying to keep up with constantly evolving guidelines, especially when the stakes are high like well your upcoming exam, welcome to the deep dive, your shortcut to staying well informed and hopefully gaining that crucial edge. Our mission today, it's a really crucial one. We're taking a deep dive into the 2025 Canadian hypertension guidelines. We'll highlight the key details you absolutely need to know and Crucially, we'll compare them directly to the uh the 2020 guidelines. We'll unpack therapeutic choices, medication algorithms, essential tips, all designed to give you clarity, accuracy, and practical insights for exam success and, you know, peace of mind, too. This deep dive is brought to you by the Pharma Board Group, and we're leveraging insights from the CTC reference. We understand that many of you listening are not native English speakers, so we'll be taking our time. We want to make sure every crucial detail is easy to follow.

That's absolutely right. And as pharmacists, our role in hypertension management in Canada is well it's vital. We've actually seen some um declining trends in hypertension treatment and control across the country recently. So these new 2025 guidelines they really aim to improve populationwide control especially within primary care. They offer a new pragmatic kind of two-part approach. Understanding these updates isn't just about passing an exam. It's really critical for your practice.

Okay, let's really dive into this then. One of the biggest shifts it seems in the 2025 guidelines is how we actually define hypertension. This feels like a fundamental change, right? Right at the diagnostic threshold.

Precisely. Yeah. If you look back at the 2020 guidelines, the diagnostic thresholds, they actually varied a bit. It depended on how the blood pressure was measured. For automated office blood pressure, A OBP, a mean systolic of 135 or diastolic of 85 was considered high. But for the standard office blood pressure measurement, OBPM, it was a higher threshold, 140 over 90.

Okay, so that's the history. Now, bring us up to date. How different is 20 25. What's the new number?

The 2025 guideline simplifies this quite significantly. It recommends a uniform definition. Blood pressure equal to or greater than 130 over 80 millg. That's when measured with a validated device under optimal conditions. Of course, this new lower threshold um it really reflects this growing body of evidence associating cardiovascular risk with lower BP levels than we maybe previously thought.

Wow. 130 over 80. That's a big change. That lower threshold probably means more people will be diagnosed, right? Mhm.

So, how does the guideline make sure we're accurate with this uh lower number prevent overdiagnosis?

That's a really key point. This new definition absolutely emphasizes accurate blood pressure measurement. It's critical. The 2025 guidelines, they actually prefer validated automated ocelometric devices over the old oscultatory spigo monometers. They're just easier to use, less prone to human error, and seem to have better reproducibility. And they recommend a very standardized protocol, a one to five minute rest and three measurements a minute apart. And you average all the val values. Consistency is key.

Okay. Consistency, automated devices. And what about measuring outside the office like at home?

Right. Out of office BP assessment. So 24-hour ambulatory monitoring, ABPM or home BP monitoring, HBPM. That's strongly recommended now to confirm the diagnosis. It's especially important to rule out things like white coat hypertension.

There it's high in the office but normal otherwise.

Exactly.

And also masked hypertension, which is the opposite normal in the office but high outside for Home monitoring the standard is measuring BP in duplicate twice a day for a week and importantly you shouldn't count the first day's readings they tend to be higher these out of office measurements they just correlate more closely with actual cardiovascular events so they're very valuable

okay so diagnosis is clearer more rigorous let's shift gears once diagnosed how do the treatment targets compare between 2020 and 2025

yeah another area of change the 2020 guidelines had while varied targets depending on patient risk in coorbidities. For example, low-risk patients, the target was less than 140 over 90. But for high-risisk patients, say with existing cardiovascular disease or older adults, they aimed for more intensive systolic targets, sometimes less than or equal to 120 based on AOBP. Patients with diabetes had a specific target, systolic less than 130, diastolic less than 80. And for non-diabetic chronic kidney disease, targets were kind of individualized. If they were sprint eligible, they aimed for systolic less than 120.

Seems a bit complex. to track all those variations. So, what's the 2025 approach to targets? Is it simpler?

Much simpler. The 2025 guideline really streamlines this. It's a single consistent target for most adults. Basically, achieve a systolic blood pressure less than 130 millm or HG as long as the treatment is well tolerated. This simplified approach, it's really about ease of implementation, making it clear though it does acknowledge, you know, patient specific factors like frailty or fall risk might need individualization. maybe a slightly higher systolic target and interestingly there's no specific diastolic target recommended now they note that cardiovascular risk is pretty low when the systolic is below 130 anyway

okay single target less than 130 systolic for most now the big one for pharmacists initial phicotherapy what's changed here this sounds critical

this is another major major shift the 2020 guidelines they primarily recommended starting with monotherapy or maybe a single pill combination SPC from a list of firstline choices beta lockers, for instance. They could be first line, but generally only for younger patients.

Okay, here comes. This sounds like where things get really interesting for 2025. What's the new approach?

The 2025 guidelines strongly recommend lowdose combination therapy as the initial treatment right from the start and ideally as a single pill combination and SPC. This involves drugs from two of these three main classes. An ACCE inhibitor or an ARB, a thioide or thioid like diuretic and a long acting dihydropodian calcium channel blocker or CCB. And here's a key point. Beta blockers are no longer recommended as first-line therapy for just hypertension. Not unless there's a specific clinical reason like heart failure, anggina, or maybe postiocardial infarction.

Wow. Straight to combination therapy.

Yeah.

Why the big shift away from starting with one drug? What's the rationale?

Well, the evidence really points this way now. Combining lower doses from different classes gives you additive BP lowering effects, but importantly, it often minimizes adverse effects compared to maxing out one drug. drug better tolerability and SPC's single pill combinations. They significantly improve BP control compared to monotherapy. They also enhance adherence. People are more likely to take one pill than two and persistence, plus potentially cost savings down the line.

Makes sense. Get more bang for your buck pharmacologically and it's easier for patients. So, what if BP isn't controlled with those two drugs? What's step three?

Good question. If BP is still above target despite that two drug combo, the 2025 guideline recommends adding a third firstline agent. So you'd pick from the remaining class. You'd end up with say an ACI or ARB plus a thazide diuretic plus a long acting dihydropodine CCB.

Okay, triple therapy with the main classes.

What about those really tough cases resistant hypertension?

Right. If BP is still above target even with that three drug combination at maximally tolerated doses, then the addition of spironolactone is suggested. This is based on evidence showing it gives a substantial BP reduction in these cases. Though it's worth noting the long-term cardiovascular outcome data for spironolactone as a fourth agent specifically are still a bit limited, but this aligns pretty well with the 2020 guideline which also flags spironolactone as a strong option for resistant hypertension. Just have to be mindful of monitoring potassium of course, especially with an ACI or ARB on board.

Absolutely. Monitoring is key there. Okay, shifting away from meds for a moment. Yeah. What about lifestyle changes? Still important. Any updates?

Oh, absolutely foundational. Both the 2020 and 2025 guidelines hammer this home. Healthy lifestyle changes are crucial for all adults with hypertension. It includes reducing sodium intake, aiming towards 2,000 milligs a day, and reminding patients, you know, most sodium comes from processed foods,

not just the salt shaker.

Exactly. Also, increasing dietary potassium, fruits, vegetables, weight reduction if needed, aiming for a BMI in the 18.5 to 24.9 range, regular physical activity like 30 to 60 minutes of moderate intensity activity most days of the week, and of course, reducing alcohol consumption.

Let's clarify that. alcohol guidance. It can be confusing sometimes. What do the 2025 guidelines say specifically?

Yeah, it's nuanced. Building on 2020, they note that um while overall reduction is generally good for adults who are already consuming two or more drinks per day, just cutting back to two drinks didn't seem to affect BP much. However, if they were consuming more like three, four to five or six or more drinks per day, then reducing their intake was associated with significant drops in systolic BP. So, the suggested limits remain generally two drinks or less per day for men and one drink or less per day for women.

Okay, that's helpful clarification. Now, what about specific populations? I remember 2020 had detailed sections on pregnancy, children. How does 2025 handle that?

This is a really important distinction to make about the 2025 guidelines. They are specifically focused on adults in primary care. They are not intended for children or pregnant individuals. There are separate specialized guidelines for those groups because their needs are quite different.

Okay, so PDC candidates still need to know about those other guidelines separately.

Yes, absolutely. It's crucial for exam candidates to still be aware of the general principles from the 2020 guidelines and other companion documents for these populations. For instance, remembering that in pregnancy ACE inhibitors and ARBs are generally a no-go due to terodogenic risks and that specific drugs like leettool, mephylopa or long-acting nephetapine are preferred firstline oral agents and knowing which drugs are generally considered okay during breastfeeding like leettool methylopa, nifidapine and a lapal caprill. And for children, you know, the BP thresholds are different based on age, sex, height percentiles. Monotherapy is usually the start often with ACEs, ARBs or long acting CCMs, aiming for BP below the 95th percentile.

Got it. So the 2025 guidelines streamlines for primary care adults, but keep the broader knowledge for exams. What about routine monitoring and lab tests? Any changes there?

Not really major changes to the core tests. Both guidelines recommend routine testing for all hypertensive patients at baseline and during maintenance. This includes things like uran analysis, blood chemistry focusing on potassium, sodium creatinine, also fasting blood glucose or an A1C, a lipid panel, and a standalled 12LE ECG. How often you repeat these depends on the clinical situation, but that baseline set of investigations is still standard.

Okay, standard tests remain.

Finally, let's talk about putting it all into practice, adherence, and implementation strategies. How do the guidelines help us actually achieve these goals in the clinic or pharmacy.

Yeah, this is key, right? Both guidelines stress improving patient adherence. It's a multi-pronged approach. Things like tailoring pill taking to daily habits, simplifying regimens, which is where those SPCs really shine, and providing good patient education. The 2025 guidelines specifically highlight leveraging the WHO's hearts framework for implementation in primary care.

The hearts framework, can you remind us what that involves?

Sure. HARTS is an acronym for healthy lifestyle counseling, evidence-based treatment protocol, calls access to essential medicines and technology, risk based management, team- based care, and systems for monitoring. So, it's about having these practical, accessible tools and algorithms, a systematic approach. This focus is really key to improving BP control on a population level.

That makes a lot of sense. A systematic approach for better outcomes. Well, we've covered a huge amount today from those new diagnostic thresholds and the streamlined treatment targets to the really critical pharmacotherapy updates like upfront combination therapy. and other essential tips for navigating the 2025 Canadian hypertension guidelines. Our hope is that this deep dive has really provided you with clarity, accuracy, and maybe a bit more peace of mind as you prepare for your PBC exams and of course as you step into your vital role as a Canadian pharmacist.

Absolutely. Understanding these nuances, especially the shifts from 2020 to 2025, it's not just about passing an exam. It's truly about optimizing patient care and contributing to better cardiovascular health outcomes right across Canada. This knowledge really empowers you in practice.

Good. agree more. This deep dive was brought to you by the Pharma Board Group based on the CTC reference. Now, just to check your understanding, here's a quick multiple choice question for you to think about. According to the 2025 Hypertension Canada guideline for the diagnosis and treatment of hypertension in adults in primary care, what is the new recommended definition of hypertension in adults when measured with a validated device under optimal conditions? Is it a BP over 190 millime HG, BP or 190 mill CP, BP 180 mm HG? Uh DSBP 120 mm HG.

Think carefully about that key shift, that simplification we discussed today.

We really encourage you to continue exploring these guidelines. Remember, the journey to becoming a well-informed pharmacist, it's an ongoing deep dive. And please take your time absorbing this critical information. Make sure it all sinks in. Until next time, keep learning, keep growing, and keep making a difference.

دیابت
Welcome to the deep dive. Today we're tackling a topic absolutely vital for any aspiring Canadian pharmacist, diabetes malatus. Uh our mission is really to cut through all that information overload.

Yeah, there's a lot out there.

Exactly. We want to distill the core therapeutic choices, medication algorithms, and you know, there's essential practical insights you need for your Canadian pharmacist PBC exams.

Basically, give you clarity, accuracy, and hopefully some peace of mind. Make sure nothing crucial gets missed. for exam day.

And this deep dive, it's brought to you from the Pharma Board Group, and we're basing it all on the therapeutic choices reference material, the CTC.

That's right. And uh just a quick note, we understand many of you might not be native English speakers, so we'll definitely make sure our discussion keeps a clear, comfortable pace, easy to follow.

Perfect. Okay, let's unpack this then. What exactly is diabetes malitis at its heart?

Well, at its core, it's a chronic metabolic issue. The hallmark is high blood sugar, hypoglycemia, either when fasting or after meals.

But it's not just one thing, is it? It's more complex,

right? It's a heterogeneous syndrome. It comes down to either the body not making enough insulin or the body not responding properly to the insulin it does make that's insulin resistance. Or sometimes it's a bit of both.

And there's this term dislycemia. Why is that important for us pharmacists?

Ah, good question. Dislymia refers to abnormal blood glucose levels that maybe don't quite meet the full diagn agnostic criteria for diabetes yet.

Okay.

But the key thing, even these minor elevations, they're linked to an increased risk of cardiovascular problems down the road. So, we can't ignore them.

Which leads us straight into the long-term complications, doesn't it?

It does. Diabetes can really damage blood vessels over time. We talk about microvascular issues, small vessels, think eyes, kidneys, nerves,

retinopathy, nephropathy.

Exactly. And then macrovascular problems, the large vessels. That's where heart disease stroke, peripheral artery disease come in.

Heart disease is the big one.

It's the most common cause of death unfortunately, which is why managing things like blood pressure and cholesterol alongside blood sugar is absolutely critical. It's integrated care.

Got it. So, how do we uh classify diabetes? What are the main types?

Okay, so type 1 diabetes malitis T1DM, that's about 5 to 10% of cases. It's fundamentally an autoimmune disease.

Body attacks itself

precisely. It destroys the insulin producing beta cells in the pancreas. So, you end up with an absolute lack of insulin

and that usually appears when

typically it presents pretty acutely often in children adolesccents or young adults and there's a high risk of diabetic ketoacidosis DKA if it's not treated promptly

you sometimes hear about LADA too

right late autoimmune diabetes of adults it's a slower onset form of autoimmune diabetes that appears in adults still type one essentially

okay then the big one type two

type two diabetes malitis TTDM that's the vast majority maybe 90% of c Here the picture is different. It's primarily insulin resistance where the body cells don't respond well to insulin combined with a relative insulin deficiency the pancreas just can't keep up over time.

And this one is often found

often it's discovered incidentally during routine checkups in adults but worrying trend. We're seeing it diagnosed more and more in adolescence and even children especially those struggling with obesity.

That is concerning. Are there other types?

Yep. There's gestational diabetes or GDM. That's glucose intolerance. That's first recognized during pregnancy.

Okay.

And then there are other specific causes maybe less common but important to know things like monogenetic syndromes like mody or diabetes resulting from pancreatic diseases certain infections or even some medications.

Ah the medication link that's super relevant for pharmacists. What should we know?

Definitely the CTC reference our source material lists several drugs that can cause dislycemia or worsen existing diabetes. You think things like Obviously,

right?

Some beta blockers, statins, yes, even statins can have a small effect. Second generation anticyotics, certain diuretics like thioides and loops, even things like checkpoint inhibitors in cancer therapy or produce inhibitors used for HIV.

So, quite a few potential culprits. What's the clinical takeaway?

The key message is this. If a patient genuinely needs one of these medications for a clear clinical reason, the fact that it might affect blood sugar should not stop stop you from using it.

Okay. So, you treat the underlying condition.

Exactly. You manage the diabetes or the dislycemia alongside it. You don't withhold necessary therapy just because of the glucose effect. Managing the diabetes remains paramount.

Makes sense. Okay. Diagnosis and screening in Canada. How might a patient present?

It's really varied. Some people are completely asymptomatic. You know, it just pops up on routine blood work,

incidental finding.

Yeah. Others might have really non-specific symptoms, feeling tired, maybe unexplained weight changes. Sometimes the first sign is actually a complication like neuropathy or kidney issues.

Wow. Okay.

Or they could have those classic acute metabolic symptoms, excessive thirst, frequent urination, what we call polyypsia and polyura. And in severe cases, especially with type one, the first presentation could even be DKA.

So what are the actual diagnostic numbers in Canada? The thresholds we need to know for the PBC,

right? The criteria you need one of these random plasma glucose 11.1 millm moles per liter or higher. or fasting plasma glucose FTG that's no food for at least 8 hours 7.0 or higher.

Okay.

Or a 2-hour plasma glucose value of 11.1 or higher after drinking a standard 75 gram glucose strength. It's the oral glucose tolerance test, the OGTT

and HBOC.

Yes, HB1C can also be used specifically in adults. A value of 6.5% or higher as diagnostic. But there are caveats conditions that can affect A1C accuracy like anemas or hemoglobinopathies. You need a viable lab test.

And what if someone's asymptomatic but has one high reading? Is that enough?

No. And this is a critical point for your exam. If the patient has no symptoms, a single abnormal test isn't enough. The diagnosis must be confirmed with a repeat test on a different day.

Using the same test ideally.

Ideally, yes. Use the same test for confirmation if possible. Makes it clear.

Okay. What about screening? Who should we be screening?

For T1DM, routine screening in people with normal glucose levels isn't generally recommended right now. Though there are new developments likeab But that's a different discussion,

right? Focus on T2DM screening.

Yes. For type two, the recommendation is screening every 3 years for individuals aged 40 or older.

Okay. Everyone over 40. Every 3 years

or screening sooner and maybe more often for anyone younger than 40 who has significant risk factors.

And those risk factors, what are the key ones? Think like a quick reference table for the exam.

Okay. Key risk factors for TTVM. Age 40 plus. Obviously, having a first-degree relative parent, Sibly with type two, belonging to a high-risisk population group, indigenous peoples, South Asian, Asian, African, Hispanic heritage.

Got it. What else?

A personal history of pre-diabetes that's impaired fasting glucose or impaired glucose tolerance or a history of gestational diabetes. Already having signs of end organ damage that diabetes can cause like retinopathy or neuropathy.

Vascular risk factors too.

Absolutely. Things like abdominal obesity, high blood pressure, hypertension, abnormal cholesterol levels, dyspademia, and smoking and also associated diseases conditions like polycystic ovary syndrome, PCOS, obstructive sleep apnea, certain psychiatric disorders.

So knowing these helps supply the screening algorithm.

Exactly.

It helps you identify who needs screening and guides the process especially if you get say conflicting results between different tests like FPG and A1C. The algorithm helps decide when maybe an O GTT is needed.

All right, let's shift to management. The non-drug approaches first. These seem foundational.

They absolutely are. Diabetes is for the most part a self-managed condition. What the patient does daytoday is pivotal for long-term success.

So education is key.

Huge self-management education is vital. Patients need to understand the basics. What diabetes is, the role of their diet, exercise, their medications, how to monitor their own blood sugar.

What else falls under that umbrella?

Things like sick day management, what to do when they're ill, recognizing the signs of low blood sugar, hypoglycemia, and crucially, how to treat it. Proper foot care is essential to prevent complications. Understanding heart health, risk factors, awareness of other organs that can be affected like eyes and kidneys

and nutrition

critical. Ideally, counseling should come from a registered dietitian. For many with type two who are overweight, even modest calorie reduction helps. For anyone on intensive insulin therapy, carbohydrate counting is often a really important skill.

What about exercise?

Immen benefits. Improves cardiovascular function. Makes the body more sensitive to insulin. Helps lower blood pressure and lipids. And for type two, it directly improves glycemic control.

What's the recommendation?

The general guideline is at least 150 minutes of moderate to vigorous aerobic activity per week spread over at least 3 days plus resistance training like weights or resistance bands at least twice a week.

Important point for pharmacists regarding insulin users and exercise.

Yes, very important. You need to educate patients using insulin about how exercise can lower their blood glucose sometimes significantly. They need to know how to potentially adjust their insulin doses or their food intake around exercise to prevent hypoglycemia.

Good point. Okay. Monitoring glucose, the feedback loop as you called it,

right? We have two main methods. Capillary blood glucose or CVG, that's the traditional finger prick test,

the one most people know.

Yeah. And then continuous glucose monitoring or CGM, which uses a small sensor usually on the arm or abdomen to measure glucose in the interstatial fluid just under the skin.

Why is monitoring so important?

It's For most patients, especially anyone on insulin, it helps them see the immediate effect of food activity and medication. Crucially, it helps them recognize and manage low blood sugar. Provides that direct feedback for therapy adjustments.

How often should people monitor?

Well, for those on basil bullis insulin regimens, multiple injections a day. The minimum is usually three times a day, often more, like before meals and at bedtime. For non-insulin users, the frequency is much more individualized based on their therapy and goals.

CGM versus CBG. Pros and cons.

CGM gives you a much richer picture. Continuous data, trends, alerts for highs and lows. It can really improve control and reduce hypoglycemia. The downside is cost and access can be issues. CBG is more affordable, accessible, gives you that point in time value. Both have their place.

And HBA1C monitoring still relevant.

Absolutely. It gives you the bigger picture. That average glucose control over the past 2 3 months, typically checked every 3 months. targets aren't being met or therapy is changing and maybe every six months for stable patients who are at target.

Okay. What about monitoring other organ systems? The ongoing checks

crucial for preventing or catching complications early. Annually, patients need their blood pressure checked, a thorough foot examination, including checking sensation with a monofilament. Those at high risk might need referral to a foot care specialist. Yes, annual kidney function screening.

That means checking serum creatinine to estimate GFR and a urine test for albiman to creatinine ratio ACR. to detect early kidney damage,

lipids and eyes,

lipid profile, a diagnosis, and then generally annually or more often if they're on lipid lowering therapy. And a dilated eye examination by an opthalmologist or optometrist is essential for retinopathy screening frequency depends on risk factors and findings

and immunizations often overlooked maybe

shouldn't be. People with diabetes are at higher risk for complications from infections. So annual flu shot, keeping up with CO 19 vaccines, and ensuring they have other Health Canada recommended Vaccines like numaccoal are really important protective measures.

Okay, let's dive into the pharmacologic side. Insulin therapies first. Obviously essential for type one.

Cornerstone for type one. Yes, it could be given by syringe, insulin pen devices or insulin pumps. We have human insulin and insulin analoges. The analogs generally cause less antibody formation and offer more predictable profiles.

For the PBC, understanding the different insulin types and their pharmacocinetics is key, right? Like that table three in the CTC.

Absolutely crucial. You need to know the main classes. Maybe some brand examples and critically their onset, peak and duration. Let's break it down.

Okay. Rapid acting

rapid acting insulin analoges. Think insulin aspart Novore rapid glucosine aided lispro humalogue. And they're even faster versions now like fast acting aspartas.

What's the profile?

Very quick onset maybe 51 15 minutes. Peak action around 1.5 hours. Duration is relatively short maybe four or five hours. Great for covering meals offering fibility because you can take them right before eating or even shortly after. Okay. Short acting

that's basically regular human insulin. Humulan R novel Toronto onset is a bit slower 30 60 minutes peaks later around 2 4 hours and lasts maybe 68 hours needs to be taken further ahead of the meal.

Intermediate acting insulin primarily NPH insulin humin and novelin ghee NPH onset 1 2 hours peak around 5 8 hours duration maybe 12 18 hours often used as basil insulin maybe once twice a day but has a more pronounced peak than the long acting analoges

and the long acting analoges these seem important now

very much so these include insulin digludec tresba detimir levir and glargene both u 100 lantis bessagler and the concentrated u300 duch

what's special about them

they provide a much flatter more peakless profile compared to NPH this gives more predictable prolonged basil insulin coverage often lasting 24 hours or even longer like dludec this generally translates to a lower risk of glycemia especially overnight and now there's even a once-weekly basil insulin analog insulin iicodc weekly just coming into play.

Wow, once weekly. Okay, so for type 1 regimens, what's the goal?

The landmark DCCT trial really set the standard. It showed that intensive insulin therapy aiming for nearn normal blood glucose levels significantly reduces the long-term risk of microvascular complications like eye and kidney disease and long-term follow-up showed benefits for cardiovascular events and mortality too.

So intensive is preferred. How is that usually achieved?

The preferred approach for intensive management is typically a multiple dose insulin MDI regimen often called basil bolus. That means using a long acting analog for basil coverage plus rapid acting insulin before each meal for bolus coverage.

You mentioned the honeymoon phase earlier. Can you explain that again? Super relevant for PBC.

Yes. Soon after diagnosis of T1DM, some patients experience this temporary period where if their remaining beta cells actually recover some function, their insulin requirements can decrease. quite dramatically for a while.

So pharmacists need to be aware.

Absolutely. If you're not aware of the honeymoon phase, you might overshoot with insulin doses as the patients own production kicks back in temporarily leading to hypoglycemia.

It requires careful monitoring and dose adjustment in newly diagnosed patients.

How is insulin typically started for T1DM?

A common starting point is about 0.5 units per kilogram of body weight per day. Maybe split 50/50 between basil and bolus, but that's highly ind idualized doses are then titrated every few days based on blood glucose readings

and timing with meals matters.

Yes, regular insulin needs to be taken about 30 minutes before the meal. The rapid acting analoges offer more flexibility, usually 0 to 15 minutes before eating or sometimes up to 20 minutes after starting the meal.

What about insulin pumps?

Insulin pumps or continuous subcutaneous insulin infusion CSI deliver rapid acting insulin continuously for basil needs plus allow the user to program bololises for meals and corrections. They can potentially offer tighter control and less hypoglycemia for some.

Downsides,

they are more expensive, require significant patient training and motivation, including diligent carbohydrate counting and understanding correction factors. It's a bigger commitment.

Okay, let's move to insulin in type 2 diabetes. When does it come into play? It's not usually first line.

Correct. Insulin is typically considered in T2DM when HBA1C targets aren't being met despite optimizing other non-insulin medications or if there's evidence of significant end organ damage, severe symptoms of hypoglycemia or what we call metabolic decompensation also during pregnancy if needed.

Why the delay sometimes you mentioned patients might be hesitant.

Yeah, there are common barriers. Fear of injections, perceived complexity of insulin regimens, concerns about weight gain, and definitely the fear of hypoglycemia. Good counseling is needed to address these.

So, what's the usual approach when starting insulin in T2DM? The step-wise plan like in table four,

it often starts simply The most common initial strategy is adding basil insulin only, usually once daily, typically a long- acting analog like glargine, dete or diglude.

How is the dose determined?

You might start empirically, say 5 or 10 units at bedtime, or use a weight-based approach like 0.1 to 2 units per kilogram. Then the dose is titrated up gradually, usually every few days, based mainly on fasting blood glucose readings, aiming for a target typically below 7 millod.

And other meds like metformin.

Metformin is almost always continued when basil insulin is added unless there's a contraindication. It works well in combination.

What if basil insulin alone isn't enough?

The next step might be a basil plus regimen. You continue the basil insulin and add one injection of rapid acting insulin before the largest meal of the day.

And if that's still not hitting targets,

then you might advance to a full basil bololis regimen similar to T1DM intensive therapy basil insulin plus bololis insulin before all main meals. Multiple daily injections Are there simpler options?

Yes, premixed insulins are available. These combine a rapid or short acting insulin with an intermediate acting one in a fixed ratio. They offer convenience. Usually taken twice daily before breakfast and dinner.

The trade-off,

less flexibility. You can't adjust the meal time and basil components independently, which can make fine-tuning control harder and might increase hypoglycemia risk compared to basil bolus.

Okay, let's talk adverse effects. Hypoglycemia is the big one with insulin.

By far the most common and concerning adverse effect. It can happen for various reasons. Taking too much insulin, skipping or delaying a meal, exercising more than usual without adjusting, drinking alcohol on an empty stomach.

What are the symptoms pharmacists should counsel patients about?

They fall into two categories. Adraic symptoms usually come first. Things like hunger, sweating, shakiness or tremors, anxiety, palpitations, or rapid heartbeat.

And if it gets worse,