Introduction to pharmacology

Pharmacology is.....................

Medication Calculation

mg- milligram

mcg-microgram

Formula:  ML Desired equals ML total (in package) multiplied by Mg desired divided by Mg total (in package)

Medications below:

Acetominophen

Ketorolac (Toradol) is a nonsteroidal anti-inflammatory drug (NSAID)  (Analgesic) In some anesthesia texts, a single dose of IV ketorolac is said to confer analgesia equivalent to 10 mg of IV morphine (without narcotic-related side effects)! There’s some evidence from the EM world that suggests an analgesic “ceiling effect” at 10 mg of IV ketorolac beyond which only more side effects are seen, but others argue a higher dose may translate to a longer duration of action due to more time spent at a therapeutic plasma concentration. ‍⚕️
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NSAIDs, including ketorolac, should be used cautiously in patients with kidney injury as they inhibit prostaglandins that regulate flow through the afferent renal arterioles. Furthermore, COX-1 inhibition can lead to gastric ulcerations due to changes in the mucosal barrier defense mechanisms.
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Interestingly, although NSAIDs are typically associated with bleeding, the risk of thrombosis in post-coronary artery bypass grafting (CABG) patients is a specific concern raised by an FDA black box warning. This can be attributed to an imbalance in COX-1 and COX-2 inhibition. COX-1 normally results in thromboxane A2 synthesis - a potent platelet aggregator (pro-thrombotic). COX-2 creates the antithrombotic prostaglandin I2. Inhibition of COX-1 and COX-2 can, therefore, result in bleeding and clotting, respectively.
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For the aforementioned reasons, it’s essential to consider the COX-1 and COX-2 inhibitory properties of all NSAIDs. While selective COX-2 inhibitors (ie, celecoxib) may be beneficial in terms of minimizing bleeding and gastric ulceration, they may also lead to a higher risk of thrombosis.

Calcium chloride (CaCl2) is an ionic form of intravenous calcium repletion with roughly THREE TIMES MORE bioavailable calcium than its organic counterpart - calcium gluconate.
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The teaching that one needs a functional liver to metabolize calcium GLUCONATE before calcium becomes bioavailable isn’t true as shown in patients undergoing liver transplantation during the anhepatic phase. In addition, there are plenty of cited cases where the extravasation of calcium CHLORIDE from peripheral veins led to injuries (pain, tissue necrosis, etc.) as the medication is a vesicant. So why don’t we just use higher doses of calcium gluconate for repletion? ‍♂️
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In the OR and ICU settings, the cardiac Pyxis and crash carts are stocked with calcium chloride. Perhaps the lack of options drives our practices? Or maybe in these acute care settings, the ability to get more “bang for the buck” with a single syringe of calcium chloride is more prudent?
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I routinely use calcium chloride (yes, even in large peripheral IVs) as a way to mitigate citrate toxicity from massive transfusions, as an inotrope/vasopressor, and to stabilize the myocardial membranes in cases of hyperkalemia. If patients are hemodynamically stable with limited access, then of course I’ll consider using calcium gluconate as an alternative. ‍⚕️

Lidocaine is a class Ib, anti-arrhythmic.

Lidocaine is a Class Ib antiarrhythmic (sodium channel blocker). By blocking sodium channels, lidocaine increases the electrical stimulation needed to cause impulses to occur and to travel in the hearts electrical system.

Lidocaine can be given in ventricular fibrillation and pulseless ventricular tachycardia with an initial bolus of 1.0 to 1.5mg/kg. In cases of refractory ventricular fibrillation or pulseless ventricular tachycardia, it may be repeated at a dose of 0.5 to 0.75mg/kg every 5 - 10 minutes. Maximum total dose: 3mg/kg. A continuous infusion should be initiated after ROSC at 1 to 4mg/minute. Should there be a return of arrhythmia with continuous infusion a bolus of 0.5mg/kg should be administered followed by an increase of infusion.

Lidocaine may be used as a local anesthetic for patients with a intraosseous line with a dose of 40mg given over 1-2 minutes followed by letting lidocaine sit for 60 seconds prior to flushing.

Pediatric Dosage:
Ventricular Fibrillation/Pulseless Ventricular Tachycardia: 1mg/kg followed by an infusion of 20-50mcg/kg/min.
IO: 0.5mg/kg 40mg - over 1-2 minutes

⏱ Lidocaine when given via bolus has a onset of action of 45-90 seconds with a duration of 10-120 minutes.

Hypersensitivity, Adam-Strokes Syndrome, Wolff-Parkinson-While Syndrome, high grade SA, AV or intraventricular blocks.

Premixed Lidocaine may contain core derived dextrose which makes it contraindicated for patients with a corn allergy .

setting: Steroids like Decadron or Solumedrol do more for our patients than just “reduce inflammation”. These steroids are undoubtedly part of our cocktail we reach for in patients presenting with acute asthma, allergic reactions or anaphylaxis - and traditional clinical logic has taught us these drugs work to reduce inflammation in the airways and reduce bronchial mucus production.

It has long been held that steroids take longer to activate and as a result, administration of steroids tends to take a “back seat” and fall down the algorithm for many providers. I do not agree with this… 

Let me be clear when I say, steroid administration should not take precedence over agents like epinephrine or direct beta-agonists in the management of acute asthmatics or anaphylactic patients. BUT….

What I do want to reiterate is that steroids have an otherwise unknown, immediate benefit for these patients. In fact, in the acute phases of steroid administration, they actually upregulate beta receptors - as Jace mentioned. Essentially meaning, they allow for more beta receptors to “show up” and be engaged for drugs to bind to them – say like our epinephrine and albuterol. 

 

 

 

 

 

The mechanism by which steroids induce beta regulation has been studied since the 1980’s, surprisingly. There are two mechanisms by which steroids can augment beta receptors and catecholamine responses:*

 

 

 

Steroids increase the number of available adrenergic receptors on cell surfaces. 

 

The exact mechanism by which this occurs is rather complex but to be brief: glucocorticoids increase the genes responsible for the transcription factors that produce the adrenergic receptors themselves on cell surfaces. Bear in mind, patients with chronic asthma or even COPD may be on long-acting beta agonists and at baseline, their beta receptors have become de-sensitized to beta agonists. Steroids can help to upregulate these receptors when acute on chronic exacerbations occur. 

 

 

 

Steroids help create a “high affinity” state of these available receptors for beta agonist drugs

 

Our adrenergic receptors are part of a larger class of molecules known as G-coupled protein receptors. When a naturally occurring catecholamine (like epi or norepinephrine) bind to our adrenergic receptor it activates this G-coupled protein and causes a cascade of events within the cell known as a second messenger system and it results in the response we understand – alpha 1 for vasoconstriction, beta 1 for increased contractility and chronotropy, etc. However, these catecholamines don’t just sit and stay on the receptor. They eventually release… glucocorticoids help here in this gap by helping the receptor to “recover” to its previously sensitized state faster so it is ready to receive its next catecholamine. 

 

 

 

 

 

How is this “practice changing”??

 

 

 

All of the science is cool (to me, at least) but the question I always seek to answer is: how does this affect my everyday practice? Here’s the scoop:

 

 

 

I found myself reaching for the steroids a little earlier in the treatment algorithm than I had before. Epi and albuterol are still my mainstay pharmacological treatments in severe asthma and anaphylaxis but steroids are the next drug I reach for. 

 

 

 

If steroids upregulate the number of available adrenergic receptors (our alpha and beta’s) then theoretically it would have a synergistic effect with our first line agents of Epi and Albuterol as it makes available more sites for these agents to attach to. Once attached, steroids secondarily put these receptors in a high affinity state ready to receive the drugs in the acute setting. 

Hypertonic Saline is a form of Sodium Chloride that contains a higher concentration of sodium and chloride compared to 0.9% Sodium Chloride.

Hypertonic Saline is available in a number of different forms but 3% is most commonly seen in the prehospital and critical care transport setting. Hypertonic saline is used in the setting of increased intracranial pressure ⏫.  Hypertonic saline creates an osmotic shift of fluid from the intracellular space to the interstitial and intravascular space by increasing the serum osmolarity of blood. In the setting of increase intracranial pressure, this shift decreases intracranial pressure and edema. 3% Hypertonic Saline has a similar osmolarity to 20% Mannitol (1026 vs 1098). Hypertonic saline may be preferred over Mannitol in certain cases as HTS has less of a diuretic effect.

3% Hypertonic Saline may be administered as a bolus or continuous infusion through a large bore peripheral IV. Any concentration 23.4% must be given through a central line. 23.4% is usually administered as a rescue therapy that is refractory to standard therapy.

⏱A 3% bolus of 250mL is typically administered over 30 minutes, however may be administered faster in some circumstances.

⚠️ Monitor for extravasation as thrombophlebitis or tissue necrosis may occur if extravasated. Hypotension can occur when given as a rapid bolus.

Extravasation

   Monitor serum sodium & serum osmolarities. Typically a serum sodium goal of 150-155mEq/L which closely correlates with a serum osmolarity of 320 to 340 mOsm/L

HYPEROSMOLAR THERAPY COMPARISON
0.9% Sodium Chloride = 154mEq/L (sodium concentration) = 308mOsm/L (Osmolarity)
3% = 513mEq/L = 1026mOsm/L
23.4% = 4,000mEq/L = 8008mOsm/L

Midazolam (Versed) is a relatively short-acting benzodiazepine ("benzo") which can be administered IV, PO, PR, and even within the neuraxial space to extend the duration/strength of the epidural/spinal block. For these reasons, it's the most commonly used benzo in anesthesiology. Like all medications in this class, midazolam potentiates the effects of GABA (an inhibitory neurotransmitter) on the GABA(A) receptor by increasing the frequency of chloride flux. This results in neuronal hyperpolarization causing sedation, anterograde amnesia, relaxation, anticonvulsant activity, and anxiolysis.
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As an anesthesiologist, I use midazolam as an adjunct for anxiolysis and amnesia for procedural sedation although I prefer agents like propofol, remifentanil, and dexmedetomidine. A small dose can also help treat emergence delirium from ketamine (my favorite!)
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As an intensivist, I'm wary about utilizing benzos due to their unfavorable context-sensitive half times when run as infusions for sedation, deliriogenic effects (especially in the elderly), and risk for benzo tolerance/withdrawal. One must also be mindful about drug interactions leading to altered plasma concentrations as midazolam is metabolized by the P450 system! It's certainly a medication that should be administered in low doses at first to see the subsequent physiologic effects before uptitrating. ‍⚕️
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Tag a friend who should know about midazolam, let me know if/where you’ve seen it used, and drop me a co

Administering a drug through the schnauze

Don't have them sniff. The act of sniffing generates negative pressure generated by inspiration. You want the medication to stay in the nose and not go down the throat. In addition, you want to aim at the helix (top) of the ear. 

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3 Ways We Screw Up Intranasa👃 Administration

Dosing
Use volume of < 1 mL per nare (ideally 0.2 to 0.5 mL), dividing evenly per nostril 😤.
Double the IV dose

Positioning
Aim at the helix (top) of the ear👂. Don't have them sniff. The act of sniffing generates negative pressure generated by inspiration. You want the medication to stay in the nose and not go down the throat.

Pushing 💉
Remember to add an additional 0.1 mL of air to account for “dead space” in the atomizer, as 0.1mL will be left within the device.

https://www.foamfratblog.com//post/well-that-didn-t-work-my-story-with-intranasal-fentanyl

https://www.foamfratblog.com/post/well-that-didn-t-work-my-story-with-intranasal-fentanyl

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• Pain medication - acetaminophen, aspirin, ibuprofen, naproxen - these are all inexpensive, sold in large quantities, very cheap, and relatively safe. Acetaminophen has the dual use of also acting as a fever reducer. Choose which one you and your family prefer and build a small cache. 

• Allergy medication - benadryl is the go-to here. While daily allergies can be an annoyance, they will be low on the list of priorities if the world falls. That is why I recommend Benadryl. It can be used for allergic reactions both mild and severe. It is also beneficial for anxiety, insomnia, and nausea. Preparing is about most bang for the buck, not necessarily most effective. Benadryl is dirt cheap so it fits the bill. 

• Anti-Diarrheal - Loperamide (Imodium) is the best option here. If you don’t have access to clean water, GI bugs are inevitable. Imodium can save you some much-needed hydration by reducing your diarrhea. 

• Decongestant - Pseudoephedrine (Sudafed) and/or guaifenesin (Mucinex) - Sudafed is a decongestant which helps to reduce the symptoms of both upper and lower respiratory tract infections. The mechanism of action is not ideal but in a pinch it can be very beneficial. Mucinex is an expectorant which increases the viscosity of your bodies’ secretions. This helps the body move infected fluids out of the body and clear infections. Of course, adequate hydration is the the first step. 

• Steroids - Prednisone - this is useful for treating a wide range of ailments. It is a very potent anti-inflammatory and for that reason it can be useful for pain, allergic reactions, and autoimmune issues. This should not be used lightly and must be tapered off. 

Antibiotics are more challenging because of the specialized nature of these medications. Many people think antibiotics will help any time they are sick when in fact many illnesses are viruses, which antibiotics will not help. Infections such as sinus infections, bronchitis, sore throat, and even pneumonia are most commonly viral in nature. 

The symptoms can give you a reasonable idea if you are dealing with a viral or bacterial infection. Viral infections tend to cause a low grade fever (100F-102F), last a lot longer, and are often less severe with improvement after 3-5 days. Bacterial infections often cause high-grade fever (>102F), tend to be more severe, often getting worse after 3-5days. 

Antibiotics should only be used when you have a bacterial infection. They are specially designed to kill certain types of bacteria. Below I will give broad guidelines of which antibiotic to use by infection type. 

• Cephalexin (Keflex) - Used for skin infections, ear infections, urinary infections, and can be used for upper respiratory infections (sinus infection, bronchitis), typically not pneumonia. 

• Ciprofloxacin (Cipro) - One of the most powerful antibiotics we use. Can cover GI infections, UTIs, bone infection, pneumonia, and many others. This does have a risk of causing tendinopathy and should be used cautiously. 

• Metronidazole (Flagyl) - This is great for GI infections which cause dysentery (severe watery diarrhea). It is also used less effectively for infections in the GI tract, skin, lungs, etc. 

• Antibiotic ointment - Bacitracin, hydrocortisone, clotrimazole - These are useful for skin infections. Bacitracin can be used for cuts and stings which are at risk of becoming infected. Make sure you clean them out well. Hydrocortisone is useful for minor allergic reactions or skin conditions like eczema. Clotrimazole is useful for fungal infections like athletes foot, jock itch, yeast infections, ringworm etc. These all spread quickly in close quarters.

The final and most obvious list of medications is your own medication list. If the end of the civilization happens, you want access to the medications you need to take every day. Whether this is insulin, heart medications, thyroid medications, etc. You need to consider what happens if you lose access to these and know how to taper yourself off. This is especially true for habit-forming medications, which brings me to my next section. 

Some drugs will be very, very difficult to stockpile. Controlled substances like benzodiazepines, opioids, stimulants, sleeping meds, and many others are highly controlled right now. In a catastrophic event, you may be forced to wean yourself off these medications. You should know what withdrawal looks like for these medications, and how to best cope with it. The same goes for alcohol. If you drink daily (please consider cutting down), your risk of withdrawal is high when the supply is cut off. These medications will also be in high demand. This will open you up to violence as people try gain access to them. Plan accordingly. 

Gaining access to all of these medications prior to the apocalypse can be a challenge. The best way to start is simply discussing it with your physician. If they are not open to it, maybe find another one. If you cannot do that, you can access many of these medications over the counter. Many physicians are also willing to write 90 day prescriptions which may be beneficial. Ensure you don’t use your emergency supply for everyday use. Always rotate which medication you are using so that the newest medications are added to the stockpile and the oldest are used for daily life. This will extend the life of your stockpile. 

Epinephrine (adrenaline) is an incredibly versatile catecholamine! It can be administered by intravenous, subcutaneous, intramuscular, and inhalational routes to treat various clinical conditions, including anaphylaxis, croup, cardiogenic shock, bronchospasm, and cardiac arrest. Epinephrine is routinely added to local anesthetics to provide vasoconstriction, but literature shows that its adrenergic effects may independently confer analgesia too. ☺️
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Epinephrine's mechanism of action is highly dependent on its dose - "beta" effects are seen first followed by "alpha" effects at higher doses. For this reason, it's important to understand how the adrenergic system works rather than thinking "epi increases blood pressure." For example, as a cardiac anesthesiologist, I often use epinephrine for patients with debilitating systolic dysfunction (especially right heart failure after bypass). Beta effects allow me to increase a patient's chronotropy (heart rate) and inotropy (contractility) while simultaneously vasodilating vascular smooth muscle to decrease afterload. The net effect? Promoting forward flow! ❤️
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Some points to think about: epinephrine can create a type B lactic acidosis even in aerobic conditions due to the accumulation of pyruvate and saturation of the PDH/TCA pathways. Systolic anterior motion (SAM) of the mitral valve misdiagnosed as anaphylaxis and treated with epinephrine can lead to hemodynamic collapse. Patients who are taking beta-blockers (especially mixed agents like labetalol) may not manifest the typical hemodynamic responses one would expect with small doses of epinephrine. It's important to consider how the simultaneous adrenergic agonism/antagonism will present clinically. ‍⚕️