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pharmacology notes

Drug Interactions Review

 Let’s talk drug-drug interactions 💊

🌟 With millions of potential drug interactions, figuring out what you need to commit to memory can be overwhelming 😵 . However, with the right approach and some (or a lotta 😆) practice, you’ll be able to see more of a pattern.

✨ TIPS FOR SUCCESS: ✨

1. Know the interactions that are STRONG. 💪🏻 A strong inhibitor or inducer can lead to 5x the concentration of a drug while a weak inhibitor or inducer will cause less of a change. Higher concentrations lead to adverse side effects. Check out today’s post to help you remember the major inducers and inhibitors of CYP450 enzymes.

2. Know the interactions where the outcome is BAD. ❌ For example, tamoxifen is a prodrug. Strong 2D6 inhibitors such as fluoxetine, paroxetine, and bupropion can prevent the conversion of tamoxifen to its active form, therefore, increasing the risk that your patient will experience a reoccurrence of cancer. The same goes for the antiplatelet prodrug clopidogrel.

3. Start with the most COMMON drug interactions seen as they will likely be on exams and boards. 📝 Check out today’s post to see some examples of some of the major drug interactions.

4. Understand the MECHANISM of the drug interaction. 🧐 Inducers can ramp up the metabolism of a medication leading to decrease drug levels while inhibitors block the enzymes that break down the drug leading to higher drug concentrations.


Drug Interactions Review Read More »

Antibiotic Coverages

⭐ Knowing antibiotic coverage starts with memorizing the antibiotics that cover the major categories of bacteria such as anaerobes, atypical, MRSA, and pseudomonas. ⁠

⭐ Studying for an upcoming exam? >>LISTEN<< These are a MUST for you to know. Review the post and quiz yourself to see how much you can remember. 🧠⁠

Antibiotic Coverages Read More »

Hypertension in Pregnancy

Anti-hypertensives in pregnancy 🤰🏻⁠

✏️ Hypertension is defined as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg. Chronic hypertension occurs before pregnancy or before 20 weeks gestation and gestational hypertension occurs after 20 weeks⁠

⚠️ Complications of high blood pressure include increased risks for preeclampsia/eclampsia/stroke for the mother and preterm delivery for the baby⁠

📖 As with most medications in pregnancy, antihypertensives have not been evaluated in robust randomized controlled trials. Check out the post for the preferred anti-hypertensive drugs used in pregnancy. ⁠

⭐ Methyldopa is recommended first-line due to its proven safe and effective use in pregnancy due to its long history of safety in pregnancy but its use in clinical practice may be less due to adverse reactions (e.g., fatigue, dizziness).⁠

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Aminoglycosides

Aminoglycosides – ‘The 3 Amigos’⁠

⭐ AMINOglycosides are antibiotics comprised of AMINO acid sugars that are linked together. ⁠

3️⃣ The three most commonly used are (mnemonic: TAG): ⁠
-Tobramycin⁠
-Amikacin⁠
-Gentamicin⁠

Other agents include plazomicin, streptomycin, and neomycin. ⁠

⭐ They are used for serious infections caused by gram-negative bacteria such as complicated UTIs, sepsis, or intraabdominal infections. They can also be used in combination with other agents for infectious caused by gram-positive bacteria in endocarditis. ⁠

⭐ MOA: they kill bacteria by binding onto 30S ribosomal subunits inhibiting the bacteria’s ability to synthesize proteins, leading to cell death⁠

⭐ Other key facts to know:⁠
-Adverse effects include nephrotoxicity and ototoxicity⁠
-They are approximately 70-95% excreted renally⁠
-They are concentration-dependent bacterial killers, which means bacterial killing increases with rising drug concentrations⁠
-Monitor serum drug levels (troughs and peaks), serum creatinine, BUN, urine output, and hearing⁠.

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Hypothyroidism

🌟 The thyroid gland produces thyroid hormones (T3 and T4, with T3 being the more active form) that affect metabolism, brain development, respiration, cardiac, nervous system functions, body temperature, muscle strength skin dryness, and so much more!⁠⠀
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👉🏻 HYPOthyroidism is a result of an UNDERactive thyroid vs. HYPERthyroidism is an OVERactive thyroid. ⁠⠀
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👉🏻 Common causes of hypothyroidism: having low levels doesn’t feel good – HAIL⁠⠀
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-Hashimoto’s disease⁠⠀
-Amiodarone⁠⠀
-Iodine deficiency/interferons⁠⠀
-Lithium⁠⠀
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👉🏻To compensate for an UNDERactive thyroid, synthetic versions of thyroid hormones are administered. Levothyroxine is the drug of choice due to its once-daily dosing, low cost, and more uniform potency. ⁠⠀
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Pharmacokinetics⠀

⭐Test your knowledge and check your answers on the second slide.

🚶🏻Think of pharmacokinetics (PK) as the drug’s journey into, through, and out of the body. This journey passes through four phases that can be remembered using the mnemonic ADME or “add me”. ⠀

-Absorption: the process of the intake of the drug into the body⠀
-Distribution: the process of the dispersion of the drug into the bloodstream and tissues⠀
-Metabolism: the process of the parent compounding into daughter metabolites⠀
-Excretion: the process of eliminating the drug from the body⠀

🗻 This journey varies depending on patient-specific factors such as renal function, sex, age, and genetics. All of these factors can affect the drug’s half-life, rate of elimination, and distribution and subsequently lead to toxicity or therapeutic failure. Knowledge of pharmacokinetics can assist with adjusting doses correctly especially in drugs that require therapeutic drug monitoring. ⠀

☝🏻 Additionally, drugs go through different processes of metabolism and elimination called first-order and zero-order kinetics. The biggest difference is that zero-order kinetics undergo constant elimination regardless of the plasma concentration while first-order kinetics depends on concentration. A good analogy is relating the concentration of drug to cake: 🎂⠀

-Regardless of how big of a cake you are served, you can only eat one bite (a certain amount) at a time, that’s zero-order kinetics (15 mg/hr)⠀
-With first-order kinetics, you suddenly can eat portions of the cake at a time so the bigger the cake the bigger the portion of cake you can eat (eliminate) at a time (50%/hr)⠀

Pharmacokinetics⠀ Read More »

Calcium Channel Blockers⁠

💊 Calcium channel blockers (CCBs) are used in the treatment of many cardiovascular conditions including hypertension and angina so needless to say they easily make the top 200 drugs prescribed.⁠⠀
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👉🏻 They are divided into subclasses, non-dihydropyridines, and dihydropyridines and differ by their pharmacokinetic properties, clinical uses, response, and selectivity. ⁠⠀
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👉🏻 Dihydropyridine CCBs end in the suffix ‘-ine’: ⁠⠀
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-AmlodipINE⁠⠀
-NicardipINE⁠⠀
-NifedipINE⁠⠀
-NimodipINE⁠⠀
-FelodipINE⁠⠀
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👉🏻 Non-dihydropyridine CCBs don’t end in the suffix ‘-ine’ hinted by the name of the subclass, NOn-dihydropyridINE:⁠⠀
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-Verapamil⁠⠀
-Diltiazem⁠⠀
⁠⠀

Calcium Channel Blockers⁠ Read More »

Antibiotic Mechanism of Actions⁠⠀ ⁠⠀

⭐ There are 5 basic antibiotic mechanisms of action against bacteria: ⁠⠀
⁠⠀
1) Inhibition of cell wall synthesis⁠⠀
2) Alteration of cell membranes⁠⠀
3) Inhibition of protein synthesis ⁠⠀
4) Inhibition of nucleic acid (DNA/RNA) synthesis ⁠⠀
5) Inhibition of folic acid synthesis ⁠⠀
⁠⠀
‼️ Due to increasing resistance to these antibiotics and their mechanisms, developing new antimicrobials and understanding their mechanisms of action are important. ⁠⠀
⁠⠀

 If you’re looking to learn more, check out our Youtube video for a full review! 

Antibiotic Mechanism of Actions⁠⠀ ⁠⠀ Read More »

Warfarin INR Goals

⭐Test your knowledge and check your answers on the second slide!

Let’s talk warfarin INR goals 🤓⁠

💊 Warfarin is a vitamin K antagonist that requires INR (international normalized ratio) monitoring due to its narrow therapeutic index. Dosing is affected by many factors including diet, drug interactions, genetics, and close INR monitoring is required to decrease the risks of bleeding and/or clotting.⁠

🤔 Overall, direct oral anticoagulants (DOACs) are now recommended over warfarin in the majority of clinical situations unless there is a compelling reason for them to on warfarin such as valvular atrial fibrillation, severe renal dysfunction, patient costs, or close therapeutic anticoagulation monitoring required.⁠

🔑 Key points about INR monitoring:⁠

-Baseline INRs are recommended prior to initiating warfarin therapy⁠
-Warfarin requires overlap or ‘bridging’ with heparin or LMWH for 5 days and until INR is within goal for 24 hours (TIP: warFARin takes a long time to achieve full anticoagulation so think FAR into the future compared to other anticoagulants)⁠
-Changes in the INR is typically seen 2-3 days after administration of the dose (TIP: a physician I use to work with always said Jesus rose on the 3rd day and so will your INR 😅)⁠
-Prior to making a dose adjustment, assess for any missed doses, drug interactions, dietary intake or supplements, documentation of bleeding, or other changes that can affect the INR⁠

How many of the INR goals did you get correct? TIP is to memorize the outlier – the majority of the time, the INR goal is 2-3 except in high-risk patients such as those with mechanical valve replacements in the MITRAL position (goal is higher 2.5-3.5)⁠

Warfarin INR Goals Read More »

Clozapine

💊 Clozapine is an FDA-approved atypical antipsychotic medication for treatment-resistant schizophrenia. ⁠

❌ Clozapine is not the first-line drug of choice due to its range of adverse effects including agranulocytosis (a serious condition with a severely low number of neutrophils – a type of white blood cell).⁠

⭐️ Due to this adverse effect, a patient must be enrolled in the clozapine REMS registry by a certified clinician in order to receive treatment. ⁠

⚖️ Clozapine is also associated with significant weight gain, diabetes type 2, diabetic ketoacidosis, and increased lipid levels-all due to increased insulin resistance.⁠

Clozapine Read More »

Beta-Blockers⁠⠀

🔝 Beta-blockers are one of the top 200 drugs prescribed as they are indicated for many different cardiovascular diseases such as hypertension, angina, atrial fibrillation/flutter, and heart failure with reduced ejection fraction. ⁠⠀
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⭐Generally, there are two types of beta-adrenergic receptors, beta-1 and beta-2 receptors.⁠⠀
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-Non-selective beta-blockers block both beta-1 (β1) and beta-2 (β2) adrenoceptors. ⁠⠀
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-Cardioselective beta-blockers are relatively selective for β1 adrenoceptors (remember you have 1 heart) and tend to be favored in patients with diabetes or COPD/asthma. ⁠⠀
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-Some beta-blockers also cause vasodilation through blockade of vascular alpha receptors making them great for use in hypertension.⁠⠀
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🧠 Use the mnemonic – Be (β1) selective about your MAN BABE to help you remember the beta-blockers that are cardioselective. ⁠⠀

Beta-Blockers⁠⠀ Read More »

Lithium

💊 Lithium is a common ‘mood stabilizer’ used to treat the manic episodes of bipolar disorder, a mood disorder that is characterized by episodes of mania, hypomania, and depression. ⁠⠀
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🤔 The exact cause of bipolar disorder is unknown but is highly linked to family history, genetics, and abnormalities in neurotransmitters. This makes it tricky to pinpoint exactly how lithium works to treat bipolar but there are many proposed mechanisms of action. ⁠⠀
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🧠 Whenever you see the medication lithium, always think SALT as lithium (Li+) is located close to sodium (Na+) on the periodic table and they share similar structures. Because of this, lithium levels are often affected by salt and water balance as well as renal function (excreted mainly through kidneys). ⁠⠀
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💦 Dehydration can cause lithium levels to increase while increasing sodium intake can cause lithium levels to decrease. Medications that affect water and salt balance (ex: diuretics, NSAIDs, ACEI) can also alter lithium concentrations. ⁠⠀
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🗓️ The starting dose of lithium is 300 mg two or three times a day (The brand name is Lithobid to help you remember that it can be given BID or twice daily)⁠⠀
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🤰🏻Lithium is considered teratogenic due to the potential for fetal cardiac defects. The risks and benefits should be discussed with a healthcare provider before starting it in women of childbearing age.⁠⠀
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⭐ Lithium is a popular drug that often shows up on tests due to its narrow therapeutic index and many side effects. ⁠⠀

Lithium Read More »

ACE-inhibitors ⁠

 Let’s talk about ACE-inhibitors ⁠⠀
⁠⠀
💊 Angiotensin-converting enzyme (ACE) inhibitors are a class of drugs mainly used in the treatment of hypertension and heart failure with reduced ejection fraction (HFrEF). They are one of the top 200 drugs prescribed and because of that, they are an important class to know. ⁠⠀
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⭐ Drugs in this class end in the suffix ‘-pril’ such as: ⁠⠀
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-LisinoPRIL⁠⠀
-FosinoPRIL⁠⠀
-EnalaPRIL⁠⠀
-RamiPRIL⁠
-QuinaPRIL⁠
-BenazePRIL⁠⠀
⁠⠀
❗Do not use this medication in patients who: ⁠⠀
⁠⠀
-Have a hypersensitivity to ACE inhibitors or any of their components⁠⠀
-Pregnant or breastfeeding: box warning for patients who are or may become pregnant as it can cause fetal toxicity⁠⠀
-History of angioedema, bilateral renal stenosis, and concurrent use with aliskiren in patients with diabetes⁠⠀
⁠⠀

ACE-inhibitors ⁠ Read More »

Chronic Kidney Disease

 Renal adjustments in CKD and AKI 

😏 Acute kidney injury is not very cute ⁠

💧 Most drugs, particularly water-soluble drugs and their metabolites, are eliminated largely by the kidneys in urine. ⁠

⭐️ It is important to know which drugs require dose adjustments to prevent accumulation and toxicity in patients with chronic kidney disease (CKD) as well as those with acute kidney injury. ⁠

🤔 Things to keep in mind when renally adjusting medications: ⁠

👉🏻 Use estimated GFR or CrCl to determine drug dosing⁠
👉🏻 If the patient is on hemodialysis, the type of HD will also determine drug dosing⁠
👉🏻 CrCl should be monitored periodically in patients with AKI to determine if doses need to be adjusted when CrCl improves⁠
👉🏻 Some medications require individualized therapy (ex: serum drug level monitoring, vital signs, adverse effects) when dose adjusting⁠


Chronic Kidney Disease Read More »

Antidepressants

🌧️ Major depressive disorder (MDD) is a mood disorder characterized by persistent feelings of sadness and loss of interest that interferes with normal daily functioning.⁠

⭐️ The exact chemical basis for depression is poorly understood but is thought to be linked to decreased levels of the neurotransmitters, serotonin, dopamine, and norepinephrine. This cause is also known as the monoamine hypothesis.⁠

👉🏻 Because of this, the drugs developed to treat MDD selectively target the reuptake of serotonin and norepinephrine, increasing levels of these neurotransmitters in the synapse and enhancing NT signaling.⁠

⭐️ SSRIs are generally first-line due to their improved tolerability compared to the others (TCAs and MOAIs) and relative safety in cases of overdose.⁠

⭐️ Studies have shown equivalent efficacy among antidepressants, therefore the initial choice is made empirically based on patient factors and the nuances of each drug.⁠

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