Antibiotic-Resistant Bacteria: An Overview of the Major Superbugs

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Since Halloween is coming up, we have teamed up with @ideasinmykitchen to discuss a scary subject, antibiotic-resistant bacteria, with these sweet microbe cookies!

What are superbugs? 

Superbugs are bacteria that are genetically changed to withstand the effects of most antibiotics used to treat the infections they cause. Yet, the overuse of antibiotics continues to promote their growth. Each year, drug companies spend millions of dollars on research to develop new antibiotics that can combat these resistant strains of bacteria.

We will be reviewing 6 of the highest-ranked superbugs. The Center for Disease Control’s (CDC) Antibiotic Resistance Threats in the United States, 2019 (AR Threats Report), puts these superbugs at the top of their list for serious to urgent threats requiring immediate attention. Each year, at least 2 million people in the United States are reported to have antibiotic-resistant infections. An infection without an antibiotic to treat it can lead to poor prognosis and bad outcomes.

 

Methicillin-resistant Staphylococcus aureus (MRSA)

 

Staphylococcus aureus are gram-positive bacteria commonly found on the skin. The first-line antibiotic to treat staph infections was previously an anti-staphylococcal penicillin (methicillin) until the bacteria became resistant, hence the name methicillin-resistant Staphylococcus aureus. Methicillin resistance was developed by acquiring the mecA gene producing an altered penicillin-binding protein, PBP2a, with a lower affinity for beta-lactam antibiotics. The gene enables transpeptidase activity to continue in the presence of beta-lactam antibiotics, allowing the bacteria to replicate as normal.

Use of recreational IV drugs can increase the risk of developing severe and invasive MRSA infections, including endocarditis, bacteremia, and meningitis.

 

MRSA infections are divided into two categories by source: hospital-acquired (HA-MRSA) secondary to hospitalization, long-term care, dialysis, invasive device, surgery, etc. or community-acquired (CA-MRSA). The antibiotic of choice for MRSA infections varies by the type and site of infection.

 

Hospital-acquired MRSA

Community-acquired MRSA

Vancomycin

Daptomycin

Linezolid

Ceftaroline

Telavancin

Dalbavancin

Oritavancin

Sulfamethoxazole/Trimethoprim

Doxycycline

Minocycline

Clindamycin

Linezolid 

Vancomycin-resistant Enterococci (VRE)

Enterococci are gram-positive bacteria that include Enterococcus faecalis and Enterococcus faecium, typically found in the human intestines and female genital tract. E. faecium accounts for more than 70% of VRE strains. Enterococci resistance develops through the gene van A, and leads to resistance to vancomycin, the mainstay antibiotic for Enterococci infections.

 

The most common infections caused by VRE include wound infections, bacteremia, and urinary tract infections (UTIs). Other serious infections include endocarditis and meningitis. Antibiotic treatment options vary by severity, site of infection, and susceptibilities.

Primary Antibiotic Treatments

Alternative Antibiotic Treatments

Ampicillin

Gentamicin*

Linezolid

Daptomycin

Doxycycline

Nitrofurantoin+

Fosfomycin+

Chloramphenicol

Tigecycline

Quinupristin/dalfopristin
*used in combination with ampicillin for endocarditis. +for urinary tract infections

ESBL-producing Enterobacteriaceae

Enterobacteriaceae (also called Enterobacterales) is a family of gram-negative bacteria that commonly cause infections in the healthcare setting. Examples of bacteria in this family include Escherichia coli, Proteus mirabilis, and Klebsiella pneumonia.

 

Enterobacteriaceae can develop resistance by producing enzymes called extended-spectrum beta-lactamases (ESBLs) that break down and destroy commonly used beta-lactam antibiotics such as penicillins and cephalosporins. Treatment of ESBL-producing Enterobacteriaceae can be challenging and depends on the site and severity of infection and local resistance patterns.

Antibiotic Treatments

Clinical Notes

Carbapenems

Drug of choice*-ertapenem preferred

Piperacillin-tazobactam

Equivalent to carbapenems in UTI and biliary tract infections

Amoxicillin-clavulanic acid

Equivalent to carbapenems in UTI and biliary tract infections; convenient for oral switch

Ceftolozone-tazobactam

Reserved for multi-drug resistant P. aeruginosa infection
*Despite the preference for carbapenems in treating ESBL infection, use of other susceptible agents are suggested due to the rate of carbapenem resistance.

Carbapenem-resistant Enterobacteriaceae (CRE)

Resistance to carbapenems occurs through multiple mechanisms, including carbapenemase enzyme production (enzymes that break down antibiotics), efflux pump-action (carbapenem pumped out of bacteria), and decrease bacteria cell membrane permeability to carbapenem.

 

Treatment of CRE depends on the site of infection, the type of gram-negative pathogen, resistance profiles. It is essential to consult an infectious disease specialist to assist with appropriate antibiotic regimens as optimal CRE treatment is mostly unknown and based on small retrospective studies. Typical treatment includes an antibiotic backbone coupled with other susceptible antibiotics.

Isolate susceptibility

Drugs

Susceptible to a Beta-lactam

Backbone: ceftazidime-avibactam (preferred) or meropenem-vaborbactam; alternatively, meropenem (if MIC <8 mg/liter) or ceftazidime or aztreonam

PLUS

Accompanying drug: colistin, tigecycline, aminoglycoside, or fosfomycin (if isolate intermediate to the backbone drug, consider using 2 of these)

Resistant to all Beta-lactam

Backbone: colistin

PLUS

Accompanying drug: tigecycline, aminoglycoside, or fosfomycin

Resistant to all Beta-lactam and colistin

Backbone: tigecycline or aminoglycoside

PLUS

Accompanying drug: tigecycline, aminoglycoside, or fosfomycin

Pandrug-resistant or susceptible to only one drug

Meropenem plus ertapenem or ceftazidime-avibactam plus aztreonam; add any active drug; consider active investigational drug if available

Pseudomonas aeruginosa

Pseudomonas aeruginosa are gram-negative bacteria common in the community and hospital setting. It is a ‘water-loving’ bug as it is common in swimming pools, whirlpools, hot tubs, sinks, mops, hydrotherapy pools, and humidifiers. As an opportunistic pathogen, it can cause severe infections in critically ill patients in the hospital. Some strains of Pseudomonas aeruginosa may be highly resistant to many antibiotics, including carbapenems. P. aeruginosa can develop antibiotic resistance through lower outer membrane permeability coupled with adaptive genes or mutational processes.

Infections caused by Pseudomonas aeruginosa include pneumonia, bloodstream infections, urinary tract infections, and surgical site infections.

IV Antibiotic Treatments

Oral Antibiotic Treatments

Piperacillin/tazobactam (Zosyn)

Ticarcillin/clavulanate (Timentin)*

Cefepime

Ceftazidime

Meropenem

Imipenem

Tobramycin

Gentamicin

Amikacin

Ciprofloxacin

Levofloxacin

Aztreonam

Colistin

Ciprofloxacin

Levofloxacin

Fosfomycin+
*Not available in the United States + only for uncomplicated UTIs

Clostridioides difficile

Clostridioides difficile (also known as C. diff) are gram-positive toxin-producing anaerobes that commonly causes diarrhea and severe inflammation of the colon (colitis). It is a normal bacterium in the intestines and colon, but can lead to C. diff infections in patients taking antibiotics. Antibiotics disrupt the normal gastrointestinal flora by killing good bacteria leading to an overgrowth of harmful bacteria, such as C. difficile. Higher incidences of C. difficile infection have been associated with antibiotics such as ampicillin, amoxicillin, cephalosporins, clindamycin, and fluoroquinolones.

 

Other risk factors for C. difficile infections include age greater than 65 years old, recent hospitalization for an extended period, residence in a nursing home, immunocompromise patients, and previous exposure to C. difficile.

 

The rate of resistance to antimicrobials has significantly increased with this pathogen, limiting treatment options. With these new developments, the Infectious Disease Society of America (IDSA) guidelines updated their recommendation for the treatment of C. difficile in 2018.

Clinical Definition

Recommended Treatment

Initial episode, non-severe*

Vancomycin 125 mg 4 times a day x 10 days

OR

Fidaxomicin 200 mg twice daily x 10 days

Initial episode, severe+

Vancomycin 125 mg 4 times a day x 10 days

OR

Fidaxomicin 200 mg twice daily x 10 days

Initial episode, fulminant$

Vancomycin 500 mg 4 times a day by mouth or NG tube. If ileus, consider adding vancomycin rectally

PLUS

IV metronidazole 500 mg every 8 hours

First reoccurrence

Vancomycin 125 mg 4 times a day x 10 days if metronidazole was used for the initial episode

OR

Tapered and pulsed dose vancomycin regimen (e.g., 125 mg 4 times per day for 10-14 days; then 2 times per day for a week; and then every 2 or 3 days for 2-8 weeks)

OR

Fidaxomicin 200 mg twice daily for 10 days if vancomycin used for the initial episode

Second or subsequent reoccurrence

Vancomycin in a tapered and pulsed regimen

OR

Vancomycin 125 mg 4 times per day x 10 days followed by rifaximin 400 mg 3 times daily x 20 days

OR

Fidaxomicin 200 mg twice daily for 10 days

OR

Fecal microbiota transplantation
*Leukocytosis with a WBC count <15,000 cells/mL and a serum creatinine level <1.5 mg/dL +Leukocytosis with a WBC count >15,000 cells/mL and a serum creatinine level >1.5 mg/dL $Hypotension or shock, ileus, megacolon
Some patients are colonized with strains of antibiotic-resistant bacteria but do not develop any symptoms. Consider withholding antibiotics in patients who are clinically stable and monitor to decreased the possibility of resistance to the remaining antibiotic options. To prevent the emergence of these multi-drug resistant bacteria, it is important to optimize antibiotic treatments and deescalate as soon as cultures return.

Need to take a break from studying? Find this sugar cookie recipe from @ideasinmykitchen to create your own scary good superbugs!

For more antibiotic study material, check out our Antibiotics Pharmacology Coloring Book!

References and further reading suggestions

  • CDC. Antibiotic resistance threats in the United States, 2019. Accessed October 28, 2020. Link.
  • Palchak M, Sahni J, Desai N, Randhawa A, Mcginty L, Skirvin JA. Vancomycin-Resistant Enterococcus. USPharmacist. Published August 20, 2014. Link.
  • Lister PD, Wolter DJ, Hanson ND. Antibacterial-resistant Pseudomonas aeruginosa: clinical impact and complex regulation of chromosomally encoded resistance mechanisms. Clin Microbiol Rev. 2009;22(4):582-610. doi:10.1128/CMR.00040-09. Link.
  • Banawas SS. Clostridium difficile Infections: A Global Overview of Drug Sensitivity and Resistance Mechanisms. Biomed Res Int. 2018;2018:8414257. Published 2018 Feb 21. doi:10.1155/2018/8414257. Link.
  • Cho JM, Pardi DS, Khanna S. Update on Treatment of Clostridiodes difficile infection. Mayo Clin Proc. April 202;95(4):758-769. Link.
  • Ng K. Updates in the Management of Clostridium Difficile for Adults. USPharmacist. Published April 19, 2019. Link.
  • Smith H, Kendall B. Carbapenem-Resistant Enterobacteriacea. Statpearls. Updated July 31, 2020. Link.
  • Singleton A, Cluck D. The Pharmacist’s Role in the Treating Extended-Spectrum Beta-Lactamase Infections. USpharmacist. Published April 18, 2019. Link.

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Antibiotics that cover anaerobes

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Mnemonic_Antibiotics that cover anaerobes
Anaerobic bacteria are bacteria that do not live or grow when oxygen is present. In humans, these bacteria are most commonly found in the gastrointestinal tract. ⁠ ⁠ 🔺 They play a role in conditions such as appendicitis, diverticulitis, and perforation of the bowel so it is important to make sure we have adequate anaerobic coverage when empirically treating these infections. ⁠ ⁠ 💊 There are several antibiotics that cover anaerobes in addition to other bacteria. ⁠

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Antibiotics that cover Pseudomonas

Leave a Comment / Infectious Diseases /
Pseudomonas is a type of bacteria (bug) that is found commonly in soil and in water. Of the many different types of Pseudomonas, the one that most often causes infections in humans is called Pseudomonas aeruginosa, which can cause infections in the blood, lungs (pneumonia), or other parts of the body after surgery.⁠ ⁠ 🔺 Pseudomonas aeruginosa treatment has become increasingly difficult as bacteria become more resistant to the available antibiotics on the market. If they develop resistance to several types of antibiotics, these germs can become multidrug-resistant.⁠

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Antituberculosis Agents

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Tuberculosis (TB) is caused by Mycobacterium tuberculosis (aerobic, non-spore forming bacillus). Active TB is transmitted by aerosolized droplets (sneezing, coughing, talking, etc.) and is highly contagious. ⁠ ⁠ Active disease treatment is divided into two treatment phases, initial and continuation. To avoid treatment failure due to resistance, the preferred initial treatment consists of a 4 drug regimen of rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE). ⁠ ⁠ These 4 drugs are taken for about 8 weeks during the initiation phase. In the continuation phase, the regimen is narrowed based on susceptibilities.

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Asthma 1: What is asthma?

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Think of yourself as a visual learner? Check out our video above that uses graphics and animation to discuss the material below!

Definition:

Asthma is often defined as a chronic inflammatory disorder of the airways.

So what does that mean? Well normally, our body has an amazing filtering system for the air we breathe that starts at our nose. Our nose secretes this thick and sticky substance called mucus that traps unwanted particles like dirt, pollen, or smoke. Small hairs called cilia move in wave like motions pushing the mucus to the back of our throat where it either gets swallowed or spit out.  Have you ever noticed a lot of post-nasal drip during pollen season?  As irritating as it can be, that is your nose is working overtime to clear out the pollen before it reaches your lungs.  This is completely normal and our body’s way of protecting us from particles that may contain bacteria or viruses that can lead illnesses.

Pathophysiology:

In asthma, the body’s inflammatory process goes into overdrive! This occurs when the immune system is exposed to something called an allergen or trigger such as pollen, pet dander, smoke, or mold. It mistakenly tags it as something bad by producing antibodies to it called IgE. 

Upon reexposure to the same allergen, the body’s hyperinflammatory system remembers the allergen and causes the release of IgE antibodies that bind to and activate mast cells. Mast cells are a type of immune cell that function as the body’s first line of defense against harmful allergens preventing them from entering the body. They do this by releasing granules that contain such as histamine, prostaglandin and leukotriene. These granules sound fancy but they are just names for types of mediators of anaphylaxis. These mediators go on to cause constriction of the airway smooth muscle and increase mucous production. This process is something called the ‘early asthmatic response. This is followed 3-6 hours later by a ‘late asthmatic response’ where proinflammatory cytokine proteins recruit and activate additional immune cells such as eosinophils that contribute to continued and sustained bronchoconstriction and mucous production.

Symptoms:

These series of events lead to the symptoms of asthma including: 

  • Wheezing
  • Breathlessness
  • Chest tightness
  • Coughing

In asthma, the smooth muscles around the airways tighten and shrink  making them narrower leading to chest tightness. In addition, overproduction of mucous produces mucous plugs throughout the lining of the airway that can cause coughing. This makes it tough to move air through and almost causes a whistling sound as air passes through the narrow space. This is known as wheezing. The narrow and inflamed airways not only lead to decrease oxygenation but also decrease ventilation as air gets trapped inside the lungs. The increase work of breathing to get air in and out can lead to exhaustion and breathlessness as seen in patients with asthma.

Diagnosis:

In addition to the patient’s symptoms, medical history and physical exam, physicians commonly use a spirometer to diagnose asthma. A spirometer is a device used to measure the volume of air inspired and expired by the lungs. A physician will have a patient use the spirometer after administering a medication called a beta agonist. If there is an improvement in the spirometry readings after using the beta agonist, this is a good indication of asthma since it is reversible with medications, unlike COPD. Once the diagnosis is confirmed, initial asthma management depends on how often they have symptoms such as nighttime awakenings, the need for a rescue inhaler to control symptoms, activity limitations due to asthma and daytime symptoms.

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Asthma 2: Asthma Medications Made Simple

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Think of yourself as a visual learner? Check out our video above that uses graphics and animations to discuss the material below!

Main Asthma Medications:

The main medications used to treat chronic asthma are easiest to remember using the following mnemonic. 

I like lazy Saturdays!

I is for inhaled corticosteroids because I come first to help you remember that they are the first line of treatment in asthma!  Like is for leukotriene modifiers, Lazy is for long acting beta-2 agonist (these are used even on a lazy day!) Saturdays is for short acting beta-2 agonist because on Saturday college football players may require a short acting beta-2 agonist.  Let’s dive into each of these further.

Treatment Goal: 

The goals of asthma treatment are to prevent chronic symptoms that can interfere with daily living, and decrease the need for rescue inhalers, maintain pulmonary function and activity level, and prevent exacerbations.

Inhaled Corticosteroids:

Inhaled corticosteroids are considered the key controller medications that work by reducing inflammation specifically in the lungs. They do this by binding onto glucocorticoid receptors which go on to inhibit the transcription of inflammatory genes such as cytokines as well as the activation of esoinophils and the release of inflammatory mediators. Cytokines are like your messenger proteins that alerts other immune system cells to the site of inflammation. Eosinophils are a type of white blood cell that can cause inflammation and swelling. The inflammatory mediators like leukotrienes, histamine, or prostalgandins directly lead to the symptoms of inflammation. By inhibiting them, this reduces the hyperinflammatory cascade that leads to bronchial hyperreactivity, swelling and mucus production, making it easier to breath and preventing future asthma attacks.

It is the preferred medication for controlling asthma over the long term since hyperinflammation is the main cause of asthma. Examples include: 

  • Budesonide (Pulmicort)
  • Beclomethasone (QVAR)
  • Fluticasone (Flovent),
  • Mometasone (Asmanex)
  • Clicosenide (Alvesco)

Steroids often end in the suffix ‘onide’ or ‘-asone’ similar to prednisone or cortisone (naturally occurring corticosteroid). 

Luckily, Inhaled corticosteroids work locally and have relatively few side effects compared to oral corticosteroids. The common side effects of inhaled corticosteroids can be remembered using the mnemonic HOCUS:   

  • Hoarseness
  • Oral thrush/candidiasis (Be sure to counsel patients to rinse their mouth and throat with warm water and spit to prevent this from occuring)
  • Cough
  • Upper respiratory tract infections (is rare and often occurs with high doses or long-term use)
  • Sore throat

Inhaled Beta-2 Agonists:

Beta-2 agonists are bronchodilators that work to relax the smooth muscle bands that tighten around the airways and are divided into two forms, short-acting and long-acting beta-2 agonists. These forms differ by their duration of action with short acting beta-2 agonists working rapidly within 5 minutes to reverse bronchoconstriction and relieve or stop asthma symptoms which makes this a great rescue inhaler. Long-acting beta-2 agonists help keep the airways open for 12 hours or longer and are used on a daily basis to prevent asthma attacks.

Beta-2 agonists work by binding on to beta-2 receptors located on smooth muscles of the airways in the lungs. If you can recall, beta-2 receptors are commonly located on the lungs while beta-1 receptors are mainly located on cardiac muscles. Remember, we have 2 lungs (beta-2) and 1 heart (beta-1).

Activation of beta-2 receptors causes an increase in cyclic AMP which leads to a decrease in calcium release. Since calcium plays a big role contraction, a decrease in calcium leads to a decrease in contraction of airway smooth muscles and bronchodilation.

Beta-2 agonists can cause some unwanted side effects with the heart at high doses such as increased heart rate, palpitations, blood pressure, and anxiety. You can remember this as the beta symbol also looks like a heart turned sideways. Other side effects include tremors, hyperglycemia, hypokalemia, and cough.

It is important to monitor how often patients are using their rescue inhaler as frequent use can indicate that their asthma is not under control. Other things to monitor include BP, HR, blood glucose and potassium. Also, since this class of medications works quickly, they are often used prior to exercise or in exercise induced asthma. They can be taken 5-15 minutes before exercise and last 2-3 hours. Remember back to how the football player may need this on the sidelines at his Saturday game?

 

Beta 2 agonists mechanism of action

Activation of beta-2 receptors causes an increase in cyclic AMP which leads to a decrease in calcium release. Since calcium plays a big role contraction, a decrease in calcium leads to a decrease in contraction of airway smooth muscles and bronchodilation.

Beta-2 agonists can cause some unwanted side effects with the heart at high doses such as increased heart rate, palpitations, blood pressure, and anxiety. You can remember this as the beta symbol also looks like a heart turned sideways. Other side effects include tremors, hyperglycemia, hypokalemia, and cough.

It is important to monitor how often patients are using their rescue inhaler as frequent use can indicate that their asthma is not under control. Other things to monitor include BP, HR, blood glucose and potassium. Also, since this class of medications works quickly, they are often used prior to exercise or in exercise induced asthma. They can be taken 5-15 minutes before exercise and last 2-3 hours. Remember back to how the football player may need this on the sidelines at his Saturday game?

Long-acting beta-2 agonist or LABA works just like a SABA, it just lasts longer with a duration of action of 12 hours and are used with a twice daily dosing regimen.  Examples include salmeterol and formoterol.

You can remember this because they contain words similar to metro in their names. Metro trains run long distances, so these are long-acting.

 

Because they have no anti-inflammatory action, these medications should not be used alone in asthma due to increased risk of asthma-related deaths.  That is why they are often found in combination with an inhaled corticosteroid like Symbicort which includes budesonide and formoterol or Advair including salmeterol and fluticasone. 

Side effects are similar to short-acting beta2 agonist. Remember, long-acting beta-2 agonists with inhaled corticosteroids are considered controller medications and should be taken daily even on a lazy day to prevent asthma exacerbations. 

Now that we have talked about specific counseling points about the different types of inhaled medications, let’s review how to counsel a patient on using their metered dose inhaler using the mnemonic: SPORTT

  • Shake well before each use
  • Prime before first use by shaking well for 5 seconds and then spraying into the air 3 times.  This should be repeated if the inhaler has not been use for more than 7 days.
  • Out. Take a deep breath and breathe out all the way
  • Rest the inhaler in the mouth and close your lips around it.
  • Take a deep breath in as you press all the way down on the inhaler to release the medication.
  • Ten seconds. Hold your breath for as long as you can up to 10 seconds

Spacers should be used for children as they help to ensure proper delivery of the medication

There are several different types of inhalers that deliver medications in a slightly different way such as dry powder inhalers, respimats, accuhalers, elliptas and more. Always double check the package inserts when educating patients on how to use their new inhaler.   

Leukotriene Modifiers:

Leukotriene modifiers are a great add on therapy in patients with allergies since they block the action of leukotrienes. If you can recall, leukotrienes are a type of proinflammatory chemicals that cause bronchiole smooth muscle contraction as well as recruit other proinflammatory mediators such as histamine and prostaglandin into tissues. By inhibiting leukotrienes, we can see a reduction in airway swelling, smooth muscle contraction, inflammation and nasal congestion often associated with allergies. 

Examples include: 

  • Montelukast
  • Zafirlukast
  • Zileuton

They all have the suffix “-luk” in the name reminding you that it is a Leuk-otriene modifier. 

Clinical pearl! This class of medications is dosed based on age not weight.  Other side effects include headache, dizziness, abdominal pain, increased LFTs, upper respiratory infections, sinusitis, and pharyngitis.  Behavior and mood changes are rare side effects that include aggressive behavior, agitation, hostility, depression and/or suicidal thoughts and is an important counsel point for patients. Though this may all sound like a lot, they are relatively well tolerated.

Theophylline:

Theophylline is an oral bronchodilator medication that you may see in the treatment of asthma. Its use has declined due to the greater efficacy of inhaled corticosteroids and beta-2 agonists as well as the numerous drug interactions and side effects associated with it (nausea, headache, tachycardia, insomnia, tremor, and nervousness, arrhythmias, confusion, seizures).

It has a narrow therapeutic index of 10-20 mcg/mL and requires frequent lab draws to monitor drug levels. It’s mechanism of action is not fully known but it is believed to block phosphodiesterase resulting in bronchodilation and mild anti-inflammatory effects.  

Inhaled Anticholinergics:

Short-acting inhaled anticholinergics such as ipratropium can commonly be used with beta-2 agonists in acute asthma exacerbations. They inhibit acetylcholine from binding onto muscarinic receptors on airway smooth muscle cells (hence why they are called anti-cholinergics) leading to bronchodilation. They have few side effects (mainly just dry mouth that is common with tiotropium) due to the fact that they are inhaled locally and are poorly absorbed into the circulation. Long-acting inhaled anticholinergics (Spiriva or tiotropium) provide modest improvements in asthma exacerbations and are reserved in patients with uncontrolled asthma despite being on an ICS-LABA.

Omalizumab (Xolair):

Omalizumab (Xolair) is a subcutaneous injection made of IgG monoclonal antibodies that inhibit IgE binding to mast cells. If you can recall, IgE is one the main culprits that lead to asthma symptoms. Omalizumab is indicated in patients with moderate to severe persistent allergic asthma despite being on max doses of ICS-LABA. It has a box warning for anaphylaxis and requires that it be administered in a healthcare setting where patients can be monitored. Other side effects include injection site reactions, muscle pain, dizziness, fatigue, and dermatitis. 

Wrapping it up:

To wrap it up, when initiating medications in a newly diagnosed asthma patient, assess their symptoms and start them on a rescue inhaler such as a short-acting beta2 agonist as needed. If their symptoms worsen, they can escalate therapy using higher doses of their controller medications. Lastly, if a patient has allergies and is not responding to other therapies, they may benefit from an add-on medication such as a leukotriene modifier.

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Asthma, Management of

Leave a Comment / Pulmonology /
📖 Asthma is a common airway disease and has a range of severity, from a very mild, occasional wheeze to acute, life-threatening airway closure. It usually presents in childhood and is associated with other features of atopy, such as eczema and hayfever.⁠ ⁠ 💊 Medical management includes bronchodilators like beta-2 agonists and muscarinic antagonists (salbutamol and ipratropium bromide respectively) and anti-inflammatories such as oral or nebulized steroids. Theophylline was once popular but is rarely used due to its narrow therapeutic index and side effect profile. However, it is still important to note as there are patients still treated with it. ⁠ ⁠ 💊 Patients with life-threatening asthma are managed with high flow oxygen inhalation, systemic steroids, back-to-back nebulizations with short-acting beta 2 agonists, and short-acting muscarinic antagonists, and intravenous magnesium sulfate.⁠ ⁠ 💊 Antibiotics should only be used if an infection is suspected (positive CXR, symptoms of cough and purulent sputum production, fever, high WBC, etc.) and should be withheld if not, to reduce the rise of antimicrobial resistance. ⁠

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Beta-1 Cardioselective Beta-Blockers

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❤️ Cardioselective beta-blockers work on the beta-1 receptors. Beta-1 receptors primarily are found in cardiac tissues whereas beta-2 receptors are located in the lungs (remember: 1 heart, two lungs). ⁠ ⁠ ❤️ Cardioselective beta-blockers exert their effect by binding to the beta-1 receptor sites selectively and inhibiting the action of epinephrine and norepinephrine on these sites. They are often preferred in patients with respiratory disease as they are less likely to cause constriction of airways or peripheral vasculature.⁠

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Calcium Channel Blockers

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Calcium channel blockers (CCBs) are used in the treatment of many cardiovascular conditions including hypertension and angina. They are divided into subclasses, non-dihydropyridines and dihydropyridines and differ by their pharmacokinetic properties, clinical uses, response, and selectivity.

 

Key Points

The non-dihydropyridine CCBs do not end in the suffix ‘-ine’ hinted by the name of the subclass, non-dihydropyridines. They cause more cardiac depression and less vasodilation than dihydropyridine CCBs resulting in a reduction in heart rate and cardiac contractility.

  • Verapamil
  • Diltiazem

 

Dihydropyridine CCBs end in the suffix ‘-ine’ and have more vascular selectivity and fewer cardiac effects. They act primarily as peripheral vasodilators and are used in the treatment of hypertension and angina. They do not suppress AV node conduction or SA node automaticity.

  • Amlodipine
  • Nicardipine
  • Nifedipine
  • Nimodipine
  • Felodipine

 

Mechanism of Action:

The name of this class, calcium channel blockers, hints at its mechanism of action – inhibits the entry of calcium into cells of the cardiac and peripheral vascular smooth muscles. 

  • Calcium entry into L-type channels of cardiac and peripheral vascular cells is needed for them to contract or constrict more strongly. 
  • By blocking calcium entry, calcium channel blockers cause 
    • peripheral vascular smooth muscle relaxation (decreases blood pressure)
    • decreased myocardial contractility (decrease myocardial demand making them effective in angina)
    • decrease heart rate and conduction velocity (useful in arrhythmias). 

Indications:

Non-dihydropyridines 

  • Hypertension
  • Arrhythmias

Dihydropyridines

  • Hypertension
  • Angina
  • Migraines

 

Side Effects: 

The main side effects of calcium channel blockers are hypotension and dizziness which is related to their effects on vasodilation so it is easier for you to memorize. 

In addition, they can also cause the following side effects by subclass:

  • Non-dihydropyridines
    • Constipation, gingival hyperplasia, worsening cardiac output, and bradycardia.
  • Dihydropyridines
    • Peripheral edema, headache, flushing

Clinical Pearls/Education:

  • Non-dihydropyridines are contraindicated in patients with decompensated heart failure, second or third-degree AV blockade, and sick sinus syndrome due to their inhibitory effects on the SA and AV node, slowing cardiac conduction and contractility. 
  • Monitor patients for hypotension, edema, and bradycardia. 
  • Peripheral edema is dose-dependent and may occur within 2 to 3 weeks of initiating calcium channel blocker therapy, particularly dihydropyridines. Peripheral edema due to the redistribution of fluid from the intravascular space to the interstitium. 
  • Diphydroyridines can cause reflex tachycardia and acute hypotension due to their potent vasodilating effects. This effect is more common with first-generation short-acting dihydropyridines (e.g. immediate-release nifedipine) and less with newer agents that are longer acting (e.g. amlodipine). The effect may be lessened by using sustained-release formulations.
  • Diltiazem decreases AV node conduction and heart rate to a lesser extent than verapamil but these drugs should be monitored closely for bradycardia especially with patients on beta-blockers. 
  • Verapamil and diltiazem are considered moderate cytochrome P450 3A4 enzyme inhibitors and should be monitored for drug interactions. 
  • Constipation is a more common side effect with verapamil and occurs to a lesser extent with diltiazem. 

References:

  • McKeever RG, Hamilton RJ. Calcium Channel Blockers. [Updated 2020 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482473/
  • Maclaughlin EJ, Saseen JJ. Hypertension. In: DiPiro JT, Yee GC, Posey L, Haines ST, Nolin TD, Ellingrod V. eds. Pharmacotherapy: A Pathophysiologic Approach, 11e. McGraw-Hill.

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Calcium Channel Blockers (Mechanism of Action)

Leave a Comment / Cardiology, Top 200 Drugs /
💊 Calcium channel blockers (CCBs) are used in the treatment of many cardiovascular conditions including hypertension and angina. They are divided into subclasses, non-dihydropyridines, and dihydropyridines and differ by their pharmacokinetic properties, clinical uses, response, and selectivity. ⁠ ⁠ 💊 The name of this class, calcium channel blockers, hints at its mechanism of action – inhibits the entry of calcium into cells of the cardiac and peripheral vascular smooth muscles. ⁠ ⁠ 🗒️ Calcium entry into L-type channels of cardiac and peripheral vascular cells is needed for them to contract or constrict more strongly. ⁠ ⁠ 🗒️ By blocking calcium entry, calcium channel blockers cause:⁠ 👉🏻 peripheral vascular smooth muscle relaxation (decreases blood pressure)⁠ 👉🏻 decreased myocardial contractility (decrease myocardial demand making them effective in angina)⁠ 👉🏻 decrease heart rate and conduction velocity (useful in arrhythmias). ⁠

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Cholinergic Muscarinic Agonist Effects

Leave a Comment / Miscellaneous /
👉🏻 Cholinergic muscarinic agonists are drugs that bind to and activate muscarinic cholinergic receptors and increase the activity of the parasympathetic nervous system. They are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder, and eye. They may also be used to reduce heart rate. ⁠ ⁠ 👉🏻 Direct cholinergic agonists work by resisting acetylcholinesterase, thus preventing its breakdown. Drugs in this class include bethanechol, carbachol, and methacholine, and pilocarpine.⁠ ⁠ 👉🏻 Indirect cholinergic agonists work by inhibiting the acetylcholinesterase enzyme preventing the degradation of acetylcholine. Drugs in this class include neostigmine, physostigmine, galantamine, donepezil, and rivastigmine. ⁠

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