Friday, August 9, 2024

Terminology of names of targeted bio-therapies

 The Names of Targeted Therapies Give Clues to How They Work | ONS Voice

The passage below was cut and pasted from the abovementioned article: 

Very helpful

Presently, two main families of targeted therapies exist—monoclonal antibodies and small molecule inhibitors. The ending letters (stem) of the generic names are like surnames that tell what family the drug is from and how the drug works to kill cancer cells. Monoclonal antibodies end with the stem “-mab” and small molecule inhibitors end with the stem “-ib”. The “-mab” family of targeted therapies has three distinct methods for interfering with cancer cell growth.

  1. Attach to receptors on the outside of cells to prevent the receptors from interacting with signaling molecules (e.g., growth factor receptors and growth factor interaction)
  2. Deliver radioactive molecules or toxins to the inside of the cells through attachment to cellular receptors
  3. Activate the body’s natural immune response

The “-mab” family is used when receptor targets are overexpressed on the outside of cancer cells. Conversly, the “-ib” family targets processes within the cell and therefore must be small enough in molecular weight to enter the cell and interfere with proteins on both the inside and outside of the cell. Proteins that code for growth or inhibit growth are some of the targets of these small but powerful family of drugs.

The sub stem of the generic names of the “-mabs” identifies the source where the antibodies were generated or cloned. The three most common sources are

  1. Chimeric human-mouse—drugs ending in “-ximab” (i.e., rituximab)
  2. Humanized mouse—drugs ending in “-zumab” (i.e., bevacizumab)
  3. Fully human—drugs ending in “-mumab” (i.e., ipilimumab).

Finally, both “-mabs” and “-ibs” contain an additional stem to describe the targeted therapies bullseye. For example, the “tu” in rituximab indicates the target is the tumor, the “ci” in bevacizumab designates the circulatory system, and the “li” in ipilimumab identifies the immune system target. Some of the intracellular targets for the “-ibs” include:

  1. Tyrosine kinase inhibition—sub stem “-tinib” (i.e., imatinib)
  2. Proteasome inhibition—“-zomib” (i.e., bortezomib)
  3. Clyclin-dependent kinase inhibition—“-ciclib” (i.e., seliciclib)

The prefix of the generic names and the drug market names are where researchers and pharmaceutical companies—like the parents of the young dancers—take creative liberty.  

The development of targeted therapies is expected to accelerate as new targets are identified, as a result, oncology nurses will need to stay up to date on the new medications so they can educate their patients on the way these therapies work as well as the possible side effects of the medications. Unfortunately, many people may have the idea that there are few if any side effects associated with targeted therapy. Although side effects can be less than those of standard chemotherapy, targeted therapies also affect normal cells to some degree.

So how do nurses keep up on the new therapies? Recently, ONS merged two key special interest groups (SIGs) the Targeted and Biologic Therapies SIG and the Chemotherapy SIG. The new SIG is now called the Chemotherapy and Biotherapy SIG. Another resource I found especially helpful was an animated video titled Understanding Targeted Cancer Therapies presented by the National Institute of Health.

Friday, March 22, 2024

Lung Ultrasound to Evaluate Pulmonary Edema

 

Prospective clinical study of 44 newborns, mean body weight 3 kg. All with critical congenital heart diseases and underwent heart surgery. CXR and Lung US were compared to guide management of diuretics, vasoactive inotropes, etc. Good correlation was noted.

An element of subjective assessment is needed. Probably, may not replace CXR. Or, it will take a very long time to replace CXR as an exclusive tool to assess pulmonary edema.

Basak Kaya et al. Pediatrics & Neonatology 2024 xxx (xxx) xxx.

Friday, October 6, 2023

Dysautonomia and Pregnancy

 Short article in Dysautonomia International blog page: Link to the article

By Dr. Svetlana Blitshteyn

Guest author Svetlana Blitshteyn, MD is the Director of the Dysautonomia Clinic and a Clinical Assistant Professor of Neurology at the University at Buffalo School of Medicine and Biomedical Sciences.

Excerpts:

  • POTS patients may have associated gynecologic issues such as endometriosis and fibroids. Therefore, needs careful evaluation by gynecologist, POTS physician and patient.
  • During pregnancy, 60% women with POTS reported severe hyperemesis gravidarum and 40% fatigue. Higher rate of miscarriage is reported.
  • During pregnancy, 30-50% women reported worsening of POTS symptoms. (50% had no change in their POTS symptoms.
  • After delivery, 50% of women reported improved symptoms for 6 months after delivery. In a different study, 30% reported worsening symptoms after delivery. 70% reported stable symptoms after delivery.
  • POTS medicines during pregnancy:
    • There are no POTS meds in Class A list by FDA (these are considered safe during pregnancy).
    • I have used low-dose beta-blocker during pregnancy to control tachycardia
    • Florinef and Pyridostigmine (Mestinon) are continued during pregnancy if necessary.
    • Less experience with Midodrine (its newer).
    • Women on SSRI's may switch to Prozac.
    • Medications that need to be weaned off or used sparingly include Benzodiazepines (e.g. Clonazepam, Ativan), Xanax (Alprazolam) and stimulants (Ritalin, Adderall).
  • POTS Medicines, to be stopped during pregnancy
    • Ideally, stop all medicines prior to conception. But, this may be unrealistic.
    • Planned pregnancy: 1st trimester - stop meds or reduce dose to minimum. If planning a pregnancy, slowly wean benzodiazepines and stimulants.
    • Unplanned pregnancy: wean above meds on a faster schedule.
  • Risk to the baby (in utero or postpartum)
    • 4 studies - no negative effects.
    • Does fainting harm the baby? No
    • But, recurrent syncope may reduce placental blood flow and therefore, may need an active management.
  • Breastfeeding
    • Metoprolol is safer than atenolol.
    • Prozac which is acceptable during pregnancy may be more harmful to the baby via breastmilk (Zoloft is better).
  • Will the child develop POTS?
    • Not enough studies to answer this question. 
    • Familial incidence occurs in 13-40% of patients.
References:
1. Blitshteyn S, Bett GL, Poya H. Pregnancy in Postural Tachycardia Syndrome: clinical course and maternal and fetal outcomes. J Matern Fetal Neonatal Med. 2012; 25: 1631-1634.

2. Kanjwal KK, Karabin B, Grubb BP. Outcomes of pregnancy in patients with Postural Orthostatic Tachycardia Syndrome. PACE 2009; 32:1000-1003.

3. Peggs, KJ, Nguen H, Enayat D, et al., Gynecologic disorders and menstrual cycle lightheadedness in postural tachycardia syndrome. Int J Gynaecol Obstet. 2012; 118: 242-246.

4. Kimpinski K, Iodice V, Sandroni P, Low PA. Effect of pregnancy on Postural Tachycardia Syndrome. Mayo Clin Proc 2010; 85: 639-644.

5. Powless CA, Harms RW, Watson WJ. Postural tachycardia syndrome complicating pregnancy. J Matern Fetal Neonatal Med 2010; 23: 850-853.

Monday, May 9, 2022

IV Sotalol - Registry study in children

 85 patients

Age range 1 day - 36 yrs)

Treated with IV Sotalol (Average dose 1 mg/kg/dose; Range = 0.5 - 1.8 mg/kg/dose).

Infused 

over a median period of 60 min (Range 30 min - 5 hours).

Successful in 49%, Improved in 30% (Improved = HR decreased to the extent of allowing overdrive atrial pacing).

QTc prolonged >465 ms in 16% (Prolonged >500 ms in 4%).

Conlcusion: Safe as effective.

Successful or Improved in 79%.

Most common dose is 1 mg/kg/dose, infused over 60 min.

Link to reference: Mollory-walton LE at al. JAHA 2022. 

Rivaroxaban (Xarelto, Janssen Pharmaceuticals, Inc)

 FDA approved for 2 pediatric indications:

1) Venous thromboembolism in children - after at least 5 days of parenteral anticoagulant treatment.

2) Thromboprophylaxis in pediatric patients < 2 yrs of age after Fontan operation.


Link to manufacturer information page and IFU.

Mavacamten for HOCM

 FDA approved Mavacamten (Camzyos from Bristol-Myers Squibb) for HOCM for children (May 2022).

Mavacamten is allosteric inhibitor of Myosin


Explorer-HCM trial data showed 

    (i) improved in peak VO2 and 

    (ii) stabilization or improvement in NYHA function class

compared to placebo.


Long-term extension study showed that benefits lasted at 1-year follow up. There was improvement in QoL reported by patients.


Valor-HCM - addition of Mavacamten to maximally-tolerated medical management, reduced the need for surgical or cath intervention for septal reduction.


News from TCTMD dt. 4/29/22