Parasympathomimetics (Cholinergics)

These notes are based on this youtube video, double-checked that the information is correct from the book below.

Direct (bind directly to acetylcholine receptors and act like acetylcholine)

Be My Parasympathetic Choline

• Bethanechol (used for Bowel and Bladder emptying in atonic bladders because they increase motility)
• Methacholine (used in asthma diagnosis)
• Pilocarpine (increases sweat, tears and salivation and increases aqueous humor outflow and miosis, so used in glaucoma and dry mouth diseases)
• Carbachol (increases aqueous humor outflow and miosis, so used in glaucoma)

Indirect (act by inhibiting acetylcholinesterase and thereby prolonging effect of acetylcholine)

End in ‘stigmine’

Reversible cholinesterase inhibitors

• Neostigmine/pyridostigmine
• Physostigmine (only one that crosses CNS and can be used in toxicity of atropine)
• Edrophonium (in diagnosis of myasthenia gravis because it is short acting)

Irreversible cholinesterase inhibitors

• Echothiphate (glaucoma)

Reference:

Mycek, M.J.; Harvey, R.A.; Champe, P.C. (2000). Lippincott's Illustrated Reviews - Pharmacology 2nd ed. 

Student Notes: Non-invasive Prenatal Screening for Fetal Anomalies (OBG)

Prenatal screening was (and still kind of is) a bit of a confusing/pain-in-the-bum subject. I've managed to summarize it for myself in a bearable way and share it.

Note: Keep in mind these are all NOT diagnostic and NON-invasive (as opposed to chorionic villus sampling, amniocentesis, etc.)

The indications of doing each test and contraindications are not the topic of this post.

Possible non-invasive screening tests:

1. U/S: measures nuchal translucency:Which is a sac of fluid behind the neck of the fetus. It is present in all fetuses but is increased in those with Trisomy 21. (Figure below)
2. Pregnancy Associated Plasma Protein A (PAPP-A): this is a glycoprotein produced by the trophoblasts and is most accurately measured during the 1st trimester. It becomes less accurate after that and is therefore not measured in the 2nd trimester.
3. Quadruple screen/triple screen/maternal serum screen: which is a blood test composed of 3 or 4 components (depending on which is chosen).

Retrieved from: http://www.ultrasoundscan4d.co.za/pregnancy-scans/nt-pregnancy-scans/

Patterns of Prenatal Fetal Screening
There are a few patterns of doing the prenatal fetal screening. Depending on the detection rate and false positives of each one, a type is chosen during pregnancy.

1. 1st trimester: doing Nuchal Translucency Ultrasound only (the detection rate in Figure 1 below is the lowest)
2. 1st trimester: doing blood screen + Nuchal Translucency (this is also known as the First Trimester Screen and is explained below)
3. 2nd trimester: doing a Triple Screen also known as Maternal Serum Screen or Quadruple Screen,  (the Triple Screen has a lower detection rate than the Quadruple Screen)
4. Done in both trimesters: Integrated Prenatal Screening (this has the highest detection rate of Down Syndrome as seen below at 94-96%)
5. Done in both trimesters: Integrated Serum Screening

Figure 1: Retrieved from http://slideplayer.com/slide/4092725/

Prenatal Fetal Screening Patterns Explained
First Trimester Screening (FTS) (Red in Figure 1)

What is it?It is a combination of both a blood test and an ultrasound (U/S):

1. Blood test:
1. B-hCG
2. PAPP-A
2. U/S:
1. measures nuchal translucency

When is it done? It is a 1st trimester test done at 9-13 weeks gestation

Advantages:

• 1 blood sample drawn only
• Done early (in the 1st trimester) so useful where parent wants early results and can also offer follow up with a Chorionic Villus Sampling if positive, since Chorionic Villus Sampling can only be done between 10-13 weeks of gestation)
• Can detect Trisomy 21 and 18

Disadvantages:

• Does not estimate risk of open Neural Tube Defects (NTDs) and therefore must combine it with a Maternal Alpha Fetoprotein (MAFP) at 15-20 weeks gestation for detecting NTDs.
• Not as accurate as Integrated Prenatal Screening
• False positive rate: 5%

Maternal Serum Screening (MSS) AKA Triple screen

• What is it?The MSS is also known as a Triple Screen. If the Inhibin A is also tested, it is known as the Quadruple Screen(obviously because then 4 components will have been looked for). If Inhibin A is not done, it is known as a Triple Test (genius naming really!).
  It is composed of only a blood test with the following components:
1. B-hCG
2. Maternal Serum Alpha Fetoprotein (MSAFP):
3. Estriol (Unconjugated Estrogen)
4. Inhibin A
• When is it done? It is a 2nd trimester test done at 15-20 weeks gestation
• Advantages:
• 1 blood sample drawn only
• Can detect Trisomy 21 and 18 and NTDs
• Disadvantages:
• Late detection (in 2nd trimester), so no chance of offering chorionic villus sampling.

Integrated Prenatal Screening

• What is it?It is the combination of both tests: the MSS + FTS
  So an U/S is done in the first semester along with a blood test AND a blood test in the second semester looking for the respective components mentioned above in each test.
• When is it done?At the respective timings of the MSS and FTS
• Advantages:
• Most accurate screening schedule
• False positive rate: 2%
• Can detect Trisomy 21 and 18 and NTDs
• Disadvantages:
• 2 blood samples to be drawn
• Late detection (in 2nd trimester), so no chance of offering chorionic villus sampling.

Integrated Serum Screening

• What is it? It is the combination of ONLY the blood tests from the FTS and MSS (again the naming geniusly indicates this)
• When is it done? At the respective timings of the MSS and FTS

2nd Trimester U/S

• What is it?
  U/S scan done to look for fetal anomalies, fetal growth, location of placenta and number of fetuses (also for gestational age if no prior U/S done)
• When is it done? It is a 2nd trimester scan done at 18-20 weeks of gestation

Abnormalities in Screening tests

FTS
Down Syndrome (Trisomy 21): 

• Nuchal translucency: increased
• B-hCG: increased
• PAPP-A: decreased

MSS

Open Neural Tube Defects:

• MSAFP: increase
• B-hCG: normal
• Unconjugated estrogen (estriol): normal
• Inhibin A: normal

Down Syndrome (Trisomy 21):

• MSAFP: decreased
• B-hCG: increased
• Unconjugated estrogen (estriol): decreased
• Inhibin A: increased

Edward Syndrome (Trisomy 18):

• MSAFP: decreased
• B-hCG: decreased
• Unconjugated estrogen (estriol): decreased
• Inhibin A: normal

References:

1. ACOG practice bulletin no. 77: screening for fetal chromosomal abnormalities.

2. Essential Med Notes 2015: Obstetrics - Table 3, OB6