Monday, January 16, 2017

Opioids


Plants and microorganisms produce over 150,000 natural molecules, some of which are bioactive in humans.  I am writing this post in response to the wave of celebrity deaths, some of which may be attributed to drug overdoses.

Figure 1: Opium poppy (Papaver somniferum) courtesy of the DEA Museum website
The opium poppy is the source of morphine and codeine. Hydrocodone (e.g., Vicodin) is a semi-synthetic opioid synthesized from codeine. According to the US DEA, hydrocodone is the most frequently prescribed opioid in the United States and is associated with more drug abuse and diversion than any other licit or illicit opioid. Dextromethorphan (pronounced "dex-tro-meth-orphan") is a molecule that resulted from a search for a non-addictive analogue of codeine that still retained cough relief. Unfortunately, it still carries a risk for abuse.

Figure 2: Most widely used (and abused) opioids
This year, the musician Prince is said to have died from a fentanyl overdose. A structurally similar molecule, demerol, is primarily used in labor and delivery. Demerol was the first wholly synthetic opioid developed, in 1939. Fentanyl was discovered in 1960 by screening demerol analogues. To my eyes, it isn't easy to see the structural similarity between the plant-based opioids (natural and semi-synthetic) and the synthetic opioids.



Figure 3: Red region of the molecules mimics the endogenous ligand for opioid receptor, a GPCR
There are multiple types of opioid receptors: mu (MOR), delta (DOR), and kappa (KOR) among them.  The drugs mentioned here mimic the endogenous morphine, also known as endorphin.  There are multiple types of endorphin peptides, but one endorphin peptide met-enkephalin (structure not shown) shares a common substructure with the plant-based opioids (shown in red in Figure 3).

Figure 4: Selectivity of opioids for three classes of opioid receptors
Different opioids have varying degrees of selectivity for the different classes of opioid receptors. This selectivity may explain why distinct substructures can have a similar effect.

Figure 5: A set of structurally related anti-diarrheal compounds in current use

Orienting the fentanyl molecule differently reveals its structural similarity to other anti-diarrheals, Immodium and the combination drug called Limodil. A side effect of opioids is constipation. Everything I know about opioid abuse, I learned from the movie Trainspotting.


References:

John Wiley & Sons, 2007.


Chahl, Loris A. "Opioids - mechanisms of action" Australian Prescriber, 1996.

Saturday, January 7, 2017

Central Coast Trip

We had a wonderful 5-day (4-night) vacation in Grover Beach this New Year's.  My panniers weighed about 26 pounds.  The raingear was not used, but rain was in the forecast so it was good we had it just in case.  The most valuable items were the windbreaker, yoga pants, and a zip-up hoodie.

It was easy to catch the Amtrak from Glendale.  The Holiday Inn Express provided continental breakfast, of which we used to make lunches of peanut butter & jelly sandwiches.  This helped keep the cost of our trip low.  Our walks and bicycle rides were completely free.  We considered seeing a movie, but there wasn't anything we could agree upon.

I am providing our modest itinerary and detailed packing list for our own documentation, but also I would hope it would help you consider what you would bring if you had to carry everything.  There are things I missed, but I used everything I brought.  It felt really good to simplify our lives if only for a week.

It was really fun to be able to take the bus.  The 5-cities transit was awesome!  We bought a $5 all-day pass for the day we went to San Luis Obispo, since we took two different bus lines.  Even though we were early for the bus (which runs only once per hour) we took the opportunity to do some "Bus Stop Calisthenics." Analogous to my favorite passtime, "Train Yoga."  When you consider the urban landscape one big playground for adults, and stop caring what people think, life can be more fun!


Itinerary

Day 1: Fri. Dec. 30

Boarded train at 3:17pm
Arrived at 7:54pm
Biked to hotel
Dinner at Carl's Jr

Day 2: Sat. Dec. 31

Bike ride to Grover Beach beachfront
Viewing of Monarch Grove
Bike tour of Pismo Beach downtown
Walk to 5 Cities Center, Branch Street
Bus ride back to K Mart
Dinner at AJ Spurs

Day 3: Sun. Jan. 1

Bike ride to Avila Beach
Walk to Grand Avenue
Dinner at Round Table Pizza

Day 4: Mon. Jan. 2

Bus ride to San Luis Obispo
Tour of Mission San Luis Obispo de Tolosa
Shopping at Phoenix Books

Day 5: Tue. Jan. 3

Lunch at Station Grill
Boarded train at 1:55pm
Arrived at 6:50pm
Biked home


Packing List

Outerwear
Raingear + Stocking cap
Light jacket + Windbreaker
Sun hat + Cycling cap
Scarf + Headscarf
Bicycling gloves
Underwear
Undershirts (1 camisole, 3 t-shirts)
Long sleeve cycling jersey
Boxers or panties (5+ pair)
Socks (5+ pair)
Bras (1 sports and 2 regular)
Tops
Hoodie (zip up)
Sunglasses + case + cleaning cloth
Bicycle helmet
Safety vest
Bottoms
Hiking pants (Convertible)
Yoga pants
Dress pants
Cycling shorts
Toiletries
Face wash, lotion, eye cream, serum
Toothpaste/toothbrush
Contact lens case/solution
Chapstick, face SPF 50, body SPF 30
Comb, headband, tampons, medication
Electronics
Phone + Charger
GoPro + Charger
Lights + Charger
Computer + Charger
Music player + Charger
Other
Swimsuit
Resort Dress
Footwear
Cycling & Walking shoes 
Flip-flops

Friday, December 30, 2016

Zion NP Packing List

Outerwear

Coat (heavy)

Jacket (windbreaker)

Hat (stocking)

Scarf

Gloves (ski/waterproof)


Underwear

Tights

Long Underwear

Undershirt (camisole, t-shirt)

Performance shirt (long sleeve)

Boxers (briefs or panties)


Tops

Sweatshirt

Fleece (zip up)

Backpack + water bladder

Sunglasses

Sun hat


Bottoms

Thermal socks

Performance socks (2 pair)

Hiking pants

Hiking boots

Flip-flop (sandals, thongs)


Other

Swimsuit

Snacks (Clif bars)


Monday, December 19, 2016

Bike Racks

We got our Smart Car in August 2011.  Since then, we've taken it on many trips.  We've had to do little things to maintain the car in the last year, such as brakes ($427.69) and new tires ($647.35). These we have had done at Boulevard Auto Repair in Van Nuys.  We get regular service (e.g. oil changes) here at Glendale Lube Center.

Photo credit: Anne Hamersky (January 2012)
In academic years 2011-2012 and 2012-2013, I was driving 80 miles per weekday!  I'm so glad I don't have to do that anymore.  We got rid of our 2nd car in February of 2015 and thank goodness for that.  I overheard two people discussing the Public Transit Subsidy Program at CSUN, specifically in regards to Metrolink.
CSUN employees who opt to use the bus, rail, or train to campus may be eligible for a discount of up to 60% off the cost of the monthly transit pass. The total monthly discount will not exceed $100.
One person was explaining to the other that the discount really starts to pay off when you become a single-car family.  Now we drive when we have to (or want to) but if we don't want to drive, we take the Metrolink train with our bicycles.

April 2015 we got the rack, June 2015 we got the bike (Fuji)
Free2Go Bike Rack (#FREE2GO) $109.00 + $15.00 via Flat Rate USA = $124.00

Becoming a single-car household wasn't without its challenges.  We had a bike rack for our old 4-door Honda Civic, but we needed a way to transport at least one bicycle in the case of an emergency. The first rack we purchased is the Free2Go.  As long as your bike weighs less than 45 pounds, this rack will work.  In fact, it's even my preferred rack for transporting our beach cruiser bike, due to the shape of its frame.  At around 2 pounds, the Free2Go bike rack can even be slipped into your messenger bag or backpack if you are driving a rented SmartCar.  The car-sharing company car2go operates in 9 US cities, including San Diego, but not yet in Los Angeles.


October 2015 we got the bike (Fix-D), October 2016 we got the rack
Thule Helium Aero 3 Bike $399.95 + $189.95 Hitch (U-Haul) + $60 Installation + Tax? = $697.10
Fix-D 700C Road Bike - Silver/Red (28") = $98.09

This year, we upgraded our carrying capacity with a 3-bike rack, which is kind of ironic since we have a 2-passenger car.  It was pretty expensive to get the hitch installed, but we finally got the car paid off so it seemed like the right time to start making modifications (spending the money we would have put into a car payment).  We're considering where to take this rack.  So far, we've used it to go out to Riverside and over to the LA River Bike Path with out-of-town guests.  At 20 pounds, the Thule rack can be installed by one female (me) solo.  It has a load-capacity of 110 pounds.

I'm not wild about the Los Angeles car culture, but there are still some remote areas that are not well-served by public transportation (e.g. Point Mugu) where we would like to camp and bring our bicycles.  I'm still not totally sure what we're doing over the winter break, but it will most likely involve our new bike rack.  Even though we have a really tiny house, we both fantasize about the next bicycles we want to buy.

Saturday, December 3, 2016

Ye Olde Holiday Tyme

How to decorate your bike for the holidays!


$19.99 Fry's Electronics Cosmic Brightz http://www.frys.com/product/8141075
  • 10 feet of LEDs 
  • 3 AA batteries=20+ hours
  • 8 colors
  • Waterproof 

$14.99 per wheel Fry's Electronics Wheel Brightz http://www.frys.com/product/8140975
  • 20 LEDs in clear, flexible tubing
  • 3 AA batteries=48+ hours
  • Durable battery pack attaches onto spokes
  • 8 colors
  • Waterproof

$12.99 for a 2-pack at Target http://www.target.com/p/led-decorative-ultra-slim-wire-multicolor-2pk/-/A-13506341 (or $15.51 at Home Depot) (or $13.38 for Martha Stewart's Brand)
  • 9 Ft long with 36 lights
  • 3 AA Battery Operated
  • Phasing and flashing options
  • 4 colors

$6.99 per light Fry's Electronics Spokelit Green http://www.frys.com/product/6828866
  • 2 Button Cell batteries=20+ hours
  • attaches onto spokes

Then join us on Sunday, December 18th at 5:30pm at Nibley Park in Glendale, CA.  We'll be riding a little over 6 miles at a SLOW pace through neighborhoods.  We'll be enjoying FREE HOT COCOA at Gaucho's Village as well. Bring water, a helmet, and a bike in good working condition. ALL AGES WELCOME!  Kids younger than 8 should be able to ride several miles or be on a safe child carrying device to participate on the ride.


The route is posted here: https://ridewithgps.com/routes/17669774 There will be a competition for "safest and brightest bike" and "safety facts for safe night riding."  Spread the word!

 

Wednesday, November 23, 2016

Greatest Hits

This post is for all the science teachers out there seeking a practical chemistry lesson.  We're constantly encouraging our students to apply critical thinking to real world problems.  We also want them to exercise public speaking skills.  Around this time of year students get bored no matter how exciting the lesson and it's good to get them actively involved in a dynamic lesson to keep them engaged in learning.

I've been keeping this blog for 8 years and periodically I will write about a molecule or a related group of molecules.  I always try to include the chemical name and structure of the molecule.  I printed out the text of each of the posts below and gave students about 20 minutes to read and analyze the content.  I asked them to answer the following 3 questions in an oral presentation using the board:

Tell us about your molecule:

  • What does it do?
  • How does it work?
  • Draw its structure!

I had the students complete this exercise in pairs.  It was one of the most engaging lessons of the entire semester.  After each group made their presentation to the class, we spent the remaining 15 minutes covering the Drug Free Campus Policy information for students.  We talked about how some of the molecular stories were about depressants, stimulants, and club drugs.  We talked about how just because a drug is available by prescription, doesn't mean it isn't dangerous.

If you're interested in receiving the text only of the following blog posts (without all the sidebar and URL information) send me an email and I can send you a .pdf.  It's so important to engage students in the fun and exciting (and practical) applications of chemistry to give them some incentive to learn all the basics we are trying to teach them.  

Even though my class was populated with college freshmen (who have no Organic Chemistry experience) we were able to recognize common substructures in molecules with a common effect in vivo. The students can identify 5- or 6-membered rings, as well as noting heterocyclic rings and sidechain lengths, without formal training in functional groups.

I plan to write my next blog about the class of benzodiazapines including Lorazepam (Ativan) and Alprazolam (Xanax), which share a common substructure.  These molecules have a high potential for abuse.  Stay tuned!


We were able to talk about Kary Mullis in the following class period and how he enjoyed making analogues of LSD until that practice became illegal.  Maybe I can also write about ayahuasca.


Amphetamine: http://bitchonabike.blogspot.com/2016/09/a-bargain-is-not-always-bargain.html
Adderall: http://nyti.ms/2dWJvDY

Antioxidants: http://bitchonabike.blogspot.com/2014/04/nopal-antioxidant.html

NSAIDs: http://bitchonabike.blogspot.com/2009/08/i-dont-like-drugs-but-drugs-like-me.html
Celebrex: https://n.pr/2fhF6Jq

Cycloastragenol: http://bitchonabike.blogspot.com/2012/01/fountain-of-youth.html

Goldenseal: http://bitchonabike.blogspot.com/2011/08/goldenseal-friend-or-foe.html

Henna: http://bitchonabike.blogspot.com/2014/06/my-first-tattoo.html

Isoflavones (Part I): http://bitchonabike.blogspot.com/2011/02/to-soy-or-not-to-soy.html
Isoflavones (Part II): http://bitchonabike.blogspot.com/2011/02/to-soy-or-not-to-soy-part-ii.html

Lithium: http://bitchonabike.blogspot.com/2015/03/lithium-orotate.html

Opioids: http://bitchonabike.blogspot.com/2017/01/opioids.html

Retinoate: http://bitchonabike.blogspot.com/2012/02/advanced-maternal-age.html

Serotonin: http://bitchonabike.blogspot.com/2010/10/selective-serotonin-reuptake-inhibitors.html

Sumatriptan: http://bitchonabike.blogspot.com/2013/09/impatient-scientist.html

Monday, October 31, 2016

MultiModal Weekend (Part III)

Having taken a bike on Friday afternoon, a car on Friday night, and a walk to the bus on Saturday (both ways), we knew we had to take a train on Sunday.  Luckily, it was a CicLAvia (open street) weekend in Downtown LA and we got to ride bicycles from Glendale to MacArthur Park with an awesome group of people.


Since we had spent the majority of the weekend talking about bike advocacy, we cut our CicLAvia experience short and caught the early train back to Glendale.


The nice thing about catching Metrolink is that it is a short 10-12 minute train ride back to Glendale and then a 10-12 minute bike ride back to our house.


Metrolink monthly pass holders (like us) can ride the train system (bus and light rail, too) for free on weekends.  Non-monthly pass holders have access to the entire system by purchasing a $10 weekend pass.  There is now an app that you can use to purchase your Metrolink pass virtually, in case your trip starts with a bus instead of starting at the Metrolink station (like we did). Screenshots from the Metrolink app are shown side-by-side below.

Remember, your bus pass will not get you on the light rail.  Nor will your light rail pass get you onto the Metrolink train.  But a Metrolink ticket will get you on the bus and light rail.

Last, but not least, if you're going for a short trip, your one-way ticket on Metrolink will be cheaper than a Day Pass.  But if you're traveling a long way (Lancaster to LA Union Station, which costs $11.50 one way) then the Day Pass will be cheaper even if you're not returning on that day to your original destination.  The app makes it easier to comparison shop on your own schedule, without having to mess around with the ticket vending machine (TVM) at the actual train depot.

There is an agreement between Amtrak and the Glendale Beeline and several other bus providers for free transfers, but LA Metro buses only offer a discount to Amtrak passengers, according to Fox 5 News San Diego. If you do take Amtrak, you must call and make a bike reservation (800-USA-RAIL).  Roll-on service is possible on the Pacific Surfliner AND the Coast Starlight.  I guess Amtrak also has a mobile app, but I don't have experience with it yet.


Also, I learned that a Metro TAP card is how you use Metro Bike Share, but I haven't tried it myself yet. Have you?