Oblivion 2013

This film was totally brilliant! I love it!

It was released on 19th April here in Poland. Back then, I saw the ads on some small billboards in Warsaw, but I couldn’t figure out what the title was because the title was in Polish, Niepamiec. And I have not seen a lot of trailers like I used to, lately. So that’s one of the reason for not knowing about this movie in advance hahah. Blame it all on Pharmacology

Oblivion 2013

Oblivion 2013

Jack & Julia Harper – Oblivion 2013

Watch online

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By the way, I’m now doing Paediatrics clinics. Today, my group went to see an 8-year-old boy, Marcin, who is suffering from Haemophilia type A. He was admitted to the hospital for physiotherapy session. He currently receives infusion of factor VIII concentrate.

Our doctor mentioned that before the factor infusion was introduced as management for Haemophilia, plasma and cryoprecipitate (Cryoprecipitated Antihaemophilic Factor) or “cryo” for short was used. Nowadays, they are largely replaced by the factor concentrates.

Marcin is going to stay in the ward for another two weeks. Our doctor said that he has no parents, he is an orphan so it might be another reason for him not being really cheerful. When our doctor said that, my heart sank. He was cute, a little bit shy and all but by looking at his face I knew (or felt like I knew) that he is lonely.

He was very well-behaved though. He was cooperative and didn’t mind us doing the whole body examination on him. It took quite a while but he was very patient with us. At the end of the interview, our doctor asked him to show his “treasures” which he kept inside the drawer of the side table. He showed us some cards of some football players.

I hope that he would be healthy for all his life. And hopefully the factor concentrate would prevent him from getting crippled in the future. I hope that he will be happy

Tags: 2013, Andrea Riseborough, clinics, colony, cryo, cryoprecipitate, drones, Factor VIII, factor VIII concentrate, film, Haemophilia, haemophillia, julia harper, Julia Rusakowa, Morgan Freeman, Niepamiec, Oblivion, Olga Kurylenko, orphan, paediatrics, pharmacology, Poland, Sally, sci-fi, space, Tet, Tom Cruise, Victoria, Warsaw

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Administration - Part 1 of what seems like 1,000,000 things to remember

As I said, I’m using a ton of resources but truly am leveraging Mosby’s Memory Cards to help me stay organized.

Today’s topic is all about Medication Administration.

Six Rights of Medication Administration and Routes of Medication

The Six Rights of Medication Administration are:

MedicationRouteTimePatientDosageDocumentation

Routes of Administration

Enteral or oral (most common) – ingested into gastrointestinal tract.- Liquid or pillParenteral – injected into blood or body tissues (intravenous (IV), intramuscular (IM), subcutaneous (SC).  – Think of a shotTopical – absorbed across skin or mucous membrane – Think of a patch or a creamInhalation – inhaled directly into the lung to elicit local effects – Think of an inhalerRectal or vaginal suppository – inserted for local effects – Thinking you figured this out.

 Well, this is only Day 1 of many more and I am thinking this may not be as bad as I thought…..hang in there and just learn these items.   Tomorrow we’ll take on the Nursing Implications!

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Naloxone: The Antidote (aka The Cruel Awakening)

This drug is the OPPOSITE OF FUN.  For real.  You do NOT want naloxone (Narcan) unless you absolutely, positively need it.  Naloxone is an opioid receptor antagonist.  Think about it.  Owwwwww.

The most important thing to know about naloxone is that it is the best way to rescue someone that has either overdosed on or had a bad reaction to morphine/heroin/any opioid.  The reason it is NOT a fun drug is that it actually kicks morphine (and other opioid agonists) off the mu receptors, essentially reversing the peaceful, pain-free, near-death experience and throwing it into the complete opposite.

It’s certainly a nice thing to have around, and an absolute necessity when you are giving an opioid analgesic, but please, use it with care!

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“We’re evolving towards systems pharmacology”

A theoretical chemist by training, Jordi Mestres started up the chemogenomics lab of the IMIM, currently part of the GRIB, in 2003. The structure of the group, made up of graduates and doctors in chemistry, biology, biotechnology and computer science, perfectly reflects its three main lines of research: molecules, proteins and programming to predict the interaction between them.

“We apply our predictions to both drug discovery and chemical biology”, summarises Mestres. This last discipline consists of using small molecules to sound out biology, for example inhibiting a protein to understand its function. According to the scientist from Girona the optimisation of these chemical probes is just as important as that for drugs. “They have been used for years as if they were selective for a single target protein, but now we are beginning to understand that they are not.”

In fact, drugs do not owe their effectiveness to the fact that they are very selective for a single target, rather to their affinity for a whole group of proteins. “We are evolving towards systems pharmacology, where the drug is placed in the context of all of the proteins with which it can potentially interact, the organs it can reach, the polymorphisms of the person that takes the drug, and so on”, explains the head of the group.

 A multitude of projects

The laboratory is involved in several European projects, including Open PHACTS, where they have developed an interactive tool to show ligand-protein interactions via the web (www.pharmatrek.org), and eTOX coordinated by Ferran Sanz (GRIB), where they design new methods to predict drug safety profiles. “Drug safety profiles are not really known until they are on sale and the drug is exposed to millions of users. If we were able to anticipate any adverse effects before entering the market and we understood the mechanisms, we could modify the structure of the drug in advance”, reasons Mestres.

They also look at ethnopharmacology, and try to explain how medicinal plants work. “We have made predictions for 109 plants and we are trying to rationalise their use for cardiovascular disease.”

In collaboration with Pilar Navarro (IMIM) they have found molecules inhibiting the formation of b-amyloid plaques that work as well or better than memantine, an Alzheimer’s drug. The research was funded by a pharmaceutical company and has generated two patents. In total, the group has four patents in collaboration with companies and one with the CSIC.

The creation of a spin-off

In some cases, they are asked by companies or other groups to prioritise which molecules to use at the beginning of a research project or to predict the proteins of active molecules in phenotypic trials. This was the origin of Chemotargets, in 2006, where currently three people work. “The students who were doing this could not publish anything, so we created this spin-off service”, explains the head of the group.

Chemotargets is still going and has quite a lot of work. They are currently designing the screening collection for the Karolinska Institute in Stockholm, with more than 10,000 molecules. They did something similar for the CRG, creating a list of small molecules that interact with proteins of interest to the researchers. Lately, they have also been contracted by the Swiss foundation ‘Medicines for Malaria Venture’ (MMV) to investigate the action of 400 antimalarials identified in phenotypic tests. “Chemotargets predicts targets for each molecule. Afterwards it is necessary to confirm the predictions experimentally, and this work is usually outsourced”.

It is, according to Mestres, the future of drug design. “Everything will be done from an office in a skyscraper in Manhattan or London, outsourcing molecule design to companies like Chemotargets, synthesis to a chemical company in China, and the trial to a pharmacology firm in India”, he predicts. “In fact it is already happening with the big pharmaceutical companies -they close their research centres, but do not abandon projects: they subcontract them out”.

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Tobacco Products..... A Desire for Unwanted Death

WHO Framework Convention on Tobacco Control (FCTC) defines tobacco product as completely or partially made from tobacco. Actually, these products are small, nicotine delivery devices which are categorized as follows:

Rolls: These are the products that are made by rolling tobacco in a wrapper (paper, tobacco leaf, tendu leaf etc.). This category includes Cigar, Cigarette, Bidi, Kretek, Roll-your-own cigarettes etc.Pipes: these are made by metals or glass and hold a small amount of tobacco at one end where it is ignited in order to inhale smoke from the other end. Water pipe (Hookah) is also included in this category.Snuffs: This category includes powdered tobacco specially made for inhaling through the nose.Chewable: these are made by processing the tobacco with lime and other flavoring substances for chewing or sucking purpose. Gutkha, Khaini etc. are the popular forms included in this category.

Cigarette is the most popular form, of all above mentioned products, worldwide. However in India, Bidis constitute more than 50% of total tobacco consumption. Bidis out sale cigarettes by 8/1. Bidis are made by rolling crude, unprocessed tobacco in tendu or tamburni leaf that gives it peculiar taste and a disguising natural look. Various surveys indicate that natural appearance is one of the major reasons for consumption of this tiny Indian cigarette among a large fraction of population. Kreteks are manufactured in Indonesia and mainly contain cloves along with tobacco. Cigar is made by rolling the tobacco in a tobacco leaf itself.

Tobacco product manufacturers are focusing on allurement of the tobacco users by changing the information about their products to more appealing with a safety point of view. Mild/low tar cigarettes or herbal cigarettes are good examples of that misleading, though effective, way of marketing the very same lethal product.

Manufacturers put their business ahead of public health despite having undisputed data on toxic effects of tobacco. They are very much aware about the nature of highly addictive component of tobacco that is Nicotine. Once you start getting a high with these products you become addicted to it with an alarmingly fast rate. This starting point is what manufacturers keep in mind when they launch a product in the market. Their prime target is young population as they can pay money for these nicotine delivery devices for an expected longer period.

Interesting fact is that all types of tobacco products are consumed for nicotine only, which has pharmacological activities. It is the only component that has stimulatory effects on nervous system. However, people might not be aware about those more than 4,000 chemicals that are released when a cigarette is smoked, or those cancer causing agents (around 100) present in all types of tobacco either smoked or smoke less.

Is it perceptible to get yourself exposed to highly noxious agents just for a single stimulatory one? Which itself is causing various kinds of debilities. Cigarettes are known to cause a great number of morbidity and mortality by developing cardiovascular diseases (CVDs), Lung Inflammatory diseases (Chronic Obstructive Pulmonary Disease, Bronchitis, Pulmonary Fibrosis, Asthma, Emphysema), Lung cancer and cancers of other organs. If, on a crude level, we combine the number of deaths caused by cigarettes, it can outnumber the deaths caused by other reasons.

   It is a preventable cause of such kind of deaths and we can avoid this danger to our lives. We just need to be aware about the toxic manifestations of tobacco products and the misleading promotion of these products by manufacturers.

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Parkinson's Disease Drugs

Point: Parkinson’s Disease is due to loss of dopaminergic neurons with an excess of cholinergic activity resulting. The goal of therapy is to increase CNS dopaminergic activity. Dopamine can’t cross the BBB until it reacts with tyrosine to form Levodopa. Levodopa is administered with other  agents (illustrated below) to prevent its degradation and improve its bioavailability.

Visual Aid: The picture helps  demonstrate the agents administered to improve dopamine delivery. Think of the BBB as the front door to the house (brain). Notice the stop sign turning dopamine away as it tries to enter. Outside the front door  there is a CARport with a DOBerman pinscher (Carbidopa). It scares off DOPA-decarboxylase and protects dopamine from degradation in the periphery. Also notice that the COMeT monster (COMT) is kept at bay by AL CAPONE (Tolcapone) who prevents COMT from degrading levodopa. Once in the CNS, levodopa is converted to dopamine. Officer SLY GLEEN (Selegiline) prevents MAO-B from degrading dopamine in the CNS thereby increasing its bioavailability.

Summary of drugs and their target:

Carbidopa-DOPA-decarboxylase
Tolcapone-COMT
Selegiline-MAO-B

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Muscarinic Receptors: Blood Vessels, Sweat*, and Tears**

Sit back and relax after a meal, recline and let your heart slow down, feel the warmth of your extremities…and secrete those fluids!

Ewwwwww…secretions!!  Diaphoresis, urination, vasodilation, lactation, and all kinds sweaty gooey things coming out and doing their thing!  In a very crude and stunted way, this is a main function of the parasympathetic nervous system. 

Muscarinic receptors are usually what we are talking about when we refer to anything “cholinergic”.  This is because their function works to balance the agonism of adrenergic (sympathomimetic!) receptors, thus allowing our body to essentially work “normally”.  So if you remember nothing else at all about muscarinic agonists (or “cholinergic drugs”), do remember the words REST and WET.  Now, to delve into more detail.  Woot!

There are 5 subtypes of muscarinic receptor, and they are all G Protein Coupled Receptors (if you don’t know what I’m talking about see “Our Friends the Receptors” in the basic pharmacology section).  Let’s make that easier and cut out the last two, because they are mostly in the CNS and the jury is still out on what exactly they do.  Actually, the jury is still out on almost every receptor type, but researchers have dedicated their work to studying them and make new discoveries every day!

Anyway, for our purposes there are 3 muscarinic subtypes: M1, M2, and M3.  I recommend remembering them as head, heart, and trunk.  While not entirely encompassing, it’s a start!

1.  M1:  Head.  These guys are in the CNS, on salivary glands, and surrounding your esophagus.  So they help regulate parasympathetic signals from the CNS, help to begin the digestive process (which starts with salivation!), signal the stomach to secrete digestive “juices”, and speed along signals to your organs.

2. M2:  Heart.  These are the important receptors that help regulate the conduction speed and contractile force of the atria in your heart.  They, too, are in the CNS and on the heart itself!  In the atria, they counter the effect of sympathetic stimulation by relaxing how hard those amazing atrial cardiomyocytes are pumping…Negative Inotropic! They also monitor signals from the CNS to ease up on the stimulation given to the AV node and slowing the conduction…Negative dromotropic!

3.  M3:  Trunk (and Eye…I know, this messes it up).  These guys are in the CNS, on the ciliary bodies in your eye (remember the little guys that control your pupil?), on your bronchioles, on your blood vessels, and all over your digestive system, from start to finish!  The most important thing to remember is that they help you digest by enhancing secretions from the salivary glands down to the colon.  Pretty amazing, huh?  In your lungs, they actually cause a bit of bronchoconstriction, which is why we have to be very careful using muscarinic agonists.  One of the coolest (IMHO) features of M3 receptors is how they affect the blood vessels.  I will nerd out on this in another post, so for now, just remember vasodilitation!  In the eyes, they cause myosis, or pupillary constriction.

Can you guess what the opthamologist drops in your eyes to make your pupils HUGE?

So there you go.  Secretions and rest (mostly). Here is a summary of what muscarinic receptors are in charge of:

1.  Secretions along the digestive tract

2. Reduced contractility and conduction of the atria

3. Vasodilitation

4. Myosis

5. Speeding along autonomic signals

6. Bronchoconstriction

There was a lot of information in this post!  I needed help too (one can only pack so much into the Rolodex), so I consulted the humongous bag of notes I have.  These notes came from two lecturers:

Robert Mouton at Concordia University, Austin, TX.  He is a cell biologist and incredible professor of pharmacology and physiology.

Dr. Sue Greenfield at Columbia University, New York, NY.  She is a nurse practitioner and PhD who has a vast clinical knowledge of drugs and has the amazing ability to put their use into simple terms!

*But…why didn’t we talk about sweat??  Well, as I was writing this, I realized that the simplest way to remember muscarinic drugs is by their parasympathetic activity.  So…diaphoresis is indeed a muscarinic activity, but it is modulated by the sympathetic nervous system.  I know, I know!!  It’s very complicated.  If I were you, I’d just remember that most things wet come from M receptors.

**But…why didn’t we talk about tears??  Lacrimation is one of those tricky things that happen via the CNS, more specifically the cranial nerves.  The “tear signal” from that good old cranial nerve VII is modulated by muscarinic receptors.  Again, don’t cry over it.  Just assume that wet is muscarinic and if you are very curious then look it up!

So I sacrificed complete accuracy for a good title.

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