Pharmacokinetics Overview

Pharmacokinetics Overview

(Absorption and distribution of drugs)

The study of the time course of drugs and their metabolites in the body (what the body does to the drug) consisting of:

administration

absorption

distribution

metabolism

excretion

Administration

Enteral (passes through intestine)

oral (mouth)

buccal/sublingual (applied in cheek/under tongue)

Gastrosomy (surgical opening through the abdomen into the stomach)

Topical (applied directly)

Nasal

Rectal

Ophthalmic (eyes)

Parentral (injection)

Intravenous (into veins)

intramuscular (into muscles)

intradermal (within layers of skin)

subcutaneous (under the skin)

Drug molecules move around the body either through bulk flow (bloodstream, lymphatics or cerebrospinal fluid) or diffusion (molecule by molecule over short distances)

Absorption 

Passage of drug from its site of administration into plasma - important for all routes except intravenous injection.

Injection

IV = fastest route of administration

bolus injection = very high concentration of drug

rate limiting factors = diffusion through tissues and removal by local blood flow

Drugs need to pass through membranes (cell membranes, epithelial barriers, vascular endothelium, blood-brain barrier, placenta barrier etc) via

passive diffusion through lipids

carrier-mediated

passage through membrane pores/ion channels

pinocytosis (ingestion into a cell by the budding of small vesicles from the cell membrane)

Diffusion through lipid

non-polar molecules can dissolve freely in membrane lipids

the rate is determined by the permeability coefficient (P)(solubility in the membrane and diffusibility) and the concentration difference across the membrane

pH and Ionisation

Many drugs are weak acids or weak bases

exist in unionised or ionised forms

pH = balance between the two forms

ionised forms have low lipid solubility

uncharged however the drug is usually lipid soluble

ionisation affects:

rate of drug permeation through membranes

steady state distribution of drug molecules between aqueous compartments if pH difference exists between them

Therefore:

urinary acidification accelerates the excretion of weak bases and slows that of weak acids

alkalisation has opposite effect

increasing plasma pH causes weak acids to be extracted from CNS into plasma

Reducing plasma pH causes weakly acidic drugs to become concentrated in CNS, increasing neurotoxicity

Bioavailibility

Bioavailibility (F) indicates the fraction of an orally administered dose that reaches systemic circulation intact, taking into account both absorption and local metabolic degradation

determined by comparison between oral and IV absorption

affected by:

drug preparation

variation in enzyme activity of gut

gastric pH

intestinal motility

Volume of Distribution

Vd is defined as the volume of fluid required to contain the total amount, Q, of drug in the body at the same concentration as that present in the plasma, Cp

determined by relative strength of binding between drug and tissue compared with drug and plasma proteins

tight binding to tissue but not plasma –> drug appears to be dissolved in large volume –> large Vd (eg chloropromazine)

tight binding to plasma –> V can be very close to blood volume –> low Vd (eg warfarin)

KINETICS OF ELIMINATION

Bookmark Printables (via Google Drive) 

Would you guys be interested in free bookmark printables?

I’ve never done these before so feedback would be appreciated (good or bad!). If you guys like these then I could maybe make a better (more pretty) series or even custom ones.   

More free printables here. 

Some of my favourite printables! Firstly,apologies for the awful photos,it’s a rainy day and by the time I got home it was getting dark but I just had to post them.

Daily Agenda from @euphoricstudying I really,really like this printable. It’s clean and big,no messing about. However,I liked the grid background on the original which didn’t show up very well on my printed version? This may have just been an issue with the printer(although the grid showed up on another printable so maybe not). All in all this is such a useful printable! I’m likely to use it at the weekends/for particularly busy days and it does everything I need,and well!

To-Do List and Homework Planner from @meddiestudies This is such a cute little to do list!!!! It has just enough spaces so as not to be too overwhelming,I like to use it alongside the daily agenda for specific homework tasks as opposed to general appointments and reminders/scheduling. A really lovely little page!!

Weekly Planner from @arystudies I love love love this planner. It’s everything I could hope for in a weekly planner;simple,grid background, black and white so I can add my own colour schemes weekly! I love the fact Saturday and Sunday have smaller boxes since my weekdays are busier than my weekends what with school. I would definitely recommend trying this planner out,it even has a lovely little water tracker!

Yearly Planner from @emmastudies This is a lovely calendar,I went for the purple colour but there are a few to choose from to match everyone’s tastes. It’s a lovely and simple lay out with plenty of space in each box and some really lovely lettering for the months!

MEDICAL BOOKS

If you’re looking for some medical (non-textbook) books to read in your limited amount of spare time, check out some of my favorites below:

The House of God by Samuel Shem

A classic pre-medical school book. It details residency life in the 1970s. You can talk about this book with almost any medical student or attending. It is practically a medical school requirement. 

Intern: A Doctor’s Initiation by Sandeep Jauhar

A more modern look into medicine residency intern year from the perspective of Cardiologist Dr. Sandeep Jauhar. Comes with the highs and lows you can expect. After having been through 6 months of residency, I would say it is very accurate.

Gifted Hands: The Ben Carson Story by Ben Carson. Just because I find Ben Carson incompetent as a politician does not mean I do not respect him as a doctor. He is a phenomenal pediatric neurosurgeon and this book details his story.

On Doctoring: Stories, Poems, Essays by Richard Reynolds

A book of stories and poems from doctors throughout time and also from famous poets and authors depicting their views of medicine.

Private Practice: In the Early Twentieth-Century Medical Office of Dr. Richard Cabot by Christopher Crenner

An interesting look into a Boston medicine clinic from the early 1900′s. With excerpts from old patient notes which I found very interesting. 

And if you have an interest is something more dark:

Blind Eye by James B. Stewart

The real story of a doctor murderer from the 1990′s who killed multiple patients without getting caught for several years.

Devil in the White City by Erik Larson 

The story of the World’s Fair in Chicago in the late 1800′s. A great look into the history of Chicago and the murderous doctor who roamed its streets.

And lastly:

The Hitchhiker’s Guide to the Galaxy by Douglas Adams. Just a great book in general. My favorite.

Suggested by other users:

The Making of a Woman Surgeon by Dr. Elizabeth Morgan

Suggested by http://thetay-in-the-757.tumblr.com

This book is my all time favorite, as I am a female aspiring to work in the healthcare system myself. Dr. Morgan chronicles her own journey in the male-dominated arena of medicine in the 1970s and 1980s, as she struggles to maintain an appropriate balance between remaining empathetic towards her patients and yet must toe the line of not becoming too emotionally involved with her patients so that she burns out, as well as maintaining her own femininity in a man’s world.

When Breath Become Air by Dr. Paul Kalanithi

Suggested by http://nandemokandemo.tumblr.com

When Breath Becomes Air is an autobiography written by an esteemed neurosurgeon who discovers he has Stage IV lung cancer in his final stages of residency. It appeals to not only medical students, with his profound impressions of cadaver dissection and his first life and deaths, but also to current medical professionals by questioning philosophical domains of mortality and what a meaningful life is, as well as to non-medical professionals with moving thoughts on family, life, death and meaning. It is not a novel to be missed by any person.