Lecture 2: Routes of Administration Flashcards
What the inherited risk of addiction (%)?
40-60% risk
What are three problems with studies involving inheritance of addiction?
- difficult to access adoption records
- adopted children are not representative of the entire population
- study designs do not negate prenatal drug exposure (which is more likely in adoptive children than general population)
Describe the findings of research that had to do with examining of candidate genes?
looking at specific gene variation and drug abuse/depedence
examples: looking at dopamine transporter protein (DAT), dopamine receptor (D2), and mu opiod receptors (OPRM1)
some studies say that theres a link between predisposition between genes and addictions and some say no
very unreliable data
What is one critic of examining candidate genes?
the bias and how theres an expectation to find specific genes which makes the research hard to analyze
What is the Genome-wide association studies (GWAS)?
instead of comparing specific genes, the GWAS compares all genes in the human genome between dependant and non-dependant subjects
- this will show any differences in genetic locations
what was the results of GWAS?
showed the addiction is highly polygenic (lots of genes involved)
Also found that theres alot of genes that are involved in neuronal adhesion (imp. for plasticity)
other genes included those for DNA/RNA processing, trasncriptional regulation, cell structures
the genes show differences regardless of the drug abused and represent small but many changes in alot of genes
what are some critisims associated with traditional genetic approaches (pre-GWAS)?
they lack reproducibility, which is partly due to the fact that its hard to define someone who is truly dependent because theres a large spectrum of dependence
what are some critisims of GWAS?
that they didnt have statistical analysis before the experiment and variable studies across people
what are 4 administrative routes of drugs that are abused?
- mouth (eating/drinking) –> has to bypass the liver, which will metabolize most of the drug and leave less in the blood stream
- injection –> intramuscular injection is injecting drug into the muscle and it depends on how vascularized the muscle is and this can differ the absoprtion rate. Intravenous injection is faster and its injecting it right into the vein which is immediate access to the circulation… it passes from the heart to the brain in 10s or less
- inhalation —> fastest route because it goes to the brain quicker since it bypasses the left side of the heart. Has strongest abuse rate
- insufflation (snorting)
What makes a route of administration be the fastest?
- they have the highest peak concentration in the brain
- they correlate with stronger reported high
- result in the drug being in the brain for a shorter amount of time
what makes a route of administration slow?
- peak concentration is not as high
- high is not as intense
- it is in the brain for a longer period of time
what is the relationship between peak time and residency of the drug in the brain?
they are inversly correlated.
for example, if the drug has a very fast peak time then its residency time in the brain is less
if the drug has a slower peak time, then its residency time in the brain is more
rank the routes of administration from fastest/most intense high to the slowest/less intense high?
- inhalation
- injection
- snorting/snuffing
- ingestion
what are 3 properties of a drug for it to be administered orally?
- must withstand acidic pH and not be deactivated by food, and must be neutral (so that it can pass the gut lining)
- must be able to pass cells lining in the guy –> only lipid soluble drugs can be absorbed
- very lipophillic drugs though can have a problem passing aqueous layer coating the cells in the GI (i.e. why pot brownies have very slow absorption)
What is first pass metabolism?
some drugs might be completely metabolized by enzymes in the liver or gut before they enter general circulation
many drugs, a percentage is metabolized each time it passes through the liver
this is where the concentration of the drug is greatly reduced before it gets to the circulation
what are three ways of injecting drugs?
- intravenous (IV)
- Intramuscular (IM)
- subcutaneous (subQ)
why is IV usually a preferred method of drug intake by users? (4 reasons)
- it goes directly in the circulation
- causes less irritation so you can inject drugs that have contaminants
- you can control and deliver high concentrations
what are 2 very dangerous side effects of using drugs intravenously?
- veins eventually collapse and cause no more blood flow beyond that point
- there are collateral health risks like HIV, hepatitis, bacteria infection
what are the two main factors in determining absorption from IM and subQ injection sites?
- diffusion through the tissue
2. removal by local blood flow
What are three reasons why IM is preferred over subQ?
- aborption is more rapid because better blood supply, and less layers of fat to get throguh
- larger volumes of drug can be administered
- less chance of irritation and necrotic tissue (which is what happens commonly in subQ)
What are three reasons why inhalation is preferred over IV and other routes of administration?
- drug gets to brain faster than IV (5-8 seconds)
- theres is large surface area where drugs can enter the blood stream in the lungs
- blood from lungs gets to the brain rapidly –> blood doesnt have to go from veins into the heart, and then through the lungs and then brain like IV does… so inhalation by passes the heart and goes straight from lungs to brain
What is the downside of inhalation of drugs? what is a way people make up for that?
the dose control is more difficult but depends on the drug amount they are inhaling (i.e. the higher dose of nicotine given to smokers, the less puffs of smoke they take)
what are some other routes of administration?
transdermal (patches), rectal, vaginal, rectal
cocaine snorting –> mucous membrane of the nose
chewing tobacco –> absorbed by mucosa of oral cavity
both avoid liver metabolism on first pass
what kind of drugs have the most abuse potential?
ones that are done IV or smoked (with an exception of marijuana)
i.e. heroine (IV), crack (inhaled cocaine), and amphetamine smoked
