Lecture 2: Routes of Administration

Question 1

What the inherited risk of addiction (%)?

Answer 1

40-60% risk

Question 2

What are three problems with studies involving inheritance of addiction?

Answer 2

1. difficult to access adoption records
2. adopted children are not representative of the entire population
3. study designs do not negate prenatal drug exposure (which is more likely in adoptive children than general population)

Question 3

Describe the findings of research that had to do with examining of candidate genes?

Answer 3

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

Question 4

What is one critic of examining candidate genes?

Answer 4

the bias and how theres an expectation to find specific genes which makes the research hard to analyze

Question 5

What is the Genome-wide association studies (GWAS)?

Answer 5

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

Question 6

what was the results of GWAS?

Answer 6

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

Question 7

what are some critisims associated with traditional genetic approaches (pre-GWAS)?

Answer 7

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

Question 8

what are some critisims of GWAS?

Answer 8

that they didnt have statistical analysis before the experiment and variable studies across people

Question 9

what are 4 administrative routes of drugs that are abused?

Answer 9

1. mouth (eating/drinking) –> has to bypass the liver, which will metabolize most of the drug and leave less in the blood stream
2. 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
3. inhalation —> fastest route because it goes to the brain quicker since it bypasses the left side of the heart. Has strongest abuse rate
4. insufflation (snorting)

Question 10

What makes a route of administration be the fastest?

Answer 10

1. they have the highest peak concentration in the brain
2. they correlate with stronger reported high
3. result in the drug being in the brain for a shorter amount of time

Question 11

what makes a route of administration slow?

Answer 11

1. peak concentration is not as high
2. high is not as intense
3. it is in the brain for a longer period of time

Question 12

what is the relationship between peak time and residency of the drug in the brain?

Answer 12

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

Question 13

rank the routes of administration from fastest/most intense high to the slowest/less intense high?

Answer 13

1. inhalation
2. injection
3. snorting/snuffing
4. ingestion

Question 14

what are 3 properties of a drug for it to be administered orally?

Answer 14

1. must withstand acidic pH and not be deactivated by food, and must be neutral (so that it can pass the gut lining)
2. must be able to pass cells lining in the guy –> only lipid soluble drugs can be absorbed
3. 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)

Question 15

What is first pass metabolism?

Answer 15

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

Question 16

what are three ways of injecting drugs?

Answer 16

1. intravenous (IV)
2. Intramuscular (IM)
3. subcutaneous (subQ)

Question 17

why is IV usually a preferred method of drug intake by users? (4 reasons)

Answer 17

1. it goes directly in the circulation
2. causes less irritation so you can inject drugs that have contaminants
3. you can control and deliver high concentrations

Question 18

what are 2 very dangerous side effects of using drugs intravenously?

Answer 18

1. veins eventually collapse and cause no more blood flow beyond that point
2. there are collateral health risks like HIV, hepatitis, bacteria infection

Question 19

what are the two main factors in determining absorption from IM and subQ injection sites?

Answer 19

1. diffusion through the tissue

2. removal by local blood flow

Question 20

What are three reasons why IM is preferred over subQ?

Answer 20

1. aborption is more rapid because better blood supply, and less layers of fat to get throguh
2. larger volumes of drug can be administered
3. less chance of irritation and necrotic tissue (which is what happens commonly in subQ)

Question 21

What are three reasons why inhalation is preferred over IV and other routes of administration?

Answer 21

1. drug gets to brain faster than IV (5-8 seconds)
2. theres is large surface area where drugs can enter the blood stream in the lungs
3. 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

Question 22

What is the downside of inhalation of drugs? what is a way people make up for that?

Answer 22

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)

Question 23

what are some other routes of administration?

Answer 23

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

Question 24

what kind of drugs have the most abuse potential?

Answer 24

ones that are done IV or smoked (with an exception of marijuana)

i.e. heroine (IV), crack (inhaled cocaine), and amphetamine smoked

Question 25

what types of drugs have the lowest abuse potentials?

Answer 25

hallucinogens like LSD< mescaline, psilocybin

Question 26

what is pharmacokinetics and ADME?

Answer 26

it is ADME: absorption, distribution, metabolism and excretion

1. the drug gets administered into the body
2. the drug gets absorbed and distributed
3. all drugs eventually make it to the liver and get metabolized/inactivated
4. metabolites of drug will get excreted via kidneys..sweat glands…lungs
5. metabolites will turn into excretion products: feces, urine, water vapour..etc..

Question 27

what does the amount of drug in the plasma depend on (3 things)?

Answer 27

1. rate of absorption
2. rate of excretion
3. rate of metabolism

most drugs are removed by either excretion, or metabolism or a combo

Question 28

which enzymes in the liver are responsible for metabolism?

Answer 28

CYP450

Question 29

what is the drug half life?

Answer 29

the time it takes for the concentration of the drug in the plasma to fall 50%

1 half life: 100% to 50%
2nd half life: 50% to 25%

the half-lives occur due to excretion and metabolism

most drug effects die out at 4 or 5 half lives

Question 30

what is a dose response curve?

Answer 30

dose response curves describe the relationshio between the amount of drug in the system and the response it produces

theres a max response for any given effect at which a certain dose beyond will cause no increase in response

this is used to measure how safe a drug is

for example for ethanol

the x axis is the dose of alcohol and the y axis is the percentage of individuals showing the effect

the top of the graph shows 3 conditions where its measuring the dose of alcohol and the % of individuals who show the condition

i.e. at low doses of alcohol, 50% of people show slow reaction time
at moderate doses of alcohol 50% of people show ataxia
at high doses of alcohol 50% of people go into a coma

Question 31

what does comparisons of dose response curves for different conditions/effects tell us?

Answer 31

tells us about the saftey of the drug

the difference between the concentration of the drug that is toxic in 50% of subjects (TD50) and the concentration that produces the desired affect in 50% of patients (ED50) provides information regarding saftey

Question 32

what is the therapeutic index?

Answer 32

TD50/ED50 = Therapeutic index (TI)

its the measurement of space between a dose’s desired affect and the dose that kills

the mores space between these two the safer the drug and less likely it can kill u

for example for LSD, the amount that gets u high is wayyyyy less than the amount it takes to kill u

in alcohol, the amount it takes to get u drunk, is closer to the amount that kill us (i.e. TI of 10)

in heroine its 6