Lecture 1 - Routes of drug administration, the journey through the body and psychopharmacology

Question 1

Intro to drugs: what are drugs?

Answer 1

• Drugs manipulate brain chemistry
• Judgements made about drugs are societal creations (good or bad)
• Drugs have aversive effects (short and long term)
• It is considered an addiction when it has a long-term negative effect on the life of an individual and the person cannot cease use

Question 2

What is psychopharmacology?

Answer 2

• The study of drug-induced changes in mood, cognition and behaviour
• Drugs are prescribed medications, legal recreational substances or illegal recreational substances
• Drugs come from natural (plant, animal) sources or synthetic (manufactured) sources
• Drugs act on receptors in neurons to induce physiological and/or psychological changes
• Drug action is the specific interaction between drugs and their target sites or receptors
• Drug effect refers to the action of a drug on the brain and body

Question 3

What are some routes of administration?

Answer 3

• Buccal
• Rectal
• Ocular
• Vaginal
• Oral
• Cutaneous
• Transdermal
• Inhalation
• Injection
• Nasal

Question 4

What is pharmacokinetics?

Answer 4

• The route of administration causes dramatic differences in the onset, intensity, and duration of a drug’s effect
• Slower onset of drug action the more gradual the build up of the effects and the longer it will last (White, 1991)

Question 5

Study: Routes of administration in rural vs. urban dug users in USA (Young, Havens & Leukefeld, 2010)

Answer 5

• 212 rural users vs. 111 urban users
• Prescription drug abuse (e.g., OxyCodone
• Urban users more likely to swallow drugs
  Rural most likely to snort drugs
• Alternative routs of administration were more likely in rural populations
• Linked to drug problem severity - higher in rural populations

Question 6

Study: Effects of ROA of Heroin on transition to regular use (Hines et al., 2017)

Answer 6

• 395 heroin users in London
• Looked at different speed of transition from first use to daily use according to ROA - injecting, snorting, smoking (chasing)
• Those injecting almost 5 times more likely to progress to daily use within 1-3 weeks of first use than other methods
• Implications for interventions and cultural norms

Question 7

What are some cultural differences in routes of administration?

Answer 7

• Cultural norms and national/local legal policies can influence ROAs for certain substances
• E.g., legal prescription opiates in USA versus intravenous heroin use
• Changing global views on cannabis and tobacco have affected ROAs
• Also changes in technology - e.g., vaping has increased the oral route

Question 8

Study: Cross-cultural differences in cannabis ROAs (Hindocha et al., 2016)

Answer 8

• Over 33,000 people from 12 countries in Europe, USA, Canada, Brazil, Mexico, Australia and New zealand
• 66% smoked cannabis with tobacco globally - most common in Europe (>77%) but uncommon in American countries (<16%)
• Using non-tobacco ROAs associated with desire and motivation to use less tobacco
• Consistent with image of smoking in USA - implications for health and interventions

Question 9

Study: Differences in cannabis ROAs according to legislation (Borodovsky et al., 2016)

Answer 9

• 2800 PTs surveyed from US states
• Various states surveyed in some cannabis legal for medical purposes (MML - medical marijuana laws), some not legal
• Higher incidence for vaping and edibles in MML states
• Longer duration MML, higher incidence of vaping and edibles - possibly related to higher number of dispensaries

Question 10

Absorption into the bloodstream - Pharmacokinetics (Rang, Dale & Flower, 2007)

Answer 10

• The more barriers (cellular) a drug has to travel through to reach the brain, the slower the effect and the more likely the drug is to be degraded
• Degree to which drug is soluble in lipids
• Degree of ionisation - ionised forms less likely to cross cellular membrane than deionised
• Size of molecule (smaller = faster)
• Difference in drug concentration on either side of the membrane i.e., diffusion (greater difference, faster crossing)

Question 11

What are the different absorption methods?

Answer 11

• Intravenous = no absorption, direct delivery to the blood stream and move to site of drug action
• Inhalation = difference in chemical concentration from lung to blood stream always high, so rapid, high lipid solubility and small particles
• Mucous membrane = several layers of cells to cross but aided by difference in concentration
• Oral = very slow, often poor because of degradation by stomach acid and enzymes

Question 12

What is drug distribution?

Answer 12

The journey through the body following absorption:
- Stores in body tissue
- Remains in blood stream
- Metabolised
All of the properties that lead to rapid absorption can lead to more distribution and less drug getting to the brain (i.e., crossing membranes easily)

Question 13

What is the importance of the blood-brain barrier?

Answer 13

• A drug must penetrate the blood-brain barrier to take effect
  The defensive system prevents potentially-damaging molecules from entering our brain
• Drugs of abuse have been developed to pass the BBB easily
• New pharmaceuticals being developed must take this into account

Question 14

Case study: Heroin vs. Morphine

Answer 14

• They are both opiates - heroin derivative of morphine
• Heroin is more lipid soluble, so crosses BBB more easily
• Heroin only lasts a couple of minutes in the body then it is converted to morphine when entering the brain

Question 15

What is OxyContin?

Answer 15

• A sustained-release oxycodone preparation
• Potent opioid
• Purdue Pharma introduced OxyContin in 1996
• $48million in 1996 to almost $1.1billion in revenue in 2000

Question 16

Is OxyContin a better drug than alternatives?

Answer 16

• Huge controversy over the prescribing of it
• Marketed as safer and more acceptable
• No advantages over other potent opioids
• Hale et al., 1999 - randomised double-blind studies comparing OxyContin given every 12 hours with immediate-release comparable efficacy and safety for use with chronic back pain
• Findings backed up by Chou et al., 2003

Question 17

Statistics about opioid use in the UK

Answer 17

• Estimated 330,000 high-risk opioid users in the UK (0.5% population) - European Monitoring Centre for Drugs and Drug Addiction (2018)
• 2,551 deaths from opioids in 2023 in England and Wales - around half of all drug-related deaths (rising for 11th year in a row)
• Study from Wales looking at opioid-related deaths from 2012-2015 suggests heroin doesn’t account for the majority of deaths, although it is the single drug responsible for most deaths (Fuller et al., 2022)

Question 18

What is drug elimination?

Answer 18

• Body works to eliminate drug through metabolism (break down of drug into metabolites that are either active or inactive) and excretion - lungs, sweat, saliva, urine
• Reverse of absorption
• Metabolism tends to take place in the liver
• Excreted by kidneys

Question 19

What is drug half-life?

Answer 19

• The plasma concentration of a drug is halved after one elimination half-life
• In each succeeding half-life drug is eliminated
• After one half-life the amount of drug remaining in the body is 50%
• After two half-lives 25% etc
• After 4 half-lives the amount of drug (6.25%) is considered to be negligible regarding its therapeutic effects