Pharmacokinetics of Alcohol and Cannabis Flashcards
Predict how lipid solubility of alcohol and cannabis will influence distribution Calculate amount of alcohol administered within specific doses and predict likely bioavailability for each dose Compare and contrast how alcohol and cannabis are absorbed and distributed throughout the body Compare and contrast alcohol and cannabis metabolism and evaluate how active metabolites contribute to drug effect
How do the octanol:water partition coefficients of alcohol and cannabis differ and how does this impact how they can cross membranes?
Delta 9-THC is extremely lipid soluble, over 6000. This allows it to cross plasma membranes very very easily. However, Ethanol’s coefficient is less than 0.1 but it is a small uncharged molecule so can simply diffuse across, and also by aqueous pores.
What are the calculations associated with figuring out alcohol dosage? What’s the average metabolism?
ABV x 0.7 x volume consumed per 100mL = amount of alcohol in a drink.
ABV x volume (ml) / 1000 = Units
The average person metabolises 10mg/100mL every 40 mins
What factors influence the rate of metabolism of alcohol?
Having a high tolerance means you metabolise alcoho l quicker meaning it has less effect. Having deficiencies in or defective alcohol metabolising enzymes would lead to a slower rate of metabolism
What are the most common administration sites for alcohol and cannabis? What is the optimal absorption site within these administration routes?
Alcohol is oral, cannabis is inhalational. Oral is small intestine, alveoli for inhalational. The plasma membrane of microvilli in small intestine and the plasma membrane of alveoli are very thin and suited to diffusion, and also very closely associated with capillaries.
Which factors limit the arrival of drugs at the target site for the inhalational route?
50% gets deep enough into the lungs to allow for absorption through the alveoli. The rest is swallowed, breathed back out, or undergoes pyrolysis (heat induced composition in smoked substances).
Limiting factors of arrival of drugs at drug targets for oral route?
If the drug is in the stomach, it can’t access the small intestine microvilli. If the stomach is empty, any liquid promotes stomach emptying as theres no need to digest and physically disperse the liquid so it goes straight into the small intestine. If the stomach is full with solid food, stomach emptying is slowed because the food needs to be digested and physically dispersed and so the alcohol is retained in the stomach. It’s absorbed much much slower.
How do the factors affecting distribution apply to cannabis and alcohol?
Capillary permeability has little effect because cannabis is lipophilic and ethanol small enough to cross membranes.
Most THCs are over 90% bound to plasma proteins so arent free to enter tissues. This means they’re metabolised slow, and so eliminated slower. Alcohol is less than 10% bound, so would be metabolised much faster than cannabis.
Regional blood flow is the same for alcohol and cannabis, ie. most drug is delivered to areas with high blood flow.
How does tissue localisation affect the distribution of alcohol?
Alcohol has a very low octanol:water partition coefficient which means its water soluble so it prefers to be in tissues with a high water content. This means it prefers to be in plasma rather than brain, but doesn’t necessarily mean that alcohol doesn’t leave the plasma and go to the brain. Brain has high water content and high regional blood flow.
How is alcohol distributed between the blood and the brain?
When the BAC is high, there is steep gradient between blood and tissues, so alcohol moves into the tissues. At equilibrium is reached, alcohol is present at higher concentrations in the blood due to the higher water content of the blood compared to the brain
How does tissue localisation affect the distribution of cannabis?
Cannabis has a very high octanol:water partition coefficient, which means it prefers to be in tissues with a high lipid content. More cannabis accumulates in the brain at equilibrium due to its high fat content. Adipose tissue has a very low blood flow so drugs would be not be delivered there very much, but cannabis still accumulates there due to its high lipid solubility. What drugs do go there are retain, if they are lipid soluble
Why are women more susceptible to alcohol?
Because they have lower body water (higher body fat) so the alcohol is less diluted in them so has stronger effects
Why are obese people more sensitive to cannabis?
Cannabis accumulates in their body fat more.
What is the process of metabolism for alcohol? Describe the product and type of reaction
Alcohol –> Acetaldehyde –> Acetic Acid. This happens via oxidation steps. All oxidations start with a hydroxylation step but as ethanol is such a simple molecule it doesnt need it. Also, ethanol can be metabolised in other ways, as can all other drugs, if they bump into the appropriate enzymes.
What is the process of metabolism for cannabis? Describe the product and type of reaction
Delta 9 THC –> 11-OH-THC –> 11-Nor-9-Hydroxy-THC
11-Nor-9-Hydroxy-THC is THC-COOH.
9-THC is very lipid soluble so is reabsorbed at the kidney tubule. The metabolites have polar groups so are more water soluble but still have a lipid soluble component so are excreted slowly.
Describe the phase 2 metabolism of cannabis
THC-COOH gets conjugated with a glucuronide which adds a big polar component which makes it far easier to excrete.
