applying PD/PK theory to examplar drugs-Psychoactive drugs; depressants

Question 1

what are depressants

Answer 1

drugs that typically suppress or slow the activity of nerves within the central nervous

Question 2

what is the most potent cannabinoid?

Answer 2

delta9-tetrahydrocannabinoid (delat9-THC)

Question 3

how is the lipid solubility of a drug determined?

Answer 3

octane/water partition coefficient

octane–>liphopilic

Question 4

how can ethanol cross lipid membrane while being water soluble?

Answer 4

lipid membrane are slightly permeable to small uncharged molecules like ethanol so it can diffuse across lipid membranes and access tissues

Question 5

how to calculate the units of alcohol?

Answer 5

alchohol by volumexvolume(mL)/1000

Question 6

how to calculate the amount of absolute alcohol?

Answer 6

alcohol by volumex0.78xvolume per 100mL

Question 7

what is the local driving limit in the UK?

Answer 7

80mg of alcohol/100mL

Question 8

what tissue membrane is more important for alcohol to reach?

Answer 8

small intestine/ileum

Question 9

what tissue membrane is more important for cannabis to reach?

Answer 9

alveoli/alveolus

Question 10

what is the major obstacle of the oral route of administration?

Answer 10

stomach

Question 11

what factors influence drug distribution?

Answer 11

regional blood flow
capillary permeability
tissue localisation
plasma protein binding

Question 12

does capillary permeability have a big impact on the ability of alcohol and cannabis to access tissues? why?

Answer 12

no
because
ethanol –> really small
cannabis –> lipid soluble

Question 13

why would alcohol be metabolised much faster than cannabis?

Answer 13

because most delta9-THC are very highly bound to plasma proteins in the blood and alcohol does not bind to plasma proteins very effectively.
only free drug can be metabolised and eliminated

Question 14

what tissue and organ have the most water content?

Answer 14

blood plasma>liver>brain»>adipose tissue

Question 15

what tissue/organ have the most fat content?

Answer 15

adipose tissue»>liver>brain>blood plasma

Question 16

2 enzymes are responsible for the majority of alcohol metabolism. what are they?

Answer 16

alcohol dehydrogenase -> responsible for 75% of the hepatic metabolism of ethanol to acetaldehyde
aldehyde dehydrogenase –> converts acetaldehyde to acetic acid

Question 17

where can we find these 2 enzymes?

Answer 17

in the stomach

Question 18

do females have more or less alcohol dehydrogenase?

Answer 18

less

Question 19

another enzyme is used for alcohol metabolism. what enzyme is it? when is it unregulated?

Answer 19

cytochrome p450

after chronic alcohol used –> alcohol tolerance

Question 20

do ethanol and delta9-THC have active metabolites?

Answer 20

acetaldehyde –> largely responsible for side effects associated with alcohol
11OH-THC–>very lipid soluble which also have the same known effects of cannabis

Question 21

what is the drug target of cannabis?

Answer 21

cannabinoid receptor

Question 22

what does the activation of the cannabinoid receptor do?

Answer 22

it decreases the activity of adenalyte cyclase which means that it decreases the activity of the cell and therefore have a depressant effect

Question 23

what is andamide?

Answer 23

endogenous agonist of the cannabinoid receptor

Question 24

does alcohol have a specific target?

Answer 24

no

it can induce weak effects on a number of different targets

Question 25

to what receptor can alcohol bind?

Answer 25

opioid receptors that have a number of binding sites

Question 26

how can alcohol have a depressant effect?

Answer 26

it needs to inhibit an excitatory effect or increase an inhibitory factor

Question 27

what are 2 common shared effects of alcohol and cannabis?

Answer 27

inducing memory loss | impairing psychomotor performance

Question 28

what parts of the brain are vital for formation of memory?

Answer 28

dentate gyrus within hippocampus

Question 29

what does the activation of cannabinoid receptors on mitochondria within the dentate gyrus do?

Answer 29

leads to impaired memory formation

Question 30

what parts of the brain are important for psychomotor performance? are cannabinoid present in these areas?

Answer 30

basal ganglia cerebral cortex cerebellum yes

Question 31

what is the most dangerous toxic effect of alcohol?

Answer 31

respiratory depression | in extreme cases: breathing rate could drop so severely -->suffocate

Question 32

can cannabis affect respiration?

Answer 32

a little bit since very little cannabinoid receptors in medulla which provides the impulse to breath

Question 33

what is the major toxic effect associated with cannabis?

Answer 33

psychosis: inability to display appropriate behiavour within a given context

Question 34

will opioid receptor affect GABA?

Answer 34

yes. opioid--> depressant receptor

Question 35

will the bioavailability be affected by the rate of metabolism?

Answer 35

no it will be affected by the stomach (whether it is empty or not)