drugs in society part 1

have been to 2 very interesting events about drugs this week

one was the high society exhibition at the wellcome collection

very well put together, thought provoking and, in places, really beautiful

the exhibit is not too large but does contain a good chunk of material

i would strongly encourage you to go

it is just round the corner & public science does not get much better than this

there are several associated events, one, a tour with the curator is on this evening (dec 16 @ 1800-1845)

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my highlights:

1) the home-made crack pipe & the crack pipe art by keith coventry

have never come across a crack pipe before & the delivery device is ingenious

the thinking behind one of keith coventry's pieces was to do with the user's experience of the pipe - they cannot experience any part of the 'moment' except where they are in relation to the pipe - serious addiction

2) drug use through history

cannabis has been used in india for thousands of years

the british used opium (which contains 12% morphine) to gain advantage over other colonising powers in china

the opium was grown (forcibly) in places like bengal & trafficked by the east india company

rich chinese smoked it using beautiful expensive pipes, the poor using simple apparatus (partly to reduce hunger)

there were also interesting insights into the tribal use of various compunds eg peyote cactus

famous users were also detailed, eg freud, coleridge & sherlock holmes (who injected opium until he was weaned by watson)

currently the (illegal) global cannabis industry ($113bn per year) is worth more than coffee ($98bn) or porn ($95bn)

3) animals on drugs

the animal experiments shown were great

NASA gave various substances to spiders & recorded their subsequent webs

the caffeine web is shoddy-looking & full of holes, the cannabis web is meticulous & unfinished

bruce alexander's 'rat park' experiments are also shown

his hypothesis was that well housed rats will be less 'addicted' to morphine

to test this he did a series of experiments comparing rats living in 'rat park', a 200 sq foot rodent paradise with play areas, privacy areas & lots more besides to similar rats living in cages

the 'free' rats were 16 times less likely to drink morphine water compared to caged rats when given a free choice

fascinating stuff!

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lots to think about as we (collectively) will consume large quantities of drugs over the holidays (alcohol, caffeine, whatever ...)

Salaam

a young man who ingested 4.5g of cocaine

we did not see this gentleman and only discussed his case very briefly

however, as a clinical pharmacologist, this was too interesting not to share

we did not get onto signs, symptoms and treatment of cocaine toxicity, but it is an important clinical issue and is worth knowing something about

eMedicine has a decent review

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this gentleman swallowed 4.5g of 'cocaine' wrapped in cling film

my first question was: what is a lethal dose?

we discussed ways of answering this question in the UK, namely toxbase, and the national poisons information service

it turns out that there is a great deal of variability as to what a lethal dose might be, and it depends on the route of administration - IV as little as 20mg, orally or intranasally 500mg-1.4g

another key issue is the purity of the cocaine - most cocaine on sale in the UK is heavily 'cut' for example with lactose, mannitol, baking powder

average purity in the UK around 34%, price £30-50 per gram (data from drug scope)

one 'line' might contain 50-200mg (depending on how big the line is)

one cocaine cigarette might contain 300mg & is more commonly associated with myocardial infarction
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the clinical pharmacology of cocaine is fascinating

cocaine powder is often the hydrochloride salt which is snorted (white lines)

it is made by pulverising coca leaves, then mixing with an alkaline substance and organic solvent and removing leaves to produce coca paste

this paste is often smoked in south america

for transport, the paste is usually converted to cocaine salt (powder) via the addition of hydrochloric acid

this chloride salt has a boiling point of 190+ degrees which means it cannot be inhaled

however it is water soluble, and thus can be absorbed through mucous membranes
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freebase & crack cocaine are made by removing the chloride to leave the base alkaloid

cocaine base sublimates at around 90 degrees - it is thus smokeable
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we did not get onto signs, symptoms & treatment of cocaine toxicity, but it is an important clinical issue and is worth knowing something about

eMedicine has a decent review



Salaam

a 20-year-old woman with a mixed overdose

apologies for the hiatus
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last week aya presented the case of a young woman who took an unspecified amount of paracetamol & aspirin tablets

she phoned her GP fairly soon after ingesting the tablets, and come into casualty soon after

she had a history of self-harm but no previous overdoses

she is managing (?) to study & work part-time
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we discussed the critical issue of timing of the overdose

this is due to the practicalities of using the paracetamol OD nomogram - see below: this can be found in the beginning of the BNF

we said:

- the graph does not start until 4 hours has been reached

- levels can be expressed in 2 different units, either mg/L or mmol/L, clearly it is crucial to know which is used in your lab

- the high risk line includes people who have had their liver enzymes induced or who are malnourished

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we had a short discussion about the nature of drug metabolism

in essence metabolism makes compounds more water-soluble, and hence more likely to be excreted via the kidneys

the enzymes involves are part of the cytochrome p450 system

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we also talked about how not very nice it is to die from paracetamol poisoning

the key measurements on day 2 are prothrombin time (or INR), pH, lactate & creatinine (NB not AST, ALT etc)

any deterioration necessitates a call to your local liver centre

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we touched on the mechanism of the toxicity

paracetamol is normally metabolised by adding a polar group, mostly sulphate or glucuronide

it can also be metabolised to NABQI (N-acetyl-benzoquinoneimine) [normally 10%]

this is a dangerous chemical as it reacts with DNA & cell proteins [it is a strong oxidiser]

NABQI is normally mopped up by glutathione [an anti-oxidant]

when glutathione stores are deplete, cell damage will occur

therefore the antidote is to give glutathione

glutathione is made from 3 amino acids, 2 of which are plentiful in cells

the third, cysteine, is the rate-limiting species, and this is the treatment: N-acetyl-cysteine or NAC [the N-acetyl- bit helps absorption]

the other antidote is (oral) methionine which is more proximal in the synthetic pathway

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this whole anti-oxidant pathway is worth being aware of 

a lot of current research in a wide variety of conditions, from IHD to autism, involves these pathways

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we mentioned the need to give NAC IV at 3 different infusion rates

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other issues we covered:

- aspirin OD, clinical & metabolic features, and treatment (alkanise urine ± dialysis)

- high risk features for recurrent suicide attempts

- social isolation & the buffering effect of friends

Salaam

sabih