cocaine toothache drops for children (1885)

Source: wikipedia


Cocaine is a compound found in the leaves of Erythroxylum Coca, and is used in medicinal use for anaesthesia, but is commonly abused in the hydrochloride form (intravenous and insufflation), and its free base form (smoking). 

The usual dose of abuse is 10 – 120mg.  Cocaine’s half life is 1½ hours (Baselt (2004), although Karch (1991) states that it is 40 minutes). 

Cocaine is rapidly inactivated, by hydrolysis of ester links, to benzoylecgonine (which can cause vasoconstriction, and has a half life of 5 – 6 hours).

In the presence of alcohol, cocaethylene is formed, which has a half life of 2 hours, and does not form in the post-mortem interval.  Cocaethylene is less active than cocaine. 

Karch (1991) describes cocaine as suffering from redistribution; cocaine and benzoylecgonine degrade in sodium fluoride preserved tubes, but less so than in non-preserved tubes.  Cocaine analysis involved GC-MS, and RIA for benzoylecgonine. 

Cocaine is eliminated in the urine, and its presence in urine is indicative of recent cocaine use.

There is a high affinity “take-up” of cocaine in the brain, but not in the peripheries.

Cocaine has a similar toxicity to amphetamine, as well as a direct cardiac effect (causing ventricular tachycardia, ventricular fibrillation, myocardial infarction, and stroke).


cocaine toxicity


  • Wetli and Fishbain (1985) – average blood cocaine concentration in cocaine-related fatalities 0.6mg/L (0.1 – 0.9mg/L)
  • Spiehler and Reid (1985) – blood cocaine concentrations in cocaine-related fatalities 4.6mg/L (0.04 – 31mg/L); benzoylecgonine concentration 7.9mg/L (0.7 – 31mg/L); brain to blood cocaine ratio in overdose 9.6, whilst ratio of 2.5 found as an “incidental” finding
  • Karch (1991) – greater than 5mg/L usually results in seizures/respiratory arrest whilst an “incidental level” was found in a gunshot wound case of 30mg/L 
  • Wetli and Wright (1979) – fatal intravenous administration 3mg/L; fatal insufflation 4.4mg/L; fatal oral ingestion 9.2mg/L
  • Baselt (2004) – average blood cocaine concentration in fatalities 5.3mg/L (0.9 – 21mg/L); average urine cocaine concentration 42mg/L (0.1 – 215mg/L) 

No upper or lower safe cocaine concentrations have been defined; tolerance from chronic use may be of importance.  Timing of cocaine use cannot be reliably determined by drug analysis alone (Stephens et al 2004/ NAME).

The risk of sudden death increases with cocaethylene some sevenfold (Bunn and Gianni 1992). 


Cocaine is stuff that starts off making you feel just grand and with everything in the garden lovely. It peps you up and you feel you can do twice as much as you usually do. Take too much of it and you get violent mental excitement, delusions [such as insects crawling on the skin] and delerium.

Description of the potential hazards of cocaine given to Hercule Poirot in The Horse of Diomedes (1947), found in the short story collection 'The Labours of Hercules'. Unlike the Diomedes of Thrace of Greek mythology, who raised his mares to be man-eaters by feeding them human flesh, Agatha Christie's General Grant had four wild daughters who subsisted on a diet of cocaine!

See Gerald MC 'The poisonous pen of Agatha Christie', 1993 University of Texas Press (buy it here ...)

when is cocaine the cause of death? (see Karch and Stephens 1991)


Of importance in determining whether cocaine is related to the cause of death is the presence of any cocaine in the blood, in the right circumstances.

The chronic effects of cocaine abuse are more important than the acute cocaine concentration – unless the case involves body packing – due to the chronic effects of cocaine on the heart, and the increased likelihood of arrhythmias.  Cocaine is associated with coronary artery spasm, and infarction and, in the letting of recent cocaine use, the acute effects of cocaine on catecholamine-induced myocardial injury (contraction band necrosis) is thought to cause death following cocaine use.  The severity of contraction band necrosis correlates well with blood cocaine concentrations.

The chronic effects of cocaine have been described as:

  • Accelerated atheroma
  • Microfocal fibrosis (healed contraction band necrosis)
  • Lymphocyte and eosinophil infiltrates (subacute damage)

Microfocal fibrosis, and inflammatory cell infiltrates in the heart can also be seen in amphetamine abuse and phaeochromocytomas. 

Chronic cocaine use is associated with marked habituation and tolerance.


Sauko and Knight state that cocaine use can be associated with acute blood pressure elevations of greater than 300mm of mercury.

myocardial effects of cocaine


  • Intramyocardial vessel spasm leading to ischaemia and arrhythmias
  • Angina/myocardial infarction
  • Coronary artery vasospasm (i.e. an inappropriate vasoconstriction mediated by alpha-adrenergic stimulation, in the face of cocaine-induced hypertension, tachycardia and increased myocardial demand; this phenomenon does not have a good dose response correlation)
  • Enhanced vasospasm in atheromatous coronary arteries
  • Old infarction
  • Endocarditis
  • Eosinophilic myocarditis
  • Onion-skinned intima
  • Acute left ventricular failure

gastrointestinal effects of cocaine abuse (Karch 1991)


  • Ischaemic colitis (endothelial disruption)
  • Peptic ulcers

respiratory system effects of cocaine abuse (Karch 1991)


  • Haemoptysis (crack cocaine)
  • Pulmonary artery hypertrophy (hyperplasia)
  • Eosinophilia (crack cocaine)
  • Pneumothorax/ pneumopericardium
  • Pulmonary oedema (catecholamine excess)

central nervous system effects of cocaine abuse


  • Cocaine leads to mydriasis, blurred vision, headaches, vomiting, vertigo, dystonia, increased reflexes, and myoclonus 
  • Vascular effects – vasculitis; stroke/haemorrhage (? Secondary to berry aneurysm, AV malformation, or even gliomas)
  • Seizures (Jonsson et al 1983)
  • Neurochemistry
    • raised central nervous system dopamine transmission, due to competitive blockade of DA receptors, and stimulation of the release of noradrenaline; mesolimbic dopaminergic system plays key role in mediating euphoria/reward system is abused drugs.
    • Chronic cocaine use leads to a reduced density of D1 receptors in striatum (? tolerance), although some authors state that the density of D1 receptors is up-regulated; unchanged D2 receptors in striatum in non-psychotic users (? Receptor sites increased according to some authors); psychotic users demonstrate a reduction in D2 receptors in the hypothalamus (supporting a hyperthermia effect); kappa opioid receptors may be increased in the amygdala; chronic cocaine use is said to increase dopaminergic neurotransmission due to dopamine uptake blockade and activation of dopamine receptors.

So, there could be a difference in dopamine receptors in the striatum in cocaine users dying of excited delirium versus those dying of cocaine-related deaths without agitation or psychosis.

  • Sampling for dopaminergic receptor analysis involves flash freezing one hemisphere sliced into one centimetre slices.
  • Ryk James (personal communication) states that upregulation of striatal D1 receptors predisposes to sudden cardiac death, in cocaine intoxication cases, but also in other psychiatric disorders, neuroleptic use, hypothermic deaths, and fear/stress.

neuropathology of cocaine abuse


  • Arterial infarcts
  • Subarachnoid haemorrhage
  • Parenchymal haemorrhage
  • Meningitis after nasal erosion
  • Small vessel angiitis and perivascular inflammation
  • Possible rupture of berry aneurysms
  • Possible embolic phenomenon secondary to cocaine-related cardiomyopathy
  • Possible involvement of spinal cord



online resources



A brief history of cocaine. Karch S. 2nd edition CRC Press 2005

Buy it here ...

Search site

© 2020 All rights reserved.

Powered by Webnode