Drugs of abuse

Question 1

When is it important to consider a toxicological cause?

Answer 1

pt is:

• difficult
• uncooperative
• cannot remember what they have been doing or explain what is wrong
• violent

Question 2

What are examples of stimulants?

Answer 2

amfetamines - dexies, MDMA, speed, MDEA
cocaine
piperazines
cathinones
synthetic cathinones

Question 3

What are examples of sedatives/dissociatives?

Answer 3

alcohol
opiates
GHB/GBL
ketamine

Question 4

What are examples of hallucinogens?

Answer 4

Magic mushrooms
LSD
Phenylethylamines
Synthetic tryptamines

Question 5

What are examples of cannabinoids?

Answer 5

CB1 and CB2 receptor agonists = biggest problem nowadays

Question 6

What are the 2 preparations of cocaine that are abused?

Answer 6

cocaine hydrochloride - snorting
cocaine base - “freebase” or “crack cocaine” - crystals of relatively pure cocaine without hydrochloride moiety for smoking

Question 7

What is cathinones?

Answer 7

khat plant been chewed for centries by indigenous populations due to its amfetamine like stimulant properties

Question 8

What is mephedrone?

Answer 8

A synthetic derivative of cathinone - exploded in UK market in 2009 - marketed as “bath salts”, pond cleaner and plant food
it has an additional methyl group added to it
class B substance
More derivatives are being developed - mexedrone

Question 9

What are the clinical features of stimulants?

Answer 9

increased alertness and self-confidence
euphoria and extrovert behaviour
increased talkativeness with rapid speech
loss of desire to eat or sleep
dilated pupils, tachycardia, hypertension
tremor, hypertonia, hyperreflexia, convulsions
agitation, paranoid delusions, hallucinations
rhabdomyolysis
hyperthermia
cardiac arrhythmias and cardiomyopathy
intracerebral and subarachnoid haemorrhage
acute renal failure
fulminant hepatic failure

Question 10

What is the management for stimulants?

Answer 10

symptomatic and supportive measures

• diazepam 10mg IV, repeat as necessary
• for hyperthermia - active cooling (cooled fluids, ice packs), possibly dantrolene (interferes with Ca efflux in skeletal muscle cells reducing contraction which reduces ridigity which can drive hyperthermia)

Question 11

What is the predominant alkaloid in opium poppy?

Answer 11

morphine 
other opiates (sedatives): heroin = diacetylmorphine

Question 12

What does it mean by heroin being a prodrug?

Answer 12

Converted to 6-MAM by esterase in the blood
then in the liver and brain 6-MAM is converted to morphine
- look for 6-MAM in the urine to determine if they’ve taken heroin

Question 13

How is heroin take and what makes it easier to cross the BBB?

Answer 13

Injecting, snorting or smoking - rapidly metabolised as it prevents first-pass metabolism
presence of acetyl groups increases lipid solubility and allows rapid passage across BBB
deacetylation occurs in the CNS to release 6-MAM then morphine

Question 14

What is the MOA of morphine?

Answer 14

Mu receptor agonist 
- analgesia 
- euphoria - makes people addicted 
effects are mediated mainly by dopaminergic pathways 
opioids also have a sedative effect

Question 15

What are the other effects of heroin?

Answer 15

sedation 
suppression of cough reflex
miosis (parasympathetic effect)
constipation 
Rare
- pulmonary oedema, cardiac conduction abnormalities

Question 16

What does excessive mu receptor stimulation cause?

Answer 16

coma

respiratory depression with low pO2 and high pCO2 - a respiratory acidosis

Question 17

What happens to people that become addicted to heroin?

Answer 17

frequent heroin admin associated with tolerance and physical dependence

Question 18

What is the management plan for heroin poisoning ?

Answer 18

ABC vital
naloxone = opiate receptor competitive antagonist- administered IV, IM or intratracheally, T1/2 = 30-60 mins, repeated doses usually required

Question 19

What is methodone and what is it used for?

Answer 19

synthetic opioid used as a heroin substitute
long half life - 20-50 hours
prescribed to mitigate opiate withdrawal symptoms in pts wanting to stop heroin
ideally methodone dose should be tapered down gradually to zero

Question 20

What are some examples of phenylethylamines?

Answer 20

NBoMe agents
- 251-NBoMe - potent serotonergic effects (high affinity for 5ht2a R) - causes hallucinations
Benzofurans
- 6-APB; benzofury - serotonin-NA-dopamine reuptake inhibitors

Question 21

What are the features of phenylethylamines ?

Answer 21

tachycardia
hypertension 
agitation and aggression 
visual and auditory hallucination s
seizures
elevated CK activity (rhabdomyolysis)

Question 22

What are the features of cannabis poisoning?

Answer 22

due to tetrahydrocannabinoids:

• euphoria
• distorted and heightened images, colours and sounds
• visual and auditory hallucinations
• confusion and depersonalisation
• panic
• psychosis

Question 23

How can cannabis be smoked?

Answer 23

synthetic cannabinoids sprayed onto smokeable plant material

Question 24

What is the MOA of synthetic cannabinoids?

Answer 24

full agonists at the cannabinoid receptors, CB1 and CB2
THC = only a partial agonist
synthetic is 10-100x more potent
now being sold in e-cigarettes

Question 25

What are the features of synthetic cannabinoids?

Answer 25

nausea and vomiting 
sinus tachycardia
coma 
acute respiratory failure - this can make you think they have take opiates 
agitation, paranoia
seizures
rarely MI, stroke, AKI