Drugs of Abuse

Question 1

What are the main drugs of abuse? (5)

Answer 1

Narcotic Analgesics
General CNS depressants
Anxiolytics
Psychomotor stimulants
Psychomimetics

Question 2

Nicotine cellular effect on CNS (5)

Answer 2

Pre- & postsynaptic causing increased transmitter release & neuronal excitation
Desensitisation also occurs
Chronic admin’ leads to receptor increase
Overall effect= balance between neuronal excitation and desensitisation

Question 3

Where are nicotine receptors found? (3)

Answer 3

Acts on α4β2 subtype of nACHR
In the cortex and hippocampus, role in cognitive function and ventral tegmental area, DA neurons to nucleus accumbens (reward pathway)

Question 4

Nicotine effects on a spinal level (3)

Answer 4

Inhibition of spinal reflexes; skeletal muscle relaxation (shows on EMG), stimulation of inhibitory Renshaw cells

Higher level brain function affected by dose and situation= ‘wake up’ or ‘calm down’ effects, EEG studies seem to support claims

Question 5

Nicotine effects on a peripheral level (4)

Answer 5

Stimulation of autonomic ganglia & sensory receptors:

Tachycardia, increased C.O. & arterial pressure, reduced GI motility, sweating.

Effects decline on chronic exposure, CNS effects remain

Smokers mean weight 4 kg less than non-smokers= reduced food intake

Question 6

How much nicotine is in cigarettes? (2)

Answer 6

Cigarette contains 9-17 mg nicotine, 10% absorbed

Question 7

How is nicotine in cigarettes absorbed? (2)

Answer 7

Rapidly absorbed from lungs, poorly from the mouth and nasopharynx= inhalation required

Question 8

Pharmacokinetics of nicotine in cigarettes (3)

Answer 8

Average cigarette over 10 mins= plasma nicotine concentration 100-200 nmol/l

Falling by half in 10 mins following (more slowly 1-2 hrs- 30 nmol/l after 90 mins)

Slower decline due to hepatic oxidation to inactive metabolite cotinine (long plasma t1/2)

Question 9

Pharmacokinetics of nicotine patch (2)

Answer 9

Plasma concentration rises to 75-150 nmol/l & remain constant

Question 10

Pharmacokinetics of gum or nasal spray (2)

Answer 10

Causes plasma concentration intermediate between actual smoking and patch

Question 11

Tolerance and dependance of nicotine (5)

Answer 11

Large dose peripheral- desensitisation block

Less central tolerance

Physical withdrawal syndrome (2-3 weeks):
- irritability, impaired psychomotor performance, aggression, sleep disturbances
- Alleviated by nicotine and amphetamine

Psychological ‘craving’ continues

Question 12

Harmful effects of smoking (6)

Answer 12

Life expectancy shortened; biggest cause of preventable death worldwide- 10% of deaths worldwide

Nicotine also excreted in breast milk sufficiently to cause tachycardia in infant

Tar and Irritants- NO2 & formaldehyde

Nicotine- retarded foetal development due to vasoconstriction

CO- heart & vascular disease due to up to 15% of haemoglobin carboxylated

Increased oxidative stress- responsible for artherogenesis and COPD

Question 13

What are the smoking deaths due to? (4)

Answer 13

Deaths due to:
Cancer- 90% of lung cancers smoking-related (tar)

CHD & vascular disease- studies suggest nicotine has direct effect along with CO

Chronic bronchitis- tar and other irritants

Harmful effects in pregnancy- reduces birth weight, increases perinatal mortality (28%), spontaneous abortion, premature delivery

Question 14

Drug treatment of nicotine dependence (4)

Answer 14

Two main ways:
- nicotine replacement therapy. Successful if given with psychotherapy (25% success)

• buproprion (Zyban) NA/DA reuptake blocker. But can lower seizure threshold & contraindicated if history of eating disorder or bipolar
• Animal trials of vaccines (nicotine-protein complex) promising- human clinical trials in progress

Question 15

What is ethanol? (3)

Answer 15

Most widely consumed drug of abuse
Low pharmacological potency
Average consumption is 10 litres/year (pure ethanol)

Question 16

How is ethanol expressed? (2)

Answer 16

Often expressed as units, 1 unit= 8 g (10 mL)

21 units/week men, 14 for women; about 33% men & 13% women exceed this

Question 17

Theories of ethanol action (5)

Answer 17

Enhancement of GABA-mediated inhibition on GABAA (similar to benzodiazepines)

Inhibition of Ca2+ entry (inhibits NT release)

Inhibition of NMDAR function

Inhibition of adenosine transport

Endogenous opioids due to action of naltrexone reducing the reward effects

Question 18

Effect of ethanol on CNS (1)

Answer 18

Increases neuronal activity by disinhibition in reward pathways

Question 19

Acute effects of ethanol (4)

Answer 19

Well known including slurred speech, motor inco-ordination, increased self-confidence, euphoria, new ability to dance.

High level of intoxication produces large mood swings (150 mg/ 100 mL)

Judgement fails- most notably ability to drive (80 mg/100 mL legal drink-drive limit in UK)

Coma occurs at around 400 and death (respiratory failure) at 500 mg/100 mL

Question 20

Other effects of ethanol (4)

Answer 20

Cutaneous vasodilation (central)- ‘beer overcoat’

Salivary & gastric secretion- reflex from irritant action (heavy spirit consumption= damaged gastric mucosa)

Endocrine- anterior pituitary stimulated to release ACTH- pseudo-Cushing’s

Diuresis- inhibition of antidiuretic hormone secretion

Question 21

Chronic effects of ethanol (5)

Answer 21

Hypertension- withdrawal increases sympathetic activity

Irreversible neurological effects
- direct from ethanol
- indirect from metabolites (acetaldehyde)

Most chronic alcoholics develop irreversible dementia with thinning of cerebral cortex

Significant enhancement of other CNS depressants- opiates, antidepressants, antipsychotics, benzodiazepines…..death

Males- feminisation due to impaired testicular steroid synthesis and hepatic enzymes increased rate of testosterone inactivation

Question 22

How does ethanol affect the liver? (5)

Answer 22

Increased fat accumulation (fatty liver)&raquo_space; Hepatitis (inflammation of liver)&raquo_space; Irreversible hepatic necrosis

Varices around liver can bleed suddenly….death by internal haemorrhage

Malnutrition, particularly thiamine deficiency (CNS damage)

Question 23

How does ethanol affect fetal development (3)

Answer 23

Fetal alcohol syndrome (FAS)
Alcohol-related neurodevelopmental disorder (ARND)
FAS & ARND

Question 24

What is FAS? (8)

Answer 24

Abnormal facial development, wide-set eyes, small cheekbones

Reduced cranial circumference

Retarded growth

Mental retardation

Cardiac abnormalities, malformation of eyes and ears

3/1000 live births

30% children born to alcoholic mothers

Mostly in binge drinkers

Question 25

What is ARND? (3)

Answer 25

Behavioural problems
Cognitive & motor deficits
9/1000 live birth

Question 26

What is FAS and RAND? (2)

Answer 26

Physical abnormalities appear related to early pregnancy (4 weeks), brain development later (10 weeks)

Weeks before pregnancy recognised crucial

Question 27

Ethanol absorption (3)

Answer 27

Ethanol is rapidly absorbed- stomach
First-pass saturation kinetics- fraction removed decreases as liver ethanol conc’ increases
Rapid absorption & portal vein conc’ high, mostly escapes into systemic circulation

Question 28

Metabolism of ethanol (4)

Answer 28

90% metabolised, 5-10% excreted unchanged in expired air & urine

Metabolism almost entirely in liver- successive oxidations with cofactor nicotinamide adenine dinucleotide (NAD+)

Availability of NAD limits oxidation to approx’ 8 g/hour in normal adults

Question 29

Pharmacokinetics of ethanol (1)

Answer 29

Constant ratio between alveolar air & blood (35 μg/100 ml & 80 mg/100 ml respectively)

Question 30

Cocaine transport (3)

Answer 30

Neuronal uptake is the most important mechanism by which the action of noradrenaline is brought to an end

Transporter has a low affinity for circulating adrenaline

Transporter inhibited by cocaine

Question 31

What effect does cocaine have? (2)

Answer 31

Cocaine produces euphoria & increased motor activity etc are due to blockade of uptake of noradrenaline, dopamine and serotinin (via NAT, DAT & SERT) in the CNS

Question 32

Adverse effects of cocaine (3)

Answer 32

Tachycardia and hypertension = severe cardiovascular toxicity both acute and chronic

Question 33

Vasoconstriction produced by cocaine (3)

Answer 33

A hole in the septum is a common complication from cocaine abuse because the drug is a potent vasoconstrictor
The hole also no longer has tissue to absorb the drug so other areas get affected
As enough support is destroyed, the nose can collapse