Cocaine and nicotine Flashcards Preview

LCRS 1 - Pharmacology > Cocaine and nicotine > Flashcards

Flashcards in Cocaine and nicotine Deck (25)
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1
Q

What is cocaine?

A

Plant-based alkaloid from leaves of Erythroxlyum coca

2
Q

What are the different forms of cocaine?

A

Cocaine HCl - heat labile
Crack
Freebase

3
Q

Summarise the administration and absorption of cocaine

A

Oral < intranasal < IV < inhalation

IV and inhalation - seconds

  • Inhalation - extremely rapid absorption – plasma conc = 500–1000 ng/mL (freebase)
  • Cocaine HCl is heat labile
  • Rapid absorption also achieved if cocaine HCl is injected i.v.
  • Snorting (cocaine HCl) – absorbed through mucous membranes lining sinuses; results in slower absorption – 100–500 ng/mL
4
Q

Why does oral administration of cocaine give a very slow rate of onset?

A
  • Cocaine has a high pKa (8.7)
  • In stomach, cocaine is mostly ionised
  • Slows down absorption as it doesn’t cross membrane easily
  • But has a prolonged action
5
Q

How is cocaine metabolised?

A
  • Mostly in liver into inactive metabolites (mainly ecgonine methyl ester and benzoylecgonine on first passage)
  • Cleared from urine quickly
  • Half-life = 90 mins
  • Both metabolites, account for 75–90% of cocaine metabolism
  • Also broken down by cholinesterases
  • Some in plasma so can be metabolised in blood straight away
6
Q

Why is cocaine so addictive?

A

The quicker you associate the euphoric effect with taking the drug, the more addictive it is

  1. Powerful euphoric effects
  2. That come on quickly (fast onset)
  3. And leave quickly (active cocaine doesn’t last long in blood)
7
Q

How can cocaine act as a local anaesthetic?

A

High dose
Blocks Na channels
Blocks nerve conduction

8
Q

How does cocaine cause euphoria?

A
  • NAcc presynaptic monoamine transporter blocker
  • Inhibits reuptake of dopamine in NAcc
  • Dopamine remains in synapse for longer
    Prolonged effects of dopamine
    Euphoria
9
Q

How does cocaine affect dopamine’s affinity and efficacy for the dopamine receptor?

A
  • It doesn’t

- Just increases number of dopamine molecules in synapse at 1 given time

10
Q

What are the mild/moderate effects of cocaine?

A
  • Mood amplification: euphoria, dysphoria
  • Heightened energy
  • Sleep disturbance, insomina
  • Motor excitement, restlessness
  • Talkativeness
  • Hyperactive ideation
  • Increased libido
  • Anger, verbal aggression
  • Mild-moderate anorexia
  • Inflated self-esteem
11
Q

What are the severe effects of cocaine?

A
  • Irritability, hostility, anxiety, fear, withdrawal
  • Extreme energy or exhaustion
  • Total insomnia
  • Compulsive motor stereotypies
  • Rambling, incoherent speech
  • Disjointed flight of ideas
  • Decreased libido
  • Possible extreme violence
  • Total anorexia
  • Delusions of grandiosity
12
Q

How does cocaine affect the CVS?

A

Strong link between cocaine use and MI:

  1. Increased symp output
  2. Vasoconstriction and platelet activation
  3. Atherosclerosis and vessel narrowing
  4. Heart must do MORE WORK
  5. DECREASED O2 SUPPLY

If severe enough:
Tissue ischaemia –> MI –> death

Also:
Prompt seizures
Vasoconstriction –> reduced blood flow to brain –> heat build-up in areas –> hyperpyrexia –> seizures, can –> epilepsy

13
Q

What is nicotine?

A

Plant-based alkaloid from Nicotiana tabacum

14
Q

How can nicotine be administered? Compare bioavailability and rate of onset

A

Spray 20-50%
Gum 50-70%
Cigarette 20% - NOT PARTICULARLY EFFICIENT
Patch 70%

Inhalation has rapid onset but effects are lost quickly

Onset = seconds

15
Q

Why is there no buccal absorption of nicotine?

A

pKa 7.9
Cigarette smoke is acidic
Nicotine is ionised tf cannot be absorbed

16
Q

How is nicotine metabolised?

A
Liver
Nicotine --> cotinine
Rapid clearance in urine
Hepatic CYP2A6 - 70-80%
Half life = 1-4 hours
Tissue half life = 2-3 hours
17
Q

Why is nicotine so addictive?

A

Rapidly broken down tf keep smoking to keep blood [nicotine] high

18
Q

How does nicotine cause euphoria?

A

Binds to and activates nicotinic AChR on cell body of dopaminergic VTA neurone
Na influx activates dopaminergic neurone
Increased firing rate
Increased dopamine secretion from NAcc

19
Q

How does nicotine affect the CVS?

A

↑ blood coagulation.
↑ myocardial work
↓ oxygen carrying capacity of blood (due to CO)
Coronary and peripheral vasoconstriction
↑ LDL and VLDL, FFA and ↓ HDL
↑ risk for atherosclerosis, myocardial infarction, cardiovascular disease

20
Q

Why do chronic smokers tend to put on weight once they stop?

A

Nicotine increases metabolic rate

Decreases appetite

21
Q

How does nicotine affect neurological systems?

A

Seems to provide some protection

  1. Parkinson’s Disease
    Increases brain CYPs
    Increases ability to metabolise neurotoxins
  2. Alzheimer’s Disease
    Decreases B-amyloid toxicity
    Decreases amyloid precursor protein
22
Q

Summarise the pharmacokinetics of nicotine

A
  • Particulate droplets reach the small airways and alveoli
  • Rapid absorption from the lung (faster than i.v.)
  • Distributes rapidly to different tissues, incl the brain (within 10-20s)
  • Chronic smokers – Plasma nicotine levels between 20-40ng/ml
  • Elimination half life – 2-3h
  • Extensive metabolism in liver (lung and brain) to cotinine (70-80%) + other metabolites
23
Q

Summarise the pharmacodynamics of nicotine

A

Low dose – sympathetic activation via peripheral chemoreceptors (or direct effect on brain) → ↑ HR and BP

Higher doses – binds to nicotinic cholinergic receptors; ganglionic stimulation and catecholamine release from the adrenals

Very high dose – ganglionic blockade and possibly vagal stimulation

24
Q

What effect does nicotine have on the reward pathway?

A

Nicotinic receptors located somatodendritically on dopaminergic VTA neurones – directly ↑ firing rate

25
Q

What are the endocrine effects of nicotine

A

↑ACTH/cortisol