Module 3.1.1 (Treatment of Nicotine Abuse) Flashcards

1
Q

How long does CNS effects take when nicotine is absorbed pulmonary? Where does nictonine act?

A

Occur in as little as 7 seconds with pulmonary absorption

> At neuronal level nicotine acts on nAChRs

> Chronic nicotine administration –> increase in the number of nAChRs –> an adaptive response to prolonged receptor desensitisation

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2
Q

What are the two broad classes of nicotoinic receptors?

> Made up of five subunits that traverse the membrane surrounding a central pore

> Two Alpha, one Beta, one Gamma and one Delta

A

muscle-type (NM) and neuronal-type (NN)

  • both result in excitatory opening of Na+/K+ channels –> increased Ca2+ conductance
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3
Q

What type of channels are nicotinic receptors? What does activation by ACh cause?

A

Nicotinic receptors (nAChRs) are ligand-gated ion channels

  • Activation by ACh causes rapid (millisecond) increase in permeability to Na+ and Ca2+ , depolarisation and excitation
  • ACh must bind to both the a-subunits –> open channel
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4
Q

Where is the NicotinicN receptor found? What effects does it have in the CNS when activated (e.g. by smoking)?

A
  • Autonomic ganglia
  • Adrenal medulla
  • Sensory nerve terminals
  • Many regions of the central nervous system (CNS)

In CNS

  • pre-synaptic and post-synaptic locations
  • presynaptic nerve terminals of neurones which secrete dopamine, ACh, and glutamate.
  • Activation of such receptors by nicotine facilitate the release of these transmitters, and thus increase their actions in the brain.
  • At spinal level –> inhibits spinal reflexes –> skeletal muscle relaxation
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5
Q

What are the pharmacological actions of nicotine? What does it act on and what does it release

A

Stimulant and depressant actions

  • Increased alertness
  • Muscle relaxation

> Acts on nicotinic acetylcholine receptors in CNS and adrenal glands releasing adrenaline and noradrenaline

Also release many neurotransmitters in CNS:

> acetlycholine enhances memory and concentration

> endorphins decreasing pain and anxiety

> dopamine trigges brain’s reward circuits

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6
Q

What are the cellular effects and behavioural effects of nicotine?

A

Behavioural effects

  • Rewarding, pleasurable properties associated with increased activity of the mesolimbic dopaminergic pathway
  • Increases alertness
  • Decreases anxiety and tension
  • Facilitates learning

Cellular effect

  • Acts on nicotinic receptors –> neuronal excitation
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7
Q

Peripheral effects of nicotine are due mainly to ganglionic stimulation, what are these effects?

A
  • Nausea & vomiting
  • Tachycardia, increased cardiac output
  • Increased blood pressure
  • Increased gut motility
  • Sweating
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8
Q

For nictoine

A) What are other acute effects (clue, surge of catecholamines …)

B) short half life and intense effects causes..

C) withdrawal effects

A

A)

  • Surge of catecholamines causes sudden increase in glucose, BP, respiration and heart rate. Also suppresses insulin output from pancreas leading to elevated BSL

B)

  • Causes nicotine to be highly re‐inforcing

C)

  • Irritability, anxiety, dysphoria, restlessness, decreased heart rate, increased appetite, reduced concentration
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9
Q

How is nicotine metabolised? How about the active metabolite cotinine?

A

Nicotine is metabolised, mainly in the liver, within 1-2 hours.

  • The active metabolite, cotinine, has a long t1/2, and can be used in blood/urine tests to monitor smoking habits.

nicotine half life = 30 minutes

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10
Q

What are some adverse effects of nicotine?

A
  • Smoking reduces life expectancy
  • Ischaemic heart disease

> both nicotine and CO may be responsible

  • Cancer

> Lung, bladder and prostate cancer

> Carcinogenic tars are responsible

  • Smoking during pregnancy

> Lowers birth weight

> Retards childhood development

> Increases abortion rate

> Increased perinatal mortality

stimulates both NicotinicN and NicotinicM receptors (see image for more)

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11
Q

Tolerance, physical dependence and compulsive use (psychological dependence) are all seen with nicotine use. Explain why

A

Nicotine is highly addictive –> excitation of mesolimbic pathway = increased dopamine release

  • Rapid tolerance –> The effects of nicotine associated with peripheral ganglionic –> desensitisation of nAChR
  • Tolerance to the central effects of nicotine (arousal) is much less than in the periphery
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12
Q

What are the some symptomns of physical withdrawal syndrome of nicotine? How long does it last?

A

increased irritability

impaired performance of psychomotor tasks, aggressiveness

sleep disturbance

> Less severe than opioids

> Can be alleviated by nicotine or amphetamine

> Last for 2-3 weeks

> Craving may last for longer –> risk of relapse

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13
Q

What is used to alleviate nicotine withdrawal syndrome?

A
  • Nicotine Replacement Therapy (NRT)
  • Varenciline
  • Bupropion
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14
Q

What is nicotine replacement therapy used for? What forms does it come in?

A

Reduces the severity of tobacco withdrawal and improves the chances of quitting

  • Nicotine replacement therapy is available in the form of nicotine gum, inhalers, lozenges, patches or sublingual tablets
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15
Q

What is the MOA of varenicline?

A
  • Partial agonist acting on α4β2 nicotinic receptor subtype
  • Antagonist effect: blocks pleasurable effects of smoking
  • Agonist effect: reduces withdrawal symptoms
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16
Q

What is the MOA of bupropion?

A
  • Mechanism of action poorly understood
  • Increasing DA activity in nucleus accumbens
  • Weak inhibition of reuptake of noradrenaline and dopamine.