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Module 1 > Booze and Fags > Flashcards

Booze and Fags Flashcards

1
Q

How is nicotine absorbed?

A
  • Through oral cavity, skin, lung, urinary bladder, GI tract
  • Absorption through membranes is pH dependent
    • ​increases as pH increases
  • Main absorption is through lungs where pH of alveoli is 7.4
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2
Q

Nicotine Metabolism

(Time, metabolite, modes of excretion)

A
  • Occurs in the liver within 1-2 hours
  • In most people it is metabolised (70-80%) to cotinine (inactive metabolite) by oxidation
  • About 50% is excreted in urine
  • Can also be excreted via faeces, bile, saliva, sweat
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3
Q

Nictonic effects on whole organism (8)

A
  1. Increased heart rate
  2. Cardiac contractility
  3. Increased blood pressure
  4. Decreased skin temperature
  5. Mobilisation of blood sugar
  6. Increase in FFA in blood
  7. Increase in catecholamine levels in blood
  8. Arousal or relaxation
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4
Q

Nicotinic effects at the cellular level (8)

A
  1. Increased synthesis and release of hormones
  2. Activation of tyrosine hydroxylase enzyme
  3. Activation of several transcription factors
  4. Induction of heat shock proteins
  5. Induction of oxidative stress
  6. Effects on apoptosis
  7. Induction of chromosome aberrations
  8. Induction of sister chromatid exchange
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5
Q

Nicotinic Effects on the Nervous System

A
  • Parasympathetic in general reduces/inhibits –> releases Ach
  • Sympathetic in general increases/activates –> releases noradrenaline
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6
Q

Cholinergic Receptors

A
  • Nm receptors - neuromuscular junction
  • Nn receptors - autonomic ganglia, adrenal gland and CNS
  • AchR made up of several subunits
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7
Q

Peripheral effects of nicotine

A
  • Result from stimulation of autonomic ganglia and peripheral sensory receptors mainly in the heart and lungs
  • Increase in HR, CO and arterial pressure
  • Reduction in GI motility
  • Sweating
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8
Q

Pathophysiology of smoking involves

A
  • Dependence
  • Increased risk of
    • coronary heart disease (MI)
    • peripheral vascular disease (hypertension)
    • lung cancer (carcinogens, tar and CO)
  • Abnormal foetal development (low birth weight)
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9
Q

General effects of Alcohol

(concentrations)

A
  • Minimal effects occur at plasma concentration of 10mmol/L
  • Severe intoxication = 150mg/100ml
  • 10x this can be lethal - 500mg/100ml - respiratory failure
  • 1 unit = 8g ethanol
  • Strength (ABV) x volume (ml) = units
  • Recommended 2 - 3 units/day, 14 units/week
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10
Q

Alcohol metabolism

A
  • Rapidly absorbed via stomach and small intestine
  • 90% metabolised, only 5-10% excreted unchanged in expired air and ruine
  • Occurs in the liver
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11
Q

Alcohols effect on the CV system?

A

Cutaneous vasodilation, feel warm but increased heat loss

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12
Q

Alcohols effect on the endocrine system

A

Diuresis familiar effect - caused by inhibition of ADH

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13
Q

What is the effect of alcohol in the GI tract?

A

Increases salivary and gastric secretion

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14
Q

What is the effect of alcohol on the liver?

A

Most serious long-term consequence

  • Increased fat accumulation
  • Hepatitis and finally hepatic necrosis and fibrosis
  • Effects on lipid metabolism, platelet function and atherosclerosis
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15
Q

What effect does alcohol have on the foetus?

A
  • Foetal Alcohol Syndrome
  • Alcohol-related Neurodevelopmental Disorder
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16
Q

What are the effects of alcohol on the CNS?

A
  • Acute intoxication
    • slurred speech
    • motor incoordination
    • increased self-confidence
    • euphoria
  • Effect on mood can vary
    • become loud and outgoing
    • morose and withdrawn
  • Intellectual and motor performance and sensory discrimination all impaired
  • Chronic intoxication
    • irreversible neurological effects (dementia, peripheral neuropathy)
    • may be due to ethanol, but also metabolites acetaldehyde, FA esters
    • some effects are due to thymine deficiency
17
Q

What is the mechanism of action of alcohol on the CNS?

A
  • General depressant effects
  • Enhancement of GABA-mediated inhibition, similar to benzodiazepines
    • effect smaller and less consistent though
  • Benzodiazepine antagonist flumazenil reverses central depressant effects of ethanol
    • not used in dependence as side effect = increased seizures
    • Inhibits transmitter release in response to nerve terminal depolarisation by inhibiting opening of voltage-dependent calcium channels in neurons
18
Q

Alcohol leads to increased risk of

A
  • CNS atrophy
  • cardiomyopathy
  • peptic ulcers
  • pancreatitis
  • liver damage
  • carices
  • testicular atrophy
19
Q

What is tolerance?

A

Decrease in pharmacological effect on repeated use of drug –> dose has to be increased to get the same effect

20
Q

What is dependence?

A

The state when drug-taking becomes compulsive (taking precedence over other needs)

21
Q

What is withdrawal (abstinence) syndrome?

A

Adverse effects, both physical and psychological after stopping the drug

22
Q

What is craving?

A

Intense desire for a drug that long outlasts the withdrawal syndrome

23
Q

What is the Reward Pathway

A

Virtually all dependence-inducing drugs activate the reward pathway - the mesolimbic/mesocortical dopaminergic pathway

Cell bodies occur in groups in the mid brain, fibres project to parts of the limbic system

  • Nicotine enhances synthesis and release of dopamine
  • Acts on cholinergic receptors in the VTA
  • Alcohol decreases the activity of GABAergic interneurons
  • Alcoholics do have hypofunction of the mesolimbic system
  • Severity is dependent on the amount consumed
24
Q

What is involved in withdrawal syndrome from nicotine?

A

Response to nicotine withdrawal:

  • increased irritability
  • Impaired psychomotor tasks
  • aggressiveness
  • sleep disturbances
  • Las 2-3 weeks, although craving for cigarettes lasts much longer
25
Q

What is involved in the withdrawal syndrome of Alcohol?

A

Response to alcohol withdrawal:

  1. First stage - tremor, nausea, sweating, fever, sometimes hallucinations (last ~24 hours)
  2. Second stage - epilepsy-like seizures
  3. Third stage - ‘delirium tremens’ - results in confusion, agitation, aggression and more severe hallucinations (develops over few days)
26
Q

Example of substitution to alleviate alcohol withdrawals

A

Benzodiazepines to blunt alcohol withdrawals

27
Q

Long term substitution for nicotine

A

Nicotine patches, chewing gum, spray, inhaler, lozenges

28
Q

What is used to block the response to nicotine?

A

Varenicline - specific antagonist for nAchR

29
Q

What drug is used for modification of craving?

A

Bupropion (anti-depressant)

30
Q

Give an example of aversive therapies

A

Disulfiram induces an unpleasant response to alcohol

Module 1 (12 decks)

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