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Medicine - Year 1 > Pharmacology, therapeutics and patient safety - Physiology > Flashcards

Pharmacology, therapeutics and patient safety - Physiology Flashcards

1
Q

Describe 5 pharmacological approaches to treat drug dependance and provide an example for each one

A
  • Substitution, to alleviate withdrawal symptoms - e.g., Benzodiazepines to blunt alcohol withdrawal
  • Long-term substitution - e.g., nicotine patches, chewing gum, spray inhaler, lozenge
  • Blocking response - e.g., Varenicline which is a specific anatgonist for nAChR
  • Aversive therapies - e.g., Disulfiram to induce unpleasant response to alcohol
  • Modification of craving - e.g., Bupropion (antidepressant)
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2
Q

Describe the absoprtion of nictoine in the lungs, relating to the pH

A
  • pH of aveoli is 7.4
  • At this pH about 31% of nictoine from cigar smoke (pH 8.5) is unchanged and easily crosses the alveolar membrane into blood
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3
Q

Describe the metabolism and excretion of nicotine

A
  • Occurs in liver within 1-2hrs in humans
  • In most people nicotine is metabolised tocontinine (inactive metabolite) by oxidation
  • About 50% of nictoine is excreted in urine
  • Nicotine can also be excreted via faeces, bile, saliva and sweat
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4
Q

Describe the effects of nicotine on the whole body

A
  • Increased heart rate
  • Cardiac contractibility
  • Increased blood pressure
  • Decreased blood temperature
  • Mobilisation of blood sugar
  • Increased FFA (free fatt acids) in blood
  • Increase catecholamines (adrenaline and noradrenaline) levels in blood
  • Arousal or relaxation
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5
Q

Describe the effects of nictoine on a cellular level

A
  • Increased synthesis and release of hormone
  • Activation of tyrosine hydroxylase enzyme
  • Activation of several transcription factors
  • Induction of heat shock proteins
  • Induction of oxidative stress
  • Effects of apoptosis
  • Induction of chromosome aberrations
  • Induction of sister chromatid exchange
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6
Q

Describe the effects of nicotine on the autonomic nervous system

A
  • Inhibits effects of parasympathetic activation (inhibits acetylcholine)
  • Generally activates sympathetic activity (activates noradrenaline)
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7
Q

a) What are cholinergic receptors?
b) Describe the two types of cholinergic receptors?

A

a) Receptors on the surface of cells that get activated when they bind to a type of acetylcholine

b)

Nicotonic (nAChR) - pentameric ligand-gated ion channeles

Muscarinic (mAChR) - seven-helic G-protein coupled membrane proteins

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8
Q

a) There are 2 types of nicotinic chonlinergic receptors (nAChR). What are the two called? and where will you find them?
b) Which one des nicotine act on?

A

a)

  1. Nm recetors - neuromuscular junction
  2. Nn receptors - autonomic ganglia, adrenal gland and CNS

b) Nictoine acts on Nn receptors

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9
Q

a) Describe how does peripheral effects of nicotine receptor occurs
b) List 5 peripheral effects of nicotine receptor activation

A

a) Occurs from stimulation of autonomic ganglia and peripheral sensory receptors mainly in heart and lungs

b)

  • Increase in heart rate
  • Increase in cardiac output
  • Increase in arterial pressure
  • Reduction in GI motility
  • Sweating
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10
Q

Describe the pathophysiology of smoking

A
  1. Depedance
  2. Increased risk of:
  • Coronary heart disease (myocardial infarction)
  • Peripheral vascular disease (hypertension)
  • Lung cancer (carcinogens, tar and CO)
  • COPD (chronic bronchitis and emphysema)
  • Abnormal foetal development (low birth weight)
  • Systemic atherosclerosis
  • Peptic ulcers
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11
Q

What is the UK recommended intaken of alcohol in men and women

A

For both men and women: 2-3 units/day (14 units/week)

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12
Q

Where is ethanol metabolised?

A

Liver

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13
Q

Describe the effects ethanol has on the body

A

Cardiovascular system

  • Cutaneous vasodilation which causes warm feeling but actually increases heat loss

Endocrine system

  • Diuresis which is caused be inhibition of release of ADH hormone from the pituitory

GI tract

  • Increased salivary and gastric secretion

Liver - most serious long-term consequence

  • Increased fat accumulation which leads to hepatitis and finally hepatic necrosis and fibrosis
  • Effects of lipid metabolism, platelet function and atherosclerosis

Foetal development

  • Foetal alcohol syndrome (FAS)
  • Alcohol-related neurodevelopment disorder (ARND)
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14
Q

Describe the effects of ethanol on the CNS

A
  1. Acute ethanol intoxication effects:
  • Slurred speech
  • Motor incoordination
  • Increased self confidence
  • Euphoria
  • Effect on mood can vary - loud and outgoing morose and withdrawn
  • Intellectual and motor performance and sensory discrimination all show uniform impairment
  1. Chronic ethanol intoxication
    * Irreversible neurological effects (e.g., dementia, peripheral neuropathy)
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15
Q

Describe the mechanism of action of alcohol on CNS

A
  • General depressant effects
  • Enhancement of GABA-mediated inhibition (similar to acttion of benzodiaepines but effects smaller and less consistent)
  • Inhibits transmitter release in response to nerve terminal depolarisation by inhibiting opening of voltage dependant calcium channels in neurons
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16
Q

Describe the pathaphysiology of alcohol

A
  1. Alcohol
  2. Increased risk of:
  • CNS atrophy
  • Cardiomyopathy
  • Peptic ulcers
  • Pancreatitis
  • Liver damage
  • Varices
  • Testicular atrophy
17
Q

What is ‘addiction’?

A

Not having control over doing, or usng something to the point where it could be harmful to you

18
Q

What are the “4 C’s” of addiction?

A
  1. Compulsion
  2. Continues use despite harm
  3. Cravings
  4. Loss of control
19
Q

What causes people to become addicted to drugs?

A
  1. A combination of geentic and risk factors in life
  2. Genetic factors - affected by environmental factors
  3. Risk factors in life
  • Home, family, life circumstances
  • Peer pressure
  • Early use of drugs
  • Availability of drugs
20
Q

Define ‘tolerance’

A

Decrease in pharmological effect on repeated administration of drug, so dose has to be increased to get same effect

21
Q

Define ‘dependance’

A

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

22
Q

What is withdrawal (abstinence) syndrome?

A

Adverse effects, both physical and psychological, occurring after stopping taking drug

23
Q

What does ‘craving’ for a drug mean?

A

Intense desire for a drug that long outlasts the withdrawal (abstinence) syndrome

24
Q

What does ‘sensitization’ mean?

A

Dopamine receptors are more responsive/sensitive to dopamine

25
Q

What does ‘incentive sensitization’ mean?

A

Wanting more and more increases with greater exposure to the drug

26
Q

What does ‘abnormal sensitization’ mean?

A

Wanting more drugs/substance/behaviour but the pleasure derived from is diminishing (e.g., has been cited by heroin addicts)

27
Q

What does ‘cross-sensitization’ mean?

A

Taking one drug might increase the urge to take others

28
Q

Outline the pathways and areas within the brain that play a role in addiction

A
  • Virtually all dependance-producing drugs activate the reward pathway which is called the mesolimbic/mesocortical dopaminergic pathway
  • This begins in the ventral tegmental area (VTA) above the brain stem.
  • The VTA creates a synapse to
  1. Prefrontal cortex - focuses attention on that pleasure
  2. Nucleus accumbens - involved in the motor control e.g., grabbing, finding
  3. Amygala - processes the emotions and how it made us feel
  4. Hippocampus - memory
  • All addicitons leads to a release of dopamine which leads to pleasure
29
Q

Describe the habituation mechanism of nicotine

A
  • Enhances synthesis and release of dopamine
  • Acts on cholinergic receptors on dopamine cell bodes in the ventral tegmental area (VTA)
30
Q

Describe the habituation of alcohol

A
  • Decreases activity of GABAergic interneurones (exact mechanism, unclear)
  • Alcoholics have hyopfunction of mesolimbic system
31
Q

What does a continual dopamine over-stimulation also known as de-sensitization lead to?

A
  • A reduction of dopamine receptors
  • A reduced sensitivity to dopamine
  • A reduced dopamine productio
32
Q

Withdrawal (abstinence) syndrome develops in response to nicotine withdrawal. Decribe the clinical representation of this

A
  • Increased irritability, impaired psychomotor tasks, aggressiveness, sleep disturbance
  • Lats 2-3 weeks, although craving for cigarettes lasts much longer
33
Q

A well-defined withdrawal (abstinence) syndrome also develops in response to ethanol withdrawal. Describe the 3 stages of abstinence syndrome of ethanol

A
  • 1st stage: main symptoms are tremor, nausea, sweating, fever and sometimes hallucinations (last about 24hrs)
  • 2nd stage: epilepsy-like seizures
  • 3rd stage: ‘delirium tremens’ which results in confusin, agitation, aggression and more severe hallucinations (develops over a few days)
34
Q

What pharamological approach can be used to blunt alcohol withdrawal?

A

Benzodiazepines

Medicine - Year 1 (61 decks)

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