Pharmacology, therapeutics and patient safety - Physiology Flashcards
Describe 5 pharmacological approaches to treat drug dependance and provide an example for each one
- 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)
Describe the absoprtion of nictoine in the lungs, relating to the pH
- 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
Describe the metabolism and excretion of nicotine
- 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
Describe the effects of nicotine on the whole body
- 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
Describe the effects of nictoine on a cellular level
- 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
Describe the effects of nicotine on the autonomic nervous system
- Inhibits effects of parasympathetic activation (inhibits acetylcholine)
- Generally activates sympathetic activity (activates noradrenaline)
a) What are cholinergic receptors?
b) Describe the two types of cholinergic receptors?
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
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)
- Nm recetors - neuromuscular junction
- Nn receptors - autonomic ganglia, adrenal gland and CNS
b) Nictoine acts on Nn receptors
a) Describe how does peripheral effects of nicotine receptor occurs
b) List 5 peripheral effects of nicotine receptor activation
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
Describe the pathophysiology of smoking
- Depedance
- 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
What is the UK recommended intaken of alcohol in men and women
For both men and women: 2-3 units/day (14 units/week)
Where is ethanol metabolised?
Liver
Describe the effects ethanol has on the body
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)
Describe the effects of ethanol on the CNS
- 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
- Chronic ethanol intoxication
* Irreversible neurological effects (e.g., dementia, peripheral neuropathy)
Describe the mechanism of action of alcohol on CNS
- 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
Describe the pathaphysiology of alcohol
- Alcohol
- Increased risk of:
- CNS atrophy
- Cardiomyopathy
- Peptic ulcers
- Pancreatitis
- Liver damage
- Varices
- Testicular atrophy
What is ‘addiction’?
Not having control over doing, or usng something to the point where it could be harmful to you
What are the “4 C’s” of addiction?
- Compulsion
- Continues use despite harm
- Cravings
- Loss of control
What causes people to become addicted to drugs?
- A combination of geentic and risk factors in life
- Genetic factors - affected by environmental factors
- Risk factors in life
- Home, family, life circumstances
- Peer pressure
- Early use of drugs
- Availability of drugs
Define ‘tolerance’
Decrease in pharmological effect on repeated administration of drug, so dose has to be increased to get same effect
Define ‘dependance’
The state when drug-taking becomes compulsive (taking precedence over other needs)
What is withdrawal (abstinence) syndrome?
Adverse effects, both physical and psychological, occurring after stopping taking drug
What does ‘craving’ for a drug mean?
Intense desire for a drug that long outlasts the withdrawal (abstinence) syndrome
What does ‘sensitization’ mean?
Dopamine receptors are more responsive/sensitive to dopamine
What does ‘incentive sensitization’ mean?
Wanting more and more increases with greater exposure to the drug
What does ‘abnormal sensitization’ mean?
Wanting more drugs/substance/behaviour but the pleasure derived from is diminishing (e.g., has been cited by heroin addicts)
What does ‘cross-sensitization’ mean?
Taking one drug might increase the urge to take others
Outline the pathways and areas within the brain that play a role in addiction
- 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
- Prefrontal cortex - focuses attention on that pleasure
- Nucleus accumbens - involved in the motor control e.g., grabbing, finding
- Amygala - processes the emotions and how it made us feel
- Hippocampus - memory
- All addicitons leads to a release of dopamine which leads to pleasure
Describe the habituation mechanism of nicotine
- Enhances synthesis and release of dopamine
- Acts on cholinergic receptors on dopamine cell bodes in the ventral tegmental area (VTA)
Describe the habituation of alcohol
- Decreases activity of GABAergic interneurones (exact mechanism, unclear)
- Alcoholics have hyopfunction of mesolimbic system
What does a continual dopamine over-stimulation also known as de-sensitization lead to?
- A reduction of dopamine receptors
- A reduced sensitivity to dopamine
- A reduced dopamine productio
Withdrawal (abstinence) syndrome develops in response to nicotine withdrawal. Decribe the clinical representation of this
- Increased irritability, impaired psychomotor tasks, aggressiveness, sleep disturbance
- Lats 2-3 weeks, although craving for cigarettes lasts much longer
A well-defined withdrawal (abstinence) syndrome also develops in response to ethanol withdrawal. Describe the 3 stages of abstinence syndrome of ethanol
- 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)
What pharamological approach can be used to blunt alcohol withdrawal?
Benzodiazepines
