Alcohol week Flashcards
Daily units for men and women?
3-4 Men
2-3 Women
Criteria for alcohol dependence syndrome?
A strong desire/compulsion to consume alcohol
Impaired capacity to control drinking
physiological withdrawal state
Evidence of alcohol tolerance
Neurological alcohol related disabilities?
Epilepsy
Peripheral neuropathy
Cerebellar degeneration
WKS
GI alcohol related disabilities?
Gastritis
Peptic ulceration
Pancreatitis
Oesophageal varices
Psychiatric alcohol related disabilities?
Alcohol dependence
Depression/anxiety
Steps of normal ethanol metabolism in the liver?
Ethanol to Acetaldehyde (catalysed by Alcohol dehydrogenase) - NAD to NADH
Acetaldehyde to Acetate (Acetaldehyde dehydrogenase) NAD to NADH
How much alcohol is metabolised in the normal system and how much in the MEOS system?
80-90% in normal
10-20% in MEOS system
What are the steps of alcohol metabolism in the MEOS system?
Ethanol to acetaldehyde (catalysed by CYP2E1)
During: NADPH + H+ + O2 = NADP+ + 2H2O
Stops there
What damage is done by acetaldehyde?
Flushing (dilated capillaries
Nausea and Vomiting
Liver Damage from free radicals
How does acetaldehyde cause liver damage?
Inhibits glutathione which protects agains H2O2 damage
Binds and inhibits enzymes that prevent free-radical damage
How are alcoholics treated pharmacologically, how’s it work?
Disulfiram - inhibits ALDH (which breaks down acetaldehyde into acetate)
How are there differences in people’s ability to process alcohol?
ADH, ALDH and CYP2E1 can all have genetic differences that can make them more or less effective.
Drinking history - levels of gastric ADH decrease and levels of CYP2E1 increase
Gender - females have lower gastric ADH
Quantity - as more alcohol is consumed more is processed by the MEOS pathway
Stages of liver damage?
Fatty Liver
Hepatitis/Fibrosis
Cirrhosis
What causes an increased NADH to NAD ratio in alcohol consumption?
The conversion of ethanol to acetaldehyde by ADH
The Conversion of acetaldehyde to acetate
Both produce NADH from NAD
What does the increased NADH to NAD ratio cause?
Fatty liver
Ketoacidosis
Lacticacidosis
hyperuricaemia
Hypoglycaemia
How does an increased NADH to NAD ratio cause a Fatty Liver?
NADH increases the availability of glycerol-3-phosphate
This means triacylglycerides are converted to VLDS
How does increased NADH lead to ketoacidosis?
Fats that are oxidised to acetyl CoA are encouraged to enter ketogenesis rather than the TCA cycle due to the presence of high concentrations of NADH
High amounts of alcohol also increases the amount of acetate, which is a preferential fuel to ketones and means there are more ketones in the body
How are lacticacidosis and hyperuricaemia caused by the increased NADH to NAD ratio?
NADH encourages lactate to be formed instead of pyruvate after glycolysis producing lacticacidosis
lactic acid decreases uric acid excretion = hyperuricaemia
How is hypoglycaemia caused by the high NADH to NAD ratio?
The reduction of gluconeogenesis
Reduced as less pyruvate is formed (lactate instead)
Other factors prevented from entering Gluconeogenesis as well, such a:s oxaloacetate
Presenting signs of an alcoholic?
Resting tachycardia
Hepatomegaly
Ascites (belly)
peripheral neuropathy
An alcoholics blood results? Why?
Reduced RBC + Haemoglobin, increased clotting time, hyperbillirubic due to reduced liver function
HCHb (Hb per cell) is normal there is just reduced cells
Why do alcoholics have a decreased appetite? why is this problematic?
Due to high calorie content of alcohol, problematic as will eat less and will get less nutrition.
Main nutrients that are deficient in alcoholism?
Thiamin, Folate, B12
What does thiamin deficiency cause?
Initially: Weight loss, irritability
Later: peripheral neuropathy, tachycardia, headache
What does folate deficiency cause?
Megaloblastic anaemia due to altered RBC formation
What does B12 deficiency cause?
Megaloblastic anaemia and also it is used to form myelin and so neuropathy
What does Lowered albumin cause?
Decreased synthesis of clotting factors
Expansion of ECF = ascites
What is Wernicke-korsakoff syndrome (WKS)?
Confusion, Ataxia and Opthalmoplegia
Nutritional management of alcoholic?
Parentovite (thiamin + others)
Complete multivit/min
Folate
Differentiate between decriminalisation and legalisation of drugs?
Decriminalisation - making the possession of drugs no longer a criminal offence
Legalisation - Making drug use, possession, production and distribution legal, but strictly controlled
Reasons to decriminalise drugs?
- Public health approach could be taken, perhaps improving the ability to tackle a major health issue
- Purity and potency could be controlled
- Reduce burden on police
- Reduced Crime
- Taxes will make money
- Could boost economy/provide jobs
Reasons not to decriminalise drugs?
- Could give the impression drug use is safe
- Not lead to reduced crime
- More people at risk of harm
What do drugs of abuse target in the brain to bring about their addictive quality?
Mesolimbic dopaminergic pathway and the nucl
Main categories of drugs of abuse and examples?
Narcotic analgesics - opioids
Psychomotor stimulants - cocaine, amphetamines, nicotine
Psychomimetic stimulants - LSD, Cannabis, MDMA
CNS depressants - Alcohol, Benzodiazepines, solvents
Definition for tolerance?
An increased dosage needed to obtain the same effects as in the past
Two types of dependence and their definitions?
Physical dependence - a state in which the person only functions normally under the influence of the drug
Psychological - consists of cravings
Pharmacological approaches to treating opioid withdrawal?
Methadone - to alleviate withdraw and long term substitution
Buprenorphine and lofexidine can also be used to allieveiate withdrawal symptoms
Effects of cocaine?
Euphoria
Alertness
Increased confidence
Increased sexual feelings
Mechanism of cocaine’s action?
Inhibits re-uptake of 5-HT, NA and DA in the synaptic cleft
Blocks Na+ channels, a1-adrenoceptor agonist
Effects of amphetamines and their mechanism of action?
Euphoria and excitement
Increased stamina
acute schizophrenic attack
Displaces NA and DA and inhibits their action
Formula to work out units of alcohol?
%ABV x vol (ml) / 1000
Why do we use a BDZ to help with alcohol withdrawal?
It acts on GABA receptors, which alcohol acts on and so will produce relief of some withdrawal symptoms, but will not become dependent
Alcohol withdrawal symptoms?
Uncomplicated:
Insomnia Increased BP Tachycardia Pyrexial Anxiety
Complicated:
Seizures
Hallucinations
Delirium
Delusions
(can use antipsychotic)
What is Wernicke-Korsakoff syndrome, what causes it?
Ataxia, Loss of memory activity and memory (can be severe), visual changes
Caused by a lack of thiamine (vit. B1)
Symptoms of opioid OD?
Pin point pupils depressed respiratory rate Hypotension Bradycardia Cool Moist skin
Adverse effects of amphetamines?
Anxiety irratibility and restlessness
Tolerance/dependence
Pharmacological treatments for nicotine dependence?
Alleviate withdrawal: Clonidine (a2 adrenoceptor agonist)
Nicotine replacement therapy
Block responses: Mecamylamine
Modification of cravings: Bupropion (antidepressant)
Mechanism of cannabis’ action?
Binds to CB1 cannabinoid receptors
Pharmacological treatments for alcohol dependence?
BDZ, or clonidine (a2 receptor agonists)
Disulfiram (induve unpleasant response to alcohol)
Bupropion (antidepressant)
How is dopamine involved in reward circuits?
Mesolimbic pathways: D2 receptors inhibit cAMP production in the NAcc, It inhibits activity in the medial forebrain which is inhibitory projecting to the prefrontal cortex, this is disinhibition to the prefrontal cortex
What are the neuroanatomical factors of addiction?
Drug associated cues activate dopamine and endorphin release in the: Amygdala, striatum and other areas
What is the biological basis of dependence and tolerance?
Repeated use of the drug leads to down-regulation of neurotransmitter release and upregulation of autoreceptors, this produces tolerance, meaning more is required to bring about the same response
Synaptic plasticity alters the weight of existing connections in the mesolimbic pathway, there is excessive NA output from the locus ceruleus
What two areas do drugs of dependence have an effect on?
The VTA and the NAcc
The tree groups of harms of substance misuse?
Social, psychological, Physical
How many units do men and women have to be having daily to be at an increased risk drinking group, and a higher risk drinking group?
Above 3-4 for men to be increased, 2-3 for women
More than 8 units a day for men and 6 for women to be at a higher risk group
What are teratogens?
Agents that cause defects or malformations in the developing embryo or foetus
Clinical features of Foetal Alcohol Syndrome?
Thin upper lip, Flat mid-face
Growth retardation
Learning difficulties, hearing loss
What amounts of drinking give a particular risk to FAS?
above 5 units in one session in first trimester
3-4 units a day
The vomiting centre and the CTZ use what receptors?
Vomiting centre: Muscarinic and Histamine
CTZ: 5HT3 and dopamine
