Alcohol and Alcohol Abuse

Introduction

Alcohol is the most dangerous addictive drug in the world. It kills around 15 Australians every day. Alcohol abuse is widespread in Western Society, and is a common presenting complaint in Emergency Departments, both with and without clinical manifestations.

The recommended weekly intake of alcohol is:

• 14 Units for all individuals (regardless of gender) – UK Guidelines
• No more than 2 standard drinks on any given day, and 2 alcohol-free days per week – Australian Guidelines

• City Workers
• Barmen (drink 7x greater than average)
• Chefs (5x)
• Publicans (10x)
• Seamen
• Architects and accountants drink the least
• Doctors drink just very slightly above the average. Psychiatrists are significantly higher than other specialities.

• Russia
• Scandinavia
• Eastern Europe
• France
• Britain (above average, but not as high as those mentioned above)

Physiology of alcohol and pathological consequences

• The first areas to be affected are those responsible for learned ideas and tasks, whilst mechanical inhibition comes later on.
• Despite what you may believe at the time – there is no increase in any mental or physical functions – unless these have been previously suppressed by anxiety (e.g. nervousness).
• All the effects of alcohol are very closely related to the blood alcohol concentration. However, in those with dependence, tolerance can reduce these effects.

Cardiovascular effects

• Moderate intake – can be cardio-protective – as it reduces the aggregation of platelets, and increases HDL’s. The type of alcohol drunk is probably not important.
  • This effect is probably greatest at 1U/day, and is lost at >3U/day.
• Higher Intake – increases BP by increasing sensitivity to catecholamines. This increased the risk of IHD, CVA’s and stroke.
• High intake – can cause arrhythmias – especially AF. This can occur either in acute or chronic alcohol abuse.
  • Alcoholic cardiomyopathy is a dilated cardiomyopathy caused by alcohol. It will only partially recover when alcohol intake is reduced. It can lead to heart failure. 10U/day for 8-10 years will cause this.
  • It is the 3^rd most common type of cardiomyopathy. It causes thickening of the heart muscle, which will produce enlarged ECG traces. The most common complication of this is atrial fibrillation, although ventricular fibrillation is not unheard of can be deadly.
• In the short term, alcohol is generally a vasodilator – that is why people often feel warm when they have had a drink – but in reality you are more likely to lose body heat. In some circumstances (e.g. drunk man falls asleep on park bench), this can result in hypothermia.

Hepatic effects

• Hypoglycaemia – the metabolism of alcohol produces excess protons – which encourages the conversion of glucose to lactic acid. Alcohol abusers often have a low carbohydrate diet – making the situation worse.
• Hypoglycaemia tends to occur several hours after heavy alcohol intake (hence having a kebab on the way home!), and is a contributing factor in the seizures seen in withdrawing alcoholics.
• Lactic acidosis predisposes to the synthesis of saturated fatty acids which lead to fatty liver.
• Fatty liver – this is the first sign. It can either be steatohepatitis, or steatohepatosis.
• Alcoholic hepatitis – this leads to fibrosis, then micronodular cirrhosis of the liver.
• Clotting factors no longer produced – the liver normally produces factors 2, 7, 9 & 10. Without these the patients may easily bruise, and bleeding is not easily stopped.
• Reduced albumin production – albumin is the thing that holds all the bloods contents in the blood – it provides osmotic pressure. Without it, products normally contained in the blood easily escape into peripheral tissue, causing peripheral oedema.
• Asterixis – this is a shaking of the hands caused by encephalopathy. Secondary to build up of toxic metabolites in the brain which can no longer be properly metabolised by the liver.
• Jaundice – the liver is essential for removing bilirubin from the body. It conjugates it so it is soluble and can be excreted in the bile. Some of this is metabolised by bacteria in the gut and re-absorbed, and it is then excreted in the urine. Without proper liver function, this will not happen.
• You can probably survive with about ¼ of a normal liver. There is a sudden cut off point at which your liver can no longer survive. This varies slightly from person to person, and there is no way to determine where this cut-off point is. When it occurs though, many of these symptoms will start abruptly.
• Oseophageal Varices – if the liver is damaged, then intra-hepatic pressure increases causing portal hypertension. This then leads to oesophageal and rectal varices, as the blood tries to find another way to bypass the liver back to the systemic circulation. These varices can burst and bleed, and they are a common cause of death. GI bleeding is a common emergency presentation in patients with alcoholic liver damage.
• Cirrhosis – individual susceptibility varies massively – but in most people drinking 8 U/day for 10 years is enough to cause cirrhosis. In women, it is thought that 4U/day is enough.
• Induction of drug metabolising enzymes – so some drugs (e.g. warfarin) become less effective.

GI problems

• Gastritis – probably caused by increased gastric secretions that are induced by alcohol intake. Peptic ulcers are also 3x more common in heavy drinkers.
• Pancreatitis – may be precipitated by high triglycerides, or due to proteinous secretions induced by alcohol intake.
  • 50% of all cases of chronic pancreatitis are due to heavy drinking
• Mouth – alcoholics often have poor dental care. They will have bad teeth, and often will have scurvy due to lack of vitamin C. Scurvy causes inflammation and recession of the gums.
• Oesophagus
  • Varices
  • Reflux oesophagitis due to alcohol’s relaxation effect – the lower oesophageal sphincter becomes dilated, as does the stomach
  • Mallory-Weiss tear
• Stomach
  • Gastritis
  • Increased risk of ulcers
• Diarrhoea
• Malnourishment; due to:
  • Not much food eaten
  • Low nutritional quality of food eaten
  • Pancreatitis means food might not be properly digested
  • Liver damage means food is not metabolised properly

Blood disorders

Sexual function

• Sexual desire is increased in the short term, but the ability to maintain erection is reduced (due to vasodilation)
• In the long term, there can be damage to the Leydig cells resulting in less testosterone production, which can cause:
  • Loss of libido
  • Infertility
  • Loss of male body hair
• There may also be alteration of steroid production which can cause gynaecomastia in men as a result of increased oestrogen production.

Neuropsychiatric effects

• Alcoholics are likely to have vitamin deficiency due to poor diet, as a result of neglecting their need for food in favour of their addiction. A combination of high alcohol intake, low vitamin B₆ and low thiamine (B₁) can predispose peripheral neuropathy and dementia. In the acute withdrawal setting this can be particularly problematic (discussed later). The peripheral neuropathy can be both sensory and motor, and is most prominent in the lower limbs. It will rarely improve with treatment.
• Alcohol is an anticonvulsant. Thus in withdrawal, it can cause convulsions – even in those with no history of epilepsy.
• Effects on sleep – alcohol tends to allow you to get to sleep more easily, but the quality of sleep it induces is poorer; there is decreased REM sleep but increased stage 4 sleep. Withdrawal induces periods of REM sleep – which is associated with nightmares.
• Impaired memory
• Depression / anxiety
• Subdural haematoma – rare – but more common after head injury than in non-drinkers.
• Korsakoff’s syndrome – this is caused by a lack of thiamine (vitamin B1) in the brain. In this condition, consolidation of new memories is not possible, but usually, old memories are not forgotten. These patients may hold a conversation with you in which they totally make up what they are talking about; e.g. ‘Oh I saw you down in the café getting a snack’ – ‘oh yes – I had a jacket potato too’ – when in actual fact they have been in bed all day! Often alcoholics present just before their deficiencies are low enough for this syndrome to occur, so every alcoholic coming into hospital is put on a thiamine drip within an hour of admission!
• General thiamine deficiency – It causes irreversible cerebellar nerve damage and thus will affect gait and eye movement.
• Peripheral neuropathy – like that seen in diabetes – it affects the extremities of the body – hands, feet and toes. However, unlike diabetes, it is very painful.

Carcinogenesis and teratogenesis

• ↑Risk of mouth, oesophagus and liver with heavy alcohol use
• Foetal alcohol syndrome – this can occur even if the mother just drinks on one occasion only during the whole pregnancy term! Obviously the risks are greater, the more the mother drinks. The risk is also greatest if alcohol is drunk during the early part of pregnancy. it is most common in children who had a heavy drinking mother. It causes impaired learning and memory in the child.
• Genetic susceptibility of the foetus plays a part.

Endocrine effects

• Problems with metabolism of oestrogen to testosterone – this causes feminisation of many patients – they will lose their body hair, their testicles will atrophy etc.
• Diabetes due to liver cirrhosis

Psychological effects

• Alcohol is a depressive – it naturally inhibits brain activity
• Alcohol abuse can cause social problems – e.g. relationship problems, employment issues, debts, problems with friends
• The depression starts first and the individual turns to alcohol for relief – in the short term, alcohol use can provide an escape from depression, and many people use it as a coping mechanism.

• ½ of all men who attempt suicide are alcohol dependant
• Anxiety is particularly marked during alcohol withdrawal

Memory disorders

• Alcoholic amnesia – not being able to remember what happened during a period of heavy drinking (e.g. not remember what happened the night before when you wake up in the morning)
• Korsakov’s Syndrome
• Alcoholic dementia – may resolve on cessation of alcohol intake

Social Problems

• At work
• At home – don’t forget impotence!
• Crime

Pharmacokinetics of alcohol

• Some absorbed in stomach, most from small intestine
• High conc. Of alcohol (>20%), presence of food (particularly fat and carbohydrate) all inhibit gastric emptying – and thus alter the peak blood alcohol concentration – with long periods of gastric emptying the peak concentration is likely to be reduced.
• Has large first pass metabolism. This metabolism has a fixed capacity – so if you absorb a lot of alcohol slowly (e.g. when drinking with food), more alcohol will be removed by first pass than if you drink on an empty stomach.
• Continued alcohol metabolism is at a constant rate (about 8-10ml/hour)
• The effects on the brain are most pronounced as the concentration of alcohol rises – this shows that the brain exhibits a short-term tolerance of alcohol.
• 90% is removed by the liver – mostly by the enzyme alcohol dehydrogenase – producing acetaldehyde. This is then further metabolised by aldehyde dehydrogenase to acetic acid. The other 10% is expired from the lungs,or excreted in the urine unchanged – this occurs at a rate proportional to the blood concentration of alcohol – and thus forms the basis of the breath test, and the urine test.

Drug interactions

• Headache
• Sweating
• Nausea

Consequences due to drunkenness

• Trauma
  • Fights
  • Falls
• Vomiting – this can lead to aspiration, which if light, is likely to cause pneumonia, but if serious could lead to death as the patient is unable to breathe.
• Radial nerve palsy – if you fall asleep with your arm in an unusual position (e.g. over the back of a chair) then your radial nerve can get stuck in the radial groove and compressed. This can lead to nerve damage. The typical sign of this damage is a drooping wrist. Sometimes it is permanent, but in some cases it may only last a couple of weeks.
• Risk taking behaviours – e.g. climbing trees, swimming across rivers etc.
• Vasodilatation – this is not necessarily very dangerous, unless you combine it with being in a cold place for a long time – e.g. sleeping in the park after a drunken night out. In this case it may lead to hypothermia.
• Hyperglycaemia
• 50% of weekend hospital admissions in some cities (Manchester included) are due to alcohol.

• At home – this may be suitable for those with:
  • No history of DT or other withdrawal syndromes
  • Good family / social support
  • No psychological complications (e.g. depression)
  • No physical complications )e.g. liver disease)
  • It will involve a community alcohol team.
  • Drugs (see below)
  • In recent years there has been more emphasis on helping patients to detox at home. Studies have shown that it is safe, with high completion rates. Some studies have suggested it is more effective than detox in an inpatient unit, and is between 10-20x time cheaper!
  • Contraindications include:
    • Previous withdrawal seizures
    • Suicidal ideation
    • Co-existing drug addiction
    • History of DT
    • No access to safe housing or appropriate social support
• At hospital – if the patient does not meet the above criteria, they can be treated in hospital

Example of when home detox may be appropriate

Principles of managing alcohol dependence

Knowing ‘when to give up’ is a difficult question. Many patients know they ‘should’ give up, but struggle with the motivation to:

• Plan a serious detox attempt
• Stick to the detox regimen
• Maintain abstinence

Using the 5As approach to assess and treat may be appropriate (see Addiction and drug abuse).

Benzodiazepines – these are given both for sedation, and also for their anticonvulsant effects. Thus you should chose a drug which has both these effects. The dose is gradually reduced over 7-10 days. Usually you start off reducing the dose by 20%, but if the patient is still experiencing severe symptoms, reduce the dose at a lower rate.

• Chlordiazepoxide is often the drug of choice (in the UK), but diazepam may also be used (1st line in Australia).
• Clomethiazole used to be used but it has a high risk of dependence. Clonidine is particularly useful at reducing the sympathetic effects seen in withdrawal.
• These can be given every 4 hours (orally), or IV if necessary. You should not give them for more than 14 days due to risk of benzodiazepine addiction
  • Dosing of benzodiazepines is often based on withdrawal symptoms – e.g. in hospital – guided by the patient alcohol withdrawal scale score
• Lorazepam, haloperidol – these drugs may be used to control aggression in alcoholics in the acute situation.

Thiamine and other vitamin supplements – these are essential! They help to prevent Wernicke’s encephalopathy. They often have to be given IV – and may need to be given for up to 1 month after.
Fluid replacement – dehydration can be particularly severe. There is also a very real risk of Hypocalcaemia and hypomagnesia.
Disulfiram – is a drug that inhibits acetaldehyde dehydrogenase and thus causes nasty side effect when taken with alcohol. It can help to maintain abstinence – although it usually needs to be given with psychotherapy to be effective
Acamprosate – inhibits glutamate – which is an excitory amino acid implicated in cravings. Acamprosate can help reduce cravings.

Managing alcohol detox at home

• Consider a contract with the patient (example at NPS medicine wise – box 1)
• Consider urine drug screen (co-existing drug abuse is a contraindication to home detox)
• Take a set of baseline observations (HR, BP, temperature)
• Take some baseline blood tests – including LFTs, U+Es, FBC, iron studies, random glucose, CMP
• Prescribe thiamine. This redcues the risk of Wernicke’s encephalopathy
  • 300mg PO or IV for 3-5 days in acute withdrawal, then 100mg for 1 week
  • In those with a planned detox give 200mg OD for 2 weeks
  • The dose for continuing drinkers is lower – 100mg OD
• Prescribe a weaning regimen of benzodiapines
  • Chlordiazepoxide or diazepam recommended in UK
  • Diazepam recommended in Australia. Oxazepam may be considered in patients with significant hepatic impairment
  • Typically the dose is weaned over 7 days
• Review daily – either by GP or specialist nurse
• Consider other supportive treatemnts
  • Melatonin may help with sleep disturbance
  • Advise to eat frequent, small meals, high in protein. This can help to prevent hypoglycaemia as well as supplementing thiamine intake
  • Encourage patient to enrol in a alcohol support programme – such as Alcoholic’s Anonymous (AA)

Possible weaning regimens with diazepam

Mild and moderate based on criteria listed above. From the Author – Dr Tom Leach – I must admit that in my practice (I work in Emergency as well as in primary care) I typically use higher doses in primary care that are listed here – based on clinical experience  from the doses I have seen given, and been advised to give by the drug and alcohol team in hospital!

• eTherapeutic Guidelines recommends 20mg diazepam every 2 hours PRN – maximum daily dose of 60mg

Managing Alcohol Addiction in the acute admission

1. Give IV vitamin B12 + thiamine (pabrinex : vitamin B1) + other B vitamins –  Patients are likely to be deficient as a result of diet, due to the fact they are drinking so much – they are unlikely to eat properly for various reasons (Alcohol is appetite suppressant, maybe not able to afford food, etc.). There is often coexistent macrocytic anaemia. these also protect against Wernicke encephelopathy and the longer term Korskoff’s Syndrome
   1. Thiamine 300mg IV or oral for 3-5 days recommended in acute withdrawal
2. Drain any ascites and test the fluid (infection, blood, transudate / exudate)
3. Give diazepam or librium (chlordiazepoxide). Typical dose (librium) of 10-50mg/Kg every 6 hours for the first 3 days. Then wean over the following 7-14 days. Reduces hallucinations.
   1. Doses used in the inpatient setting are generally higher than outpatients
4. Provide Adequate nutrition – 35Kcal/Kg/day in non-protein energy, PLUS 1.5g/Kg/day of protein. This has been shown to reduce sepsis, mortality and encephalopathy.
5. Consider the use of Steroids – calculate the Maddrey Discriminant Factor. a score of >32 indicates severe disease, and should be treated with 40mg/day for 5 days, with a tapering dose of the subsequent 3 weeks. Mortality correlated with the Maddrey Discriminant Factor Score.
   1. Severe disease mortality – 50% in the first 30 days
   2. Mild disease mortality – 5% in the first 30 days
   3. 1 year mortality regardless of severity – 40%
6. Give tramadol and laxatives. Tramadol is an opiod used commonly to relieve neuralgia. You should give the laxatives to avoid constipation. Constipation can be dangerous as it can allow excess production of bacterial toxins, which the liver is unable to remove..
7. Give potassium sparing diuretics (e.g. spironolactone). Loop diuretics are more effective at diuresis in normal patients, but are contraindicated in alcoholics:
   1. Alcoholic patients have a low blood volume due to hypoalbuminaemia. The synthetic function of the liver is damaged, and so alcoholic patients have a low blood albumin level. Their renin-angiotensin system is already activated to a much larger extent than usual due to their low blood volume. This system causes retention of sodium to retain fluid in the body. However in patients with liver failure, the sodium doesn’t stay in the blood, and instead dissipates to the peripheral tissues causing oedema and ascites. So, you must block this system, to allow proper fluid excretion..
   2. Patients should be weighed every day to see if they are losing fluid. Ideally they should lose 0.5-1kg a day (i.e. 0.5-1L of fluid) for the first few days, until the noticeable oedema is gone. After this, they should lose no more than 0.5L per day. To ensure this is achieved, you have to restrict the patient’s fluid intake. Losing more weight per day than this can cause dangerous fluid shifts.
   3. Huge doses are often required! (e.g. 200-300mg spironolactone)
   4. Many patients will also be on furosemide

Long-term management of patients with alcohol dependence

• Alcohol dependence should be viewed as a a chronic relapsing and remitting condition
• It is associated with a change in the motivation and control systems in the brain
• Long-term management of alcohol dependence aims to target these regulation systems
• These management strategies should include psychological and rehabilitation therapies, in conjunction with a pharmacological approach (where indicated)
  • Pharmacological strategies are generally reserved for those with more severe disease
• Typical treatment plans will last 3-6 months

Three main medications are available to assist with long-term management of alcohol dependence – Acamprosate, disulfiram and naltrexone. However, they have different indications:

• Acamprosate and disulfiram are recommended for those who have achieved abstinence and with to maintain it
• Naltrexone is recommended for patients who wish to reduce their alcohol intake

There are several other medications that may also be used, but are typically prescribed only by specialist in particular situations. These can include baclofen, topiramate and disulfiram.

Naltrexone

• Useful in patient still drinking to reduce the positive effects
• Can also be used in those who have stopped drinking as a deterrent to restarting
• A mu opioid receptor antagonist
  • Contraindicated in those on opioids
  • Related to the opiod overdose reversal agent – naloxone
  • If opiates are prescribed, naltrexone should be ceased
• It reduces the euphoric reward feeling associated with alcohol
• It can be given in combination with acamprosaate but evidence in this setting is lacking
• Side effects:
  • Headache
  • Nausea
  • Lethargy
  • Dysphoria
  • There are no specific negative effects if patients drink whilst taking naltrexone
• Contraindications
  • Taking opioids
  • Liver failure – an important consideration in this context
    • Do NOT prescribe if ALT >3x normal limit
• Typical dose
  • 50mg PO OD
  • Half dose may be recommended in those who are still drinking

Acamprosate

• First line in those seeking to maintain abstinence
  • Much more effective than alternative medications for this purpose
• A structural analogue of GABA (neurotransmitter)
• Thought to work by altering the action of calcium channels and affecting neurotransmission on GABA and glutamine pathways in the brain
• It does not interact with other medications commonly prescribed around the time of alcohol withdrawal – such as benzodiazepines, antidepressants or naltrexone
• It can be given safety in liver failure
• It does not have any potential for abuse
• Dose: 333mg tabs x2 TDS (if weight >60Kg)
  • If <60kg – 333mg x2 tabs mane, 1 tab lunch and 1 tab dinner
  • Compliance may be difficult due to the large number of tablets to be taken

Disulfiram – Antibuse

• Disulifram interferes with the metabolism of alcohol
• If patients drink after taking it – they generally feel quite unwell!
• As a result of the altered alcohol metabolism, it causes an increase in the levels of acetaldehyde dehydrogenase – which results in:
  • Hot flushes
  • Sweating
  • Palpitations
  • Tachycardia
  • Headaches
  • Dyspnoea
  • Hyperventilation
  • Chest pain
  • “Feeling of impending doom”
  • Can result in seizures and cardiorespiratory failure – deaths have been reported
  • Contraindications include ischaemic heart disease, psychosis
• Patients should be highly motivated not to drink – and should be warned of these effects if alcohol is consumed
• Dose – 100mg PO OD, increasing to 300mg OD. Increase dose slowly over a period of weeks

References

• Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
• Oxford Handbook of General Practice. 3rd Ed. (2010) Simon, C., Everitt, H., van Drop, F.
• Beers, MH., Porter RS., Jones, TV., Kaplan JL., Berkwits, M. The Merck Manual of Diagnosis and Therapy
• Alcohol limits and unit guidelinesReduce your risk: new national guidelines for alcohol consumption
• Home Detox – NPS Medicinewise
• Long term drug treatment of patients with alcohol dependence – NPS Medicinewise

Read more about our sources

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