a) Muscle weakness b) Amnesia
c) Ataxia d) Confusion e) Bradycardia
Answer
Adverse effects include:
Drowsiness and lightheadedness
Confusion and ataxia (especially in the elderly), amnesia, muscle weakness
Headache, vertigo, tremor, dysarthria, hypotension, decreased libido, erectile dysfunction, gynaecomastia, urinary retention
Paradoxical effects such as talkativeness, excitement, irritability, aggression, anti-social behaviour, and suicidal ideation
Withdrawal symptoms, for example anxiety, depression, anorexia, impaired concentration, insomnia, abdominal cramps, palpitations, tremor, tinnitus and perceptual disturbances
Tolerance and dependence (people who use benzodiazepines longer term can develop tolerance and eventual
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6/9/2017 Tolerance and dependence (people who use benzodiazepines longer term can develop tolerance and eventualAnaesthetics and CNS FRCEM Success dependence)
Notes
Mechanism of action
Benzodiazepines are gamma-aminobutyric acid (GABA) receptor agonists which enhance inhibitory synaptic transmission throughout the central nervous system, with sedative, hypnotic, anxiolytic, anticonvulsant, and muscle relaxant properties.
Indications
Benzodiazepines are indicated for the short-term relief (two to four weeks only) of anxiety that is severe, disabling, or causing the patient unacceptable distress, occurring alone or in association with insomnia or short-term
psychosomatic, organic, or psychotic illness. The use of benzodiazepines to treat short-term ‘mild’ anxiety is inappropriate. Benzodiazepines should be used to treat insomnia only when it is severe, disabling, or causing the patient extreme distress.
Prescribing of these drugs is widespread but dependence (both physical and psychological) and tolerance may occur.
Therefore hypnotics and anxiolytics should be reserved for short courses to alleviate acute conditions. Withdrawal of a benzodiazepine should be gradual because abrupt withdrawal may produce confusion, toxic psychosis, convulsions, or a condition resembling delirium tremens.
Benzodiazepines possess useful properties for premedication including relief of anxiety, sedation, and amnesia; short-acting benzodiazepines taken by mouth are the most common premedicants. Benzodiazepines are also used in intensive care units for sedation, particularly in those receiving assisted ventilation.
Contraindications
Benzodiazepines are contraindicated in:
Respiratory depression
Marked neuromuscular respiratory weakness, such as unstable myasthenia gravis Obstructive sleep apnoea syndrome (symptoms may be aggravated)
Severe hepatic impairment (the elimination half-life of diazepam may be prolonged; increased risk of coma) Phobic or obsessional states, chronic psychosis or hyperkinesis (paradoxical reactions may occur)
Cautions
Benzodiazepines should be used with caution in:
Respiratory disease
Muscle weakness and myasthenia gravis (symptoms may be aggravated) Organic brain disease
Severe renal impairment (increased cerebral sensitivity to diazepam; a reduced dose may be appropriate) Dependent, obsessive-compulsive, or avoidant-type personality disorders (may increase the risk of dependency)
http://frcemsuccess.com/rev/sc54/ 78/215 Frailty and the elderly (increased falls risk; a reduced dose may be appropriate)
A history of drug and/or alcohol misuse or dependency (increased risk of dependency) Patients taking other central depressants concomitantly e.g. alcohol, barbiturates Adverse effects
Adverse effects include:
Drowsiness and lightheadedness
Confusion and ataxia (especially in the elderly), amnesia, muscle weakness
Headache, vertigo, tremor, dysarthria, hypotension, decreased libido, erectile dysfunction, gynaecomastia, urinary retention
Paradoxical effects such as talkativeness, excitement, irritability, aggression, anti-social behaviour, and suicidal ideation
Withdrawal symptoms, for example anxiety, depression, anorexia, impaired concentration, insomnia, abdominal cramps, palpitations, tremor, tinnitus and perceptual disturbances
Tolerance and dependence (people who use benzodiazepines longer term can develop tolerance and eventual dependence)
Toxicity
Features of benzodiazepine toxicity include:
drowsiness ataxia dysarthria nystagmus
occasionally respiratory depression and coma
Flumazenil is used to antagonise the effects of benzodiazepines. It can be used to reduce the sedative effects of benzodiazepines in anaesthesia, intensive care, diagnostic procedures and in overdose.
Type examples
Midazolam has a short duration of action (< 6 hours), lorazepam and temazepam have an intermediate duration of action (12 – 18 hours) and diazepam and chlordiazepoxide have a long duration of action (24 – 48 hours). Shorter-acting compounds may be preferred in patients with hepatic impairment but they carry a greater risk of withdrawal symptoms.
Chlordiazepoxide is routinely used for symptoms associated with acute alcohol withdrawal.
Diazepam is used to produce mild sedation with amnesia. It is a long-acting drug with active metabolites and a second period of drowsiness can occur several hours after its administration.
Temazepam is given by mouth for premedication and has a shorter duration of action and a more rapid onset than oral diazepam; anxiolytic and sedative effects last about 90 minutes although there may be residual drowsiness.
Lorazepam produces more prolonged sedation than temazepam and it has marked amnesic effects.
6/9/2017 Anaesthetics and CNS FRCEM Success
Lorazepam produces more prolonged sedation than temazepam and it has marked amnesic effects.
Midazolam is a water-soluble benzodiazepine that is often used in preference to intravenous diazepam; recovery is faster than from diazepam, but may be signi cantly longer in the elderly, in patients with a low cardiac output, or after repeated dosing. Midazolam is associated with profound sedation when high doses are given intravenously or when it is used with certain other drugs.
Regarding paracetamol, which of the following statements is CORRECT:
a) Paracetamol commonly causes photosensitivity.
b) Paracetamol can cause gastric irritation, particularly in the elderly.
c) Liver damage peaks 3 to 4 days after paracetamol ingestion.
d) Paracetamol overdose is most commonly complicated by renal failure.
e) Paracetamol is contraindicated in severe heart failure.
Answer
Liver damage peaks 3 to 4 days after paracetamol ingestion. Adverse effects are rare with paracetamol. Paracetamol does not cause gastric irritation. Paracetamol doses greater than the maximum daily dose of 4 grams can lead to hepatotoxicity (and, less frequently, acute kidney injury). There are no contraindications to the use of paracetamol.
Notes
Paracetamol is a non-opioid analgesic, similar in ef cacy to aspirin, with antipyretic properties but no
anti-in ammatory properties. It is well absorbed orally and does not cause gastric irritation. Paracetamol is a suitable rst-line choice for most people with mild-to-moderate pain, and for combination therapy.
Contraindications and cautions
There are no contraindications to the use of paracetamol.
Paracetamol should be used with caution in:
Alcohol dependence Dehydration
Chronic malnutrition Hepatic impairment People who weigh < 50 kg Adverse effects
Adverse effects are rare with paracetamol. However, paracetamol doses greater than the maximum daily dose of 4 grams can lead to hepatotoxicity (and, less frequently, acute kidney injury). In some people this may be fatal.
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http://frcemsuccess.com/rev/sc54/ 80/215 Paracetamol overdose
Overdose with acetaminophen results in accumulation of a minor metabolite, N-acetyl-p-benzoquinone, which is responsible for hepatotoxicity. When the enzymes for glucuronide and sulfate conjugation of acetaminophen and the reactive metabolite become saturated, an alternative glutathione conjugation pathway (cytochrome P-450 dependent) becomes more important. If hepatic glutathione is depleted, such as may occur with alcohol consumption, the reactive metabolite accumulates and may cause hepatic damage by interaction with cellular macromolecules, such as DNA and RNA.
People who have taken an overdose of paracetamol (accidentally or intentionally) may require urgent admission to hospital, depending on the quantity of paracetamol taken and the presence of risk factors for liver damage, including:
alcohol dependence, pre-existing liver disease, malnutrition, and the use of liver enzyme inducing drugs (such as rifampicin, carbamazepine, and phenytoin).
Early symptoms of paracetamol toxicity are nausea, vomiting, and abdominal pain which usually settle within 24 hours.
Symptoms of liver damage include right subcostal pain and tenderness. Liver damage peaks 3 to 4 days after paracetamol ingestion. The person may develop encephalopathy, bleeding, hypoglycaemia, and cerebral oedema.