clinical pharmacology

Question 1

Paracetamol overdose management

Answer 1

The minority of patients who present within 1 hour may benefit from activated charcoal to reduce absorption of the drug.

Acetylcysteine should be given if:
the plasma paracetamol concentration is on or above a single treatment line

there is a staggered overdose* or there is doubt over the time of paracetamol ingestion, regardless of the plasma paracetamol concentration; or

patients who present 8-24 hours after ingestion of an acute overdose of more than 150 mg/kg of paracetamol even if the plasma-paracetamol concentration is not yet available

patients who present > 24 hours if they are clearly jaundiced or have hepatic tenderness, their ALT is above the upper limit of normal
acetylcysteine should be continued if the paracetamol concentration or ALT remains elevated whilst seeking specialist advice

Question 2

criteria for liver transplantation

Answer 2

King’s College Hospital criteria for liver transplantation (paracetamol liver failure)

Arterial pH < 7.3, 24 hours after ingestion

or all of the following:
prothrombin time > 100 seconds
creatinine > 300 µmol/l
grade III or IV encephalopathy

Question 3

features of tricyclic overdose?

Answer 3

Amitriptyline and dosulepin (dothiepin) are particularly dangerous in overdose.

Early features relate to anticholinergic properties: dry mouth, dilated pupils, agitation, sinus tachycardia, blurred vision.

Features of severe poisoning include:
arrhythmias
seizures
metabolic acidosis
coma

Question 4

ECG changes in Tricyclic overdose?

Answer 4

sinus tachycardia
widening of QRS
prolongation of QT interval

Widening of QRS > 100ms is associated with an increased risk of seizures whilst QRS > 160ms is associated with ventricular arrhythmias

Question 5

Management of Tricyclic overdose?

Answer 5

IV bicarbonate
first-line therapy for hypotension or arrhythmias
indications include widening of the QRS interval >100 msec or a ventricular arrhythmia
other drugs for arrhythmias

intravenous lipid emulsion is increasingly used to bind free drug and reduce toxicity

Question 6

features of salicylate overdose?

Answer 6

mixed respiratory alkalosis and metabolic acidosis. Early stimulation of the respiratory centre leads to a respiratory alkalosis whilst later the direct acid effects of salicylates (combined with acute renal failure) may lead to an acidosis.

Features
hyperventilation (centrally stimulates respiration)
tinnitus
lethargy
sweating, pyrexia*
nausea/vomiting
hyperglycaemia and hypoglycaemia
seizures
coma

Question 7

Treatment of Salicylate overdose?

Answer 7

general (ABC, charcoal)
urinary alkalinization with intravenous sodium bicarbonate - enhances elimination of aspirin in the urine
haemodialysis

Indications for haemodialysis in salicylate overdose
serum concentration > 700mg/L
metabolic acidosis resistant to treatment
acute renal failure
pulmonary oedema
seizures
coma

Question 8

acute indications for dialysis?

Answer 8

A - Acidosis

E - electrolyte - hyperkalaemia

I - ingestion or intoxification

O - overload

U - uraemia

Question 9

Features of beta blocker overdose?

Answer 9

bradycardia
hypotension
heart failure
syncope

Question 10

management of beta blocker overdose

Answer 10

if bradycardic then atropine
in resistant cases glucagon may be used

Question 11

Features of Opiod overdose?

Answer 11

rhinorrhoea
needle track marks
pinpoint pupils
drowsiness
watering eyes
yawning
respiratory depression

Question 12

Management of opioid overdose?

Answer 12

IV or IM naloxone: has a rapid onset and relatively short duration of action

Question 13

management of opioid dependance?

Answer 13

patients are usually managed by specialist drug dependence clinics although some GPs with a specialist interest offer similar services
patients may be offered maintenance therapy or detoxification
NICE recommend methadone or buprenorphine as the first-line treatment in opioid detoxification

Question 14

what is Oculogyric crisis?

Answer 14

An oculogyric crisis is a dystonic reaction to certain drugs or medical conditions

Features
restlessness, agitation
involuntary upward deviation of the eyes

Question 15

What causes Oculogyric crisis?

Answer 15

Causes
antipsychotics
metoclopramide
postencephalitic Parkinson’s disease

Question 16

How is Oculogyric crisis managed?

Answer 16

cessation of causative medication if possible
intravenous antimuscarinic: benztropine or procyclidine

Question 17

features of Digoxin Toxicity?

Answer 17

generally unwell, lethargy, nausea & vomiting, anorexia, confusion, yellow-green vision
arrhythmias (e.g. AV block, bradycardia)
gynaecomastia

Question 18

Precipitating factors for Digoxin Toxicity ?

Answer 18

classically: hypokalaemia
digoxin normally binds to the ATPase pump on the same site as potassium. Hypokalaemia → digoxin more easily bind to the ATPase pump → increased inhibitory effects
increasing age
renal failure
myocardial ischaemia
hypomagnesaemia, hypercalcaemia, hypernatraemia, acidosis
hypoalbuminaemia
hypothermia
hypothyroidism
drugs: amiodarone, quinidine, verapamil, diltiazem, spironolactone (competes for secretion in distal convoluted tubule therefore reduce excretion), ciclosporin. Also drugs which cause hypokalaemia e.g. thiazides and loop diuretics

Question 19

Management of Digoxin toxicity?

Answer 19

Digibind
correct arrhythmias
monitor potassium

Question 20

Clinical features of Ectasty Poisoning?

Answer 20

neurological: agitation, anxiety, confusion, ataxia
cardiovascular: tachycardia, hypertension
hyponatraemia
this may result from either syndrome of inappropriate ADH secretion or excessive water consumption whilst taking MDMA
hyperthermia
rhabdomyolysis

Question 21

Management of Ecstasy poisoning?

Answer 21

supportive
dantrolene may be used for hyperthermia if simple measures fail

Question 22

Symptoms of methanol poisoning?

Answer 22

Methanol poisoning causes both the effects associated with alcohol (intoxication, nausea etc) and also specific visual problems, including blindness. These effects are thought to be secondary to the accumulation of formic acid.

Question 23

management of methanol poisoning?

Answer 23

fomepizole (competitive inhibitor of alcohol dehydrogenase) or ethanol
haemodialysis
cofactor therapy with folinic acid to reduce ophthalmological complications

Question 24

Cyanide poisoning

Answer 24

Cyanide may be used in insecticides, photograph development and the production of certain metals. Cyanide inhibits the enzyme cytochrome c oxidase, resulting in cessation of the mitochondrial electron transfer chain.

Presentation
‘classical’ features: brick-red skin, smell of bitter almonds
acute: hypoxia, hypotension, headache, confusion
chronic: ataxia, peripheral neuropathy, dermatitis

Management
supportive measures: 100% oxygen
definitive: hydroxocobalamin (intravenously), also combination of amyl nitrite (inhaled), sodium nitrite (intravenously), and sodium thiosulfate (intravenously)

Question 25

what is carbon monoxide poisoning?

Answer 25

Carbon monoxide has a high affinity for haemoglobin and myoglobin resulting in a left-shift of the oxygen dissociation curve and tissue hypoxia. There are approximately 50 per year deaths from accidental carbon monoxide poisoning in the UK.

Pathophysiology
carbon monoxide binds readily to haemoglobin, forming carboxyhaemoglobin → reduced oxygen-carrying capacity
in carbon monoxide poisoning the oxygen saturation of haemoglobin decreases leading to an early plateau in the oxygen dissociation curve

Question 26

Features of Carbon monoxide poisoning?

Answer 26

headache: 90% of cases
nausea and vomiting: 50%
vertigo: 50%
confusion: 30%
subjective weakness: 20%
severe toxicity: ‘pink’ skin and mucosae, hyperpyrexia, arrhythmias, extrapyramidal features, coma, death

Question 27

Investigations for carbon monoxide poisoning?

Answer 27

pulse oximetry may be falsely high due to similarities between oxyhaemoglobin and carboxyhaemoglobin
therefore a venous or arterial blood gas should be taken
typical carboxyhaemoglobin levels
< 3% non-smokers
< 10% smokers
10 - 30% symptomatic: headache, vomiting
> 30% severe toxicity
an ECG is a useful supplementary investgation to look for cardiac ischaemia

Question 28

Management for carbon monoxide poisoning?

Answer 28

100% high flow oxygen for min 6 hours
Hyperbaric oxygen

Question 29

features of lead poisoning?

Answer 29

abdominal pain
peripheral neuropathy (mainly motor)
neuropsychiatric features
fatigue
constipation
blue lines on gum margin (only 20% of adult patients, very rare in children)

Question 30

Investigations for lead poisoning?

Answer 30

he blood lead level is usually used for diagnosis. Levels greater than 10 mcg/dl are considered significant
full blood count: microcytic anaemia. Blood film shows red cell abnormalities including basophilic stippling and clover-leaf morphology
raised serum and urine levels of delta aminolaevulinic acid may be seen making it sometimes difficult to differentiate from acute intermittent porphyria
urinary coproporphyrin is also increased (urinary porphobilinogen and uroporphyrin levels are normal to slightly increased)
in children, lead can accumulate in the metaphysis of the bones although x-rays are not part of the standard work-up

Question 31

Management of led poisoning ?

Answer 31

dimercaptosuccinic acid (DMSA)
D-penicillamine
EDTA
dimercaprol

Question 32

Management of Benzo OD?

Answer 32

Flumazenil
The majority of overdoses are managed with supportive care only due to the risk of seizures with flumazenil. It is generally only used with severe or iatrogenic overdoses.

Question 33

management of lithium overdose?

Answer 33

Management
mild-moderate toxicity may respond to volume resuscitation with normal saline
haemodialysis may be needed in severe toxicity
sodium bicarbonate is sometimes used but there is limited evidence to support this. By increasing the alkalinity of the urine it promotes lithium excretion

Question 34

Management fo warfarin overdose?

Answer 34

Vitamin K, prothrombin complex

Question 35

Management of heparin overdose?

Answer 35

Protamine sulphate

Question 36

management of Ethylene glycol poisoning

Answer 36

Management has changed in recent times
ethanol has been used for many years
works by competing with ethylene glycol for the enzyme alcohol dehydrogenase
this limits the formation of toxic metabolites (e.g. Glycoaldehyde and glycolic acid) which are responsible for the haemodynamic/metabolic features of poisoning
fomepizole, an inhibitor of alcohol dehydrogenase, is now used first-line in preference to ethanol
haemodialysis also has a role in refractory cases

Question 37

Management of Iron OD?

Answer 37

Desferrioxamine, a chelating agent