Capsule cases Flashcards

1
Q

How to deal with suspected poisoning / overdose ?

A
Assess :
    - Level of consciousness - Glasgow 
      coma scale 
    - Breathing - respiratory rate , pulse 
     oximetry if possible. 
   - circulation - BP , pulse , temperature 
   - examination 
   - Taking history 

The history should include:
0 Why was the substance taken?
0 What substance(s) were taken?
0 When was it taken? - exact time of ingestion - especially important for paracetamol poisoning.
0 Who was involved - Age , sex , past medical history etc.

Arrange emergency transfer to hospital following the immediate assessment of the person if:
- The person is unconscious or has a reduced level of consciousness.

-  reduced respiratory rate or oxygen 
 saturation is reduced. 
- hypotension. 
- tachycardia or bradycardia or a irregular 
  pulse. 
- hypothermic or hyperthermic
- having seizure 
If there are any other concerning clinical features

Assess - in the case of self harm a mental state of patient.

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2
Q

Consquences /(signs / symptoms of Paractamol poisoning ?

A
  • NOTE - PARACETONOL OVERDOSE - MOST COMMON CAUSE OF ACUTE LIVER INJURY

COMMON

  • Nausea and Vomiting (only early signs - settle with 24hrs)

UNCOMMON

  • Right subcostal pain - development (suggest Hepatic necrosis) -
    Hepatic necrosis can lead to :
  • encephalopathy -effects the function/ structure of brain) )
    (occcurs because liver dysfunction impairs its function to remove toxins so these build up in blood and eventually travel to the brain.)
  • Hypoglycaemia
  • haemorrhage
  • cerebral oedema

OTHERS - Jaundice
- asterixis
(signs of acute liver injury)

*if have loin pain or proteinuria at least 24 hrs after para ingestion or serum creatinine > 300 mircomoles / L - sign of acute kidney injury
( if presenting 24 hrs after para ingestion - suspect kidney failure)

  • People may also present with coma or a reduced level of consciousness if they have taken paracetamol with a drug that reduces the level of consciousness, e.g. opioids (for example a combined paracetamol/opioid preparation) or alcohol.
  • Toxic doses of paracetamol may cause severe hepatocellular necrosis and, much less frequently, renal tubular necrosis. Liver damage is maximal 3–4 days after paracetamol overdose and may lead to hepatic failure, encephalopathy, coma, and death.

RISK FACTORS

  • History of self harm
  • history of repeated / frequent use of medications for pain relief.
  • Glutathione deficiency ( glutathione aids in detoxification of products of paracetamol, when this happens the toxic products bind to hepatic tissue and cells & cause damage ) - seen in pl with malnourishment.
  • drugs that induce liver enzymes (Cytochrome p450 inducers e.g. arbamazepine, phenobarbital, phenytoin, primidone, rifampicin, rifabutin, efavirenz, nevirapine, and St John’s wort.)
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3
Q

What patients should be urgently referred in the case of posioning?

A
  • All children and young people who have deliberately self-poisoned.
  • Adults who have deliberately self-poisoned.
  • People who are symptomatic.
  • People who have taken poisons with a delayed action. These include aspirin, iron, paracetamol, tricyclic antidepressants, co-phenotrope and all modified-release preparations.
  • Where the type of poison is unknown.
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4
Q

Treatment of paracetamol poisoning ?

A

IV - Acetylcysteine / N- Acetylcysteine - IV INFUSION!!!!!!

(can be given oral if IV not possible - unlicensed ) - 3 IV infusion over 21 hours.

0 Prevents or reduces the severity of liver damage if given within 24 hours (possibly beyond) of ingesting paracetamol.

0 Most effective if given within 8 hours of paracetamol ingestion, after which effectiveness declines.

Methionine is an alternative agent given orally - treats acetaminophen (american name )/paracetamol poisoning

  • LOOK AT FOLLOWING - THIS IS THE ONE YOU SHOULD MEMORISE

ACUTE SINGLE OVERDOSE

Supportive care + (consider activated charcoal ) + ( consider acetylysteine )

Consider activated charcoal if within 1 hour of ingesting more than 150mg/kg of paracetamol.

  • be careful of activated charcoal - in those with reduced GI molitilty (risk of small bowel obstruction) & comatose or drowsy (risk of aspiration)

Consider acetylsteine - if ingested more than 150 mg.kg taken within one hour (or acute overdose) & there will be a delay of more than 8 hours in getting serum paracetamol conc. ———————————————————————————-> if ingested less than 150mg/kg - wait for blood results before starting acetylcysteine - if one or above treatment threshold give acetylcysteine. ( treatment line will be down my nonogram (graph)

  • Can consider anti -emetic (ondasetron) - vomiting common for acetylcysteine - vomiting does not effect efficacy of treatment

STAGGERED OVERDOSE

Supportive treatment +
GIVE ACETYLCYSTEINE IMMEADIETELY irrespective of serum para concentration
( why ? - staggered overdoses are high risk & associated with reduced survival - bcc more likely to have risk factors older , more likely to abuse alcohol etc. )

Consider anti-emetic

THERAPEUTIC EXCESS

1ST LINE

Supportive treatment

PLUS ACETYLCYSTEINE if therapeutic excess + any one of these :

  • Serum para conc >/= 10mg/L
  • ALT is above upper level
  • INR > 1.3

Consider anti - emetic

  • note acetylcysteine indusion - should only be given closely mointored area - monitor for reactions : nausea , vomiting , flushing , urticarial rash , angioedema , tachycardia & bronchospasm - COMMON SIGNS ,
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5
Q

Overall treatment of poisoning / overdose ?

A

Activated Charcoal - Give by mouth - mixed with liquid .
* increases elimination of drug , passes through the GI tract faster - less absorbed into body.

0 Effective with 2 hours of ingestion.

If vomiting occurs - give anti -emetic (vomiting can reduce Charcoal efficacy )

Charcoal, activated should not be used for poisoning :

  • petroleum distillates,
  • corrosive substances,
  • alcohols,
  • malathion,
  • cyanides
  • metal salts including iron and lithium salts.
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6
Q

Side effects -of Acetylcysteine ?

A

Rash - most common - continue treatment.

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7
Q

What is aspirin ? - what is it derived from .

Consequences of Salicylate poisoning ?

A

Salicylates - derivatives of salicylic acid.

Aspirin is a salicylate . (acetylsalicylic acid)

  • Hyperventilation,
  • tinnitus, (ringing in the ears)
  • deafness,
  • vasodilatation,
  • sweating.
  • Coma if very severe poisoning.(uncommon)

Patients present with respiratory acidosis followed by metabolic acidosis.

*hyperglycaemia - recognised complication of this overdose.

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8
Q

Treatment of Aspirin poisoning ?

A

Haemodialysis -
severe salicylate poisoning
considered :

  • when plasma-salicylate concentration exceeds 700 mg/litre (5.1 mmol/litre)
  • in the presence of severe metabolic acidosis.
  • Activated charcoal can be given within 1 hour of ingesting more than 125mg / kg of aspiring.

0 Alkalisation of urine - IV Sodium bicarbonate - (increase PH of urine ) - increases elimination of salicylates.

  • Plasma-potassium concentration should be corrected before giving sodium bicarbonate as hypokalaemia may complicate alkalinisation of the urine.
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9
Q

Precise treatment of paracetamol poisoning for single acute Overdose ?

A

0 -8 Hrs
 Consider activated charcoal if
presentation within 1 hour from
ingestion.

 Take bloods 4 hours after
ingestion and await plasma
paracetamol levels.

 Treat if above, on, or slightly
below the appropriate treatment
line

8- 24
 Take bloods
 If >150 mg/kg give acetylcysteine
immediately.
 If < 150 mg/kg, wait for blood
results before considering
treatment.
>24
 Take bloods
 If patient is jaundiced or has
hepatic tenderness treat with
acetylcysteine.
 Otherwise wait for blood results
before commencing treatment.
Treat if:
 Paracetamol detected.
 INR >1.3
 ALT > X2 times the upper limit of
normal.
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10
Q

What groups should be treated for a paracetamol poisoning at lower levels ?

A
  • Alcoholics
  • HIV positive
  • Malnourished
  • Epileptics
  • Cirrhotic

Those with pre-existing liver disease or on enzyme-inducing drugs e.g. phenytoin, carbamezopine for epilepsy need treatment at lower paracetamol levels.

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11
Q

What is Methotreaxte and Sulfaslazine ?

A

Immunosuppressant - treat inflammatory conditions

Rheumatoid arthritis - 7.5mg
- Psoriasis - include - psoriasis arthritis.
also sarcoidosis

  • taken once a week
  • folic acid can be given in conjunction . Take day after methotrexate. (Methotrexate can decrease levels of vitamin e.g. folate) - METHOTREXATE - FOLIC ACID ANTAGONIST.)
  • methotrexate - cytotoxic agent (kills cancer cells and can damage normal tissue)

Sulfasalazine - Anti -inflammatory drug

Treat :
Rheumatoid A
Ulcerative colitis
Crohns disease.

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12
Q

What is Methotreaxte and Sulfaslazine ?

A

Immunosuppressant - treat inflammatory conditions

Rheumatoid arthritis - 7.5mg
- Psoriasis - include - psoriasis arthritis.
also sarcoidosis

  • taken once a week
  • folic acid can be given in conjunction . Take day after methotrexate (\BCC THE 2 DRUGS HAVE OPPOSING EFFECTS). (Methotrexate can decrease levels of vitamin e.g. folate) - METHOTREXATE - FOLIC ACID ANTAGONIST.)

Multi- Vitamin supplements should be avoided as have Folic acid and could interfere with action of methotrexate.

  • methotrexate - cytotoxic agent (kills cancer cells and can damage normal tissue)

Sulfasalazine - Anti -inflammatory drug -orange / yellow colour ( can cause orange ting to urine)

Treat :
Rheumatoid A
Ulcerative colitis
Crohns disease.

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13
Q

What needs to be monitored with methotrexate therapy ?

A

Chest X ray recommended before starting therapy. ( mostly with rheumatoid athritis)

Increased concentrations can be toxic can cause:

  • liver damage - if substantial hepatic functions abnormalities - treatment suspended for minimum 2 weeks. Substance toxic to the liver should also be avoided e.g. alcohol. if abnormalities back to normal therapy can continue.
  • Kidney damage
  • Suppression of cell production from bone marrow.
  • profound drop in WBC or platelet count - stop treatment. )
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14
Q

Methotrexate and NSAIDS ?

A

Use of them together is safe providing monitoring of methotrexate levels is done.

Risk of methotrexate toxicity in High dose patients -

( * inhibit the synthesis of prostaglandins resulting in a fall in renal perfusion, which could lead to a rise in serum methotrexate levels accompanied by increased toxicity. )

NSAIDS

0 Ibuprofen
0 Dicofenac
0 Aspirin
0 Naproxen

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15
Q

Trimethoprim , methotrexate ?

A

DON’T USE TOGETHER.

Trimethoprim - folate anatgonist and so is Methotrexate

Also impairs bone production , trimethoprim makes it worse. ( myelosuppression)

Both increase risk of nephrotoxicity.

  • reported to cause acute megaloblastic pancytopenia in rare instances.
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16
Q

What should be prescribe alongside Prednisolone (especially high risk groups)

A
  • Bisphosphonates - 1ST line - Alendronic acid

With Calcium and Vitamin D supplementation. (Adcal D3 - CA and VD preperation)

17
Q

Characteristics of Nephrotic syndrome ?

A

hypoalbuminemia - low albumin in blood
proteinuria,- protein in urine
oedema, hypercholesterolaemia - high cholesterol in the blood.
.

Nephrotic syndrome is a condition that causes the kidneys to leak large amounts of protein into the urine. This can lead to a range of problems, including swelling of body tissues and a greater chance of catching infections.

18
Q

Treatment of Osteoporosis ?- post menopausal women - non Glucocorticoid induced

A

Not Glucocorticoid (steriod) induce women

Post menopausal 
1st line - 
O Alendronic Acid or risedronate sodium ETC - biphosphonate
-zoledronic acid
- ibandronic acid

2ND LINE

Denosumab - rank ligand inhibitor

abaloparatide
or Teriparatide - PTH
( should follow with antiresorptive agent e.g biphosphonate,
When treatment with teriparatide or abaloparatide is stopped, bone loss can be rapid and alternative agents should be considered to maintain bone mineral density (BMD).)

Only given IV and if Oral Bisphosphonate , rank ligand , PTH cannot be tolerated/ contraindicated or t score is very low

4TH LINE
raloxifene or
bazedoxifene Selective oestrogen receptor modulators ( SERM)

5TH LINE

HRT

6TH LINE

Intranasal calcitonin

7TH LINE

oestrogens, conjugated/bazedoxifene - ONLY for post men women who still have uterus.

8TH LINE

romosozumab - only if all others fail/ contraindicated

Romosozumab (Evenity) is in a class called sclerostin inhibitors and is considered an anabolic agent. Sclerostin is a protein that helps regulate bone metabolism. Produced by osteocytes (bone cells), it inhibits bone formation (making new bone).

Vitamin D & calcium supplements e.g. ergocaliferol & calcium - SHOULD ALWAYS BE GIVEN WITH EVERY LINE OF TREATMENT

19
Q

What are the different Types of Ulcers ?

A
  • Venous - stasis -most common - damage to veins - insufficient blood flow back to heart - develop on inner side of ankle , leg and beneath knee
  • Arterial - ischaemic - damage to arteries bcc of lack of blood flow. - develop on outer side of ankle. feet, toes and heels.
  • Stomach
  • Neurotrophic - occur mainly in diabetic patients -
    (have lost peripheral sensation so cute etc go unnoticed and may develop into ulcers. )
  • located on pressure points on the sole of foot.
  • People with diabetes should not walk barefoot and inspect feet daily.
  • peripheral neuropathy - most common case diabetes type 1 and 2 . High glucose levels damage nerves - diabetic polyneuropathy.
20
Q

What are the different Types of Ulcers ?

A
  • Venous - stasis -most common - damage to veins - insufficient blood flow back to heart - develop on inner side of ankle , leg and beneath knee
  • Arterial - ischaemic - damage to arteries bcc of lack of blood flow. - develop on outer side of ankle. feet, toes and heels.
  • Stomach
  • Neurotrophic - occur mainly in diabetic patients -
    (have lost peripheral sensation so cute etc go unnoticed and may develop into ulcers. )
  • located on pressure points on the sole of foot.
  • People with diabetes should not walk barefoot and inspect feet daily.
  • peripheral neuropathy - (nerve sin extremities damaged) most common case diabetes type 1 and 2 . High glucose levels damage nerves - diabetic polyneuropathy.
  • Malignant Ulcers.
  • Vasculitic ulcers- caused by conditions which cause inflammation of BV -vasculitis
21
Q

What is Atelectasis ?

A

Airways and air sacs in lung collapse / deflate

Either due to

  • blocked airway
  • pressure from outside lung

general anaesthesia common cause (given during surgery) - changes pattern of breathing and effects gas exchange - causing alveoli to deflate.

22
Q

Treatment of osteoporosis- men ( non Glucocorticoid induced,)

A

1ST LINE

Biphosphonate -

2ND LINE

Teriparatide - PTH
Plus - antiresorptive agent
Vitamin D & calcium supplements e.g. ergocaliferol & calcium

ADJUNCT - TESTERONE

( should follow with antiresorptive agent e.g biphosphonate,
When treatment with teriparatide or abaloparatide is stopped, bone loss can be rapid and alternative agents should be considered to maintain bone mineral density (BMD).)

3RD LINE

  • Denosumab

Vitamin D & calcium supplements e.g. ergocaliferol & calcium - SHOULD ALWAYS BE GIVEN WITH EVERY LINE OF TREATMENT

23
Q

Treatment of osteoporosis _ Glucocorticoid induced?

A

1ST LINE

Biphosphonate - alendron , risedronate , zoledronic

2ND LINE

Teriparatide - PTH receptor agonist
Plus - antiresorptive agent
Vitamin D & calcium supplements e.g. ergocaliferol & calcium

( should follow with antiresorptive agent e.g biphosphonate,
When treatment with teriparatide or abaloparatide is stopped, bone loss can be rapid and alternative agents should be considered to maintain bone mineral density (BMD).)

3RD LINE

  • Denosumab

Vitamin D & calcium supplements e.g. ergocaliferol & calcium - SHOULD ALWAYS BE GIVEN WITH EVERY LINE OF TREATMENT

24
Q

Denosumab

  • common side effects ( not exhaustive)
  • cautions
A
Constipation 
Increased risk of infection
Scaitica 
Pain
Skin reactions 
Cataract 

Side effect - rare

  • atypical femoral fractures ( should repeat any usual pain of the hip, thigh or groin on this medication)
  • osteoporosis of jaw- Cancer indications

Caution

Pregnancy - risk of fetal harm ,still births etc - women of chile bearing age should have effective contraception during treatment 5 months after stopping.

Risk of hypocalcemia- plasma calcium monitoring is recommended for some indications

25
Q

Tereparatide

Cautions

A

Avoid in pregnancy.

Contraindications

Hyperparathyroidism ( bcc it is PTH agonist).

Bone metastases;hyperparathyroidism;metabolic bone diseases;Paget’s disease;pre-existing hypercalcaemia;previous radiation therapy to the skeleton;skeletal malignancies;unexplained raised alkaline phosphatase

26
Q

What is Atrial Myxoma ?

A

Type of Benign Cardiac Tumour (Cardiac tumours are rare - this is the most common form)

Usually found in left atrium attached to septum.

SYMPTOMS

  • Dyspnoea

(Linked to Mitral valve obstruction)

  • Syncope
  • Dizziness
  • CHF/Pulmonary oedema
  • Systolic or diastolic murmur
  • About 34% of patients have constitutional or systemic symptoms (fever, weight loss, fatigue, myalgia, arthralgia, Raynaud’s phenomenon

RISK FACTORS

  • Female sex
  • Age 40 -60
27
Q

Diagnosis of Atrial Myxoma ?

A

0 Echocardiogram
(mass seen on imaging)

0 ECG
- (hypertrophy, rhythm disorder , conduction abnormalities - non -specific symptoms)

0 FBC - anaemia (found in some)

0 CXR (cardiomegaly , pulmonary oedema , calcification of myxoma - can be some or all etc)

CAN CONSIDER

ESR , CRP ,
(elevated)

CT , MRI chest , Biopsy - can be done to differentiate btw mass and thrombus..

28
Q

Treatment of Atrial Myxoma ?

A

Surgical candidate

1ST LINE

Myxoma resection (Atriotomy)

Adjunct -
O valve repair/replacement + / - coronary bypass graft

O Post - operative aspirin ,

O Treatment if Dysrythmia (beta- blockers etc) , Heart failure or embolisation (ACE inhibitors , Beta blockers , Furosemide etc.)
(THIS WOULD BE ALSO USED AS FIRST LINE FOR NON SURGICAL CANDIDATE)

29
Q

Side effects of biphosphonates?

A

Bisphosphonates can cause a variety of oesophageal problems

0 Oesophagitis
, oesophageal ulcers ( discontinue)(especially alendronate)

0 irritation to the foodpipe

0 heartburn

swallowing problems (dysphagia)

stomach pain - gastric ulcer

0 fever , malaise

0 joint pain

0 hypocalcemia (electrolyte imbalance)

Osteonecrosis of the jaw is arare side effect - if history of dental problems see dentist before starting.

If ALENDRONATE NOT TOLERATED GIVE RISENDEONATE

30
Q

What is Ramsey hunt syndrome?

A

Ramsay Hunt syndrome (RHS) is arare neurological disordercharacterized by paralysis of the facial nerve (facial palsy) and a rash affecting the ear or mouth. Ear abnormalities such as ringing in the ears (tinnitus) and hearing loss may also be present.

Caused by varicella zoster infects facial causing inflammation.

31
Q

What is Carbon monoxide poisoning ?

A

SIGNS / SYMPTOMS

  • Cherry red flushed skin colour
  • Nausea & Vomiting
  • Vertigo
  • Headache - tension type headache
  • Altered conciousness
  • dizziness
  • dyspnoea - SOB
  • pain
  • sleep changes (fatigue , tiredness, sleep disturbance)

Delayed neuropyschiatric signs - memory impairment , disorientation, apathy , irritable , difficulty concentration , personality change , neuropathy , chorea , apraxia . pyschosis , dementia , parkinsonism

  • Severe poisoning - neurolohical symptoms - cerebral oedema , conciousness impairment.
32
Q

Diagnosis of Carbon monoxide poisoning ?

A

COMA - ask to determine likelihood

0 C -Cohabitees/companions Is anyone else in the property affected (including pets)?
0 O - Outdoors Do the symptoms improve when out of the building?
0 M- Maintenance Are any fuel-burning appliances and vents properly maintained?
0 A - Alarm Does the affected building have a carbon monoxide alarm?

if likely :

0 Blood gas analysis ( not 02 monitor cause CO has same affinity for haem as 02)

0 ECG - may be associated with angina , ischeamia

0 Cardiac monitoring - check for arrythmias etc.

0 BP

0 FBC - look for
leukocytosis

0 Blood glucose - normal or elevated.

0 U & E

0 Troponin

0 Creatine kinase- elevated if sketelal muscle damage.

CONSIDER :

CXR - IF SEVERE - can develop pulmomary complications

CT head - rule out other causes - if diziness , confusion , headache, seizure etc.

  • Liver function test
33
Q

Treatment of CO poisoning ?

A

1ST LINE

Oxygen
(100 % , reservior mask 15L /min)
+ supportive care +monitoring

Can consider Hyperbaric oxygen therapy (( administration of 100% oxygen at pressures higher than atmospheric pressure.) - not rountinely recommended

ndications for hyperbaric oxygen include:[16]

Loss of consciousness at any stage
Neurological signs or symptoms other than headache
Myocardial ischaemia/arrhythmia diagnosed by ECG
Pregnancy.

34
Q

How should standard release nitrate preparations be taken?

A

Assymetric doses (basically if taking 2 doses - take 1st dose then leave time in between to prevent building up tolerance. —> prevent nitrate tolerance.

e.g. Isorbide dinitrate.

35
Q

Different types of paracetamol overdose ?

A

Acute overdose - excess amounts of para taken within 1 hour (usually self harm)

Staggered overdose - excessive amounts of para ingested over longer than 1 hour (usually self harm)

Therapeutic excess - taken to treat pain or fever (no meant to self harm) e.g taken more than one paracetamol containing product.

Serious toxicity may occur if if ingested more than 150mg/kg in 24 hrs.
(below 75mg/kg in 24hrs unlikely to cause toxicity -but increased for 2 or more days - risk increaes. )

36
Q

For knowlegde - what is the west haven critera?

how do these grades effect treatment?

A

0 Grade 0: subclinical; normal mental status but minimal changes in memory, concentration, intellectual function, coordination.

0 Grade 4: coma, with or without response to painful stimuli

0 Grade 3: drowsy but rousable, unable to perform mental tasks, disorientation to time and place, marked confusion, amnesia, occasional fits of rage, speech present but incomprehensible

GRADE 3 & 4

  • NEED:
  • Intubation (endotracheal tube - tube placed through mouth into airway - so that patient can be placed on ventilator to assist bretahing )
  • Mechanical ventilation

0 Grade 2: drowsiness, lethargy, gross deficits in ability to perform mental tasks, obvious personality changes, inappropriate behaviour, intermittent disorientation

  • Require intensive monitoring as at risk of decompensation.

0 Grade 1: mild confusion, euphoria, or depression, decreased attention, slowing of ability to perform mental tasks, irritability, disorder of sleep pattern such as inverted sleep cycle

0 Grade 0: subclinical; normal mental status but minimal changes in memory, concentration, intellectual function, coordination.

37
Q

Investigation of paracetamol overdose?

A
  • Serum paracetamol concentration
  • (Escalate to critical care if the serum paracetamol concentration is very high (>700 mg/L) and is associated with coma and elevated lactate level.)

LFT -
(ALT above upper limit of normal - indicate acute liver injury)

PTT & INR
(may be prolonged
INR > 1.3 - urgent referral
PTT > 30 sec - referral)

Blood glucose - hypogycemia (<3.3 mmol/L)
( indicate acute liver injury )

U & E , & Creatinine

ABG or venous blood gas
(check serum lactate - Lactate acidsosis
refer urgently if
> 3.5 on admission or > 3.0 mmol/L post paracetomol ingestion or after fluid resus)

FBC - may show :

  • leukocytosis
  • anaemia
  • thrombocytopenia

CONSIDER :

Urine analysis (looking for proteinuria / haematuria - suggest AKI. )k

0 Urine drug screen

38
Q

Types of paracetamol overodose ?

A

Acute overdose - excess amounts of para taken within 1 hour (usually self harm)

Staggered overdose - excessive amounts of para ingested over longer than 1 hour (usually self harm)

Therapeutic excess - taken to treat pain or fever (no meant to self harm) e.g taken more than one paracetamol containing product.

Serious toxicity may occur if if ingested more than 150mg/kg in 24 hrs.
(below 75mg/kg in 24hrs unlikely to cause toxicity -but increased for 2 or more days - risk increaes. )