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Flashcards in Pharmacology Deck (35)
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1
Q

Palliative care prescribing pain

A

NICE guidelines

In 2012 NICE published guidelines on the use of opioids in palliative care. Selected points are listed below. Please see the link for more details.

Starting treatment

when starting treatment, offer patients with advanced and progressive disease regular oral modified-release (MR) or oral immediate-release morphine (depending on patient preference), with oral immediate-release morphine for breakthrough pain

if no comorbidities use 20-30mg of MR a day with 5mg morphine for breakthrough pain. For example, 15mg modified-release morphine tablets twice a day with 5mg of oral morphine solution as required

oral modified-release morphine should be used in preference to transdermal patches

laxatives should be prescribed for all patients initiating strong opioids

patients should be advised that nausea is often transient. If it persists then an antiemetic should be offered

drowsiness is usually transient - if it does not settle then adjustment of the dose should be considered

SIGN guidelines

SIGN issued guidance on the control of pain in adults with cancer in 2008. Selected points

the breakthrough dose of morphine is one-sixth the daily dose of morphine

all patients who receive opioids should be prescribed a laxative

opioids should be used with caution in patients with chronic kidney disease. Alfentanil, buprenorphine and fentanyl are preferred

metastatic bone pain may respond to strong opioids, bisphosphonates or radiotherapy. The assertion that NSAIDs are particularly effective for metastatic bone pain is not supported by studies. Strong opioids have the lowest number needed to treat for relieving the pain and can provide quick relief, in contrast to radiotherapy and bisphosphonates*. All patients, however, should be considered for referral to a clinical oncologist for consideration of further treatments such as radiotherapy

Other points

When increasing the dose of opioids the next dose should be increased by 30-50%.

In addition to strong opioids, bisphosphonates and radiotherapy, denosumab may be used to treat metastatic bone pain.

Opioid side-effects

Usually transient

Usually persistent

Nausea
Drowsiness

Constipation

2
Q

Tuberculosis: drug side-effects and mechanism of action

A

Rifampicin

mechanism of action: inhibits bacterial DNA dependent RNA polymerase preventing transcription of DNA into mRNA

potent liver enzyme inducer

hepatitis, orange secretions

flu-like symptoms

Isoniazid

mechanism of action: inhibits mycolic acid synthesis

peripheral neuropathy: prevent with pyridoxine (Vitamin B6)

hepatitis, agranulocytosis

liver enzyme inhibitor

Pyrazinamide

mechanism of action: converted by pyrazinamidase into pyrazinoic acid which in turn inhibits fatty acid synthase (FAS) I

hyperuricaemia causing gout

arthralgia, myalgia

hepatitis

Ethambutol

mechanism of action: inhibits the enzyme arabinosyl transferase which polymerizes arabinose into arabinan

optic neuritis: check visual acuity before and during treatment

dose needs adjusting in patients with renal impairment

Ethambutol is associated with optic neuropathy and development of colour blindness. It should be discontinued if these symptoms develop. In clinical practice pyridoxine (vitamin B6) is given concurrently with ethambutol to try to prevent these side effects.

3
Q

Quinolones

A

Quinolones are a group of antibiotics which work by inhibiting DNA synthesis and are bactericidal in nature. Examples include:

ciprofloxacin

levofloxacin

Mechanism of action

inhibit topoisomerase II (DNA gyrase) and topoisomerase IV

Mechanism of resistance

mutations to DNA gyrase, efflux pumps which reduce intracellular quinolone concentration

Adverse effects

lower seizure threshold in patients with epilepsy

tendon damage (including rupture) - the risk is increased in patients also taking steroids

cartilage damage has been demonstrated in animal models and for this reason quinolones are generally avoided (but not necessarily contraindicated) in children

lengthens QT interval

Contraindications

Quinolones should generally be avoided in women who are pregnant or breastfeeding

avoid in G6PD

4
Q

Mefloquine

A

Mefloquine (brand name Lariam) is used for both the prophylaxis and treatment of certain types of malaria. There has long been a concern about the neuropsychiatric side-effects of mefloquine. A recent review has however led to ‘strengthened warnings’ about the potential risks.

The following advice is therefore given:

certain side-effects such nightmares or anxiety may be ‘prodromal’ of a more serious neuropsychiatric event

suicide and deliberate self harm have been reported in patients taking mefloquine

adverse reactions may continue for several months due to the long half-life or mefloquine

mefloquine should not be used in patients with a history of anxiety, depression schizophrenia or other psychiatric disorders

patients who experience neuropsychiatric sife-effects should stop mefloquine and seek medical advice

5
Q

Antibiotics

A

Nitrofurantoin is a relatively old and unique antibiotic which has enjoyed a new lease of life with increasing antibiotic resistance. It is actually an inactive pro-drug which is reduced in vivo to active forms by the bacterial flavoprotein nitrofuran reductase, and it is these reduced forms of the drug which exert their antibiotic properties by damaging bacterial proteins. In order to be effective at treating urinary tract infections, nitrofurantoin needs to be concentrated in the urine and an adequate glomerular filtration is required for this to occur. An eGFR of less than 40-60ml/min means that the drug is wholly ineffective as a bactericidal agent and is not recommended in patients with CKD stage 3 or worse due to the likelihood of treatment failure. Coupled with this is the risk of drug toxicity in the patient. Without adequate renal filtration, the drug is likely to accumulate. Although bacterial flavoproteins activate nitrofurantoin more readily, human enzymes can reduce this drug to generate many highly active radical species, which can cause side effects including peripheral neuropathy, which may not be reversible, hepatotoxicity and acute and chronic pulmonary reactions and fibrosis.

Patients taking nitrofurantoin should be advised that this drug will discolour the urine. It is also a safe drug to use in pregnancy except at full term when there is a risk of haemolysis in the neonate.

Amoxicillin and co-amoxiclav are widely used antibiotics in the treatment of urinary tract infections and are relatively safe in renal impairment. Dose reduction is recommended in severe chronic renal disease, i.e. an eGFR <15-30ml/min to avoid the risk of crystalluria. Similarly, a reduction in dose is necessary for ciprofloxacin in CKD to avoid crystalluria although this is recommended from an eGFR of 30-60ml/min.

Trimethoprim is an antibiotic which is entirely safe to use in all but the most severe forms of chronic kidney disease where a modest dose adjustment is required. It should be noted however that use of trimethoprim is likely to affect the results of renal function tests since the drug inhibits tubular secretion of creatinine leading to a rise in serum levels in all patients, including those with previously normal renal function. This is without any effect on the glomerular filtration rate.

6
Q

Prescribing in patients with renal failure

A

Questions regarding which drugs to avoid in renal failure are common

Drugs to avoid in renal failure

antibiotics: tetracycline, nitrofurantoin

NSAIDs

lithium

metformin

Drugs likely to accumulate in chronic kidney disease - need dose adjustment

most antibiotics including penicillins, cephalosporins, vancomycin, gentamicin, streptomycin

digoxin, atenolol

methotrexate

sulphonylureas

furosemide

opioids

Drugs relatively safe - can sometimes use normal dose depending on the degree of chronic kidney disease

antibiotics: erythromycin, rifampicin

diazepam

warfarin

Side-effects of common drugs: antibiotics

The table below summarises characteristic (if not necessarily the most common) side-effects of drugs used antibiotics

Drug

Side-effect

Amoxicillin

• Rash with infectious mononucleosis

Co-amoxiclav

• Cholestasis

Flucloxacillin

• Cholestasis (usually develops several weeks after use)

Erythromycin

• Gastrointestinal upset
• Prolongs QT interval

Ciprofloxacin

• Lowers seizure threshold
• Tendonitis

Metronidazole

• Reaction following alcohol ingestion

Doxycycline

• Photosensitivity

Trimethoprim

• Rashes, including photosensitivity
• Pruritus
• Suppression of haematopoiesis

All tetracyclines should be avoided in pregnancy.

It should be noted that the above prescriptions are not necessarily the recommended first-line treatments

7
Q

Prescribing in pregnant patients

A

Very few drugs are known to be completely safe in pregnancy. The list below largely comprises of those known to be harmful. Some countries have developed a grading system - see the link.

Antibiotics

tetracyclines

aminoglycosides

sulphonamides and trimethoprim

quinolones: the BNF advises to avoid due to arthropathy in some animal studies

Other drugs

ACE inhibitors, angiotensin II receptor antagonists

statins

warfarin

sulfonylureas

retinoids (including topical)

cytotoxic agents

The majority of antiepileptics including valproate, carbamazepine and phenytoin are known to be potentially harmful. The decision to stop such treatments however is difficult as uncontrolled epilepsy is also a risk

8
Q

Digoxin and digoxin toxicity

A

Digoxin is a cardiac glycoside now mainly used for rate control in the management of atrial fibrillation. As it has positive inotropic properties it is sometimes used for improving symptoms (but not mortality) in patients with heart failure.

Mechanism of action

decreases conduction through the atrioventricular node which slows the ventricular rate in atrial fibrillation and flutter

increases the force of cardiac muscle contraction due to inhibition of the Na+/K+ ATPase pump. Also stimulates vagus nerve

digoxin has a narrow therapeutic index

Monitoring

digoxin level is not monitored routinely, except in suspected toxicity

if toxicity is suspected, digoxin concentrations should be measured within 8 to 12 hours of the last dose

Digoxin toxicity

Plasma concentration alone does not determine whether a patient has developed digoxin toxicity. Toxicity may occur even when the concentration is within the therapeutic range. The BNF advises that the likelihood of toxicity increases progressively from 1.5 to 3 mcg/l.

Features

generally unwell, lethargy, nausea & vomiting, anorexia, confusion, yellow-green vision

arrhythmias (e.g. AV block, bradycardia)

gynaecomastia

Precipitating factors

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

Management

Digibind

correct arrhythmias

monitor potassium

9
Q

Calcium channel blockers

A

Calcium channel blockers are primarily used in the management of cardiovascular disease. Voltage-gated calcium channels are present in myocardial cells, cells of the conduction system and those of the vascular smooth muscle. The various types of calcium channel blockers have varying effects on these three areas and it is therefore important to differentiate their uses and actions.

Examples

Indications & notes

Side-effects and cautions

Verapamil

Angina, hypertension, arrhythmias

Highly negatively inotropic

Should not be given with beta-blockers as may cause heart block

Heart failure, constipation, hypotension, bradycardia, flushing

Diltiazem

Angina, hypertension

Less negatively inotropic than verapamil but caution should still be exercised when patients have heart failure or are taking beta-blockers

Hypotension, bradycardia, heart failure, ankle swelling

Nifedipine, amlodipine, felodipine
(dihydropyridines)

Hypertension, angina, Raynaud’s

Affects the peripheral vascular smooth muscle more than the myocardium and therefore do not result in worsening of heart failure

Flushing, headache, ankle swelling

10
Q

Metformin

A

Metformin is a biguanide used mainly in the treatment of type 2 diabetes mellitus. It has a number of actions which improves glucose tolerance (see below). Unlike sulphonylureas it does not cause hypoglycaemia and weight gain and is therefore first-line, particularly if the patient is overweight. Metformin is also used in polycystic ovarian syndrome and non-alcoholic fatty liver disease

Mechanism of action

acts by activation of the AMP-activated protein kinase (AMPK)

increases insulin sensitivity

decreases hepatic gluconeogenesis

may also reduce gastrointestinal absorption of carbohydrates

Adverse effects

gastrointestinal upsets are common (nausea, anorexia, diarrhoea), intolerable in 20%

reduced vitamin B12 absorption - rarely a clinical problem

lactic acidosis* with severe liver disease or renal failure

Contraindications

chronic kidney disease: NICE recommend that the dose should be reviewed if the creatinine is > 130 µmol/l (or eGFR < 45 ml/min) and stopped if the creatinine is > 150 µmol/l (or eGFR < 30 ml/min)

metformin may cause lactic acidosis if taken during a period where there is tissue hypoxia. Examples include a recent myocardial infarction, sepsis, acute kidney injury and severe dehydration

iodine-containing x-ray contrast media: examples include peripheral arterial angiography, coronary angiography, intravenous pyelography (IVP); there is an increasing risk of provoking renal impairment due to contrast nephropathy; metformin should be discontinued on the day of the procedure and for 48 hours thereafter

alcohol abuse is a relative contraindication

Starting metformin

metformin should be titrated up slowly to reduce the incidence of gastrointestinal side-effects

if patients develop unacceptable side-effects then modified-release metformin should be considered

*it is now increasingly recognised that lactic acidosis secondary to metformin is rare, although it remains important in the context of exams

11
Q

Side-effects of common drugs: diabetes drugs

A

The table below summarises characteristic (if not necessarily the most common) side-effects of drugs used to treat diabetes mellitus

Drug

Side-effect

Metformin

Gastrointestinal side-effects
Lactic acidosis

Sulfonylureas

Hypoglycaemic episodes
Increased appetite and weight gain
Syndrome of inappropriate ADH secretion
Liver dysfunction (cholestatic)

Glitazones

Weight gain
Fluid retention
Liver dysfunction
Fractures

Gliptins

Pancreatitis

NICE recommend that the dose of metformin should be reviewed if the creatinine is > 130 micromol/l (or eGFR < 45 ml/min) and stopped if the creatinine is > 150 micromol/l (or eGFR < 30 ml/min)

Important for meLess important

Metformin is the drug that needs to be stopped in this case. NICE recommendations on the use of metformin in the treatment of diabetes mellitus specify that:

A review of the dose of metformin be undertaken if the serum creatinine exceeds 130 micromol/litre or the estimated glomerular filtration rate (eGFR) is below 45 ml/minute/1.73m²

Stop Metformin if the serum creatinine exceeds 150 micromol/litre or the eGFR is below 30 ml/minute/1.73m²

12
Q

St John’s Wort

A

Overview

shown to be as effective as tricyclic antidepressants in the treatment of mild-moderate depression

mechanism: thought to be similar to SSRIs (although noradrenaline uptake inhibition has also been demonstrated)

NICE advise ‘may be of benefit in mild or moderate depression, but its use should not be prescribed or advised because of uncertainty about appropriate doses, variation in the nature of preparations, and potential serious interactions with other drugs’

Adverse effects

profile in trials similar to placebo

can cause serotonin syndrome

inducer of P450 system, therefore decreased levels of drugs such as warfarin, ciclosporin. The effectiveness of the combined oral contraceptive pill may also be reduced

13
Q

Gentamicin

A

Aminoglycosides are nephrotoxic

Importance: 50

is an amino glycoside antibiotic with excellent cover of gram negative bacteria. It is used for severe infections, and is particularly useful for severe infections of the urinary tract and within the abdomen.

A common complication associated with gentamicin usage is nephrotoxicity.

This is because of the narrow therapeutic window required to achieve a therapeutic dose. If we go above this index we risk nephrotoxicity.

Another common complication is ototoxicity and this is often examined in final exams.

More on Gentamicin - http://qjmed.oxfordjournals.org/content/102/12/873

Gentamicin is a type of aminoglycoside antibiotic. It is poorly lipid-soluble and is therefore given parentally (e.g. for infective endocarditis) or topically (e.g. for otitis externa).

Adverse effects

ototoxicity

due to auditory or vestibular nerve damage

irreversible

nephrotoxicity

accumulates in renal failure

the toxicity is secondary to acute tubular necrosis

concomitant use of furosemide increases the risk

lower doses and more frequent monitoring is required

Contraindications

myasthenia gravis

Dosing

due to the significant ototoxic and nephrotoxic potential of gentamicin it is important to monitor plasma concentrations

both peak (1 hour after administration) and trough levels (just before the next dose) are measured

if the trough (pre-dose) level is high the interval between the doses should be increased

if the peak (post-dose) level is high the dose should be decreased

14
Q

P450 enzyme system

A

Induction usually requires prolonged exposure to the inducing drug, as opposed to P450 inhibitors, where effects are often seen rapidly

Inducers of the P450 system include

antiepileptics: phenytoin, carbamazepine
barbiturates: phenobarbitone

rifampicin

St John’s Wort

chronic alcohol intake

griseofulvin

smoking (affects CYP1A2, reason why smokers require more aminophylline)

Inhibitors of the P450 system include

antibiotics: ciprofloxacin, erythromycin

isoniazid

cimetidine,omeprazole

amiodarone

allopurinol

imidazoles: ketoconazole, fluconazole

SSRIs: fluoxetine, sertraline

ritonavir

sodium valproate

acute alcohol intake

quinupristin

Sulfasalazine can cause lung fibrosis

15
Q

Drugs causing lung fibrosis

A

Causes

amiodarone

cytotoxic agents: busulphan, bleomycin

anti-rheumatoid drugs: methotrexate, sulfasalazine

nitrofurantoin

ergot-derived dopamine receptor agonists (bromocriptine, cabergoline, pergolide)

Side-effects of common drugs: anti-hypertensives

The table below summarises characteristic (if not necessarily the most common) side-effects of drugs used to treat hypertension

Drug

Side-effect

ACE inhibitors

• Cough
• Hyperkalaemia

Bendroflumethiazide

• Gout
• Hypokalaemia
• Hyponatraemia
• Impaired glucose tolerance

Calcium channel blockers

• Headache
• Flushing
• Ankle oedema

Beta-blockers

• Bronchospasm (especially in asthmatics)
• Fatigue
• Cold peripheries

Doxazosin

• Postural hypotension

16
Q

Lithium toxicity

A

Lithium is a mood stabilising drug used most commonly prophylactically in bipolar disorder but also as an adjunct in refractory depression. It has a very narrow therapeutic range (0.4-1.0 mmol/L) and a long plasma half-life being excreted primarily by the kidneys. Lithium toxicity generally occurs following concentrations > 1.5 mmol/L.

Toxicity may be precipitated by:

dehydration

renal failure

drugs: diuretics (especially thiazides), ACE inhibitors/angiotensin II receptor blockers, NSAIDs and metronidazole.

Features of toxicity

coarse tremor (a fine tremor is seen in therapeutic levels)

hyperreflexia

acute confusion

seizure

coma

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

17
Q

Ecstasy poisoning

A

Ecstasy (MDMA, 3,4-Methylenedioxymethamphetamine) use became popular in the 1990’s during the emergence of dance music culture

Clinical features

neurological: agitation, anxiety, confusion, ataxia
cardiovascular: tachycardia, hypertension

hyponatraemia

hyperthermia

rhabdomyolysis

Management

supportive

dantrolene may be used for hyperthermia if simple measures fail

18
Q

Drug-induced urinary retention

A

The following drugs may cause urinary retention:

tricyclic antidepressants

anticholinergics

opioids

NSAIDs

disopyramide

The BNF advises avoiding quinolones in pregnancy due to arthropathy in animal studies.

There have been some reports of an increased risk of necrotizing enterocolitis following the use of co-amoxiclav in pregnancy. The evidence is however inconclusive and the BNF states that co-amoxiclav is ‘not known to be harmful’. A link is provided both to the BNF and the UK teratology information service.

19
Q

Prescribing in pregnant patients

A

Very few drugs are known to be completely safe in pregnancy. The list below largely comprises of those known to be harmful. Some countries have developed a grading system - see the link.

Antibiotics

tetracyclines

aminoglycosides

sulphonamides and trimethoprim

quinolones: the BNF advises to avoid due to arthropathy in some animal studies

Other drugs

ACE inhibitors, angiotensin II receptor antagonists

statins

warfarin

sulfonylureas

retinoids (including topical)

cytotoxic agents

The majority of antiepileptics including valproate, carbamazepine and phenytoin are known to be potentially harmful. The decision to stop such treatments however is difficult as uncontrolled epilepsy is also a risk

20
Q

Finasteride

A

Finasteride is an inhibitor of 5 alpha-reductase, an enzyme which metabolises testosterone into dihydrotestosterone.

Indications

benign prostatic hyperplasia

male-pattern baldness

Adverse effects

impotence

decrease libido

ejaculation disorders

gynaecomastia and breast tenderness

Finasteride causes decreased levels of serum prostate-specific antigen

Finasteride is a 5 alpha reductase inhibitor which converts testosterone into DHT

Importance: 65

Finasteride is a 5-alpha reductase inhibitor given to patients suffering from benign prostatic hyperplasia. By blocking 5-alpha reductase it stops the conversion of testosterone to dihydrotestosterone, thereby reducing the size of the prostate.

Trimethoprim works by binding to dihydrofolate reductase, therefore, interfering with bacterial DNA synthesis.

Tamsulosin is an alpha blocker which selectively blocks the alpha 1 receptors in the bladder neck and prostate causing a relaxation of the smooth muscle.

Oxybutynin has a direct spasmolytic effect on the bladder smooth muscle by competitively antagonising the muscarinic receptors on the bladder.

Finally sildenafil inhibits cGMP specific phosphodiesterase type 5 therefore helping to improve blood flow to the penis to help with erectile dysfunction.

21
Q

Finasteride

A

Finasteride is an inhibitor of 5 alpha-reductase, an enzyme which metabolises testosterone into dihydrotestosterone.

Indications

benign prostatic hyperplasia

male-pattern baldness

Adverse effects

impotence

decrease libido

ejaculation disorders

gynaecomastia and breast tenderness

Finasteride causes decreased levels of serum prostate-specific antigen

22
Q

Tamoxifen

A

Tamoxifen is a Selective oEstrogen Receptor Modulator (SERM) which acts as an oestrogen receptor antagonist and partial agonist. It is used in the management of oestrogen receptor positive breast cancer

Adverse effects

menstrual disturbance: vaginal bleeding, amenorrhoea

hot flushes - 3% of patients stop taking tamoxifen due to climateric side-effects

venous thromboembolism

endometrial cancer

osteoporosis

Tamoxifen is typically used for 5 years following removal of the tumour.

Raloxifene is a pure oestrogen receptor antagonist, and carries a lower risk of endometrial cancer

23
Q

Drugs causing ocular problems

A

Cataracts

steroids

Corneal opacities

amiodarone

indomethacin

Optic neuritis

ethambutol

amiodarone

metronidazole

Retinopathy

chloroquine, quinine

Sildenafil can cause both blue discolouration and non-arteritic anterior ischaemic neuropathy

There are a number of causes of gynaecomastia in males and it is important to rule out sinister ones such as kidney failure, endocrine disturbances, liver failure or malignancy.

Another key cause is medication related, in this case the finasteride taken by this patient can cause gynaecomastia.

Finasteride works by blocking 5-alpha-reductase inhibitors those reducing the production of dihydrotestosterone and therefore shrinking the prostate, however side effects can include gynaecomastia and sexual dysfunction.

24
Q
A
25
Q

Carbon monoxide poisoning

A

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

in carbon monoxide poisoning the oxygen saturation of haemoglobin decreases leading to an early plateau in the oxygen dissociation curve

Questions may hint at badly maintained housing e.g. student houses.

Features of carbon monoxide toxicity

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

Investigations

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

Management

patients with suspected carbon monoxide poisoning should be assessed in the emergency department

100% high-flow oxygen via a non-rebreather mask

from a physiological perspective, this decreases the half-life of carboxyhemoglobin (COHb)

should be administered as soon as possible, with treatment continuing for a minimum of six hours

target oxygen saturations are 100%

treatment is generally continued until all symptoms have resolved, rather than monitoring CO levels

hyperbaric oxygen

due to the small number of cases the evidence base is limited, but there is some evidence that long-term outcomes may be better than standard oxygen therapy for more severe cases

therefore, discussion with a specialist should be considered for more severe cases (e.g. levels > 25%)

in 2008, the Department of Health publication ‘Recognising Carbon Monoxide Poisoning’ also listed loss of consciousness at any point, neurological signs other than headache, myocardial ischaemia or arrhythmia and pregnancy as indications for hyperbaric oxygen

26
Q

Paracetamol overdose: management

A

The following is based on 2012 Commission on Human Medicines (CHM) review of paracetamol overdose management. The big change in these guidelines was the removal of the ‘high-risk’ treatment line on the normogram. All patients are therefore treated the same regardless of risk factors for hepatotoxicity. The National Poisons Information Service/TOXBASE should always be consulted for situations outside of the normal parameters.

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:

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

the plasma paracetamol concentration is on or above a single treatment line joining points of 100 mg/L at 4 hours and 15 mg/L at 15 hours, regardless of risk factors of hepatotoxicity

Acetylcysteine is now infused over 1 hour (rather than the previous 15 minutes) to reduce the number of adverse effects. Acetylcysteine commonly causes an anaphylactoid reaction (non-IgE mediated mast cell release). Anaphylactoid reactions to IV acetylcysteine are generally treated by stopping the infusion, then restarting at a slower rate.

27
Q

Cocaine

A

Cocaine is an alkaloid derived from the coca plant. It is widely used as a recreational stimulant. The price of cocaine has fallen sharply in the past decade resulting in cocaine toxicity becoming a much more frequent clinical problem. This increase has made cocaine a favourite topic of question writers.

Mechanism of action

cocaine blocks the uptake of dopamine, noradrenaline and serotonin

The use of cocaine is associated with a wide variety of adverse effects:

Cardiovascular effects

myocardial infarction

both tachycardia and bradycardia may occur

hypertension

QRS widening and QT prolongation

aortic dissection

Neurological effects

seizures

mydriasis

hypertonia

hyperreflexia

Psychiatric effects

agitation

psychosis

hallucinations

Others

ischaemic colitis is recognised in patients following cocaine ingestion. This should be considered if patients complain of abdominal pain or rectal bleeding

hyperthermia

metabolic acidosis

rhabdomyolysis

Management of cocaine toxicity

in general, benzodiazepines are generally first-line for most cocaine-related problems

chest pain: benzodiazepines + glyceryl trinitrate. If myocardial infarction develops then primary percutaneous coronary intervention

hypertension: benzodiazepines + sodium nitroprusside

the use of beta-blockers in cocaine-induced cardiovascular problems is a controversial issue. The American Heart Association issued a statement in 2008 warning against the use of beta-blockers (due to the risk of unopposed alpha-mediated coronary vasospasm) but many cardiologists since have questioned whether this is valid. If a reasonable alternative is given in an exam it is probably wise to choose it

28
Q

Organophosphate insecticide poisoning

A

One of the effects of organophosphate poisoning is inhibition of acetylcholinesterase leading to upregulation of nicotinic and muscarinic cholinergic neurotransmission. In warfare, sarin gas is a highly toxic synthetic organophosphorus compound that has similar effects.

Features can be predicted by the accumulation of acetylcholine (mnemonic = SLUD)

Salivation

Lacrimation

Urination

Defecation/diarrhoea

cardiovascular: hypotension, bradycardia
also: small pupils, muscle fasciculation

Management

atropine

the role of pralidoxime is still unclear - meta-analyses to date have failed to show any clear benefit

29
Q

Alcohol - problem drinking: management

A

Nutritional support

SIGN recommends alcoholic patients should receive oral thiamine if their ‘diet may be deficient’

Drugs used

benzodiazepines for acute withdrawal

disulfram: promotes abstinence - alcohol intake causes severe reaction due to inhibition of acetaldehyde dehydrogenase. Patients should be aware that even small amounts of alcohol (e.g. In perfumes, foods, mouthwashes) can produce severe symptoms. Contraindications include ischaemic heart disease and psychosis
acamprosate: reduces craving, known to be a weak antagonist of NMDA receptors, improves abstinence in placebo controlled trials

Plasma paracetamol levels obtained less than 4 hours since ingestion cannot be interpreted

Importance: 91

A plasma paracetamol level taken less than four hours since ingestion can underestimate the total ingestion of paracetamol, as the drug is still being absorbed from the gastrointestinal tract at this point. Therefore, it is important to wait until this point to take a blood sample, which can then be plotted on the treatment nomogram.

Patients who present within one hour of ingestion may benefit from activated charcoal to reduce absorption of the drug. However, a paracetamol level at this stage is of limited value.

Patients who have an unknown ingestion time or who present having taken a staggered overdose might be started on acetylcysteine regardless of their paracetamol level. A staggered overdose refers to an overdose where the tablets are taken over a period of greater than an hour.

30
Q

Opioid misuse

A

Opioids are substances which bind to opioid receptors. This includes both naturally occurring opiates such as morphine and synthetic opioids such as buprenorphine and methadone.

Features of opioid misuse

rhinorrhoea

needle track marks

pinpoint pupils

drowsiness

watering eyes

yawning

Complications of opioid misuse

viral infection secondary to sharing needles: HIV, hepatitis B & C

bacterial infection secondary to injection: infective endocarditis, septic arthritis, septicaemia, necrotising fasciitis

venous thromboembolism

overdose may lead to respiratory depression and death

psychological problems: craving

social problems: crime, prostitution, homelessness

Emergency management of opioid overdose

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

Harm reduction interventions may include

needle exchange

offering testing for HIV, hepatitis B & C

Management of opioid dependence

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

compliance is monitored using urinalysis

detoxification should normally last up to 4 weeks in an inpatient/residential setting and up to 12 weeks in the community

31
Q

Beta-blocker overdose

A

Features

bradycardia

hypotension

heart failure

syncope

Management

if bradycardic then atropine

in resistant cases glucagon may be used

Haemodialysis is not effective in beta-blocker overdose

For each of the following drugs select the most appropriate monitoring tests once treatment has commenced

32
Q

P450 enzyme system

A

Induction usually requires prolonged exposure to the inducing drug, as opposed to P450 inhibitors, where effects are often seen rapidly

Inducers of the P450 system include

antiepileptics: phenytoin, carbamazepine
barbiturates: phenobarbitone

rifampicin

St John’s Wort

chronic alcohol intake

griseofulvin

smoking (affects CYP1A2, reason why smokers require more aminophylline)

Inhibitors of the P450 system include

antibiotics: ciprofloxacin, erythromycin

isoniazid

cimetidine,omeprazole

amiodarone

allopurinol

imidazoles: ketoconazole, fluconazole

SSRIs: fluoxetine, sertraline

ritonavir

sodium valproate

acute alcohol intake

quinupristin

Sodium valproate is an P450 inhibitor

33
Q

Prescribing in patients with renal failure

A

Questions regarding which drugs to avoid in renal failure are common

Drugs to avoid in renal failure

antibiotics: tetracycline, nitrofurantoin

NSAIDs

lithium

metformin

Drugs likely to accumulate in chronic kidney disease - need dose adjustment

most antibiotics including penicillins, cephalosporins, vancomycin, gentamicin, streptomycin

digoxin, atenolol

methotrexate

sulphonylureas

furosemide

opioids

Drugs relatively safe - can sometimes use normal dose depending on the degree of chronic kidney disease

antibiotics: erythromycin, rifampicin

diazepam

warfarin

34
Q

Phosphodiesterase type V inhibitors

A

Phosphodiesterase type V (PDE5) inhibitors are used in the treatment of erectile dysfunction. They are also used in the management of pulmonary hypertension. PDE5 inhibitors cause vasodilation through an increase in cGMP leading to smooth muscle relaxation in blood vessels supplying the corpus cavernosum.

Examples

sildenafil (Viagra) - this was the first phosphodiesterase type V inhibitor

tadalafil (Cialis)

vardenafil (Levitra)

Contraindications

patients taking nitrates and related drugs such as nicorandil

hypotension

recent stroke or myocardial infarction (NICE recommend waiting 6 months)

Side-effects

visual disturbances e.g. blue discolouration, non-arteritic anterior ischaemic neuropathy

nasal congestion

flushing

gastrointestinal side-effects

headache

The blue pill, Viagra (sildenafil), causes blue discolouration of vision

35
Q
A