MRCPCHPHARMA

bronchospasm in asthmatic patients

Salmeterol is a long-acting
2
-agonist, and is used as a bronchodilator. However, it is
associated with paradoxical bronchoconstriction, which is more common with the MDI
formulation. Indometacin, a cyclo-oxygenase inhibitor, can lead to bronchoconstriction is
susceptible patients . Atenolol, although a cardio-selective -blocker, can still cause
bronchospasm, while captopril and other ACE inhibitors can lead to bronchospasm probably
through an increase in kinin levels.
acute aspirin overdose
Overdose of aspirin leads to the following symptoms: tinnitus, vertigo and vomiting occur in
moderately severe overdose. In more severe cases, this progresses to hypoglycaemia,
hyperkalaemia, and hyperthermia. Hyperventilation leads to respiratory alkalosis, which is
then followed by metabolic acidosis. In the most severe cases, coma, cardiovascular collapse
and renal failure may develop. Deafness is not seen in acute cases.
Photosensitivity has been reported with terbinafine, amiodarone, demeclocycline (a common
feature of all tetracyclines) and sulphamethoxazole (a common feature of sulphonamides).
Amiloride has not been implicated in photosensitivity. Other drugs known to cause
photosensitivity include antimicrobials (ciprofloxacin, griseofulvin and quinine), NSAIDs
(azapropazone, piroxicam, tiaprofenic acid), thiazide diuretics and psychotropic agents
(chlorpromazine, thioridazine, imipramine).
For most adolescents and young women, side-effects of the pill are minor. Common unwanted
side-effects include bloating, breast tenderness, headaches (including migraine), acne, loss of
sex drive and mild vaginal discharge. The pill does increase the risks of DVT, myocardial
infarction and stroke, although the risk of thrombotic events for most pill users is still very low.
The risk of stroke is increased in women with certain types of migraine. There may be a small
increase in the risk of breast cancer (balanced by a reduction in risk for endometrial and
ovarian malignancies). Menstrual irregularity and increased bleeding are common adverse
effects with progestogen-only pills, but combined pills are associated with a lower risk of
dysmenorrhoea and bleeding and are often used to control menstrual symptoms.
chloroquine
Side effects include:
More common: Diarrhoea; difficulty in seeing to read ; headache; itching; loss of appetite;
nausea or vomiting; stomach cramps or pain
Less common: Blurred vision; change in vision; eye pain; loss of vision Bleaching of hair or
increased hair loss; blue-black discoloration of skin, fingernails, or inside of mouth; skin rash
Rare: haematemesis, melaena; haematuria; seizures; cough; lightheadedness; fever;
increased muscle weakness; lower back or side pain; mood or other mental changes; dysuria;
rash; tinnitus; unusual bleeding or bruising; unusual tiredness or weakness
Symptoms of overdose: Drowsiness; headache; increased excitability.

Amphetamines release stores of norepinephrine and dopamine from nerve endings by
converting the respective molecular transporters into open channels. Amphetamine also
releases stores of serotonin from synaptic vesicles. Like methylphenidate (Ritalin)
amphetamines also prevent the monoamine transporters for dopamine and norepinephrine
from recycling them which leads to increased amounts of dopamine and norepinephrine in
synaptic clefts.
Short-term physiological effects include decreased appetite, increased stamina and physical
energy, increased sexual drive/response, involuntary bodily movements, increased
perspiration, hyperactivity, jitteriness, nausea, itchy, blotchy or greasy skin, increased heart
rate, irregular heart rate, and headaches. Long term psychological effects can include
insomnia, mental states resembling schizophrenia, aggressiveness, addiction or dependence
with accompanying withdrawal symptoms, irritability, confusion, and panic. Chronic and/or
extensively continuous use can lead to amphetamine psychosis which causes delusions and
paranoia.
Short-term effects can include alertness, euphoria, increased concentration, rapid talking,
increased confidence, increased social responsiveness, nystagmus, hallucinations, and loss of
REM sleep. Long-term use and overdose effects can include tremor, restlessness, changed sleep
patterns, poor skin condition, hyperreflexia, tachypnoea, gastrointestinal narrowing, and
weakened immune system. Fatigue and depression can follow the excitement stage. Erectile
dysfunction, heart problems, stroke, and liver, kidney and lung damage can result from
prolonged use.
Sodium valproate is associated with weight gain as a result of increased appetite. It is usually
the drug of choice in pregnancy because it is effective at controlling seizures and side
effects/teratogenic effects are know. As yet none of the newer anticonvulsants has been
convincingly shown to be less teratogenic.
Reversible dementia, Hair loss, Tremor

Alpha adrenergic agonists include Dopamine in the neonatal period, metaraminol,
phenylephrine and noradrenaline. Adrenaline is Beta and alpha, isoprenaline and salbutamol
are beta. Phosphodiesterase (PDE) type 3 is inhibited by enoximone, amrinone and milrinone
leading to systemic vasodilatation. PDE type 5 is inhibited by zaprinast and sildenafil causing
pulmonary vasodilatation. ACE increases formation of angiotensin 2 from angiotensin 1.

Class 1 drugs act on the sodium channel, propafenone being in group 1c and mainly used for
atrial arrhythmias. Class 2 act on the calcium channel preventing depolarisation and are beta
blockers. Class 3 act on the repolarising potassium channel, including sotalol and amiodarone.
Class 4 block the AV node including verapamil (calcium channel) and adenosine (potassium
channel opener).
Sotalol has both class 2 and class 3 actions
Adenosine terminates SVT because it is a potassium channel opener
Flecainide is used for prophylaxis of SVT because of its 1c action on blocking the sodium channel

Erythropoietin is used to treat the anaemia of chronic renal failure, to increase the yield of
blood in normal individuals, and to shorten the period of anaemia in patients receiving
cytotoxic chemotherapy. Epoietin beta is also used for the prevention of anaemia in premature
infants.
Pyrimethamine and methotrexate (dihydrofolate reductase inhibition) interfere with folate
metabolism. Tetracycline interferes with calcium metabolism, ibuprofen with platelets and
vitamin B12 is necessary when giving folate supplements to prevent deficiency.
These are all recognised therapies for pulmonary hypertension. Magnesium sulphate is a co-
factor in endogenous nitric oxide production and sildenafil inhibits cyclic GMP breakdown.
Iloprost and prostacyclin enhance cAMP formation. Tolazoline is no longer used due to its side
effects of bleeding.
There are many side effects of ciclosporin including gingival hypertrophy, renal (dose
dependent), hypertension and hypertrichosis, but it is virtually free of myelotoxicity.
Erythromycin decreases ciclosporin metabolism.
Cimetidine increases metabolism of phenytoin, inhibits metabolism of metronidazole, warfarin
and ciclosporin but has no known effect on gentamicin

All the anthracyclines cause cardiomyopathy which depends on the total dose. Any
immunosuppressant agent may lead to oral ulceration and busulphan can cause irreversible
rare progressive fibrosis. Vincristine causes peripheral or autonomic neuropathy.
paracetamol overdose
The most sensitive prognostic marker is prothrombin time (PT). Approximately 50% of patients
with a PT of 36s at 36h after ingestion will develop ALF. Acute renal failure is usually caused by
either hepatorenal syndrome or multi-system organ failure. Acute renal failure may however
also be the primary clinical manifestation of toxicity. Pancreatitis is rare.

There is no known specific antidote to carbamazepine. Evacuate the stomach, with an emetic
or by gastric lavage, then administer activated charcoal. The use of N-acetyl-cysteine, is useful
in paracetamol poisoning. Hypokalaemia and metabolic acidosis are also features of
theophylline and salbutamol overdosage.

Erythromycin administered together with theophylline can lead to elevated blood levels of
theophylline. Theophylline passes into breast milk and may be toxic to nursing infants.
Overdose can cause agitation, restlessness, dilated pupils, sinus tachycardia, and
hyperglycaemia.
Metabolism of theophylline is inhibited by erythromycin (increased plasma concentration).
Plasma concentration of phenobarbitone are increased by valproate. Metabolism of oestrogens
accelerated by phenytoin (reduced contraceptive effect).



Many drugs can potentially be transferred in breast milk. A in a few breast feeding is
contraindicated. In many cases the individual case must be considered (e.g. is there an
alternative, how likely is a reaction, what dose is the mother taking etc.)

Lead poisoning is due to the ingestion of lead-containing compounds (deliberate (pica) or
inadvertent), contaminated water from old lead water-pipes and certain traditional remedies
such as ayurvedic medicines. Typically, acute effects of lead toxicity occur above
concentrations of 450 g/l and include nausea, abdominal pain, constipation and neurological
and haematological effects. Chronic low-grade exposure (< 450 g/l) can be associated with
mild neurodevelopmental delays. Abdominal X-rays are essential to see if there is any
unabsorbed lead present, which can be removed by whole-bowel irrigation. Oral DMSA
(dimercaptosuccinic acid), which is used in the treatment of lead toxicity, will increase the
absorption of any lead from the gastrointestinal tract. Absorption is also increased in patients
with iron-deficiency anaemia. Hypocalcaemia is associated with increased lead deposition in
bones, leading to an increased half-life of lead. Management includes complete gut
decontamination; chelation therapy with oral DMSA or intravenous EDTA
(ethylenediaminetetraacetic acid) should then be considered for patients with blood lead
concentrations over 450 g/l or signs of severe toxicity.
Chronic moderate poisoning (450600 g/l) is associated with motor neuropathies

Carbon monoxide is the commonest cause of poisoning-associated death in the United Kingdom.
Patients with pre-existing vascular disease are at an increased risk of morbidity and mortality
from carbon monoxide poisoning. Carboxyhaemoglobin concentrations are typically below 5% in
healthy patients, but may be as high as 10% in heavy smokers. Cerebellar signs are the most
reliable sign of significant neurological toxicity. Treatment consists of removing the patient
from the source of the carbon monoxide, giving high-flow oxygen (12 l/min) via a tight-fitting
mask without a re-breathing circuit and consideration of hyperbaric oxygen therapy.
Indications for this include any history of unconsciousness, carboxyhaemoglobin concentrations
over 40% at any time, pregnancy, documented neurological signs and ECG changes. There are
some relative contraindications: patients with arrhythmias that may require cardioversion,
since this is not possible within the hyperbaric chamber; and patients with asthma or COPD due
to the increased risk of pneumothorax. Although sodium bicarbonate can correct any metabolic
acidosis, it can also decrease oxygen release to the tissues.


Drug Teratogenic effect
Androgens Cardiac deformities
Alcohol Fetal alcohol syndrome
Carbamazepine Microcephaly
Diethylstilbestrol Vaginal carcinoma
Lithium Cretinism
Phenobarbital Cleft palate
Sodium valproate Neural tube defects
Thalidomide Phocomelia
Warfarin Chondrodysplasia punctata

Following overdoses of most NSAIDs, the main effects are mild gastrointestinal upset with
epigastric tenderness, nausea, vomiting and diarrhoea. These effects are mainly due to the
inhibition of cyclo-oxygenase. However, 1020% of patients will have convulsions following an
NSAID overdose. This is more common in patients who have ingested mefenamic acid. Large
overdoses can present with an acidosis, renal impairment, gastrointestinal haemorrhage and
CNS effects (drowsiness, coma, cerebellar signs). Management of NSAID overdose is with
activated charcoal in patients presenting within the first hour, and supportive care. Oral H
2
-
histamine blockers and proton-pump inhibitors may reduce the symptoms of gastrointestinal
toxicity. There is no indication for the use of multi-dose activated charcoal.

Vigabatrin is the drug of choice for infantile spasms. It may cause aggression, alopecia, retinal
atrophy and reduced peripheral vision. Tiagabine is useful in partial secondary generalised
tonicclonic seizures and is not prescribed for infantile spasms. It also reduces peripheral
vision. The other drugs are not associated with visual field defects.


Isotretinoin is a highly effective treatment for acne. It is also highly teratogenic. Women must
have a negative pregnancy test before treatment and be on effective contraception for at least
a month before the course begins, during the course, and for a month after it finishes.
Congenital deafness and CNS and heart defects may occur in children exposed to isotretinoin in
utero. The other drugs, although useful in the treatment of acne, are less effective and not so
teratogenic.

The commonest drugs used to control seizures in children are sodium valproate and
carbamazepine. Phenytoin causes serious side-effects including, gingival hypertrophy,
hirsutism, cerebellar signs, rickets and pseudolymphomas all of which are undesirable in a
child. Lamotrigine is commonly used as an adjunctive drug, although it is being used
infrequently as monotherapy. Topiramate is also used quite rarely, primarily for intractable
seizures or for ones that are difficult to control on common drugs. Phenobarbital can cause
folate deficiency, osteomalacia, neuropathy and excitement in children.
theophylline overdose
An acute overdose occurs with the ingestion of a single large dose. These patients usually
present with gastrointestinal symptoms and cardiovascular manifestations. Seizure risk is not as
great as in a chronic overdose.
A chronic overdose occurs in people who have ingested repeated doses over time that are
greater than their ability to clear the medication. These patients are more likely to have
seizures.
Cardiovascular effects include hypotension and arrhythmias. Gastrointestinal effects include
nausea, vomiting, diarrhoea, and abdominal pain or cramping. Metabolic effects include
hypokalaemia, hyperglycemia, hypercalcemia, rhabdomyolysis, and acidosis. Neurological
effects include headaches, restlessness, tremors, disorientation, hallucinations, insomnia, and
seizures.

Steroid withdrawal symptoms include weakness, fatigue, decreased appetite, weight loss,
nausea, vomiting, diarrhoea (which can lead to fluid and electrolyte abnormalities), and
abdominal pain. Hypotension can result leading to dizziness or fainting. Blood sugar levels may
drop.


Amiodarone
Due to the iodine content of the agent (37.3% by weight), abnormalities in thyroid function are
common. Amiodarone is structurally similar to thyroxine (a thyroid hormone), which
contributes to the effects of amiodarone on thyroid function. The incidence of hypothyroidism
is about 6%, while the incidence of hyperthyroidism is about 2%. Amiodarone is fat-soluble, and
tends to concentrate in tissues including fat, muscle, liver, lungs, and skin. This confers a high
volume of distribution (5000 liters in a 70kg adult) and a long half-life. Amiodarone decreases
the peripheral

deiodination of thyroxine to triiodothyronine.
AZT (Azidothymidine
The anti-retrovirus AZT is a selective, competitive inhibitor of HIV protease. Its role is to slow
down both the process in which the HIV virus reproduces and also the formation of infectious
virus. Maturation of the virus is blocked by interfering with the formation of essential proteins
and enzymes. In combination with other drugs, AZT may lower HIV viral load titre, increase
CD4 cell (T-cell) count, increase immunity and reduce likelihood of developing complications.
AZT is contra-indicated with abnormally low neutrophil counts or haemoglobin values and in
neonates with hyperbilirubinaemia requiring treatment other than phototherapy.

Odour Toxin/poison
Garlic Arsenic, selenium
Bitter almonds Cyanide
Rotten eggs Hydrogen sulphide, mercaptans
Wintergreen Methylsalicylate
Mothballs Naphthalene
Beta agonists and angiotensin II augment proto-oncogene expression, stimulate protein
synthesis and induce the synthesis of fetal forms of actin and myosin, leading to hypertrophy of
smooth muscle. Thyroxine acts directly via nuclear receptors to regulate myosin heavy-chain
gene transcription. The other drugs have no effect on proto-oncogenes.

Acetazolamide is an inhibitor of carbonic anhydrase. It is used in post-haemorrhagic
hydrocephalus (often with furosemide) and for reducing intraocular pressure. It causes
metabolic acidosis, due to bicarbonate loss in the proximal and distal tubules, by inhibiting
reabsorption. Acute interstitial nephritis (AIN) is a complication of acetazolamide therapy.
Administration of acetazolamide may cause agranulocytosis and thrombocytopenia. Macrocytic
hypochromic anaemia is not a feature.

The INR (International Normalised Ratio) is used to monitor the effect of warfarin. Theophylline
has a narrow therapeutic window and needs close monitoring of its serum level to avoid
toxicity. The maintenance dose for carbimazole is determined by measuring T
4
and TSH levels.
Regular full blood counts and urinalysis are used to monitor cyclophosphamide
The main use of ciclosporin is to reduce T-cell immune function in transplant patients and so
reduce the chances of rejection (liver, renal, pancreas, heart and bone marrow transplants).
Levels are carefully monitored for therapeutic efficacy. Renal toxicity is common with high
levels (> 200 ng/ml) and rejection is common with low serum levels. Chronic interstitial
nephritis is a major side-effect of ciclosporin therapy. It is markedly nephrotoxic, but virtually
non-myelotoxic. Hypertrichosis is a common side-effect of ciclosporin treatment. Stomatitis
and urolithiasis are not seen with ciclosporin treatment.

Multi-dose activated charcoal means giving 50 g of activated charcoal every 34 hours. It is
useful in patients who have taken significant amounts of salicylates, and should be continued
until plasma salicylate concentrations have peaked. It is also useful in the management of
patients who have taken drugs with significant enterohepatic circulation (carbamazepine,
phenobarbital, theophylline and quinine) and sustained-/modified-release preparations. It is
contraindicated in patients with signs of bowel obstruction, since activated charcoal can cause
constipation and may worsen any underlying obstruction.


Acetylcysteine (NAC) exhibits direct and indirect antioxidant properties. Its free thiol group is
capable of interacting with the electrophilic groups. This leads to intermediate formation of
NAC thiol, with NAC disulphide as a major end-product . In addition, NAC exerts an indirect
antioxidant effect related to its role as a glutathione (GSH) precursor. GSH is a tripeptide made
up of glutamic acid, cysteine and glycine. It serves as a central factor in protecting against
internal toxic agents (such as cellular aerobic respiration and metabolism of phagocytes) and
external agents (such as nitric oxide (NO), sulphur oxide and other components of cigarette
smoke, and pollution). The sulphydryl group of cysteine neutralises these agents. Maintaining
adequate intracellular levels of GSH is essential to overcoming the harmful effects of toxic
agents. GSH synthesis takes place mainly in the liver (which acts as a reservoir) and the lungs.
Reduction of the circulation of toxic metabolites- mode of action of N-acetylcysteine

Anabolic steroids can be taken orally (eg stanozolol) or may have to be injected due to high
first-pass metabolism (eg testosterone enantate). Amongst many unwanted effects, they have
effects that increase the risk of cardiovascular disease. Blood pressure is elevated. Blood lipid
profiles change, with increased LDL-cholesterol and decreased HDL-cholesterol. Haematocrit is
increased, leading to a prothrombotic tendency, although there is a protective decrease in
plasma fibrinogen concentrations with prolonged use.

This boy most probably has Kallmanns syndrome, which is a combination of anosmia, obesity
and hypogonadotrophic hypogonadism. It is an X-linked recessive disorder causing an isolated
deficiency of gonadotrophin-releasing hormone (GnRH). Long-term treatment of males with
HCG or testosterone restores pubertal development and secondary sex characteristics.
Buserelin and nafarelin acetate are GnRH analogues. Long-term administration results in the
suppression of LH/FSH release. Octreotide is a long-acting analogue of somatostatin and is used
in the treatment of acromegaly. It also suppresses the LH response to GnRH. Cyclic oestrogen
and progesterone is indicated only if the patient is female.

Cocaine reduces the reuptake of dopamine into neurones by inhibiting the dopamine-reuptake
transporter. Overdoses of cocaine are often rapidly fatal. Death may occur in minutes from
arrhythmias, seizures or respiratory depression. Cocaine has a powerful vasoconstrictive action
that can cause a hypertensive crisis leading to myocardial infarction and strokes. -- A 17-year-
old man presents with nausea, vomiting and diaphoresis. His pupils are dilated and his blood
pressure is elevated. Misuse of which substance is most likely to have caused this condition?
Opioid overdose causes miosis, slurred speech, disorientation and respiratory depression.
Alcohol intoxication produces typical effects of acute sedativehypnotic drug overdose,
vasodilatation, tachycardia and gastrointestinal irritation. Amfetamine overdoses are rarely
fatal; they can usually be managed by sedating the patient with benzodiazepines. Lysergic acid
diethylamide (LSD) produces a series of somatic, perceptual and psychological effects that
overlap each other. Dizziness, weakness and tremors occur, along with blurring of vision,
hallucinations, impaired memory, poor judgement and altered mood.

Ampicillin and amoxicillin can cause skin rashes that are not allergic in nature. All the other
antibiotics produce a diffuse, papular, non-purpuric rash that may be intensely pruritic.
--blotchy, non-pruritic purpuric rash all over his body

Bioequivalence is all about demonstrating similar biological effect. Pharmacodynamics or
pharmacokinetics may be useful comparative data, but if each one is considered in isolation it
may not necessarily tell the whole story. There may be differences between products in
excipients or delivery vehicle, which means the biological effects are different when the
products are compared.

Diethylene glycol is used mainly in polyester resins and polyols, as a humectant in the tobacco
industry and as a solvent. It achieved notoriety in 1985 when it was discovered that for a
number of years it had been added to some wines. Several pharmaceutical errors have also led
to fatalities. Nausea, vomiting and abdominal pain frequently occur, and are followed by the
development of jaundice and hepatomegaly, pulmonary oedema, metabolic acidosis, coma and
renal failure in most cases.

Supportive measures to treat the dehydration and to correct the metabolic acidosis should be
instituted promptly. Ethanol or fomepizole (4-methylpyrazole) should be administered to block
diethylene glycol metabolism, and dialysis should be employed if renal failure supervenes. A
loading dose of 50 g of ethanol orally (conveniently given as 125 ml of gin, whisky or vodka)
should be administered, followed by an intravenous infusion of 1012 g ethanol/h to produce a
blood ethanol concentration of 0.51 g/l. The infusion should be continued until diethylene
glycol is no longer detectable in the blood. If dialysis is employed, the rate of ethanol
administration will need to be increased to 1722 g/h.

Any dose of paracetamol above 150 mg/kg (as in this case) is associated with the possibility of
serious liver damage.

Amiodarone is a class III antiarrhythmic drug. Class III antiarrhythmics are potassium channel
blockers, they prolong duration of action potential with resulting prolongation of effective
refractory period. Other Class III antiarrhythmics are sotalol, disopyramide and bretylium.

Aminoglycosides, quinoline antimicrobial drugs, aztreonam and ceftazidime are least active
against anaerobic bacteria. These drugs are included in antimicrobial regimes for treating
mixed infections, though their role is clearly to suppress the facultative Gram-negative
organisms.

Warfarin competitively inhibits carboxylation of vitamin K-dependent factors. Vitamin K-
dependent factors include factors II, VII, IX and X (reverse the year 1972) and protein C. The
half-life of warfarin is approximately 44 hours. The level of warfarin in breast milk is too low to
be of any clinical significance. Autoimmune thrombocytopenia and osteoporosis are side-effects
associated with heparin rather than warfarin.

Vancomycin is bactericidal against several species of Gram-positive cocci but it is less effective
against Gram-negative cocci. It acts on multiplying organisms by inhibiting formation of the
peptidoglycan component of the cell wall. Vancomycin is poorly absorbed from the gut and it is
eliminated by the kidney. Its main side-effect is damage to the auditory portion of the VIIIth
cranial nerve.

Acetazolamide (a carbonic anhydrase inhibitor) inhibits proximal tubule bicarbonate resorption
in a similar fashion to type 2 renal tubular acidosis (RTA). Amiloride acts by inhibiting the
sodium channel in the collecting duct, which inhibits renal acid secretion or bicarbonate
resorption. All diuretics that promote sodium chloride loss and cause volume depletion are
more likely to produce a picture of metabolic acidosis.

Given the history it appears most likely that this patient has an overdose of beta-blockers.
Management of choice for profound hypotension as in this case is with iv glucagon, bolus
followed by infusion. Glucagon exerts an inotropic effect independent of beta-receptor
activation by raising myocardial cAMP levels. Predominant bradycardia is managed with
atropine +/ isoprenaline infusion. Patients who fail to respond to these two measures may
require installation of a temporary pacing wire. Hypoglycaemia may also occur in association
with beta-blocker overdose, bolus doses of iv 50% dextrose followed by 10% dextrose infusion
is the management of choice.

There is no evidence that oral administration of zidovudine at the time of conception reduces
the risk of HIV transmission. Oral zidovudine from 28 weeks gestation onwards has been used
to reduce the risk of transmission. There is also no evidence that intravenous zidovudine
during labour is of any benefit. Zidovudine is effective in reducing the risk of HIV transmission
from mother to neonate by 8.3% - 18%. The ideal treatment regimen is to commence
zidovudine as an intravenous infusion at the onset of labour and continue it until the baby is 6
weeks of age. Breast-feeding increases the risk of HIV transmission. Elective Caesarean section
may reduce the risk compared to vaginal delivery. Shortening the second stage by operative
delivery increases the risk of transmission.
Tetracycline is used to treat a Coxiella burnetii infection and psittacosis. Rifampicin therapy is
given in legionella infection and in severe cases of Mycoplasma pneumoniae. Penicillin is used
commonly in pneumococcal infection. Clarithromycin is preferred for mycoplasma infections,
while co-trimoxazole is given in Pneumocystis carinii (also known as Pneumocystis jiroveci)
infection.

HCO
3

levels are very low, w ith severe acidosis and base deficit. In this situation the next
immediate treatment is with sodium bicarbonate, the 8.4% concentration should be given via
central line over 3040 min. It is almost as important to begin treatment for inhibition of
alcohol dehydrogenase as soon as possible. Fomepizole or alcohol may be given as inhibitors of
alcohol dehydrogenase. Fomepizole has the advantage of not decreasing conscious level. It is
likely that haemodialysis will be required; in patients requiring haemodialysis either the
alcohol infusion rate or dose interval between doses of fomepizole requires alteration. As little
as 30 ml of ethylene glycol may be fatal in adults, plasma levels of >500 mg/l indicate a severe
overdose, and degree of acidosis is predictive of outcome.
Amphetamine overdose is associated with mydriasis, hypertension, tachycardia, skin pallor,
hyperexcitability and, in the initial stages, agitation and increased talkativeness. Poor
prognostic features associated with amphetamine overdose include hyperpyrexia,
rhabdomyolysis, acute renal failure and acute liver failure. Complications include intracerebral
haemorrhage, which may occur after a single amphetamine dose. Any patients who show focal
signs or decreased conscious level should raise suspicion of the possibility of intracerebral
haemorrhage. Hypertension should be controlled with beta blockade, and agitated patients may
be sedated with benzodiazepines.

Ecstasy is an amfetamine derivative (methylenedioxymethamfetamine, MDMA) and its effect is
to cause stimulation of the sympathetic nervous system. The effects of ecstasy usually occur
within 1 hour and typically last for 46 hours, although in large ingestions they can last for up
to 48 hours. Unwanted effects include cardiac arrhythmias (the principal cause of MDMA-
associated deaths), hyponatraemia, hypertension and hyperthermia. Hyponatraemia can occur
either because of an excessive fluid intake or because of SIADHS (syndrome of inappropriate
antidiuretic hormone secretion). Treatment of hyperthermia includes giving cold intravenous
fluids if the core temperature is over 39 C: if this is ineffective, it should be followed by iv
dantrolene and/or paralysis and ventilation.

Ecstasy (3,4-methylenedioxymethamfetamine, MDMA) stimulates the central nervous system.
Poisoning with this drug is usually the result of its recreational use rather than a single massive
dose.

Gastric lavage should be considered if a substantial overdose has been ingested in the
preceding 1 hour. The dehydration should be corrected. All patients should be transferred to
A&E and observed and monitored for at least 6 hours for the electrocardiogram (ECG) and
electrolyte balance. Diazepam should be given if the patient convulses. Cooling measures (fan,
sponging, ice packs, cool iv fluids) should be instigated if the rectal temperature rises above 39
C. If this is unsuccessful, the patient will need to be paralysed and ventilated.

b-Adrenoceptor blocking drugs will antagonise the peripheral sympathomimetic actions of
amfetamines. These drugs cause increased alertness and self-confidence, euphoria, extrovert
behaviour, increased talkativeness with rapid speech, lack of desire to eat or sleep, tremor,
dilated pupils, tachycardia and hypertension.

Generic medicines are produced by companies who are subject to the same tight controls as
those who make branded products. In fact, the same company often makes branded and
generic medicines. Generic medicines contain the same active ingredients, are of the same
dosage form and are identical in strength to the original medicine. They have to be
therapeutically equivalent to their branded product, which means that the maximum
concentration (C
max
), the area under the curve (AUC) and the time of maximum concentration
(t
max
) must be comparable to the already registered drug. This means that they work in the
same way in the body and are associated with the same risks and benefits of the original
medicine. Different generic forms of the same medicine will not differ in their safety and
clinical actions from each other or their branded equivalent.

A pharmaceutical company wants to bring generic ranitidine to the market after the patent has
expired.

What kind of study is needed to obtain approval to market the drug?

Phase-I bioequivalence study

Glucocorticoids include cortisone and hydrocortisone, which have a low mineralocorticoid
activity, along with prednisolone, betamethasone and dexamethasone. For replacement
therapy, hydrocortisone in combination with fludrocortisone is used; this latter drug has little
anti-inflammatory activity.
The strength of the anti-inflammatory effects of 5 mg prednisolone =
Betamethasone 750 g
Cortisone acetate 25 mg
Deflazacort 6 mg
Dexamethasone 750 g
Hydrocortisone 20 mg
Methylprednisolone 4 mg

Antacids tend to alkalinise the urine, leading to increased urinary aspirin clearance, whereas
metoclopramide enhances its absorption. Aspirin diminishes the actions of uricosuric agents
such as probenicid and sulfinpyrazone.
The following are first-line treatments for the other conditions:
Rheumatic fever: phenyloxymethylpenicillin
Meningococcal meningitis: rifampicin (ciprofloxacin for pregnant women and young
children)
Haemophilus influenzae type B: rifampicin.
NSAIDs are disease-modifying drugs. They decrease the antihypertensive effect of
angiotensin-converting enzyme inhibitors and therefore increase the risk of renal failure and
hyperkalaemia. They antagonise the effects of -blockers and inhibit cyclo-oxygenase. Many
of the renal side-effects arise from the prostaglandin-inhibiting properties of NSAIDs. In the
kidney NSAIDs cause vasoconstriction, a decreased glomerular filtration rate and sodium and
water retention, oppose the action of loop diuretics, augment the action of antidiuretic
hormone (water retention) and cause hypernatraemia, hyperaldosteronism and hyperkalaemia.
Side-effects of using NSAIDs include interstitial nephritis and nephrotic proteinuria but not
nephritic syndrome. Eosinophilic infiltrates are often found on biopsy. Other complications
include nausea and rashes.
This drug is a class 3 antiarrhythmic drug. It is a vasodilator of both the peripheral and the central
circulation, and is a negative chronotrope. It has a half-life of 78 weeks and needs a loading dose.
It acts to prolong the action potential in the refractory period. It also prolongs the QT and QRS
complexes and is a sodium channel blocker. It directly decreases the automaticity of the sinus and
the autonomic nervous system, and has a a- and -blocking properties.
What is this drug?
Amiodarone has the above properties, successfully suppresses an arrhythmia and does not
cause mortality. It was used in the Basal Antiarrhythmic Study of Infarction Survey (BASIS)
and found to be of benefit. It decreased all arrhythmias compared with a placebo and other
antiarrhythmic medication. The study did, however, conclude that -blockers were still the
best medication for a post-myocardial infarct.
Amiodarone potentiates digoxin, as it competes with it at digoxin-binding sites, warfarin,
other antiarrhythmics and iodine content. It may therefore potentiate hyperthyroidism and
may subsequently inhibit the conversion of thyroxine to active T
3
and cause hypothyroidism.
Other side-effects include reversible corneal microdeposits, optic neuritis, slate-grey skin
syndrome, photosensitivity, pulmonary fibrosis, alveolitis, hepatitis, peripheral neuropathy,
myopathy, hyperthyroidism, hypothyroidism (10%), heart block, dermatitis, tremor,
gastrointestinal disturbance, lung amiodarone pulmonary disease, bradycardia, raised
intracranial pressure, vasculitis and thrombocytopenia. It may be well tolerated in low doses
and is effective in the prevention and cardioversion of atrial flutter and fibrillation.

This antiepileptic medication is used to enhance the action of -aminobutyric acid,
which is a major inhibitory neurotransmitter. It is used in absence attacks, temporal
lobe epilepsy and myoclonic-type epilepsy. It inhibits liver enzymes and may enhance
the function of other antiepileptic agents such as phenytoin, causing toxicity.
What is this medication?
Sodium valproate has many dose-related side effects, including thrombocytopenia, tremor,
appetite stimulation, alopecia, ataxia, fatal hepatitis, gastric irritation, pancreatitis, menstrual
irregularities, encephalopathy, hyperammonaemia (20%) and hepatotoxicity (1 in 20,000).
Plasma levels are required to determine the efficacy of the clinical response. Sodium
valproate is not used for infantile spasms (nitrazepam, adrenocorticotrophic hormone or
prednisolone are used instead) or status epilepticus (lorazepam and phenytoin).
A teenager presents unconscious in the emergency department. Her parents give a
history that she had been drinking the night before. During the night, she complained of
a high fever and sweating with severe abdominal pain. She also intermittently
complained of dizziness, tinnitus and deafness. The girl became very irritable and
therefore went to bed thinking that this was due to alcohol toxicity. Next morning, she
was found unconscious.
Investigations have revealed the following results: sodium 130 mmol/l, potassium 2.9
mmol/l, urea 9.4 mmol/l, creatinine 115 mol/l, hypoprothrombinaemia and a normal
bleeding time on clotting analysis, blood glucose 2.1 mmol/l, urinalysis test positive and
blood gases showing a compensated metabolic acidosis. She has also presented with
bruising.
What is the diagnosis?
This girl has presented in a compensated metabolic acidosis due to the accumulation of
organic acid secondary to salicylate poisoning. All her symptoms are those found in the acute
phase of the condition, and loss of consciousness is found in the late phase. Other presenting
features and complications include hyperventilation, hyperpyrexia, dehydration, pulmonary
oedema, acute renal failure and irritability.
Physiologically, as there is an increase in initial respiratory alkalosis, bicarbonate is released
in the urine, causing hyponatraemia and hypokalaemia, and water is released in the urine.
This therefore causes a compensatory metabolic acidosis, promoting the accumulation of
lactate pyruvate. A stimulation of fat catabolism leads to ketone and -hydroxybutyrate
production, an increase in protein catabolism and aminoaciduria.
Treatment includes emesis and gastric lavage with activated charcoal. Electrolytes and renal
function need to be corrected, and a forced alkaline diuresis with 0.9% saline, 5% dextrose
and 1.26% bicarbonate solution is required to keep the pH of the urine between 7.5 and 8.5.
The initial hyperventilation in the acute phase causes the respiratory alkalosis and thus the
compensatory metabolic acidosis, which in turn causes the ketonuria. With regard to the
significance of the serum dose levels at 6 hours, the following should be remembered:
3500 mg/l is mild
500750 mg/l is moderate
>750 mg/l is severe.