Pharmacology - Corrections Flashcards
What is the correct rate of infusion of N-acetylcysteine in a paracetamol overdose?
IV N-acetylcysteine over 1 hour
Acetylcysteine is a common cause of anaphylactic reactions, generally managed with slower infusions (i.e. this rate reduces risk of adverse effects).
What class of drug is doxazocin?
Alpha blocker
Give 2 examples of alpha blockers
1) tamsulosin
2) doxazosin
What medications may precipitate lithium toxicity?
1) diuretics (especially thiazides)
2) ACEi/ARBs
3) NSAIDs
4) metronidazole.
How can NSAIDs predispose to lithium toxicity?
NSAIDs can cause renal impairment by decreasing prostaglandin synthesis –> decreases in glomerular filtration rate. There is evidence that these drugs can increase lithium levels and decrease renal lithium clearance.
What is the appropriate dose of IM adrenaline in anaphylaxis?
0.5mg - 0.5ml 1:1000 IM
Which drugs should be AVOIDED in renal failure?
1) Abx: tetracycline, nitrofurantoin
2) NSAIDs
3) lithium
4) metformin
Which drugs are likely to accumulate in chronic kidney disease so will need dose adjustment?
- most antibiotics including penicillins, cephalosporins, vancomycin, gentamicin, streptomycin
- digoxin, atenolol
- methotrexate
- sulphonylureas
- furosemide
- opioids
Tinnitus is an early symptom of an overdose of what?
Salicylates e.g. aspirin
Who is at risk of lactic acidosis from metformin?
Patients with severe liver or renal failure.
Review dose in patients with eGFR <45 and STOP in <30.
What monitoring investigations are required in patients on amiodarone?
TFTs & LFTs every 6 months
CXR prior to starting treatment (but not routinely)
What is G6PD deficiency?
An X-linked recessive disorder that causes a defect in the red cell enzyme glucose-6-phosphate dehydrogenase.
This deficiency leads to intravascular haemolysis which can be triggered by the ingestion of certain drugs and foods (including fava (broad) beans).
What drugs are contraindicated in G6PD deficiency?
Drugs that can precipitate haemolysis:
- antimalarials
- ciprofloxaciin
- sulphonamides (including co-trimoxazole)
- sulphonylureas
- sulphasalazine
What are quinolones?
Give 2 examples
A group of Abx that work by inhibiting DNA synthesis and are bactericidal in nature.
- ciprofloxacin
- levofloxacin
Adverse effects of quinolones?
- 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
What are the 4 key drugs used in the management of TB?
Rifampicin
Isoniazid
Pyrazinamide
Ethambutol
What are the most common side effects of rifampicin?
- orange bodily fluids
- rash
- hepatotoxicity
- enzyme inducer (drug interactions)
- flu like symptoms
What are the most common side effects of Isoniazid?
- peripheral neuropathy
- psychosis
- hepatotoxicity
- agranulocytosis
How can peripheral neuropathy as a result of isoniazid be prevented?
With pyridoxine (vitamin B6)
What are the most common side effects of pyrazinamide?
- arthralgia & myalgia
- gout (due to hyperuricaemia)
- hepatotoxicity
- nausea
What are the most common side effects of ethambutol?
- optic neuritis (check visual acuity before and during treatment)
- rash
If women take HRT for premature menopause, how long should it be continued for?
Until age of 50
Define premature menopause
Ovarian failure occurring before the age of 40.
What is the most important reason in giving HRT to women with premature menopause?
Preventing development of osteoporosis
Contraindications for metformin?
1) CKD: stop if creatinine >150 or eGFR <30
2) Can cause lactic acidosis if taken during a period where there is tissue hypoxia e.g. recent MI, sepsis, AKI and severe dehydration
3) Iodine-containing x-ray contrast media e.g. coronary angiography
4) Alcohol abuse is a relative contraindication
Why is metformin contraindicated in coronary angiography?
There is an increasing risk of provoking renal impairment due to contrast nephropathy.
When should metformin be stopped prior to coronary angiography?
On day of procedure and for 48 hours afterwards
What class of medication is amiloride?
Potassium sparing diuretic
Which TB medication can cause gout?
Pyrazinamide
What is the mechanism of action of unfractionated heparin?
Activates antithrombin III.
This in turn inhibits thrombin and factors Xa, Ixa, XIa and XIIa.
This stops fibrin formation and thrombin from activating factors V, VIII, and XI.
What is the treatment for adrenaline induced ischaemia?
Phentolamine
This drug is a competitive α-adrenoreceptor antagonist which can be injected to reverse the effects of adrenaline on the vasculature.
What are the features of salicylate poisoning (e.g. aspirin)?
What type of acid base disorder does salicylate poisoning lead to?
Leds to a mixed respiratory alkalosis and metabolic acidosis
Early stimulation of the respiratory centre leads to a respiratory alkalosis whilst later the direct acid effects of salicylates (combined with acute renal failure) may lead to an acidosis.
Note - In children metabolic acidosis tends to predominate.
Features of salicylate overdose?
- hyperventilation (centrally stimulates respiration)
- tinnitus
- lethargy
- sweating, pyrexia
- N&V
- hyperglycaemia and hypoglycaemia
- seizures
- coma
Treatment of salicylate overdose?
1) general (ABCDE, charcoal)
2) urinary alkalinisation with intravenous sodium bicarbonate - enhances elimination of aspirin in the urine
3) haemodialysis
Give some indications for haemodialysis in salicylate overdose
1) serum concentration > 700mg/L
2) metabolic acidosis resistant to treatment
3) acute renal failure
4) pulmonary oedema
5) seizures
6) coma
Why should ciprofloxacin be avoided in epilepsy?
As ciprofloxacin lowers the seizure threshold
What is the key effect of organophosphate insecticide poisoning?
The inhibition of acetylcholinesterase leading to upregulation of nicotinic and muscarinic cholinergic neurotransmission.
What are the features of organophosphate poisoning the result of?
Accumulation of acetylcholine (due to inhibition of acetylcholinesterase).
Give some features of organophosphate poisoning.
Mneumonic: SLUD
S - Salivation
L - Lacrimation
U - Urination
D - Defecation/diarrhoea
Others:
- hypotension, bradycardia
- small pupils
- fasciculations
What is the mainstay of management of organophosphate poisoning?
Atropine
Give 2 examples of tetracyclines Abx
1) doxycycline
2) tetracycline
Mechanism of tetracyclines?
protein synthesis inhibitors
Give 4 indications for tetracycliines?
- acne vulgaris
- Lyme disease
- Chlamydia
- Mycoplasma pneumoniae
What are some notable adverse effects of tetracyclines?
1) discolouration of teeth (avoid in children <12)
2) photosensitivity
3) angiodema
4) black hairy tongue
Note - avoid in pregnancy & BF due to the risk of discolouration of the infant’s teeth.
Why are tetracyclines avoided in children <12?
Due to risk of discolouration of teeth
Give some causes of drug induced photosensitivity
- thiazides
- tetracyclines, sulphonamides, ciprofloxacin
- amiodarone
- sulphonylureas
- NSAIDs e.g. piroxicam
Which 3 Abx can cause photosensitivity?
- tetracyclines
- sulphonamides
- ciprofloxacin
What class of medication is used in the treatment of erectile dysfunction?
Phosphodiesterase type V (PDE5) inhibitors
What are the 2 indications for PDE-5 inhibitors?
1) ED
2) Pulmonary HTN
How do PDE-5 inhibitors work in ED?
Cause vasodilation through an increase in cGMP, leading to smooth muscle relaxation in blood vessels supplying the corpus cavernosum.
What is the main example of a PDE-5 inhibitor?
sildenafil (Viagra)
Give 3 contraindications of sildenafil/PDE-5 inhibitors?
1) patients taking nitrates and related drugs such as nicorandil
2) hypotension
3) recent stroke or MI (NICE recommend waiting 6 months)
Give some side effects of PDE-5 inhibitors (e.g. sildenafil)?
- visual disturbances e.g. blue discolouration
- nasal congestion
- flushing
- GI side effects
- priapism
- headache
Which drug used in the management of tuberculosis is most associated with peripheral neuropathy?
Isoniazid
What are some precipitating factors for lithium toxicity
- dehydration
- renal failure
- drugs: diuretics (especially thiazides), ACE inhibitors/angiotensin II receptor blockers, NSAIDs and metronidazole.
What are the key drugs that can cause lithium toxicity?
- diuretics (especially thiazides)
- ACEi/ARBs
- NSAIDs
- metronidazole
What are some features of lithium toxicity?
- coarse tremor (a fine tremor is seen in therapeutic levels)
- hyperreflexia
- acute confusion
- polyuria
- seizure
- coma
Management of lithium toxicity?
1) mild-moderate toxicity may respond to volume resuscitation with normal saline
2) haemodialysis may be needed in severe toxicity
If metformin is not tolerated due to GI side-effects, what is next step?
try a modified-release formulation before switching to a second-line agent
What is the most appropriate time to take blood samples for therapeutic monitoring of lithium levels?
12 hours after last dose
Give some drugs that should be avoided in renal failure?
- Abx: tetracycline, nitrofurantoin
- NSAIDs
- lithium
- metformin
What are the 2 main indications for HRT?
1) vasomotor symptoms such as flushing, insomnia and headaches
2) premature menopause
What are the 2 routes of HRT?
Orally & transdermally (via a patch or gel)
What type of HRT is preferred if the woman is at risk of VTE?
Transdermal HRT
Mechanism of UH vs LMWH?
Heparins generally act by activating antithrombin III.
UH –> forms a complex which inhibits thrombin, factors Xa, IXa, XIa and XIIa
LMWH –> only increases the action of antithrombin III on factor Xa
What are 4 key adverse effects of heparin?
1) bleeding
2) thrombocytopenia
3) osteoporosis & increased risk of fractures
4) hyperkalaemia
How do heparins cause hyperkalaemia?
this is thought to be caused by inhibition of aldosterone secretion
Route of administration of UH vs LMWH?
UH - IV
LMWH - SC
Duration of action of UH vs LMWH?
UH - short
LMWH - long
Which type of heparin has a higher risk of heparin-induced thrombocytopaenia (HIT) & osteoporosis?
UH
What is heparin induced thrombocytopenia (HIT)?
Immune mediated - antibodies form against complexes of platelet factor 4 (PF4) and heparin.
This results in platelet activation and eventually thrombocytopenia.
When does HIT typically occur?
5-10 days after treatment
What is the key complication of HIT?
Despite being associated with low platelets HIT is actually a prothrombotic condition.
Features of HIT?
- 50% reduction in platelets
- thrombosis
- skin allergy
What is the 1st line treatment for severe digoxin toxicity?
Digibind
Features of digoxin toxicity?
- generally unwell, lethargy, nausea & vomiting
- anorexia
- confusion
- yellow-green vision
- arrhythmias (e.g. AV block, bradycardia)
- gynaecomastia
What is the classical precipitating factor for digoxin toxicity?
Hypokalaemia
How does hypokalaemia predispose to digoxin toxicity?
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.
What diuretics can cause lithium toxicity?
Thiazides
Give 4 drugs that commonly cause urticaria
1) aspirin
2) penicillins
3) NSAIDs
4) opiates
What is an oculogyric crisis?
A dystonic reaction to certain drugs or medical conditions.
It causes restlessness, agitation and involuntary upward deviation of the eyes.
Give 3 causes of an oculogyric crisis
1) antipsychotics (typically 1st generation/typical)
2) metoclopramide
3) postencephalitic Parkinson’s disease
Mainstay of management of an oculogyric crisis?
1) Cessation of causative medication if possible
2) IV antimuscarinic –> benztropine or procyclidine
Which 2 TCAs are particularly dangerous in overdose?
Amitriptyline & dosulepin
What are some features of TCA overdose?
Early –> dry mouth, dilated pupils, agitation, sinus tachycardia, blurred vision (relate to anticholinergic properties)
Features of severe poisoning include:
- arrhythmias
- seizures
- metabolic acidosis
- coma
ECG changes in TCA overdose?
- sinus tachycardia
- widening of QRS
- prolongation of QT interval
How oes TCA overdose affect QT interval?
prolongation of QT interval
How oes TCA overdose affect QRS complex?
widening of QRS
What are the dangers of QRS widening?
Widening of QRS > 100ms: associated with an increased risk of seizures
QRS > 160ms: associated with ventricular arrhythmias
What is the 1st line therapy of TCA overdose?
IV bicarbonate
Indications include widening of the QRS interval >100 msec or a ventricular arrhythmia.
Mechanism of aspirin to achieve an antiplatelet effect?
1) irreversibly inhibits cyclooxygenase-1 (COX-1) enzyme
2) this prevents the conversion of arachidonic acid to thromboxane A2 (a potent vasoconstrictor and platelet aggregator)
What Abx are contraindicated in pregnancy?
- tetracyclines
- aminoglycosides
- sulphonamides and trimethoprim
- quinolones
Why should cyclizine be used with caution in heart failure?
Cyclizine is a H1-receptor antagonist that acts by blocking histamine receptors in the CTZ.
Cyclizine can cause a drop in cardiac output and an increase in heart rate. For this reason, caution should be employed in patients with severe heart failure.
What class of drug is doxazosin?
Alpha blocker
What carboxyhaemoglobin (COHb) level in smokers is normal?
Smokers tend to have an increased COHb level - anything up to 10% is considered normal in a smoker.
So in carbon monoxide poisoning we would expect the COHb to be at least above 10%.
