Clinical Pharmacology Flashcards

Question

What antibiotic is contraindicated in G6PD deficiency?

Answer 1

Ciprofloxacin is contraindicated in G6PD deficiency. It can lead to potentially fatal haemolytic anaemia

Answer 2

Rituximab - monoclonal antibody against CD20 antigen on B lymphocytes. It binds to the CD20 molecules on the surface of these cells leading to cell death either through complement-dependant cytoxicity or antibody-dependant cellular toxicity. his makes rituximab effective in treating diseases characterised by excessive, malignant, or dysfunctional B cells such as non-Hodgkin's lymphoma and chronic lymphocytic leukaemia. It is also used in the treatment of rheumatoid arthritis

Answer 3

somatic cell hybridisation this involves the fusion of myeloma cells with spleen cells from a mouse that has be immunised with the desired antigen. The resulting fused cells are termed a hybridoma and act as a factory for producing monoclonal antibodies

Answer 4

The main limitation to this is that mouse antibodies are immunogenic leading to the formation of human anti-mouse antibodies. This problem is overcome by a process known as humanising. One method involves combining the variable region from the mouse body with the constant region from a human antibody.

Answer 5

infliximab (anti-TNF): used in rheumatoid arthritis and Crohn's

Answer 6

cetuximab (epidermal growth factor receptor antagonist): used in metastatic colorectal cancer and head and neck cancer

Answer 7

trastuzumab (HER2/neu receptor antagonist): used in metastatic breast cancer

Answer 8

alemtuzumab (anti-CD52): used in chronic lymphocytic leukaemia

Answer 9

abciximab (glycoprotein IIb/IIIa receptor antagonist): prevention of ischaemic events in patients undergoing percutaneous coronary interventions

Answer 10

OKT3 (anti-CD3): used to prevent organ rejection

Answer 11

patients taking liver enzyme-inducing drugs (rifampicin, phenytoin, carbamazepine, chronic alcohol excess, St John's Wort) malnourished patients (e.g. anorexia nervosa) or patients who have not eaten for a few days

Answer 12

Interestingly, acute alcohol intake, as opposed to chronic alcohol excess, is not associated with an increased risk of developing hepatotoxicity and may actually be protective.

Answer 13

by altering small bowel motility, leading to bacterial overgrowth and deconjugation of bile salts, which in turn impairs B12 absorption.

Answer 14

acts by activation of the AMP-activated protein kinase (AMPK) increases insulin sensitivity decreases hepatic gluconeogenesis may also reduce gastrointestinal absorption of carbohydrates

Answer 15

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

Answer 16

CKD - it should be reviewed if creatinine is > 130ummol/l or eGFR < 45 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

Answer 17

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

Answer 18

occurs due to increased serotonin release in the hypothalamus, which regulates body temperature. Additionally, the use of ecstasy in club settings where users are dancing and overheating can exacerbate this effect.

Answer 19

supportive dantrolene may be used for hyperthermia if simple measures fail

Answer 20

Carbon monoxide has a high affinity for haemoglobin and myoglobin resulting in a left-shift of the oxygen dissociation curve and tissue hypoxia. Pathophysiology carbon monoxide binds readily to haemoglobin, forming carboxyhaemoglobin → reduced oxygen-carrying capacity in carbon monoxide poisoning the oxygen saturation of haemoglobin decreases leading to an early plateau in the oxygen dissociation curve

Answer 21

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

Answer 22

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

Answer 23

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

Answer 24

Aspirin works by blocking the action of both cyclooxygenase-1 and 2. Cyclooxygenase is responsible for prostaglandin, prostacyclin and thromboxane synthesis. The blocking of thromboxane A2 formation in platelets reduces the ability of platelets to aggregate

Answer 25

Rifampicin is a potent inducer of the cytochrome P450 enzyme system, which is responsible for the metabolism of warfarin. This induction leads to an increased clearance of warfarin and thus, a decreased INR.

Answer 26

* Headache * Flushing * Ankle oedema Verapamil also commonly causes constipation

Answer 27

* Bronchospasm (especially in asthmatics) * Fatigue * Cold peripheries * Sleep disturbances

Answer 28

Headache * Postural hypotension * Tachycardia

Answer 29

* Headache * Flushing * Anal ulceration

Answer 30

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

Answer 31

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

Answer 32

Management supportive dantrolene may be used for hyperthermia if simple measures fail

Answer 33

Pilocarpine - used in glaucoma

Answer 34

antiepileptics: phenytoin, carbamazepine barbiturates: phenobarbitone rifampicin St John's Wort chronic alcohol intake griseofulvin smoking (affects CYP1A2, reason why smokers require more aminophylline)

Answer 35

antibiotics: ciprofloxacin, erythromycin isoniazid cimetidine,omeprazole amiodarone allopurinol imidazoles: ketoconazole, fluconazole SSRIs: fluoxetine, sertraline ritonavir sodium valproate acute alcohol intake quinupristin

Answer 36

antibiotics: tetracycline, nitrofurantoin NSAIDs lithium metformin

Answer 37

most antibiotics including penicillins, cephalosporins, vancomycin, gentamicin, streptomycin digoxin, atenolol methotrexate sulphonylureas furosemide opioids

Answer 38

Heparin: Activates antithrombin III. Forms a complex that inhibits thrombin, factors Xa, IXa, Xia and XIIa LMWH Activates antithrombin III. Forms a complex that inhibits factor Xa

Answer 39

Allopurinol is used in the prevention of gout. It works by inhibiting xanthine oxidase.

Answer 40

the British Society of Rheumatology Guidelines now advocate offering urate-lowering therapy to all patients after their first attack of gout ULT is particularly recommended if: >= 2 attacks in 12 months tophi renal disease uric acid renal stones prophylaxis if on cytotoxics or diuretics patients with Lesch-Nyhan syndrome often take allopurinol for life

Answer 41

The most significant adverse effects are dermatological and patients should be warned to stop allopurinol immediately if they develop a rash: severe cutaneous adverse reaction (SCAR) drug reaction with eosinophilia and systemic symptoms (DRESS) Stevens-Johnson syndrome Certain ethnic groups such as the Chinese, Korean and Thai people seem to be at an increased risk of these dermatological reactions. Patients at a high risk of severe cutaneous adverse reaction should be screened for the HLA-B *5801 allele.

Answer 42

Azathioprine metabolised to active compound 6-mercaptopurine xanthine oxidase is responsible for the oxidation of 6-mercaptopurine to 6-thiouric acid allopurinol can therefore lead to high levels of 6-mercaptopurine a much reduced dose (e.g. 25%) must therefore be used if the combination cannot be avoided Cyclophosphamide - allopurinol reduces renal clearance, therefore may cause marrow toxicity Theophylline - allopurinol causes an increase in plasma concentration of theophylline by inhibiting its breakdown

Answer 43

NMDA receptor antagonist

Answer 44

May be used for induction of anaesthesia Has moderate to strong analgesic properties Produces little myocardial depression making it a suitable agent for anaesthesia in those who are haemodynamically unstable May induce state of dissociative anaesthesia resulting in nightmares

Answer 45

GABA receptor antagonist

Answer 46

Extremely rapid onset of action making it the agent of choice for rapid sequence of induction Marked myocardial depression may occur Metabolites build up quickly Unsuitable for maintenance infusion Little analgesic effects

Answer 47

immune mediated - antibodies form against complexes of platelet factor 4 (PF4) and heparin these antibodies bind to the PF4-heparin complexes on the platelet surface and induce platelet activation by cross-linking FcγIIA receptors usually does not develop until after 5-10 days of treatment despite being associated with low platelets HIT is actually a prothrombotic condition features include a greater than 50% reduction in platelets, thrombosis and skin allergy address need for ongoing anticoagulation: direct thrombin inhibitor e.g. argatroban danaparoid

Answer 48

The liver normally conjugates paracetamol with glucuronic acid/sulphate. During an overdose the conjugation system becomes saturated leading to oxidation by P450 mixed function oxidases*. This produces a toxic metabolite (N-acetyl-B-benzoquinone imine) Normally glutathione acts as a defence mechanism by conjugating with the toxin forming the non-toxic mercapturic acid. If glutathione stores run-out, the toxin forms covalent bonds with cell proteins, denaturing them and leading to cell death. This occurs not only in hepatocytes but also in the renal tubules N-acetyl cysteine is used in the management of paracetamol overdose as it is a precursor of glutathione and hence can increase hepatic glutathione production *this explains why there is a lower threshold for treating patients who take P450 inducing medications e.g. phenytoin or rifampicin

Answer 49

Rifampicin is correct. Of this patient's regular medications, rifampicin is the only enzyme inducer. Induction of the P450 enzyme system results in faster metabolism and clearance of the contraceptive pill, reducing its effectiveness.

Answer 50

AIT type 1 - Excess iodine-induced thyroid hormone synthesis, Goitre present Management - Carbimazole or potassium perchlorate AIT type 2 - Amiodarone-related destructive thyroiditis Goitre - absent Management - corticosteroids

Answer 51

The pathophysiology of amiodarone-induced hypothyroidism (AIH) is thought to be due to the high iodine content of amiodarone causing a Wolff-Chaikoff effect - an autoregulatory phenomenon where thyroxine formation is inhibited due to high levels of circulating iodide Amiodarone may be continued if this is desirable

Answer 52

aspirin penicillins NSAIDs opiates

Answer 53

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 short-acting - usually taken 1 hour before sexual activity tadalafil (Cialis) longer acting than sildenafil, may be taken on a regular basis (e.g. once daily) vardenafil (Levitra)

Answer 54

patients taking nitrates and related drugs such as nicorandil hypotension recent stroke or myocardial infarction (NICE recommend waiting 6 months)

Answer 55

visual disturbances blue discolouration non-arteritic anterior ischaemic neuropathy nasal congestion flushing gastrointestinal side-effects headache priapism

Answer 56

occurs when an apparent discrepancy exists between visually perceived movement and the vestibular systems sense of movement Management the BNF recommends hyoscine (e.g. transdermal patch) as being the most effective treatment. Use is limited due to side-effects non-sedating antihistamines such as cyclizine or cinnarizine are recommended in preference to sedating preparation such as promethazine

Answer 57

Ia - quinidine, Procainamide, Disopyramide (blocks sodium channels - increases AP duration) Ib - lidocaine, Mexiletine, Tocainide (Block sodium channels - decreases AP duration) Ic - flecainide, Ecainid, propafenone (block sodium channels - no effect onAP duration) II - propranolol, atenolol, bisoprolol, metoprolol (Beta-adrenoceptor antagonists) III - amioderone, sotalol, Ibutilide, Bretylium (block potassium channels) IV - Verapamil, Diltiazem (CCB)