Pharmacology Flashcards

Question

below are all... • Tricyclics • Benzodiazepines (diazepam,midazolam,alprazolam) • Dextropropoxyphene (co-proxamol) • Digoxin, β-blockers

Answer 1

Drugs which cannot be cleared with HD include • Tricyclics • Benzodiazepines (diazepam,midazolam,alprazolam) • Dextropropoxyphene (co-proxamol) • Digoxin, β-blockers

Answer 2

• Antibiotics: tetracycline, nitrofurantoin • NSAIDS • Lithium

Answer 3

Drugs likely to accumulate in renal failure - need dose adjustment • Most antibiotics including penicillins, cephalosporins, vancomycin, gentamicin, streptomycin • Digoxin, atenolol • Methotrexate • Sulphonylureas • Furosemide • Opioids

Answer 4

Drugs relatively safe - use in normal dose • Antibiotics: erythromycin, rifampicin • Diazepam • Warfarin

Answer 5

Drug Induced Impaired Glucose Tolerance β-blockers cause a slight impairment of glucose tolerance. They should also be used with caution in diabetics as they can interfere with the metabolic and autonomic responses to hypoglycemia

Answer 6

Drug induced Liver Disease is generally divided into hepatocellular, cholestatic or mixed.

Answer 7

Hepatocellular picture

Answer 8

cholestasis +/- hepatitis *risk may be ↓ with erythromycin stearate

Answer 9

liver cirrhosis

Answer 10

• Steroids

Answer 11

• Amiodarone • Indomethacin

Answer 12

• Ethambutol • Amiodarone • Metronidazole

Answer 13

• Chloroquine, quinine

Answer 14

• Sildinafil

Answer 15

• Digoxin

Answer 16

• Phenytoin • Cyclosporin • Calcium channel blockers (especially nifedipine) Other causes of gingival hyperplasia include • Acute myeloid leukemia (myelomonocytic and monocytic types)

Answer 17

• Aspirin • Penicillins • NSAIDs • Opiates

Answer 18

• Alcohol • Barbiturates • Benzodiazepines • Halothane • Oral contraceptive pill • Sulphonamides

Answer 19

acute intermittent porphyria

Answer 20

Drug Induced Thrombocytopenia (probable immune mediated)

Answer 21

Drug Induced Pancytopenia carbimazole also causes both agranulocytosis and pancytopenia

Answer 22

Drug Induced Photosensitivity: Rash on the forearms and face is typical of a photosensitivity rash

Answer 23

patients should be offered nicotine replacement therapy (NRT), varenicline or bupropion - NICE state that clinicians should not favour one medication over another

Answer 24

NRT, varenicline or bupropion should normally be prescribed as part of a commitment to stop smoking on or before a particular date (target stop date) prescription of NRT, varenicline or bupropion should be sufficient to last only until 2 weeks after the target stop date. Normally, this will be after 2 weeks of NRT therapy, and 3-4 weeks for varenicline and bupropion, to allow for the different methods of administration and mode of action. Further prescriptions should be given only to people who have demonstrated that their quit attempt is continuing if unsuccessful using NRT, varenicline or bupropion, do not offer a repeat prescription within 6 months unless special circumstances have intervened do not offer NRT, varenicline or bupropion in any combination

Answer 25

• Adverse effects nausea & include vomiting, flu-like headaches and symptoms • Nice recommend offering a combination of nicotine patches and another form of NRT (such as gum, inhalator, lozenge or nasal spray) to people who show a high level of dependence on nicotine or who have found single forms of NRT inadequate in the past

Answer 26

Nicotinic receptor partial agonist

Answer 27

• Should be started 1 week before the patien target date to stop • The recommended course of is 12 weeks (but patients should be monitored regularly and treatment only continued if not smoking) • Has been shown in studies to be more effective than bupropion • Nausea is the most common adverse effect. Other include headache, insomnia, abnormal dreams • V arenicline should be used with caution in patients with a history of depression or self-harm. • Contraindicated in pregnancy and breast feeding

Answer 28

Norepinephrine and dopamine reuptake inhibitor, and nicotinic antagonist

Answer 29

• Should be started 1 to 2 weeks before target date. • Small risk of seizures (1: 1,000) • Bupropion should not be prescribed to individuals with epilepsy or other conditions that lower the seizure threshold, such as alcohol or benzodiazepine withdrawal, anorexia nervosa, bulimia, or active brain tumors. It should be avoided in individuals who are also taking MAOIs. When switching from MAOIs to bupropion, it is important to include a washout period of 2 weeks. Also pregnancy and breastfeeding are contraindications.

Answer 30

Salicylate Overdose: a key concept for the exam is to understand that salicylate overdose leads 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. In children metabolic acidosis tends to predominate

Answer 31

The mixed respiratory alkalosis and metabolic acidosis in a sweaty, confused patient point towards salicylate overdose. The development of pulmonary edema suggests severe poisoning and is an indication for hemodialysis

Answer 32

Features • Hyperventilation (centrally stimulates respiration) • Tinnitus • Lethargy • Sweating, pyrexia • Nausea/vomiting • Hyperglycemia and hypoglycemia • Seizures • Coma

Answer 33

Treatment • General (ABC, charcoal) • Urinary alkalinization is now rarely used - it is contraindicated in cerebral and pulmonary edema with most units now proceeding straight to hemodialysis in cases of severe poisoning • Hemodialysis

Answer 34

• Serum concentration > 700mg/L • Metabolic acidosis resistant to treatment • Acute renal failure • Pulmonary edema • Seizures • Coma

Answer 35

salicylates cause the uncoupling of oxidative phosphorylation leading to ↓ adenosine triphosphate production, ↑ oxygen consumption and ↑ carbon dioxide and heat production

Answer 36

Management: • Start N-acetyl cysteine immediately • Naloxone if there is hypoxia or respiratory depression

Answer 37

King's College Hospital criteria for liver transplantation (paracetamol liver failure) Arterial pH < 7.3, 24 hours after ingestion OR all of the following: • Prothrombin time > 100 seconds • Creatinine > 300 μmol/l • Grade III or IV encephalopathy

Answer 38

Intravenous acetylcysteine is indicated for the treatment of paracetamol (acetaminophen) overdose. When paracetamol is taken in large quantities, a minor metabolite called N-acetyl-p-benzoquinone imine (NAPQI) builds up. It is normally conjugated by glutathione, but when taken in excess, the body's glutathione reserves are not sufficient to inactivate the toxic NAPQI. This metabolite is then free to react with key hepatic enzymes P450, therefore damaging hepatocytes. For this indication, acetylcysteine acts to augment the glutathione reserves in the body and, together with glutathione, directly bind to toxic metabolites. These actions serve to protect hepatocytes in the liver from NAPQI.

Answer 39

The following patients are at ↑ risk of developing hepatotoxicity following a paracetamol overdose: • Chronic alcohol excess • Patients on p450 enzyme inducers (rifampicin, phenytoin, carbamazepine) • anorexia nervosa: ↓ glutathione stores • HIV

Answer 40

The half-life of digoxin is around 36-48 hours. This results in a delay before steady plasma levels are seen, it may take a week to start its action

Answer 41

Actions • ↓ conduction through the atrioventricular node which slows the ventricular rate in atrial fibrillation and flutter • ↑ the force of cardiac muscle contraction due to inhibition of the Na+/K+ ATPase pump

Answer 42

Features • Generally unwell, lethargy, nausea & vomiting, confusion, • Arrhythmias (e.g. AV block, bradycardia)

Answer 43

• Classically: Hypokalemia (also hyperkalaemia can worsen toxicity) • Myocardial ischemia • Hypomagnesemia, acidosis (Hypo pH), Hypercalcemia, Hypernatremia • Hypoalbuminemia • Hypothermia • Hypothyroidism • Drugs: amiodarone, quinidine, verapamil, spironolactone (compete for secretion in distal convoluted tubule therefore ↓ excretion)

Answer 44

Management • Digibind • Correct arrhythmias • Monitor K+

Answer 45

Indications for administration of Digoxin specific Fab Fragment are: • Hemodynamic instability • Life-threatening arrhythmias • Serum potassium >5 mmol/l in acute toxicity • Plasma digoxin level >13nmol/l • Ingestion of more than 10 mg digoxin in adults and 4 mg in children

Answer 46

Cyanide may be used in insecticides, photograph development and the production of certain metals. Toxicity results from reversible inhibition of cellular oxidising enzymes

Answer 47

Presentation • 'Classical' features: BRICK-RED SKIN, smell of bitter almonds • Acute: hypoxia, hypotension, headache, confusion • Chronic: ataxia, peripheral neuropathy, dermatitis

Answer 48

Management • Supportive measures: 100% oxygen • Definitive: hydroxocobalamin (intravenously), also combination of amyl nitrite (inhaled), sodium nitrite (intravenously), and sodium thiosulfate (intravenously)

Answer 49

Ethylene glycol is a type of alcohol used as a COOLANT OR ANTIFREEZE

Answer 50

Features of toxicity are divided into 3 stages: • Stage 1: symptoms similar to alcohol intoxication: confusion, slurred speech, dizziness • Stage 2: metabolic acidosis with high anion gap and high osmolar gap. Also tachycardia, hypertension • Stage 3: acute renal failure

Answer 51

Ethylene glycol toxicity management - fomepizole. Also ethanol / hemodialysis Management has changed recently: • Ethanol has been used for many years • Works by competing with ethylene glycol for the enzyme alcohol dehydrogenase, this limits the formation of toxic metabolites (e.g. Glycoaldehyde and glycolic acid) which are responsible for the hemodynamic/metabolic features of poisoning • fomepizole, an inhibitor of alcohol dehydrogenase, is now used first-line in preference to ethanol • Hemodialysis also has a role in refractory cases

Answer 52

Cardiovascular effects • Myocardial infarction • Both tachycardia and bradycardia may occur • Hypertension • QRS widening and QT prolongation • Aortic dissection

Answer 53

Neurological effects • Seizures • Hypertonia • Hyperreflexia

Answer 54

Psychiatric effects • Agitation • Psychosis • Hallucinations

Answer 55

Clinical features • Neurological: agitation, anxiety, confusion, ataxia • Cardiovascular: tachycardia, hypertension • Water intoxication • Hyperthermia • Rhabdomyolysis • Hyponatremia

Answer 56

Management • Supportive • Dantrolene may be used for hyperthermia if simple measures fail

Answer 57

Features • Paraesthesia • Visual field defects • Hearing loss • Irritability • Renal tubular acidosis

Answer 58

Lead Poisoning: Along with acute intermittent porphyria, lead poisoning should be considered in questions giving a combination of abdominal pain and neurological signs

Answer 59

Features • Abdominal pain • Peripheral neuropathy (mainly motor) • Fatigue • Constipation • Blue lines on gum margin (only 20% of adult patients, very rare in children)

Answer 60

• Microcytic anemia • Blood film shows red cell abnormalities including basophilic stippling and clover- leaf morphology • Raised serum and urine levels of delta aminolaevulinic acid may be seen making it sometimes difficult to differentiate from acute intermittent porphyria • Urinary coproporphyrin is also ↑ (urinary porphobilinogen and uroporphyrin levels are normal to slightly ↑)

Answer 61

Management - various chelating agents are currently used: • Dimercaptosuccinic acid (DMSA) • D-penicillamine • EDT A (EthyleneDiamineTetraAcetic acid) • Dimercaprol

Answer 62

Confusion, pyrexia and pink mucosae are typical features of carbon monoxide poisoning Features of carbon monoxide toxicity • Headache: 90% of cases • Nausea and vomiting: 50% • V ertigo: 50% • Confusion: 30% • Subjective weakness: 20% • Severe toxicity: 'pink' skin and mucosae, hyperpyrexia, arrhythmias, extrapyramidal features, coma, death

Answer 63

• < 3% non-smokers • < 10% smokers • 10 - 30% symptomatic: headache, vomiting, dizziness • > 30% severe toxicity: -50-60%: Syncope, tachycardia, fits -> 60%: ↑ risk of cardiorespiratory failure and death

Answer 64

Management • 100% oxygen • Hyperbaric oxygen

Answer 65

Indications for hyperbaric oxygen • Loss of consciousness at any point • Neurological signs other than headache • Myocardial ischemia or arrhythmia • Pregnancy

Answer 66

Oculogyric Crisis is a dystonic reaction to certain drugs or medical conditions Features (extra pyramidal) • Restlessness, agitation • Involuntary upward deviation of the eyes

Answer 67

Causes • Phenothiazines • Haloperidol • Metoclopramide • Postencephalitic Parkinson’ s disease.

Answer 68

Treatment • Procyclidine • Benztropine

Answer 69

• ACE inhibitors, ARBs • Statins • W arfarin • Sulfonylureas • Retinoids (including topical) • Cytotoxic agents

Answer 70

• Tetracyclines • Aminoglycosides • Sulphonamides • Trimethoprim • Quinolones: the BNF advises to avoid due to arthropathy in some animal studies

Answer 71

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

Answer 72

• Galactosemia • Viral infections - this is controversial with respect to HIV in the developing world. This is because there is such an ↑ infant mortality and morbidity associated with bottle feeding that some doctors think the benefits outweigh the risk of HIV transmission

Answer 73

Breast feeding is acceptable with nearly all anti-epileptic drugs

Answer 74

standard: Intravenous LMWH: Subcutaneous

Answer 75

standard: short LMWH: long

Answer 76

Standard: 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 77

Standard: Bleeding Heparin-induced thrombocytopaenia (HIT) Osteoporosis LMWH: Bleeding Lower risk of HIT and osteoporosis with LMWH

Answer 78

Useful in situations where there is a ↑ risk of bleeding as anticoagulation can be terminated rapidly

Answer 79

Now standard in the management of venous thromboembolism treatment and prophylaxis and acute coronary syndromes

Answer 80

Both unfractionated and low-molecular weight heparin can cause hyperkalaemia. This is thought to be caused by inhibition of aldosterone secretion.

Answer 81

Heparin-induced thrombocytopaenia (HIT) • Immune mediated - antibodies form which cause the activation of platelets • 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 • Treatment options include alternative anticoagulants such as lepirudin and danaparoid

Answer 82

Heparin overdose may be reversed by protamine sulphate, although this only partially reverses the effect of LMWH.

Answer 83

Adrenaline is a sympathomimetic amine with both α and β adrenergic stimulating properties

Answer 84

Adrenaline induced ischemia - phentolamine Phentolamine, a short acting α blocker, may be used as local infiltration in situations like accidental injection of adrenaline. It is normally used mainly to control blood pressure during surgical resection of Pheochromocytoma.

Answer 85

Indications • Anaphylaxis - 0.5ml 1:1,000 IM • Cardiac arrest - 10ml 1:10,000 IV or 1ml of 1:1000 IV

Answer 86

Phenytoin • Trough levels immediately before dose Cyclosporin • Trough levels immediately before dose Digoxin • At least 6 hrs post-dose Lithium • Range = 0.4 - 1.0 mmol/l • Take 12 hrs post-dose

Answer 87

• Blepharospasm • Hemifacial spasm • Focal spasticity including cerebral palsy patients, hand and wrist disability associated with stroke • Spasmodic torticollis • Severe hyperhidrosis of the axillae • Achalasia

Answer 88

Adverse effects • Teratogenicity: ♀s MUST be using two forms of contraception (e.g. COCP and condoms) • Dry skin, eyes and lips: the most common side-effect of isotretinoin • Low mood, depression • Raised triglycerides • Hair thinning • Nose bleeds (caused by dryness of the nasal mucosa) • Benign intracranial hypertension: isotretinoin treatment should not be combined with tetracyclines for this reason

Answer 89

• metastatic bone pain may respond to NSAIDs, bisphosphonates or radiotherapy

Answer 90

-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

Answer 91

oxycodone is preferred to morphine in palliative patients with mild-moderate renal impairment if renal impairment is more severe, alfentanil, buprenorphine and fentanyl are preferred

Answer 92

Oral codeine Oral morphine Divide by 10 Oral tramadol Oral morphine Divide by 10

Answer 93

Oral morphine Oral oxycodone Divide by 1.5-2

Answer 94

a transdermal fentanyl 12 microgram patch equates to approximately 30 mg oral morphine daily

Answer 95

a transdermal buprenorphine 10 microgram patch equates to approximately 24 mg oral morphine daily.

Answer 96

Oral morphine to Subcutaneous diamorphine - Divide by 3

Answer 97

Oral oxycodone to Subcutaneous diamorphine - Divide by 1.5

Answer 98

• 1mg prednisolone = 4mg hydrocortisone • 1mg dexamethasone = 7mg prednisolone

Answer 99

Nausea and vomiting are common side-effects of chemotherapy Risk factors for the development of symptoms include: • Anxiety • Age less than 50 years old • Concurrent use of opioids • The type of chemotherapy used

Answer 100

For patients at low-risk of symptoms then drugs such as metoclopramide may be used first-line. For high-risk patients then 5HT3 receptor antagonists such as ondansetron are often effective, especially if combined with dexamethasone

Answer 101

Features • Present for 15 days or more per month • Developed or worsened whilst taking regular symptomatic medication • Patients using opioids and triptans are at most risk • May be psychiatric co-morbidity

Answer 102

Management • Simple analgesics and triptans should be withdrawn abruptly (may initially worsen headaches) • Opioid analgesics should be gradually withdrawn

Answer 103

Doxazosin is an α-1 adrenoceptor antagonist used in the treatment of hypertension and benign prostatic hypertrophy

Answer 104

• α-1: doxazosin • α-1a: tamsulosin - acts mainly on urogenital tract • α-2: yohimbine • Non-selective: phenoxybenzamine (previously used in peripheral arterial disease)

Answer 105

β antagonists • β-1: atenolol • Non-selective: propranolol

Answer 106

Carvedilol and labetalol are mixed α and β antagonists

Answer 107

Lithium is mood stabilising drug used most commonly prophylatically 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

Answer 108

Lithium: fine tremor in chronic treatment, coarse tremor in acute toxicity

Answer 109

Mechanism of action - not fully understood, two theories: • Interferes with inositol triphosphate formation • Interferes with cAMP formation

Answer 110

Adverse effects • Nausea/vomiting, diarrhea • Fine tremor • Polyuria • Thyroid enlargement, may lead to hypothyroidism • ECG: T wave flattening/inversion • W eight gain

Answer 111

Monitoring of patients on lithium therapy • Inadequate monitoring of patients taking lithium is common - NICE and the National Patient Safety Agency (NPSA) have issued guidance to try and address this. As a result it is often an exam hot topic • Lithium blood level should ‘normally’ be checked every 3 months. Levels should be taken 12 hours post-dose • Thyroid and renal function should be checked every 6 months • Patients should be issued with an information booklet, alert card and record book Lithium toxicity generally occurs following concentrations > 1.5 mmol/L.

Answer 112

Toxicity may be precipitated by dehydration, renal failure, diuretics (Especially bendroflumethiazide) or ACE inhibitors and ARBs BNF advises that neurotoxicity may be ↑ when lithium is given with diltiazem or verapamil but there is no significant interaction with amlodipine.

Answer 113

• Coarse tremor (a fine tremor is seen in therapeutic levels) • Acute confusion • Seizure • Coma

Answer 114

Management • Mild-moderate toxicity may respond to volume resuscitation with normal saline • Hemodialysis 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.

Answer 115

Tricyclic Overdose is a common presentation to A&E departments. Early features relate to anticholinergic properties: dry mouth, dilated pupils, agitation, sinus tachycardia, blurred vision.

Answer 116

Features of severe poisoning include: • Arrhythmias • Seizures • Metabolic acidosis • Coma

Answer 117

ECG changes include: • Sinus tachycardia • Widening of QRS • Prolongation of QT interval Widening of QRS > 100ms is associated with ↑ risk of seizures whilst QRS > 160ms is associated with ventricular arrhythmias

Answer 118

Management • IV bicarbonate may ↓ the risk of seizures and arrhythmias in severe toxicity • Arrhythmias: class I-a (e.g. Quinidine) and class I-c antiarrhythmics (e.g. Flecainide) are contraindicated as they prolong depolarisation. Class III drugs such as amiodarone should also be avoided as they prolong the QT interval. Response to lignocaine is variable and it should be emphasized that correction of acidosis is the first line in management of tricyclic induced arrhythmias • Dialysis is ineffective in removing tricyclic

Answer 119

Phenytoin is associated with a large number of adverse effects. These may be divided into acute, chronic, idiosyncratic and teratogenic

Answer 120

Acute • Initially: vertigo, diplopia, nystagmus, slurred speech, ataxia • Later: confusion, seizures

Answer 121

Chronic • Common: gingival hyperplasia, hirsuitism, coarsening of facial features • Megaloblastic anemia (secondary to altered folate metabolism) • Peripheral neuropathy • Enhanced vitamin D metabolism causing osteomalacia • Lymphadenopathy • Dyskinesia

Answer 122

Idiosyncratic • Fever • Rashes, including severe reactions such as toxic epidermal necrolysis • Hepatitis • Dupuytren's contracture (although not listed in the BNF) • Aplastic anemia • Drug-induced lupus

Answer 123

Teratogenic • Associated with cleft palate and congenital heart disease

Answer 124

Adverse effects • Gastrointestinal: nausea • ↑ appetite and weight gain • Alopecia: regrowth may be curly (note that phenytoin → hirsutism while valporate → alopecia) • Ataxia • Tremor • Hepatitis (also with phenytoin) • Pancreatitis • Teratogenic

Answer 125

Anticholinesterase Effects: One of the effects of organophosphate poisoning is inhibition of acetylcholinesterase

Answer 126

Features can be predicted by the accumulation of acetylcholine (mnemonic = SLUD) • Salivation • Lacrimation • Urination • Defecation • Cardiovascular: hypotension, bradycardia • Also: small pupils, muscle fasciculation

Answer 127

Management • Atropine • The role of pralidoxime is still unclear - meta-analyses to date have failed to show any clear benefit

Answer 128

St John's Wort: 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'

Answer 129

Adverse effects • Profile in trials similar to placebo • Can cause serotonin syndrome • Inducer of P450 system, therefore ↓ levels of drugs such as warfarin, Cyclosporin. The effectiveness of the combined oral contraceptive pill may also be ↓

Answer 130

Monoamine Oxidase Inhibitors (MAOIs): • Serotonin and noradrenaline are metabolised by monoamine oxidase in the presynaptic cell

Answer 131

Non-selective monoamine oxidase inhibitors • E.g. tranylcypromine, phenelzine • Used in the treatment of depression and other psychiatric disorder • Not used frequently due to side-effects

Answer 132

Adverse effects of non-selective monoamine oxidase inhibitors • Hypertensive crisis: MAOIs reacting with tyramine containing foods e.g. Cheese, pickled herring, Bovril, oxo, marmite, broad beans, liver, wine. • Anticholinergic effects

Answer 133

Agonists • Sumatriptan is a 5-HT1D receptor agonist which is used in the acute treatment of migraine • Ergotamine is a partial agonist of 5-HT1 receptors

Answer 134

It should be noted that 5-HT receptor agonists are used in the acute treatment of migraine whilst 5-HT receptor antagonists are used in prophylaxis

Answer 135

• Pizotifen is a 5-HT2 receptor antagonist used in the prophylaxis of migraine attacks. • Methysergide is another antagonist of the 5-HT2 receptor but is rarely used due to the risk of retroperitoneal fibrosis • Cyproheptadine is a 5-HT2 receptor antagonist which is used to control diarrhea in patients with carcinoid syndrome • Olanzapine is 5-HT2 antagonist and D2 dopamin receptor blocker, it’s an atypical antipsychotic • Ondansetron and Granisetron are 5-HT3 receptor antagonist and is used as an antiemetic... They cause conistipation, dizziness and headache.

Answer 136

Triptans: are specific 5-HT1 agonists used in the acute treatment of migraine. They are generally used second line when standard analgesics such as paracetamol and ibuprofen are ineffective

Answer 137

• Should be taken as soon as possible after the onset of headache, rather than at onset of aura • Oral, orodispersible, nasal spray and subcutaneous injections are available

Answer 138

Adverse effects • 'Triptan sensations' - tingling, heat, tightness (e.g. Throat and chest), heaviness, pressure

Answer 139

Contraindications • Patients with a history of, or significant risk factors for ischemic heart disease or cerebrovascular disease

Answer 140

Indications • Parkinson's disease • Prolactinoma/galactorrhoea • Cyclical breast disease • Acromegaly

Answer 141

Adverse effects • Nausea/vomiting • Postural hypotension • Hallucinations • Daytime somnolence

Answer 142

Benzodiazepines antidote is flumazenil

Answer 143

The Committee on Safety of Medicines advises that benzodiazepines are only prescribed for a short period of time (2-4 weeks).

Answer 144

The BNF gives advice on how to withdraw a benzodiazepine. The dose should be withdrawn in steps of about 1/8 (range 1/10 to 1/4) of the daily dose every fortnight. A suggested protocol for patients experiencing difficulty is given: • Switch patients to the equivalent dose of diazepam • Reduce dose of diazepam every 2-3 weeks in steps of 2 or 2.5 mg • Time needed for withdrawal can vary from 1 month to 1 year or more

Answer 145

If patients withdraw too quickly from benzodiazepines they may experience benzodiazepine withdrawal syndrome, a condition very similar to alcohol withdrawal syndrome. This may occur up to 3 weeks after stopping a long-acting drug. Features include: • Insomnia • Irritability • Anxiety • Tremor • Loss of appetite • Tinnitus • Perspiration • Perceptual disturbances • Seizures

Answer 146

Quinidine Procainamide Disopyramide Block sodium channels Increases AP duration Quinidine toxicity causes cinchonism (headache, tinnitus, thrombocytopaenia) Procainamide may cause drug-induced lupus

Answer 147

Lidocaine Mexiletine Tocainide Block sodium channels Decreases AP duration

Answer 148

Flecainide Encainide Propafenone Block sodium channels No effect on AP duration

Answer 149

Propranolol Atenolol Bisoprolol Metoprolol Beta-adrenoceptor antagonists

Answer 150

Amiodarone Sotalol Ibutilide Bretylium Block potassium channels

Answer 151

Verapamil Diltiazem Calcium channel blockers

Answer 152

Amiodarone is a class III antiarrhythmic agent used in the treatment of both atrial and ventricular tachycardias. The main mechanism of action is by blocking potassium channels which inhibits repolarisation and hence prolongs the action potential. Amiodarone also has other actions such as blocking sodium channels (a class I-a effect)

Answer 153

The use of amiodarone is limited by a number of factors • Long half-life (20-100 days) • Should ideally be given into central veins (causes thrombophlebitis) • Has proarrhythmic effects due to lengthening of the QT interval • Interacts with drugs commonly used concurrently e.g. ↓ metabolism of warfarin = P450 inhibtor • Numerous long-term adverse effects

Answer 154

Monitoring of patients taking amiodarone • TFT, LFT, U&E, CXR prior to treatment. U&E to check hypokalemia • TFT, LFT every 6 months

Answer 155

Adverse effects of amiodarone use • Thyroid dysfunction • Corneal deposits • Pulmonary fibrosis/pneumonitis • Liver fibrosis/hepatitis • Peripheral neuropathy, myopathy • Photosensitivity • 'Slate-grey' appearance

Answer 156

Amiodarone and Thyroid: Around 1 in 6 patients taking amiodarone develop thyroid dysfunction

Answer 157

Amiodarone-induced hypothyroidism (AIH) 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)

Answer 158

AIT type 1 and AIT type 2

Answer 159

Excess iodine-induced thyroid hormone synthesis Present goitre Carbimazole or potassium perchlorate

Answer 160

Amiodarone-related destructive thyroiditis Absent goitre Corticosteroids

Answer 161

Unlike in AIH, amiodarone should be stopped if possible in patients who develop AIT

Answer 162

Flecainide is a Vaughan Williams class I-c antiarrhythmic. It slows conduction of the action potential by acting as a potent sodium channel blocker. This may be reflected by widening of the QRS complex and prolongation of the PR interval

Answer 163

The Cardiac Arrhythmia Suppression Trial (CAST, 1989) investigated the use of agents to treat asymptomatic or mildly symptomatic premature ventricular complexes (PVCs) post myocardial infarction. The hypothesis was that this would ↓ deaths from ventricular arrhythmias. Flecainide was actually shown to ↑ mortality post myocardial infarction and is therefore contraindicated in this situation.

Answer 164

Indications • Atrial fibrillation • SVT associated with accessory pathway e.g. Wolf-Parkinson-White syndrome

Answer 165

Adverse effects • Negatively inotropic • Bradycardia • Proarrhythmic • Oral paraesthesia • Visual disturbance

Answer 166

Statins inhibit the action of HMG-CoA reductase, the rate-limiting enzyme in hepatic cholesterol synthesis → Statins: ↓ cholesterol synthesis.

Answer 167

P450 inhibitors ↑ CK and myopathy

Answer 168

Nicotinic acid ↑ HDL levels

Answer 169

Adverse effects • Myopathy: includes myalgia, myositis, rhabdomyolysis and asymptomatic raised creatine kinase. Risks factors for myopathy include advanced age, ♀, low BMI and presence of multisystem disease such as diabetes mellitus. Myopathy is more common in lipophilic statins (simvastatin, atorvastatin) than relatively hydrophilic statins (rosuvastatin, pravastatin, fluvastatin) • Liver impairment: 2008 NICE guidelines recommend checking LFTs at baseline, 3 months and 12 months. Treatment should be discontinued if serum transaminase concentrations rise to and persist at 3 times the upper limit of the reference range

Answer 170

Who should receive a statin? • All people with established cardiovascular disease (stroke, TIA, IHD, peripheral arterial disease) • NICE recommend anyone with a 10-year cardiovascular risk = 20% • The management of blood lipids in type 2 diabetes mellitus (T2DM) has changed slightly. Previously all patients with T2DM > 40-years-old were prescribed statins. Now patients > 40- years-old who have no obvious cardiovascular risk (e.g. Non-smoker, not obese, normotensive etc) and have a cardiovascular risk < 20%/10 years do not need to be given a statin.

Answer 171

Statins should be taken at night as this is when the majority of cholesterol synthesis takes place. This is especially true for simvastatin which has a shorter half-life than other statins

Answer 172

NICE currently recommends the following for the prevention of cardiovascular disease:: atorvastatin 20mg for primary prevention (i.e. cardiovascular risk of >=10% or most type 1 DM or CKD if eGFR <60) -increase the dose if non-HDL has not reduced for >= 40% atorvastatin 80mg for secondary prevention

Answer 173

nicotinic acid

Answer 174

anion-exchange resins

Answer 175

Nicotinic Acid is used in the treatment of patients with hyperlipidemia, although its use is limited by side-effects. As well as lowering cholesterol and triglyceride concentrations it also raises HDL levels

Answer 176

Adverse effects • Flushing • Impaired glucose tolerance • Myositis

Answer 177

β-blocker overdose management: atropine + glucagon

Answer 178

Glucagon has a positive inotropic action on the heart and ↓ renal vascular resistance. It is therefore useful in patients with β-blocker cardiotoxicity

Answer 179

Cardiac pacing should be reserved for patients unresponsive to pharmacological therapy

Answer 180

Features • Bradycardia • Hypotension • Heart failure • Syncope

Answer 181

Management • If bradycardic then atropine • In resistant cases glucagon may be used • Hemodialysis is not effective in β-blocker overdose

Answer 182

Furosemide is a loop diuretic that acts by inhibiting chloride absorption in the ascending loop of Henle. The name of Lasix is derived from lasts six (hours) referring to its duration of action.

Answer 183

Adverse effects • Hyponatremia • Hypokalemia • Hypocalcaemia • Hypochloraemic alkalosis (Hyper pH) • Ototoxicity • Renal impairment (from dehydration + direct toxic effect) • Hyperglycaemia (less common than thiazides) • Gout

Answer 184

Bendroflumethiazide (bendrofluazide) is a thiazide diuretic which works by inhibiting sodium absorption at the beginning of the distal convoluted tubule (DCT). Potassium is lost as a result of more sodium reaching the collecting ducts. Bendroflumethiazide has a role in the treatment of mild heart failure although loop diuretics are better for reducing overload. The main use of bendroflumethiazide currently is in hypertension (part of the effect is due to vasodilation)

Answer 185

Bendroflumethiazide - mechanism of Hypokalemia: • ↑ sodium reaching the collecting ducts • Activation of the renin-angiotensin-aldosterone

Answer 186

Common adverse effects • Dehydration • Postural hypotension • Hyponatremia, Hypokalemia, Hypercalcemia • Gout • Impaired glucose tolerance, Hyperglycaemia • Impotence

Answer 187

Bendroflumethiazide

Answer 188

Spironolactone is an aldosterone antagonist which acts act in the distal convoluted tubule

Answer 189

Indications • Ascites: patients with cirrhosis develop a secondary hyperaldosteronism. Relatively large doses such as 100 or 200mg are often used • Heart failure • Nephrotic syndrome • Conn's syndrome

Answer 190

Adverse effects • Hyperkalemia • Gynaecomastia

Answer 191

RALES STUDY • NYHA III + IV, patients already taking ACE inhibitor • Low dose spironolactone ↓ all cause mortality

Answer 192

Adenosine • Dipyridamole enhances effect • Aminophylline ↓ effect The effects of adenosine are enhanced by dipyridamole (anti-platelet agent) and blocked by theophyllines. It should be avoided in asthmatics due to possible bronchospasm.

Answer 193

asthmatics

Answer 194

Mechanism of action • Causes transient heart block in the AV node • Agonist of the A1 receptor which inhibits adenylyl cyclase thus reducing cAMP and causing hyperpolarization by increasing outward potassium flux • Adenosine has a very short half-life of about 8-10 seconds

Answer 195

Adverse effects • Chest pain • Bronchospasm • Can enhance conduction down accessory pathways, resulting in ↑ ventricular rate (e.g. WPW)

Answer 196

Calcium channel blockers - side-effects: headache, flushing, ankle edema

Answer 197

Mode of action • ↓ calcium entry to smooth and cardiac muscle which in turn results in a ↓ force of contraction and slower heart rate

Answer 198

Indications • Angina, hypertension, arrhythmias (e.g. Narrow complex tachycardia), raynaud's

Answer 199

Dihydropyridines (e.g. nifedipine, amlodipine) • Effects peripheral circulation i.e. Used for hypertension, raynaud's • May bring on angina due to sympathetic reflex following vasodilation • Side-effects: headache, flushing, ankle edema

Answer 200

-Angina, hypertension, arrhythmias Highly negatively inotropic -Should not be given with beta-blockers as may cause heart block -Heart failure, constipation, hypotension, bradycardia

Answer 201

-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

Answer 202

Aspirin works by blocking the action of both cyclooxygenase-1 and 2.

Answer 203

Cyclooxygenase is responsible for prostaglandin, prostacyclin and thromboxane synthesis. The blocking of thromboxane A2 formation in platelets reduces the ability of platelets to aggregate which has lead to the widespread use of low-dose aspirin in cardiovascular disease. All patients with established cardiovascular disease should take aspirin if there is no contraindication.

Answer 204

• All people with established cardiovascular disease (stroke, TIA, IHD, peripheral arterial disease) • All people aged 50 years and over with a 10-year cardiovascular risk = 20% • All people with diabetes mellitus (type 1 or 2) who are = 50 years old or who have: diabetes > 10 years, taking treatment for hypertension or evidence of target organ damage • All people with target organ damage from hypertension

Answer 205

Potentiates • Oral hypoglycaemics • W arfarin • Steroids

Answer 206

Mechanism of action: • Inhibit the conversion angiotensin I to angiotensin II

Answer 207

Side-effects: • Cough: occurs in around 15% of patients and may occur up to a year after starting treatment. Thought to be due to increased bradykinin levels • Angioedema: may occur up to a year after starting treatment • Hyperkalaemia • 1st-dose hypotension: more common in patients taking diuretics

Answer 208

Cautions and contraindications • Pregnancy and breastfeeding - avoid • Renovascular disease - significant renal impairment may occur in patients who have undiagnosed bilateral renal artery stenosis • Aortic stenosis - may result in hypotension • Patients receiving high-dose diuretic therapy (more than 80 mg of furosemide a day) - signficantly increases the risk of hypotension • Hereditary of idiopathic angioedema

Answer 209

• Urea and electrolytes should be checked before treatment is initiated and after increasing dose • A rise in the creatinine and potassium may be expected after starting ACE inhibitors. Acceptable increases are an increase in serum creatinine, up to 50% from baseline or up to 265 μmol/l (whichever is smaller) and an increase in potassium up to 5.5 mmol/l.

Answer 210

NSAIDs or colchicine are first-line the maximum dose of NSAID should be prescribed until 1-2 days after the symptoms have settled. Gastroprotection (e.g. a proton pump inhibitor) may also be indicated colchicine has a slower onset of action. The main side-effect is diarrhoea oral steroids may be considered if NSAIDs and colchicine are contraindicated. A dose of prednisolone 15mg/day is usually used another option is intra-articular steroid injection if the patient is already taking allopurinol it should be continued

Answer 211

Indications for urate-lowering therapy (ULT) 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

Answer 212

'Commencement of ULT is best delayed until inflammation has settled as ULT is better discussed when the patient is not in pain' initial dose of 100 mg od, with the dose titrated every few weeks to aim for a serum uric acid of < 300 µmol/l. Lower initial doses should be given if the patient has a reduced eGFR colchicine cover should be considered when starting allopurinol. NSAIDs can be used if colchicine cannot be tolerated. The BSR guidelines suggest this may need to be continued for 6 months

Answer 213

the second-line agent when allopurinol is not tolerated or ineffective is febuxostat (also a xanthine oxidase inhibitor)

Answer 214

in refractory cases other agents may be tried: uricase (urate oxidase) is an enzyme that catalyzes the conversion of urate to the degradation product allantoin. It is present in certain mammals but not humans in patients who have persistent symptomatic and severe gout despite the adequate use of urate-lowering therapy, pegloticase (polyethylene glycol modified mammalian uricase) can achieve rapid control of hyperuricemia. It is given as an infusion once every two weeks

Answer 215

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 ↓ dose (e.g. 25%) must therefore be used if the combination cannot be avoided

Answer 216

Cyclophosphamide • Allopurinol ↓ renal clearance, therefore may cause marrow toxicity

Answer 217

Indications • Vasomotor symptoms such as flushing, insomnia and headaches • Premature menopause: should be continued until the age of 50 years • Osteoporosis: but should only be used as second-line treatment The main indication is the control of vasomotor symptoms. The other indications such as reversal of vaginal atrophy and prevention of osteoporosis should be treated with other agents as first-line therapies. Other benefits include ↓ incidence of colorectal cancer

Answer 218

Side-effects • Nausea • Breast tenderness • Fluid retention and weight gain

Answer 219

Potential complications • ↑ Risk of breast cancer: ↑ by the addition of a progestogen • ↑ Risk of venous thromboembolism: ↑ by the addition of a progestogen • ↓ Risk of endometrial cancer: ↓ by the addition of a progestogen but not eliminated completely. The BNF states that the additional risk is eliminated if a progestogen is given continuously

Answer 220

Combined OCP: ↑ Risk of breast cancer ↑ Risk of DVT ↓ Risk of endometrial ca.

Answer 221

Breast cancer • In the Women's Health Initiative (WHI) study there was a relative risk of 1.26 at 5 years of developing breast cancer • The ↑ risk relates to duration of use • Breast cancer incidence is higher in women using combined preparations compared to estrogen- only preparations • The risk of breast cancer begins to decline when HRT is stopped and by 5 years it reaches the same level as in women who have never taken HRT

Answer 222

• UKMEC 1: a condition for which there is no restriction for the use of the contraceptive method • UKMEC 2: advantages generally outweigh the disadvantages • UKMEC 3: disadvantages generally outweigh the advantages • UKMEC 4: represents an unacceptable health risk

Answer 223

• More than 35 years old and smoking less than 15 cigarettes/day • BMI 35-39 kg/m2 • Migraine without aura and more than 35 years old • Family history of thromboembolic disease in first degree relatives < 45 years • Controlled hypertension • Breast feeding 6 weeks - 6 months postpartum

Answer 224

• More than 35 years old and smoking more than 15 cigarettes/day • BMI > 40 kg/ m2 • Migraine with aura • History of thromboembolic disease or thombogenic mutation • History of stroke or ischemic heart disease • Uncontrolled hypertension • Breast cancer • Major surgery with prolonged immobilisation

Answer 225

Tamoxifen is a selective estrogen receptor modulator (SERM) which acts as an estrogen receptor antagonist and partial agonist. It is used in the management of estrogen receptor positive breast cancer

Answer 226

Adverse effects • Hot flushes • Menstrual disturbance: vaginal bleeding, amenorrhoea • V enous thromboembolism • Endometrial cancer • Alopecia • Cataracts

Answer 227

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

Answer 228

P450 inhibitors ↑ INR

Answer 229

INR also ↑ by ABX that kill intestinal flora by ↓ Vit K absorption

Answer 230

Dentistry in warfarinised patients - check INR 72 hours before procedure, proceed if INR < 4.0 If patient has unstable INR then it should be checked 24H prior to procedure

Answer 231

Factors that may potentiate warfarin • Liver disease • P450 enzyme inhibitors, e.g.: amiodarone, ciprofloxacin • Cranberry juice • Drugs which displace warfarin from plasma albumin, e.g. NSAIDs • Inhibit platelet function: NSAIDs

Answer 232

• Hemorrhage • Teratogenic • Skin necrosis: when warfarin is first started biosynthesis of protein C is ↓. This results in a temporary procoagulant state after initially starting warfarin, normally avoided by concurrent heparin administration. Thrombosis may occur in venules leading to skin necrosis

Answer 233

Stop warfarin Vitamin K 5mg IV Prothrombin complex concentrate - if not available then FFP

Answer 234

Stop warfarin, restart when INR < 5.0 If risk factors for bleeding then give vitamin K 0.5mg IV or 5mg PO. Risk factors include: • Age > 70 years • First year of warfarin therapy • History of gastrointestinal bleeding • Hypertension • Alcohol excess Dose can be repeated after 24 hours if INR still high

Answer 235

Stop warfarin, restart when INR < 5.0

Answer 236

Acyclovir is phosphorylated by thymidine kinase which in turn inhibits the viral DNA polymerase

Answer 237

• Effective against a range of DNA and RNA viruses • Interferes with the capping of viral mRNA

Answer 238

Inhibit synthesis of mRNA, translation of viral proteins, viral assembly and release

Answer 239

• Used to treat influenza • Inhibits uncoating of virus in cell

Answer 240

HIV: Anti-Retrovirals: Highly active anti-retroviral therapy (HAART) involves a combination of at least three drugs, typically two nucleoside reverse transcriptase inhibitors (NRTI) and either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). This combination both ↓ viral replication and also ↓ the risk of viral resistance emerging

Answer 241

HIV: anti-retrovirals - P450 interaction • nevirapine (NNRTI): induces P450 • protease inhibitors: inhibits P450

Answer 242

Nucleoside analogue reverse transcriptase inhibitors (NRTI) • Examples: zidovudine (azt), didanosine, lamivudine, stavudine, zalcitabine • General NRTI side-effects: peripheral neuropathy • Zidovudine: anemia, myopathy, black nails • Didanosine: pancreatitis

Answer 243

Non-nucleoside reverse transcriptase inhibitors (NNRTI) • Examples: nevirapine, efavirenz • Side-effects: p450 enzyme interaction (nevirapine induces), rashes

Answer 244

Protease inhibitors (PI) • Examples: indinavir, nelfinavir, ritonavir, saquinavir • Side-effects: diabetes, hyperlipidemia, buffalo hump, central obesity, p450 enzyme inhibition • Indinavir: renal stones, asymptomatic hyperbilirubinemia • Ritonavir: a potent inhibitor of the p450 system

Answer 245

Cyclosporin: is an immunosuppressant which ↓ clonal proliferation of T cells by reducing IL-2 release. It acts by binding to cyclophilin forming a complex which inhibits calcineurin, a phosphotase that activates various transcription factors in T cells

Answer 246

Ciclosporin side-effects: everything is increased - fluid, BP, K+, hair, gums, glucose • Nephrotoxicity • Hepatotoxicity • Fluid retention • Tremor • Hypertension • Hyperkalemia • Hypertrichosis • Hyperplasia of gum • Impaired glucose tolerance, hyperglycemia.

Answer 247

Indications • Crohn's disease • Rheumatoid arthritis • Psoriasis (has a direct effect on keratinocytes as well as modulating T cell function) • Following organ transplantation • Pure red cell aplasia

Answer 248

Tacrolimus is a macrolide antibiotic and is used as an immunosuppressant to prevent transplant rejection. It has a very similar action to Cyclosporin; the action of tacrolimus differs in that it binds to a protein called FKBP rather than cyclophilin

Answer 249

Azathioprine is metabolised to the active compound mercaptopurine, a purine analogue that inhibits purine synthesis. A thiopurine methyltransferase (TPMT) test may be needed to look for individuals prone to azathioprine toxicity.

Answer 250

Adverse effects include bone marrow depression nausea/vomiting pancreatitis increased risk of non-melanoma skin cancer

Answer 251

A significant interaction may occur with allopurinol and hence lower doses of azathioprine should be used.

Answer 252

Azathioprine is generally considered safe to use in pregnancy.

Answer 253

Methotrexate is an antimetabolite which inhibits dihydrofolate reductase, an enzyme essential for the synthesis of purines and pyrimidines

Answer 254

Indications • Rheumatoid arthritis • Psoriasis • Acute lymphoblastic leukaemia

Answer 255

Adverse effects • Mucositis • Myelosuppression • Pneumonitis • Liver cirrhosis

Answer 256

Pregnancy • Men and women should avoid pregnancy for at least 3 months after treatment has stopped

Answer 257

Methotrexate is taken weekly, rather than daily

Answer 258

FBC, U&E and LFTs need to be regularly monitored. The Committee on Safety of Medicines recommend 'FBC and renal and LFTs before starting treatment and repeated weekly until therapy stabilised, thereafter patients should be monitored every 2-3 months'

Answer 259

Folic acid 5mg once weekly should be coprescribed, taken more than 24 hours after methotrexate dose

Answer 260

• The starting dose of methotrexate is 7.5 mg weekly • Only one strength of methotrexate tablet should be prescribed (usually 2.5 mg) • Avoid prescribing trimethoprim or cotrimoxazole concurrently - increases risk of marrow aplasia

Answer 261

Cyclosporin + tacrolimus - MOA: inhibit calcineurin thus decreasing IL-2

Answer 262

Mycophenolate mofetil

Answer 263

Azathioprine

Answer 264

Methotrexate

Answer 265

Uses: • Non- Hodgkin's lymphoma • Rheumatoid arthritis in refractory rheumatoid disease • Used off-label to treat difficult cases of multiple sclerosis, SLE and autoimmune anemias • Pure red cell aplasia, ITP, Evans syndrome, vasculitis.

Answer 266

Side effects: • Flu-like illness • ↓BP during fever • Tumor side pain

Answer 267

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

Answer 268

indications are: • Benign prostatic hyperplasia • ♂-pattern baldness

Answer 269

Adverse effects: • Impotence • ↓ libid • Ejaculation disorders • Gynaecomastia and breast tenderness

Answer 270

Finasteride causes ↓ levels of serum prostate specific antigen

Answer 271

Bisphosphonates are analogues of pyrophosphate, a molecule which ↓ demineralisation in bone. They inhibit osteoclasts by reducing recruitment and promoting apoptosis

Answer 272

Bisphosphonates (alendronate) can cause a variety of esophageal problems

Answer 273

Clinical uses • Prevention and treatment of osteoporosis • Hypercalcemia • Paget's disease • Pain from bone metatases

Answer 274

Adverse effects • Esophageal reactions: oesophagitis, esophageal ulcers (especially alendronate) • Osteonecrosis of the jaw • MHRA has warned about an increased risk of atypical stress fractures of the proximal femoral shaft in patients taking alendronate

Answer 275

Sildenafil is a phosphodiesterase type V inhibitor used in the treatment of impotence

Answer 276

Viagra - contraindicated by nitrates and nicorandil The BNF recommends avoiding α-blockers for 4 hours after sildenafil

Answer 277

Contraindications • Patients taking nitrates and related drugs such as nicorandil • Hypotension • Recent stroke or myocardial infarction • Non-arteritic anterior ischemic optic neuropathy

Answer 278

Adverse effects • Visual disturbances e.g. Blue discoloration, non-arteritic anterior ischemic neuropathy • Nasal congestion • Flushing • Gastrointestinal side-effects

Answer 279

Octreotide • Long-acting analogue of somatostatin • Somatostatin is release from D cells of pancreas and inhibits the release of growth hormone

Answer 280

Uses • Acute treatment of variceal hemorrhage • Acromegaly • Carcinoid syndrome • Prevent complications following pancreatic surgery • VIPomas

Answer 281

Adverse effects • Gallstones (secondary to biliary stasis)

Answer 282

Theophylline, like caffeine, is one of the naturally occurring methylxanthines. The main use of theophyllines in clinical medicine is as a bronchodilator in the management of asthma and COPD

Answer 283

Theophylline poisoning features: • Acidosis, Hypokalemia • V omiting • Tachycardia, arrhythmias • Seizures

Answer 284

Management • Activated charcoal • Charcoal hemoperfusion is preferable to hemodialysis

Answer 285

Mechanism • Chronic alcohol consumption enhances GABA mediated inhibition in the CNS (similar to benzodiazepines) and inhibits NMDA-type glutamate receptors • Alcohol withdrawal is thought to lead to the opposite (↓ inhibitory GABA and ↑ NMDA glutamate transmission)

Answer 286

Features • Symptoms start at 6-12 hours • Peak incidence of seizures at 36 hours • Peak incidence of delirium tremens is at 72 hours

Answer 287

Management • Benzodiazepines • Carbamazepine also effective in treatment of alcohol withdrawal • Phenytoin is said not to be as effective in the treatment of alcohol withdrawal seizures

Answer 288

Proton Pump Inhibitors (PPI) are a group of drugs which profoundly ↓ acid secretion in the stomach. They irreversibly block the hydrogen/potassium adenosine triphosphatase enzyme system (the H+/K+ ATPase) of the gastric parietal cell. Examples include omeprazole and lansoprazole.

Answer 289

Aminosalicylates: 5-aminosalicyclic acid (5-ASA) is released in the colon and is not absorbed. It acts locally as an anti-inflammatory. The mechanism of action is not fully understood but 5-ASA may inhibit prostaglandin synthesis

Answer 290

• A combination of sulphapyridine (a sulphonamide) and 5-ASA • Many side-effects are due to the sulphapyridine moiety: rashes, oligospermia, headache, Heinz body anemia • Other side-effects are common to 5-ASA drugs

Answer 291

Mesalazine • A delayed release form of 5-ASA • Sulphapyridine side-effects seen in patients taking sulphasalazine are avoided • Mesalazine is still however associated with side-effects such as GI upset, diarrhea, headache, agranulocytosis, pancreatitis*, interstitial nephritis *pancreatitis is 7 times more common in patients taking mesalazine than sulfasalazine

Answer 292

Olsalazine • Two molecules of 5-ASA linked by a diazo bond, which is broken by colonic bacteria

Answer 293

• Formed from large pool of donors (e.g. 5,000) • IgG molecules with a subclass distribution similar to that of normal blood • Half-life of 3 weeks

Answer 294

Inhibit cell wall formation

Answer 295

Inhibit protein synthesis

Answer 296

Inhibit DNA synthesis

Answer 297

Inhibit RNA synthesis

Answer 298

Bactericidal antibiotics

Answer 299

bacteriostatic

Answer 300

Macrolides

Answer 301

aminoglycosides

Answer 302

Erythromycin may potentially interact with amiodarone, warfarin and simvastatin

Answer 303

Macrolides act by inhibiting bacterial protein synthesis. If pushed to give an answer they are bacteriostatic in nature, but in reality this depends on the dose and type of organism being treated.

Answer 304

Erythromycin is used in gastroparesis as it has prokinetic properties, Promotes gastric emptying

Answer 305

Adverse effects of erythromycin • GI side-effects are common • Cholestatic jaundice: risk may be ↓ if erythromycin stearate is used • P450 inhibitor

Answer 306

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

Answer 307

adverse effects • Lower seizure threshold in patients with epilepsy • Tendon damage (including rupture) - the risk is ↑ in patients also taking steroids. Achilles tendon ruptures. Tendon damage is a well documented complication of quinolone therapy. It appears to be an idiosyncratic reaction, with the actual median duration of treatment being 8 days before problems occur

Answer 308

• Injectable streptogrammin antibiotic • Combination of group A and group B streptogrammin • Inhibits bacterial protein synthesis by blocking tRNA complexes binding to the ribosome

Answer 309

Spectrum • Most Gram positive bacteria • Exception: Enterococcus faecalis

Answer 310

Adverse effects • Thrombophlebitis (give via a central line) • Arthralgia • P450 inhibitor

Answer 311

Linezolid is a type of oxazolidonone antibiotic which has been introduced in recent years. It inhibits bacterial protein synthesis by stopping formation of the 70s initiation complex and is bacteriostatic nature

Answer 312

Spectrum, highly active against Gram positive organisms including: • MRSA (Methicillin-resistant Staphylococcus aureus) • VRE (Vancomycin-resistant enterococcus) • GISA (Glycopeptide Intermediate Staphylococcus aureus)

Answer 313

Adverse effects • Thrombocytopenia (reversible on stopping) • Monoamine oxidase inhibitor: avoid tyramine containing foods

Answer 314

Sulfonamides: Antibacterial sulfonamides act as competitive inhibitors of the enzyme dihydropteroate synthetase (DHPS), an enzyme involved in folate synthesis.

Answer 315

Co-trimoxazole: sulfonamide antibiotic combination of trimethoprim and sulfamethoxazole

Answer 316

Treatment of individual patients with certain filarial diseases. These diseases include: lymphatic filariasis caused by infection with Wuchereria bancrofti, Brugia malayi, or Brugia timori; (ELEPHANTiasis) tropical pulmonary eosinophilia, and loiasis.