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MRCP Combined > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

what is the management of motion sickness?

A

Motion sickness - hyoscine > cyclizine > promethazine

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

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2
Q

what is motion sickness?

A

Motion sickness describes the nausea and vomiting which occurs when an apparent discrepancy exists between visually perceived movement and the vestibular systems sense of movement

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3
Q

how are monoclonal antibodies manufactured?

A

Monoclonal Antibodies: have an increasing role in medicine. They are manufactured by a technique called somatic cell hybridization. This involves the fusion of myeloma cells with spleen cells from a mouse (recent advances: rabbit B-cells) that has been immunized with the desired antigen. The resulting fused cells are termed a hybridoma and act as a ‘factory’ for producing monoclonal antibodies. The main limitation to this is that mouse antibodies are immunogenic leading to the formation of human anti-mouse antibodies (HAMAs). This problem is overcome by combining the variable region from the mouse antibody with the constant region from a human antibody

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4
Q

what type of antibody and use:
Rituximab

A

Anti-CD20
non-Hodgkin’s lymphoma

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5
Q

what type of antibody and use:
Infliximab

A

anti-TNF
rheumatoid arthritis and Crohn’s

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6
Q

what type of antibody and use:
Cetuximab

A

anti epidermal growth factor receptor
metastatic colorectal cancer and head and neck cancer

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7
Q

what type of antibody and use:
Trastuzumab

A

anti-HER2, anti EGF receptor
metastatic breast cancer

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8
Q

what type of antibody and use:
Alemtuzumab

A

anti-CD52
chronic lymphocytic leukemia

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9
Q

what type of antibody and use:
abciximab

A

anti-glycoprotein IIb/IIIa receptor
undergoing PCI, prevention of ischemic events in patients

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10
Q

what type of antibody and use:
OKT3

A

anti-CD3
prevent organ rejection

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11
Q

what are phase 1 reactions in pharmacology? what enzyme is this mainly performed by?

A

• Phase I reactions: oxidation, reduction, and hydrolysis. Mainly performed by the P450 enzymes but some drugs are metabolised by specific enzymes, for example alcohol dehydrogenase and
xanthine oxidase. Products of phase I reactions are typically more active and potentially toxic

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12
Q

what are phase 2 reactions in pharmacology?

A

• Phase II reactions: conjugation. Products are typically inactive and excreted in urine or bile.
Glucuronyl, acetyl, methyl, sulphate and other groups are typically involved.

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13
Q

where do you majority of phase 1 and phase 2 take place?

A

• The majority of phase I and phase II reactions take place in the liver.

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14
Q

what is first pass metabolism?

A

First-Pass Metabolism is a phenomenon where the concentration of a drug is greatly ↓ before it reaches the systemic circulation due to hepatic metabolism. As a consequence much larger doses are need orally than if given by other routes. This effect is seen in many drugs, including:
• Aspirin
• Isosorbide dinitrate
• Glyceryl trinitrate
• Lignocaine
• Propranolol
• Verapamil

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15
Q

what is zero-order kinetics?

A

Zero-Order Kinetics describes metabolism which is independent of the concentration of the reactant. This is due to metabolic pathways becoming saturated resulting in a constant amount of drug being eliminated per unit time. This explains why people may fail a breathalyser test in the morning if they have been drinking the night before

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16
Q

what drugs exhibit zero-order kinetics?

A

Drugs exhibiting zero-order kinetics
• Phenytoin
• Salicylates
• Heparin
• Ethanol

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17
Q

what is acetylator status?

A

Acetylator Status
50% of the UK population is deficient in hepatic N-acetyltransferase

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18
Q

what drugs are affected by acetylator status?

A

Drugs affected by acetylator status:
• Isoniazid
• Procainamide
• Hydralazine
• Dapsone
• Sulfasalazine

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19
Q

what are the p-450 dependant drugs?

A

P-450 Dependent Drugs TEWPD:
• Theophylline
• Estrogen
• Warfarin
• Phenytoin
• Digoxin

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20
Q

do p450 inhibitors cause toxicity or under dosing of p-450 dependant drugs?

A

toxicity

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21
Q

name a few p-450 inhibitors?

A

P450 inhibtors: (causing low metabolism of TEWPD → Toxicity)
• Acute alcohol intake
• Allopurinol
• Amiodarone
• Cimetidine, omeprazole
• Dapsone
• Imidazoles: ketoconazole, fluconazole
• INH
• Macrolides (Azithro-Clarithro-Erythro mycins)
• Quinolones (ciprofloxacin)
• Quinupristin
• Sodium valproate
• Spironolactones
• SSRIs: fluoxetine, sertraline
• Grapefruit juice (potent inhibitor of the cytochrome P450 enzyme CYP3A4)
• Protease inhibitors (ndinavir, nelfinavir, ritonavir, saquinavir)

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22
Q

what is auto-inducer?

A

Carbamazepine is an inducer of the P450 system. This in turn increases the metabolism of carbamazepine itself - auto- induction

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23
Q

name a few p-450 inducers?

A

• Antiepileptics: phenytoin, carbamazepine (note that valporate is an inhibitor)
• Barbiturates
• Chronic alcohol intake
• Griseofulvin
• Quinidine
• Rifampicin
• Smoking (affects CYP1A2, reason why smokers require more aminophylline)
• St John’s Wort
• Sulfa drugs
• Tetracycline
• Nevirapine (NNRTI)

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24
Q

what drugs can be cleared with haemodialysis?

A

• Barbiturate
• Lithium
• Alcohol (inc methanol, ethylene glycol)
• Salicylates
• Theophyllines (charcoal hemoperfusion is
preferable)

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25
Q

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

A

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

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26
Q

what drugs to avoid in renal failure?

A

• Antibiotics: tetracycline, nitrofurantoin
• NSAIDS
• Lithium

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27
Q

what drugs are likely to accumalate in renal failure?

A

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

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28
Q

what drugs are relatively safe in renal failure?

A

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

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29
Q

• Thiazides, furosemide (less common)
• Steroids
• Tacrolimus, cyclosporin
• Interferon-α
• Nicotinic acid (vitamin B3)
what do all the above do? what other drug may cause this slightly?

A

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

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30
Q

how do you categorise drug induced liver disease?

A

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

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31
Q

what type of liver disease do the below cause
• Alcohol
• Amiodarone
• Anti-tuberculosis: isoniazid,
rifampicin, pyrazinamide
• Halothane
• MAOIs
• Methyldopa
• Paracetamol
• Sodium valproate, phenytoin
• Statins

A

Hepatocellular picture

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32
Q

what type of liver disease do the below cause:
• Anabolic steroids, testosterones
• Antibiotics: flucloxacillin, co-amoxiclav,
erythromycin*, nitrofurantoin
• Fibrates
• Oral contraceptive pill
• Phenothiazines:
prochlorperazine/clorpromazine
• Rarely: nifedipine
• Sulphonylureas

A

cholestasis +/- hepatitis

*risk may be ↓ with erythromycin stearate

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33
Q

what type of liver disease do the below cause:
• Amiodarone • Methotrexate • Methyldopa

A

liver cirrhosis

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34
Q

what drugs cause cataracts?

A

• Steroids

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35
Q

what drugs cause corneal opacities?

A

• Amiodarone • Indomethacin

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36
Q

what drugs cause optic neuritis?

A

• Ethambutol
• Amiodarone
• Metronidazole

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37
Q

what drugs cause retinopathy?

A

• Chloroquine, quinine

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38
Q

what drug causes a blue tinge in vision and non-arteritic anterior ischemic neuropathy?

A

• Sildinafil

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39
Q

what drugs causes a yellow-green tinge in vision?

A

• Digoxin

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40
Q

what drugs cause gingival hyperplasia?what else causes this?

A

• Phenytoin
• Cyclosporin
• Calcium channel blockers (especially nifedipine)

Other causes of gingival hyperplasia include
• Acute myeloid leukemia (myelomonocytic and monocytic types)

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41
Q

what drugs cause urticaria?

A

• Aspirin
• Penicillins
• NSAIDs
• Opiates

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42
Q

what drugs can precipitate acute intermittent porphyria?

A

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

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43
Q

what are the below drugs safe in:
• Paracetamol • Aspirin
• Codeine
• Morphine
• Chlorpromazine • β-blockers
• Penicillin
• Metformin

A

acute intermittent porphyria

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44
Q

what the do the below drugs cause:
• Heparin
• Abciximab
• NSAIDs; ASA
• Diuretics: furosemide
• Quinine
• Antibiotics: penicillins, sulphonamides, rifampicin
• Anticonvulsants: carbamazepine, valproate

A

Drug Induced Thrombocytopenia (probable immune mediated)

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45
Q

what do the below drugs cause:
• Cytotoxics
• Antibiotics: trimethoprim, chloramphenicol
• Anti-rheumatoid: gold (sodium aurothiomalate), penicillamine
• Carbimazole
• Anti-epileptics: carbamazepine
• Sulphonylureas: tolbutamide

A

Drug Induced Pancytopenia
carbimazole also causes both agranulocytosis and pancytopenia

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46
Q

what do the below drugs cause and what does this present like
• Thiazides
• Tetracyclines, sulphonamides, ciprofloxacin
• Amiodarone
• NSAIDs e.g. Piroxicam
• Psoralens
• Sulphonylureas

A

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

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47
Q

what can be offered for smoking cessation therapy?

A

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

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48
Q

when should smoking cessation be offered? how long should this be prescribed for? when should further prescriptions not be offered? if unsuccessful - when should a repeat prescription be offered?

A

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

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49
Q

what are adverse effects of nicotine replacement therapy? what should be offered as part of nicotine replacement therapy?

A

• 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

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50
Q

what is the mode of action of varenicline?

A

Nicotinic receptor partial agonist

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51
Q

when should varenicline be started? what is the recommended course? is it more or less effective of bupropion? what are the adverse effects? who should this be used in caution with? what is this contraindicated in?

A

• 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

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52
Q

what is the mode of action of Bupropion?

A

Norepinephrine and dopamine reuptake inhibitor, and nicotinic antagonist

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53
Q

when should bupropion be started? what is there a small risk of? who should this not be prescribe for?

A

• 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.

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54
Q

what does salicylate overdose cause on ABG?

A

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

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55
Q

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

A

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

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56
Q

what are features of salicylate overdose?

A

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

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57
Q

what is the management of salicylate overdose?

A

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

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58
Q

what are the indications for haemodialysis in salicylate overdose?

A

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

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59
Q

how do salicylates cause pyrexia?

A

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

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60
Q

what is the management of paracetamol overdose?

A

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

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61
Q

what is the criteria for liver transplantation in paracetamol overdose?

A

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

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62
Q

how does intravenous acetylcysteine work?

A

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.

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63
Q

which patients are at an increased risk of developing hepatotoxicity?

A

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

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64
Q

what is the half-life of digoxin?

A

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

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65
Q

what are the actions of digoxin?

A

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

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66
Q

what are the features of digoxin toxicity?

A

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

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67
Q

what can precipitate digoxin toxicity?

A

• 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)

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68
Q

what is the management if digoxin toxicity?

A

Management
• Digibind
• Correct arrhythmias
• Monitor K+

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69
Q

what are indications for administration of digoxin specific Fab Fragment?

A

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

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70
Q

what is cyanide found in? what does toxicity result from?

A

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

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71
Q

what is the presentation of cyanide toxicity?

A

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

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72
Q

what is the management of cyanide toxicity?

A

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

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73
Q

what is ethylene glycol?

A

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

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74
Q

what are the features of toxicity of ethylene glycol?

A

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

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75
Q

what is the management of ethylene glycol toxicity?

A

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

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76
Q

what are the cardiovascular effects of cocaine use?

A

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

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77
Q

what are the neurological effects of cocaine use?

A

Neurological effects
• Seizures
• Hypertonia
• Hyperreflexia

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78
Q

what are the psychiatric effects of cocaine use?

A

Psychiatric effects
• Agitation
• Psychosis
• Hallucinations

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79
Q

• Hyperthermia
• Metabolic acidosis
• Rhabdomyolysis leading to renal failure.

all the above are caused by what?

A

cocaine

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80
Q

What are the clinical features of ecstasy?

A

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

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81
Q

what is the management of ecstasy use?

A

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

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82
Q

what are the features of mercury poisoning?

A

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

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83
Q

what should be considered with the combination of abdominal pain and neurological signs?

A

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

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84
Q

what are the features of lead poisoning?

A

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

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85
Q

what are the investigations found in lead poisoning?

A

• 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 ↑)

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86
Q

what is the management of lead poisoning?

A

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

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87
Q

what are the features of carbon monoxide poisoning?

A

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

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88
Q

what are typical carboxyhemoglobin levels?

A

• < 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

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89
Q

what is the management of carbon monoxide poisoning?

A

Management
• 100% oxygen
• Hyperbaric oxygen

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90
Q

what are indications for hyperbaric oxygen in carbon monoxide poisoning?

A

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

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91
Q

what is a oculogyric crisis?

A

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

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92
Q

what are causes of oculogyric crisis?

A

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

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93
Q

what is the treatement of oculogyric crisis?

A

Treatment
• Procyclidine • Benztropine

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94
Q

what drugs are contraindicated in pregnancy?

A

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

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95
Q

what antibiotics are contraindicated in pregnancy?

A

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

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96
Q

are antiepileptics contraindicated in pregnancy?

A

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

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97
Q

what non-drug contraindications of pregnancy exist?

A

• 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

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98
Q

is breast feeding safe in anti-epileptic drugs?

A

Breast feeding is acceptable with nearly all anti-epileptic drugs

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99
Q

• Antibiotics: penicillins, cephalosporins, trimethoprim
• Endocrine: glucocorticoids (avoid high doses), levothyroxine
• Epilepsy: sodium valproate, carbamazepine
• Asthma: salbutamol, theophyllines
• Psychiatric drugs: tricyclic antidepressants,
antipsychotics (except from clozapine)
• Hypertension: β-blockers, hydralazine,
methyldopa
• Anticoagulants: warfarin, heparin
• Digoxin

are safe/not safe in pregnancy?

A

SAFE

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100
Q

• Antibiotics: ciprofloxacin, tetracycline, chloramphenicol, sulphonamides
• Psychiatric drugs: lithium, benzodiazepines, clozapine
• Aspirin
• Carbimazole
• Sulphonylureas
• Cytotoxic drugs
• Amiodarone

are safe/not safe in pregnancy?

A

not safe

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101
Q

what is the administration of standard vs LMWH heparin?

A

standard: Intravenous
LMWH: Subcutaneous

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102
Q

what is the duration of action of standard vs LMWH?

A

standard: short
LMWH: long

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103
Q

what is the mechanism of action of standard vs LMWH?

A

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

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104
Q

what are the side effects of standard vs LMWH?

A

Standard:
Bleeding
Heparin-induced thrombocytopaenia (HIT)
Osteoporosis

LMWH:
Bleeding
Lower risk of HIT and osteoporosis with LMWH

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105
Q

when is standard heparin used?

A

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

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106
Q

when is LMWH used?

A

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

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107
Q

what electrolyte imbalance can be caused by both unfractionated and LMWH?

A

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

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108
Q

HIT:
-what is this caused by?
-when does this develop?
-does this increase or decrease clotting?
-what are the clinical features?
-what are the treatment options?

A

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

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109
Q

what can reverse heparin?

A

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

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110
Q

what is adrenaline?

A

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

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111
Q

what can be used for accidental injection of adrenaline?

A

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.

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112
Q

when is adrenaline indicated?

A

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

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113
Q

what 4 drugs require therapeutic drug monitoring?

A

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

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114
Q

when is botulinum toxin indicated?

A

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

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115
Q

list some adverse effects of isoretinoin?

A

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

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116
Q

what can be used for metastatic bone pain?

A

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

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117
Q

how do you initiate morphine treatment in palliative care? what else should be prescribed?

A

-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

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118
Q

in CKD what opiates should be used?

A

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

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119
Q

how do you convert oral codeine and oral tramadol to oral morphine?

A

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

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120
Q

how do you convert oral morphine to oral oxycodone?

A

Oral morphine Oral oxycodone Divide by 1.5-2

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121
Q

what is the equivalent of a transermal fentanyl 12microgram patch in oral morphine?

A

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

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122
Q

what is the equivalent of a transdermal buprenorphine 10microgram patch in oral morphine?

A

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

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123
Q

how to convert oral morphine to subcutaneous diamorphine?

A

Oral morphine to Subcutaneous diamorphine - Divide by 3

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124
Q

how to convert oral oxycodone to subcut diamorphine?

A

Oral oxycodone to Subcutaneous diamorphine - Divide by 1.5

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125
Q

how much is 1mg dexamethasone equal to in pred and in hydrocortisone?

A

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

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126
Q

what are risk factors of developing symptoms of chemo?

A

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

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127
Q

what is used for symptoms of chemo for patients at low risk or high risk?

A

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

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128
Q

what are features of medication overuse headache?

A

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

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129
Q

what is the management of medication overuse headache?

A

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

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130
Q

what is doxazosin?

A

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

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131
Q

name 4 α antagonists?

A

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

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132
Q

name 2 beta blockers

A

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

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133
Q

what are Carvedilol and labetalol?

A

Carvedilol and labetalol are mixed α and β antagonists

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134
Q

what is lithium?

A

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

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135
Q

what tremor is seen in lithium toxicity?

A

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

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136
Q

what is the mechanism of action of lithium?

A

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

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137
Q

what are adverse effects of lithium?

A

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

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138
Q

what is involved in the monitoring of patients on lithium therapy?

A

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.

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139
Q

what may precipitate lithium toxicity?

A

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.

140
Q

what are the features of lithium toxicity?

A

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

141
Q

what is the management of lithium toxicity?

A

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.

142
Q

what are the early features of tricyclic overdose?

A

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.

143
Q

what are features of severe tricyclic overdose?

A

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

144
Q

what are the ECG changes of tricyclic toxicity?

A

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

145
Q

what is the management of tricyclic toxicity?

A

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

146
Q

how can you divide the adverse effects of phenytoin?

A

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

147
Q

what are the acute adverse effects of phenytoin?

A

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

148
Q

what are the chronic adverse effects of phenytoin?

A

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

149
Q

what are the idiosyncratic adverse effects of phenytoin?

A

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

150
Q

what are the teratogenic adverse effects of phenytoin?

A

Teratogenic
• Associated with cleft palate and congenital heart disease

151
Q

what are the adverse effects of sodium valproate?

A

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

152
Q

what is one of the effects of organophosphate poisoining?

A

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

153
Q

what are the features of anticholinesterase effects?

A

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

154
Q

what is the management of anticholinesterase?

A

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

155
Q

St john’s wort:
-what has this been shown to be helpful in?

A

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’

156
Q

what are the adverse effects of st john’s wort?

A

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 ↓

157
Q

what does monoamine oxidase do?

A

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

158
Q

name a non-selective monoamin oxidase inhibitor, what is this used for and how frequently is this used?

A

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

159
Q

what are adverse effects of MOAI?

A

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

160
Q

what are serotonin (5-HT) system agonists name 2?

A

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

161
Q

how are serotonin (5-HT) modulators used in the treatment of migraine?

A

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

162
Q

list 5 serotonin (5-HT) antagonists

A

• 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.

163
Q

what are triptans?

A

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

164
Q

when should triptans be taken in migraine?

A

• 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

165
Q

what are adverse effects of triptans?

A

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

166
Q

what are contraindications to triptans?

A

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

167
Q

when are Dopamine Receptor Agonists indicated?

A

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

168
Q

what are adverse effects of Dopamine Receptor Agonists?

A

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

169
Q

what is the antidote of benzos

A

Benzodiazepines antidote is flumazenil

170
Q

how long should benzodiazepines be prescribed for?

A

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

171
Q

how should benzodiazepines be withdrawn?

A

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

172
Q

what happens if patients withdraw too quickly from benzodiazepines? when can this occur?

A

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

173
Q

Class 1a anti-arrythmics:
-give 3 examples
-what is the mechanism of action?
-give some side effects

A

Quinidine
Procainamide
Disopyramide

Block sodium channels
Increases AP duration

Quinidine toxicity causes cinchonism (headache, tinnitus, thrombocytopaenia)
Procainamide may cause drug-induced lupus

174
Q

Class 1b antiarrythmics:
-give 3 examples
-what is the mechanism of action?

A

Lidocaine
Mexiletine
Tocainide

Block sodium channels
Decreases AP duration

175
Q

Class 1c antiarrythmics
-give 3 examples
-what is the mechanism of action

A

Flecainide
Encainide
Propafenone

Block sodium channels
No effect on AP duration

176
Q

Class 2 antiarrythmics:
-what are these?
-name some

A

Propranolol
Atenolol
Bisoprolol
Metoprolol

Beta-adrenoceptor antagonists

177
Q

Class 3 antiarrythmics:
-what are these?
-name some

A

Amiodarone
Sotalol
Ibutilide
Bretylium

Block potassium channels

178
Q

class 4 antiarrythmic:
-what are these?
-name some

A

Verapamil
Diltiazem

Calcium channel blockers

179
Q

How do potassium channel blockers work to slow down the action potential i.e. amiodarone?

A

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)

180
Q

what are 5 things that limit the use of amiodarone?

A

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

181
Q

what is included in the monitoring of patients on amiodarone?

A

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

182
Q

name of few adverse effects of amiodarone?

A

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

183
Q

what proportion of patients on amiodarone suffer from thyroid dysfunction?

A

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

184
Q

what is the pathophysiology of amiodarone-induced hypothyroidism?

A

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)

185
Q

how is amiodarone induced thyrotoxicosis subdivided?

A

AIT type 1 and AIT type 2

186
Q

what is the pathophysiology/goitre presence/management of AIT type 1?

A

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

187
Q

what is the pathophysiology/goitre presence/management of AIT type 2?

A

Amiodarone-related destructive thyroiditis
Absent goitre
Corticosteroids

188
Q

should amiodarone be stopped in amiodarone-induced hypothyroidism or amiodarone-induced thyrotoxicosis?

A

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

189
Q

how does flecainide work? how does this affect the ECG?

A

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

190
Q

when is flecainide contraindicated and why?

A

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.

191
Q

when is flecainide indicated?

A

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

192
Q

what are 5 adverse effects of flecainide?

A

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

193
Q

how do statins work?

A

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

194
Q

? inhibitors ↑ CK and myopathy

A

P450 inhibitors ↑ CK and myopathy

195
Q

? ↑ HDL levels

A

Nicotinic acid ↑ HDL levels

196
Q

what are the adverse effects of a statin?
-what are the risk factors for one of these effects?

A

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

197
Q

who should receive a statin?

A

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.

198
Q

when should statins be taken?

A

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

199
Q

how should statins be prescribed i.e. what dose?

A

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

200
Q

what drug used in hyperlipidaemia causes:
Headache

A

Ezetimibe

201
Q

what drug used in hyperlipidaemia causes:
Flushing, myositis

A

nicotinic acid

202
Q

what drug used in hyperlipidaemia causes:
Myositis, pruritus, cholestasis

A

Fibrates

203
Q

what drug used in hypelipidaemia causes:
GI side-effects

A

anion-exchange resins

204
Q

what does nicotinic acid work to do?

A

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

205
Q

what are the adverse effects of nicotinic acid?

A

Adverse effects
• Flushing
• Impaired glucose tolerance
• Myositis

206
Q

β-blocker overdose management: ?

A

β-blocker overdose management: atropine + glucagon

207
Q

how does glucagon work in beta-blocker overdose?

A

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

208
Q

when should cardiac pacing be considered in beta-blocker overdose?

A

Cardiac pacing should be reserved for patients unresponsive to pharmacological therapy

209
Q

what are 4 features of beta blocker toxicity?

A

Features
• Bradycardia
• Hypotension
• Heart failure
• Syncope

210
Q

what is used in the management of beta blocker toxicity?

A

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

211
Q

how does furosemide work? where does it work? what is the duration of action?

A

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.

212
Q

what are the adverse effects of furosemide?

A

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

213
Q

how does bendroflumethiazide work?
-what does this result in the loss of?
-what does this have a role in?

A

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)

214
Q

what is the mechanism of action of hypokalaemia caused by bendroflumethiazide?

A

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

215
Q

what are the common adverse effects of bendroflumethiazide?

A

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

216
Q

below are rare side effects assoc with…
• Thrombocytopenia
• Agranulocytosis
• Photosensitivity rash
• Pancreatitis

A

Bendroflumethiazide

217
Q

how does spironalactone work?

A

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

218
Q

what are the indications of spironalactone?

A

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

219
Q

what are the adverse effects of spironalactone?

A

Adverse effects
• Hyperkalemia • Gynaecomastia

220
Q

what was found in the RALES study?

A

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

221
Q

what enhances and what inhibits the effect of adenosine?

A

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.

222
Q

who should adenosine be avoided in?

A

asthmatics

223
Q

what is the mechanism of action of adenosine?

A

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

224
Q

what are the adverse effects of adenosine?

A

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

225
Q

? - side-effects: headache, flushing, ankle edema

A

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

226
Q

what is the mode of action of calcium channel blockers?

A

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

227
Q

what are 4 indications of calcium channel blockers?

A

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

228
Q

Calcium channel blockers: Dihydropyridines (e.g. ?)
-what are these used for?
-what may these precipitate?
-what are the side effects?

A

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

229
Q

calcium channel blockers: Verapimil
-what are these used for?
-what should this not be prescribed with?
-what are the adverse effects?

A

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

230
Q

calcium channel blockers: diltiazem
-what is this used for?
-what are the adverse effects?

A

-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

231
Q

how does aspirin work?

A

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

232
Q

what is cyclooxygenase responsible for? what does the blocking of this cause?

A

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.

233
Q

who should recieve aspirin?

A

• 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

234
Q

what 3 things potentiate aspirin?

A

Potentiates
• Oral hypoglycaemics
• W arfarin
• Steroids

235
Q

what is the mechanism of ACE-inhibitors?

A

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

236
Q

what are 4 side effects of ace-inhibitors?

A

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

237
Q

name some cautions and contraindications of ACE-inhibitors

A

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

238
Q

what needs to be monitored with ace-inhibitors

A

• 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.

239
Q

what is the acute management of gout?

A

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

240
Q

what are the indications for urate-lowering therapy in gout?

A

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
241
Q

what is used first line for urate-lowering therapy in gout?

A

‘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

242
Q

what is the second line agent for urate-lowering therapy in gout?

A

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

243
Q

what may be used in refractory cases of gout for urate-lowering therapy?

A

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

244
Q

why should azathioprine and allopurinol be avoided?

A

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

245
Q

why should cyclophosphamide and allopurinol be avoided?

A

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

246
Q

what are the indications of HRT?

A

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

247
Q

what are the side effects of HRT?

A

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

248
Q

what are the potential complications of HRT?

A

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

249
Q

what pill causes:
↑ Risk of breast cancer
↑ Risk of DVT
↓ Risk of endometrial ca.

A

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

250
Q

HRT and breast cancer:
-what does the increased risk relate to?
-what preparations is there a highrer incidence?
-does the risk change with the stopping of HRT?

A

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

251
Q

Combined Oral Contraceptive Pill: The decision of whether to start a woman on the combined oral contraceptive pill is now guided by the UK Medical Eligibility Criteria (UKMEC).
describe the 4 point scale

A

• 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

252
Q

describe some UKMEC 3 conditions?

A

• 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

253
Q

describe some UKMEC 4 conditions?

A

• 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

254
Q

what is tamoxifen?

A

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

255
Q

what are the adverse effects of tamoxifen?

A

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

256
Q

what is raloxifen?

A

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

257
Q

P450 inhibitors ↑?

A

P450 inhibitors ↑ INR

258
Q

INR ? by ABX that kill intestinal flora by ↓ Vit K absorption

A

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

259
Q

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

A

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

260
Q

what factors may potentiate warfarin?

A

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

261
Q

what are side effects of warfarin?

A

• 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

262
Q

what to do in warfarin therapy and major bleeding?

A

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

263
Q

what to do in warfarin therapy and INR > 8.0 with No bleeding or minor bleeding?

A

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

264
Q

what to do in warfarin therapy and INR 6.0 - 8.0 with No bleeding or minor bleeding?

A

Stop warfarin, restart when INR < 5.0

265
Q

antivirals: how does acyclovir work?

A

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

266
Q

antiviral: how does ribavirin work?

A

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

267
Q

antiviral: how do antiviral interferons work?

A

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

268
Q

antiviral: what is amantadine used for and how does it work?

A

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

269
Q

Anti-retroviral agent used in HIV
what does HAART involve?

A

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

270
Q

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

A

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

271
Q

Nucleoside analogue reverse transcriptase inhibitors (NRTI)
• Examples:
• General NRTI side-effects:
• Zidovudine side effects
• Didanosine side effect

A

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

272
Q

Non-nucleoside reverse transcriptase inhibitors (NNRTI)
• Examples: ?
• Side-effects: ?

A

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

273
Q

Protease inhibitors (PI)
• Examples: ?
• Side-effects: ?
• Indinavir side effects
• Ritonavir side effects

A

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

274
Q

Cyclosporin
- how does this work?
- what does this cause?

A

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

275
Q

list some side effects of cyclosporin?

A

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.

276
Q

what are some indications for cyclosporin

A

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

277
Q

what is tacrolimus?

A

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

278
Q

Azathioprine: what test is needed?

A

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.

279
Q

what are adverse effects of azathioprine?

A

Adverse effects include

bone marrow depression
nausea/vomiting
pancreatitis
increased risk of non-melanoma skin cancer
280
Q

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

A

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

281
Q

Azathioprine is generally considered safe/not safe to use in pregnancy.

A

Azathioprine is generally considered safe to use in pregnancy.

282
Q

what is methotrexate?

A

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

283
Q

what are three indications for methotrexate?

A

Indications
• Rheumatoid arthritis
• Psoriasis
• Acute lymphoblastic leukaemia

284
Q

what are adverse effects of methotrexate?

A

Adverse effects
• Mucositis
• Myelosuppression • Pneumonitis
• Liver cirrhosis

285
Q

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

A

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

286
Q

how often is methotrexate taken?

A

Methotrexate is taken weekly, rather than daily

287
Q

what blood tests need to be regularly monitored in methotrexate use?

A

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’

288
Q

what should be co-prescribed with methotrexate?

A

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

289
Q

what is the starting dose of methotrexate?
-what should be avoided concurrently with methotrexate?

A

• 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

290
Q

Cyclosporin + tacrolimus - Mechaism Of Action: inhibit ? thus decreasing ?

A

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

291
Q

inhibits inosine monophosphate dehydrogenase is the mechanism of action for?

A

Mycophenolate mofetil

292
Q

metabolised to the active compound mercaptopurine a purine analogue that inhibits DNA synthesis. purine synthesis inhibitor is the mechanism of action of?

A

Azathioprine

293
Q

antimetabolite which inhibits dihydrofolate reductase is the mechanism of action for?

A

Methotrexate

294
Q

what are some uses of rituximab?

A

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.

295
Q

what are the side effects of rituximab?

A

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

296
Q

what is the mechanism of action of finasteride?

A

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

297
Q

what are the indications for finasteride?

A

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

298
Q

what are adverse effects of finasteride?

A

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

299
Q

Finasteride causes ? levels of serum prostate specific antigen

A

Finasteride causes ↓ levels of serum prostate specific antigen

300
Q

how do bisphosphonates work?

A

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

301
Q

Bisphosphonates (alendronate) can cause a variety of ? problems

A

Bisphosphonates (alendronate) can cause a variety of esophageal problems

302
Q

what are the clinical uses of bisphosphonate?

A

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

303
Q

what are the adverse effects of bisphosphonate use?

A

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

304
Q

what is the mechanism of action of sildenafil?

A

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

305
Q

what drugs are contraindicated with sildenafil?

A

Viagra - contraindicated by nitrates and nicorandil

The BNF recommends avoiding α-blockers for 4 hours after sildenafil

306
Q

what are contraindications to sildenafil?

A

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

307
Q

what are adverse effects of sildenafil?

A

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

308
Q

what is the mechanism of action of octreotide?

A

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

309
Q

what are 5 uses of octreotide?

A

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

310
Q

what are adverse effects of octreotide?

A

Adverse effects
• Gallstones (secondary to biliary stasis)

311
Q

what type of drug is theophylline?

A

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

312
Q

what are features of theophylline toxicity?

A

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

313
Q

what is the management of theophylline toxicity?

A

Management
• Activated charcoal
• Charcoal hemoperfusion is preferable to hemodialysis

314
Q

what is the mechanism of alcohol withdrawal?

A

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)

315
Q

alcohol withdrawal:
Features
• Symptoms start at ? hours
• Peak incidence of seizures at ? hours
• Peak incidence of delirium tremens is at ? hours

A

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

316
Q

what is the management of alcohol withdrawal?

A

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

317
Q

how do PPIs work?

A

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.

318
Q

how do Aminosalicylates work?

A

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

319
Q

Sulfasalazine:
-what is this?
-what are side effects?

A

• 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

320
Q

Mesalazine:
-what is this?
-what are the side effects?

A

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

321
Q

what is Olsalazine?

A

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

322
Q

how are immunoglobulins formed? what is the half life?

A

• 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

323
Q

•Penicillins
• Cephalosporins
• Isoniazid
• Vancomycin
mechanism of action?

A

Inhibit cell wall formation

324
Q

•aminoglycosides (cause misreading of mRNA)
• chloramphenicol
•macrolides (e.g. erythromycin)
• tetracyclines
•fusidic acid
•(Quin/Dalfo)pristin
• Linezolid
mechanism of action?

A

Inhibit protein synthesis

325
Q

•quinolones (e.g. ciprofloxacin)
• metronidazole
• sulphonamides
• trimethoprim
mechanism of action?

A

Inhibit DNA synthesis

326
Q

what is the mechanism of action of rifampicin?

A

Inhibit RNA synthesis

327
Q

• Penicillins
• Cephalosporins
• Isoniazid
• Aminoglycosides
• Quinupristin+Dalfopristin (combination)
• Metronidazole
• Quinolones: ciprofloxacin, levofluxacin
• Rifampicin
• Nitrofurantoin → Damages bacterial DNA

bacteriocidal/bacteriostatic?

A

Bactericidal antibiotics

328
Q

• Chloramphenicol
• Macrolides
• Tetracyclines
• Fusidic acid
• Quinupristin
• Dalfopristin
• Linezolid
• Sulphonamides
• Trimethoprim

bacteriocidal/bacteriostatic?

A

bacteriostatic

329
Q

• Erythromycin
• Tacrolimus – non antibiotics macrolide
• Azithromycin - Unique, does not inhibit CYP3A4
• Clarithromycin
• Dirithromycin
• Roxithromycin
• Telithromycin

are all…

A

Macrolides

330
Q

• Amikacin
• Arbekacin
• Gentamicin
• Kanamycin
• Neomycin
• Netilmicin
• Paromomycin
• Rhodostreptomycin • Streptomycin
• Tobramycin
• Apramycin

are all…

A

aminoglycosides

331
Q

what drugs may erythromycin react with?

A

Erythromycin may potentially interact with amiodarone, warfarin and simvastatin

332
Q

how do macrolide antibiotics work?

A

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.

333
Q

what condition can erythromycin be used in?

A

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

334
Q

what are the adverse effects of erythromycin?

A

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

335
Q

how do quinolones work?

A

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

336
Q

what are the adverse effects of quinolones?

A

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

337
Q

what are Quinupristin & Dalfopristin Antibiotics? how do these work?

A

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

338
Q

what do Quinupristin & Dalfopristin Antibiotics cover?

A

Spectrum
• Most Gram positive bacteria
• Exception: Enterococcus faecalis

339
Q

what are the adverse effects of Quinupristin & Dalfopristin Antibiotics?

A

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

340
Q

what type of antibiotic is linezolid?

A

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

341
Q

what is the spectrum of linezolid?

A

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

342
Q

what are the adverse effects of linezolid?

A

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

343
Q

how do sulfonamides work?

A

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

344
Q

what is co-trimoxazole?

A

Co-trimoxazole: sulfonamide antibiotic combination of trimethoprim and sulfamethoxazole

345
Q

what is the indication of Diethylcarbamazine?

A

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.

MRCP Combined (58 decks)

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