Prescribing And Pharmacology Flashcards
What is the usual loading dose of digoxin for atrial fibrillation?
For rapid digitalisation: 0.75-1.5mg PO over 24h in divided doses
What is the usual maintenance dose of digoxin for atrial fibrillation?
According to renal function and initial loading dose
Usual range 125-250 micrograms once daily PO
What is the dose of digoxin for heart failure for patients in sinus rhythm?
65-125 micrograms PO once daily
What investigations should be done for a patient with suspected digitalis toxicity? And what are you looking for with each?
Serum digoxin level: therapeutic level 0.6-2.6ng/mL
U and Es: acute - hyperkalaemia, chronic - hypokalaemia, hypomagnesaemia
ECG: dysrhythmia, sinus bradycardia, AV conduction block, ventricular ectopy
What is the management for acute digitalis toxicity?
Hydration with IV fluids Oxygenation and support of ventilatory function Discontinuation of drug Correction of electrolyte imbalances Activated charcoal Binding resin: cholestyramine Digoxin immune Fab (fragment antigen binding) Management of dysthymias
What blood tests need regular monitoring in patients prescribed IV vancomycin?
Renal function
Vancomycin levels
Which class of medication is first line for panic disorder? Give examples
SSRI Fluoxetine Paroxetine Sertraline Citalopram
What are typical side effects of statins?
Myalgia Headaches Nausea Hepatitis Myositis/rhabdomyolysis
What is the appropriate treatment for c diff?
Oral metronidazole or oral vancomycin
What drug is used to manage hyperthyroidism?
Carbimazole
By what mechanisms is metoclopramide an anti emetic?
Increased GI motility
Increases sphincter tone
Centrally: dopaminergic antagonist
A 44 year old man is diagnosed with TB. He has a history of mitral stenosis and AF. He is commenced on therapy. 3 weeks later his INR increased to 5.6. Which medication is likely to have caused this and why?
Isoniazid inhibits P450 system of liver enzymes so therefore inhibit warfarin metabolism and will therefore increase INR
What is the difference between unfractionated and low molecular weight heparin?
Unfractionated forms a complex which activates antithrombin III to inhibits thrombin, Xa, IXa, XIa and XIIa. IV, short duration of action. Monitor with APTT. Useful where high risk of bleeding as can be terminated rapidly
LMWH only increases action of antithrombin III on Xa. Subcutaneous, long duration of action
What is heparin induced thrombocytopenia?
Antibodies form against complexes of platelet factor 4 and heparin
Induce platelet activation by cross linking
Features include greater than 50% reduction in platelets, thrombosis and skin allergy
How do you reverse heparin overdose?
Protamine sulphate
What is the mechanism of action of clopidogrel?
Antagonist of P2Y12 ADP receptor inhibiting activation of platelets
What is bioavailability? What impact does this have on IV drugs?
Proportion of administered drug that reaches the systemic circulation
Therefore always 100% for IV drugs
Why do angina sufferers use a sub lingual spray rather than swallow a tablet?
Absorption is rapid and bioavailability is high as it goes straight into the circulation
Which is the most important of the cytochrome P450 enzymes?
CYP2D6
What is phase 1 metabolism?
Modification
Introduces reactive groups
Oxidation, reduction, hydrolysis
Enzyme catalysed by p450 system
What is phase 2 metabolism?
Conjugation
Mostly in the liver
Addition of glucuronide, sulphate and other charged groups
Give examples of p450 inducers
Barbiturates Carbamazepine Alcohol Griseofulvin Phenytoin Primidone Rifampicin CRAPGPS
Give examples of p450 inhibitors
Omeprazole Disulfiram Erythromycin Valproate Isoniazid Ciprofloxacin Ethanol (acute) Sulphonamides ODEVICES
Which fruit is an enzyme inhibitor?
Grapefruit
Give examples of drugs that are affected by enzyme induction/inhibition
Ciclosporin Citalopram Oral contraceptive Warfarin Phenytoin Protease inhibitors Acetylcholinesterase inhibitors Theophylline Statins COWPATS
What proportion of the population lack the enzyme to metabolise codeine?
8%
What percent of the population are rapid metabolisers of codeine?
1%
Why does diazepam have such a short length of activity when it has a long half life of 36 hours?
Distribution - it is highly lipid soluble so lots of it is distributed into fat
Has a high volume distribution
After how many half lives is the plasma concentration of an administered drug effectively zero?
5 half lives
What is clearance?
Volume of plasma cleared of drug per unit time
What drugs have zero order kinetics?
Phenytoin
Thiopentone
Fluoxetine
Ethanol
What is zero order kinetics?
Enzymes catalysing elimination are in short supply
Can be fully saturated if drug given in high dose
Plasma concentration - time profile during elimination phase is linear
What is Emax?
Maximum possible effect produced by activation of a receptor
What is a partial agonist?
Ligand that binds to the same receptor but produces less than a maximal response - has lower intrinsic activity
Give examples of partial agonists
Buprenorphine
Salmeterol
What drug combination treats bronchospasm?
Beta 2 agonist - salbutamol
Muscarinic antagonist - ipratropium
Give an example of a non competitive antagonist
Phenoxybenzamine - used in management of Phaeochromocytoma
What makes warfarin, lithium, vancomycin, gentamycin and theophylline dangerous?
Narrow therapeutic index
What is telbivudine?
Antiviral drug used in treatment of hep B
Synthetic thymidine nucleoside analogue so impairs DNA virus replication by leading to chain termination
What is truvada?
Emtricitabine and tenofovir
Used for HIV pre exposure prophylaxis and treatment
Which drugs can cause SIADH?
Carbamazepine Sulfonylureas SSRIs Tricyclic antidepressants Vincristine Cyclophosphamide
What are common adverse effects of thiazide diuretics?
Dehydration Postural hypotension Hyponatraemia Hypokalaemia Hypercalcaemia Gout Impaired glucose tolerance Impotence
What are examples of low dose inhaled corticosteroids and their doses?
Beclometasone dipropionate: 50/100 mcg 2 puffs BD
Fluticasone propionate: 50 mcg two puffs BD
What are examples of medium dose inhaled corticosteroids and their doses?
Beclometasone dipropionate: 100/200 mcg 2 puffs BD
Fluticasone propionate: 125 mcg 2 puffs BD
What are examples of high dose inhaled corticosteroids and their doses?
Beclometasone dipropionate: 100/250 mcg 4 puffs BD
Fluticasone propionate: 250 mcg 2 puffs BD
At what level of GFR should metformin be reviewed/stopped?
If GFR below 45, review dose
If GFR below 30, stop
A 69 year old HIV negative man has lamivudine resistant chronic hep B. What is the treatment of choice?
Tenofovir plus entecavir
A 42 year old IV drug user is hep C PCR positive. What is the best treatment option?
PEG interferon alpha with ribavirin
What type of drug are carbimazole and propylthiouracil?
Thyroid peroxidase inhibitors used in thyrotoxicosis
What are indications for warfarin and target INRs for these conditions?
VTE: target 2.5 unless recurrent then 3.5
AF: target 2.5
Mechanical heart valve: target INR depends on type of valve and location
What factors may potentiate warfarin?
Liver disease
P450 inhibitors: amiodarone, ciprofloxacin
Cranberry juice
Drugs which displace warfarin from plasma albumin: NSAIDs
Drugs which inhibit platelet function: NSAIDs
What are side effects of warfarin?
Haemorrhage
Teratogenic
Skin necrosis: protein c reduced when first starting. Temporary pro coagulant state, avoided by concurrent heparin
Purple toes
What are major side effects of colchicine?
Bleeding Burning in stomach throat or skin Convulsions Diarrhoea Fast shallow breathing Muscle weakness Nausea and vomiting
What are complications of statins?
Myalgia
Myositis
Myopathy
What is the difference in statin prescription between primary and secondary prevention?
Primary prevention: atorvastatin 20mg OD. If non HDL has not fallen by at least 40% consider titration up to 80mg
Secondary: atorvastatin 80mg OD
Which drugs make complications of statins more likely?
Fibrate
Immunosuppressants
Why can renal failure occur with statins?
Rhabdomyolysis which leads to acute renal failure secondary to myoglobinuria
What effect can lithium have on your kidneys that would cause polyuria, polydipsia and high-normal sodium?
Can cause nephrogenic diabetes insipidus
What does ergometrine cause and what are possible complications?
Uterine contraction
Can cause shock from anaphylactoid reactions
HTN
MI
What is febuxostat and how does it work?
Drug used second line in prevention of gout
Xanthine oxidase inhibitor, reduces uric acid levels in the body
Name some drugs which may cause problems in asthmatics
Adenosine: wheeze, bronchospasm
Diclofenac
Beta blockers
Morphine: can cause histamine release
Why is unfractioned heparin less frequently used than low molecular weight?
Low molecular weight act specifically on factor Xa and do not require monitoring of APTT
Effective for prophylaxis and treatment of VTE and can be used in pregnancy
Can be given in once daily doses rather than needing a continuous infusion which is required in unfractioned due to short half life
What is the dose of enoxaparine used in STEMI?
IV 3000 units
Then 1mg/kg 12 hourly for up to 8 days
What is the dose of enoxaparine used in NSTEMI and unstable angina?
Subcut 1mg/kg 12 hourly for 2-8 days
In which patients should initial starting dose of levothyroxine be lower?
Elderly
Ischaemic heart disease
After a change in thyroxine dose, how soon should TFTs be performed?
8-12 weeks
What should happen to levothyroxine dose in pregnancy?
Increased by at least 25-50 micrograms due to increased demands of pregnancy
TSH monitored carefully, aiming for low normal value
What are side effects of levothyroxine therapy?
Hyperthyroidism due to over treatment
Reduced bone mineral density
Worsening of angina
Atrial fibrillation
What monitoring is required for statins and when?
LFT at baseline, 3 months and 12 months
What monitoring is required for ACE inhibitors and when?
U and Es prior to treatment, after increasing dose and at least annually
What monitoring is required for amiodarone and when?
TFT, LFT, U and Es, CXR prior to treatment
TFT, LFT every 6 months
What monitoring is required for methotrexate and when?
FBC, LFT, U and Es before starting treatment, weekly until stabilised, then every 2-3 months
What monitoring is required for azathioprine and when?
FBC, LFT before treatment
FBC weekly for first 4 weeks
FBC, LFT every 3 months
What monitoring is required for lithium and when?
Lithium levels weekly until stabilised then every 3 months
TFT and U and Es prior to treatment then every 6 months
What monitoring needs to be done for sodium valproate and when?
LFT and FBC before treatment
LFT periodically in first 6 months
Which drug causes red man syndrome?
Vancomycin if rapidly injected
Which TB drug can cause peripheral neuropathy? Which drug can be given concomitantly to prevent this?
Isoniazid
Give pyridoxine to prevent
What thyroid disorders can be caused by Amiodarone?
Hypothyroidism
Hyperthyroidism
Which anti diabetic medications can increase risk of DKA?
SGLT2 inhibitors: canagliflozin, dapagliflozin, empagliflozin
What is the most appropriate treatment for hyperthyroidism in pregnancy? What consequence is there in breast feeding?
Carbimazole
Propylthiouracil
Use at minimum dose as both cross placenta
Excreted in small amounts in breast milk, not absolutely contraindicated but not ideal while breastfeeding
Which antibiotic is contraindicated in pregnancy due to foetal dental staining?
Tetracyclines
What is the risk of giving fluoxetine alongside sulphonylureas?
Hypoglycaemia
Give some drug examples which can raise serum lipid concentrations
Beta blockers
Thiazide diuretics
Systemic retinoids
Which cardiology drugs can cause a photosensitive rash?
Amiodarone
Thiazide diuretics
How do you calculate a breakthrough dose of morphine?
1/6th dose of daily morphine intake
What is the preferred antithyroid drug in pregnancy?
Propylthiouracil - less likely to cross placenta
Ah what point should a statin be stopped if it is causing LFT derangement?
If serum transaminase concentrations rise to and persist at 3 times upper limit of reference range
What is nicorandil?
Potassium channel activator which has vasodilatory effects on coronary arteries
What are side effects of methylphenidate?
Abdominal pain
Nausea
Dyspepsia
How do you convert a dose or oral morphine to diamorphine?
Total daily morphine divided by 3
What can precipitate lithium toxicity?
Dehydration Renal failure Diuretics (esp bendroflumethiazide) ACE inhibitors NSAIDs Metronidazole
Which drugs to treat UTI should be avoided in pregnancy?
Trimethoprim avoided in first trimester due to risk of neural tube teratogenicity
Nitrofurantoin avoided close to full time due to risk of neonatal haemolysis
What are precipitating factors for digoxin toxicity?
Hypokalaemia Increasing age Renal failure MI Hypomagnesaemia Hypercalcaemia Hypernatraemia Acidosis Hypoalbuminaemia Hypothermia Hypothyroidism Drugs: amiodarone, verapamil, diltiazem, spironolactone
What is management for digoxin toxicity?
Digibind
Correct arrhythmias
Monitor potassium
Which antibiotics should be used with caution in patients with epilepsy?
Quinolones: ciprofloxacin, levofloxacin
Which anti malarial drugs are safe in pregnancy?
Chloroquine
Proguanil if folate supplement of 5mg OD taken
What are side effects of rifampicin?
Hepatitis
Orange secretions
Flu like symptoms
What are side effects of isoniazid?
Peripheral neuropathy (prevent with pyridoxine)
Hepatitis
Agranulocytosis
Liver enzyme inhibitor
What are side effects of pyrazinamide?
Hyperuricaemia
Arthralgia
Myalgia
Hepatitis
What are side effects of ethambutol?
Optic neuritis
Dose adjust in renal impairment
What effects does metoclopramide have?
Increase GI motility
Increase sphincter tone
Central antiemetic actions through dopamine
Which drugs can cause gingival hyperplasia?
Phenytoin
Ciclosporin
Calcium channel blockers
AML
Why do PPIs increase risk of fractures?
Malabsorption of calcium and magnesium
What is the mechanism of action of quinolones? (Ciprofloxacin)
Inhibit topoisomerase II (DNA gyrase) and topoisomerase IV to prevent DNA synthesis
Bactericidal
What are adverse effects of ciprofloxacin?
Lower seizure threshold in patients with epilepsy
Tendon damage, including rupture
Cartilage damage - avoid in children
Lengthens QT interval
What is the mechanism of action of mifepristone?
Partial agonist of progesterone receptors, blocks their action
Inhibits ovulation
Sensitises endometrium to action of prostaglandins
What are the actions of misoprostol?
Induction of labour/uterine contractions
Dilation of cervix
Expulsion of products of conception
Why is hyperkalaemia a side effect of co trimoxazole?
Inhibits sodium channels in the distal nephron similar to potassium sparing diuretic amiloride
What are some adverse effects of finasteride?
Impotence
Decreased libido
Ejaculation disorders
Gynaecomastia and breast tenderness
Which antibiotic is associated with aplastic anaemia?
Chloramphenicol
Which antibiotic is associated with staining dental enamel?
Tetracyclines eg doxycycline
Which antibiotics can cause cartilage erosion and reduce fit potential?
Quinolones and fluoroquinolones e.g. Ciprofloxacin
Which antibiotic can cause a metallic taste in the mouth?
Metronidazole
What is the mechanism of action of tacrolimus?
Calcineurin inhibitor - reduce activation of nuclear factor of activated T cells (NFAT) which promotes IL2 production
What is the mechanism of action of mycophenolate mofetil?
Antimetabolite - interrupt DNA synthesis
Inhibits inosine monophosphate dehydrogenase so prevents purine synthesis
What is the mechanism of action of azathioprine?
Antimetabolite - interrupt DNA synthesis
Pro drug metabolised to 6mercaptopurine which is inserted into DNA sequence instead of purine, recognised as mismatch and triggers apoptosis
What are some associations of advanced maternal age?
Miscarriage Chromosomal abnormality HTN Diabetes Prolonged labour Low birth weight Pre term delivery Neonatal mortality
What is the mechanism of action of demeclocycline? What is it used for?
Vasopressin antagonist
Induces free water excretion
Treatment for SIADH who fail to respond to fluid restriction
What effect do macrolide antibiotics have on statins?
Inhibit metabolism by CYP3A4
Can lead to myopathy and rhabdomyolysis
Why is ciprofloxacin contraindicated in patients under 16 years?
Associated with experimental arthropathy in growing animals
Which drugs can cause gingival hyperplasia?
NCP
Nifedipine
Ciclosporin
Phenytoin
How many days before surgery should warfarin be stopped?
5 days
INR needs to go below 1.5
Which TB drug is associated with visual problems/colour blindness?
Ethambutol
What is an equivalent dose of prednisolone if a patient is on 20mg hydrocortisone?
5mg prednisolone
4:1 ratio
What may be side effects of sulfasalazine and therefore what monitoring is required?
Leucopenia
Thrombocytopenia
Oligospermia
Monitor FBC, U and Es, LFTs
Why does co trimoxazole cause hyperkalaemia?
Inhibits sodium channels in distal nephron in a similar way to amiloride
What are signs of procyclidine overdose?
Agitation
Confusion
Sleeplessness lasting up to 24 hours or more
Pupils dilated and unreactive to light
Which drugs can interact warfarin and lead to an increase in INR?
O DEVICES Omeprazole Disulfiram Erythromycin Valproate Isoniazid Cimetidine and ciprofloxacin Ethanol Sulphonamides
Which TB drug is associated with peripheral neuropathy? What is given to counteract this?
Isoniazid
Give pyridoxime
Which TB drug used in resistant and atypical cases may cause vertigo?
Cycloserine
Which TB drug is a potent hepatic enzyme inducer?
Rifampicin
Which drug is useful for speeding up gastric motility in acute migraine?
Metoclopramide
Why could bendroflumethiazide precipitate digoxin toxicity?
Could cause hypokalaemia
How do you convert a morphine dose from oral to SC?
Divide by 2
What are side effects of carbimazole?
Rash
Hair loss
Agranulocytosis
What is the most serious adverse event associated with amiodarone?
Pulmonary toxicity - pneumonitis
Why should verapamil not be given in combination with beta blockers?
May cause complete heart block
What is the mechanism of action of bupropion?
Noradrenaline and dopamine reuptake inhibitor and nicotinic antagonist
What are contraindications to bupropion?
Epilepsy
Pregnancy
Breastfeeding
Eating disorder (relative)
What is the mechanism of action of varenicline?
Nicotinic partial agonist
What is the recommended course of treatment with varenicline?
12 weeks
What are common side effects with varenicline?
Nausea
Headache
Insomnia
Abnormal dreams
In which patients should varenicline be used with caution?
History of depression or self harm
Contraindicated in pregnancy and breast feeding
What are side effects of amiodarone?
Pneumonitis/lung fibrosis Neutropenia Hepatitis Phototoxicity Slate grey skin discolouration Hypothyroidism Hyperthyroidism Arrhythmias Corneal deposits Peripheral neuropathy Myopathy
Which immunosuppressant drug used to prevent organ rejection can cause new onset diabetes after transplantation?
Tacrolimus - calcineurin inbibitor
Which antibiotics can cause photosensitivity?
Doxycycline/tetracycline
What is malarone?
Atovaquone/proguanil antimalarial
Which opioids are preferred in patients with chronic kidney disease?
Alfentanil
Buprenorphine
Fentanyl
What is the risk of concurrent prescription of methotrexate and trimethoprim?
Marrow aplasia
What are problematic side effects of ciprofloxacin?
C diff infection
Enthesitis and tendon rupture
Why are ACE inhibitors contraindicated in bilateral renal artery stenosis?
Glomerular filtration pressure dependent on vasoconstriction of the efferent arteriole because the resistance of the afferent blood vessels have been pathologically increased
Which is the recommended anti malarial for sub Saharan Africa?
Mefloquine
How long before travel does mefloquine need to be started?
2-3 weeks
How long before travel does chloroquine/proguanil need to be started?
1 week
What is the recommended antibiotic for prophylaxis of meningitis in those who have been exposed?
Ciprofloxacin
Which antibiotic is used for prophylaxis of TB in those who are exposed?
Isoniazid for 6 months
Or combo isoniazid and rifampicin for 3 months
Which drug can be given to pregnant HIV positive women who wish to reduce risk of transmission to their baby?
Zidovudine
What is the mechanism of action of finasteride?
5 alpha reductase inhibitor: prevent conversion of testosterone to active DHT
What are side effects of calcium channel blockers?
Headache
Flushing
Ankle oedema
Which drugs may interact with clarithromycin?
Warfarin
Aminophylline
Statins
What is the mechanism of action of varenicline?
Nicotinic receptor partial agonist - reduces cravings and pleasurable effects
What is the mechanism of action of bupropion? What is the major risk?
Antidepressant
Risk of seizures
Noradrenaline dopamine reuptake inhibitor
What are side effects of beta blockers?
Fatigue Orthostatic hypotension Weakness Blurred vision Stuffy nose Impotence Rash CHF Bradycardia Pulmonary oedema
What are side effects of calcium channel blockers?
Dizziness Headache Redness in the face Fluid build up in the legs Rapid heart rate Slow heart rate Constipation Gingival overgrowth
What is the mechanism of action of ivabradine?
Acts at funny channels - reduce cardiac pacemaker activity
What is advice regarding statins in pregnancy?
Stop them due to congenital abnormality risk
What is the mechanism of action of Azathioprine?
Purine analogue
Interrupts DNA synthesis and drives rapidly dividing cells into apoptosis
What is the mechanism of action of sirolimus?
Inhibitor of mTOR, mammalian target of rapamycin (protein kinase acting downstream of IL2 signalling to promote proliferation and survival of T cells)
What is the mechanism of action of tacrolimus?
Calcineurin inhibitor
Reduces activation of nuclear factor of activated T cells which is a transcription factor that promotes IL2 production
What is the interaction between iron and thyroxine?
Iron reduces the absorption of thyroxine
What are side effects of sodium valproate?
Weight gain Nausea Vomiting Hair loss Easy bruising Tremor Hepatic failure Pancreatitis
Which beta blocker is safe to use in liver failure?
Propranolol 40mg BD
In which patients should caution be used when prescribing sulfasalazine?
G6PD deficiency
Allergy to aspirin or sulphonamides
What are adverse effects of sulfasalazine?
Oligospermia SJS Pneumonitis Myelosuppresion Heinz body anaemia Megaloblastic anaemia Coloured tears/stained contact lenses
What is the conversion factor between oral codeine and oral morphine?
Divide by 10
What is the generic name for herceptin?
Trastuzumab
What are adverse effects of interferon alpha?
Flu like symptoms
Depression
Which drugs can cause pancreatitis?
Azathioprine Mesalazine Didanosine Bendroflumethiazide Furosemide Pentamidine Steroids Sodium valproate
Which antihypertensive is associated with rebound HTN following acute withdrawal?
Clonidine
Which drug when combined with beta blockers can cause complete heart block?
Verapamil
Which drugs are associated with drug induced lupus?
Antibodies to tumor necrosis factor-a Anticonvulsants: phenytoin Chlorpromazine D-penicillamine Hydralazine Interferon alfa Isoniazid Methyldopa Minocycline Procainamide
What is a side effect of minoxidil which is used for benefit in another condition?
Hirsutism - used in regaine topical minoxidil solution for treatment of baldness
Which antihypertensive can precipitate haemolysis?
alpha methyldopa
Concurrent use of what drug may make clopidogrel less effective?
PPI
Which antidiabetic drugs can cause cholestasis?
Sulphonylureas
What should be the first line agent in diabetic neuropathic pain?
Duloxetine
What is the mechanism of action of adenosine?
Transient heart block in AV node
Agonist of A1 receptor which inhibits adenylyl cyclase so reduces cAMP causing hyperpolarisation by increasing outward potassium flux
Adenosine has short half life of 8-10secs
What are side effects of verapamil?
Heart failure Constipation Hypotension Bradycardia Flushing
What are side effects of nifedipine and amlodipine?
Flushing
Headache
Ankle swelling
In which patient group should mefloquine not be prescribed?
Hx of anxiety, depression, schizophrenia or other psychiatric disorders
Which drugs are associated with causing IIH?
Oral contraceptive Tetracyclines Nalixidic acid Nitrofurantoin Growth hormone
What are side effects of cyclosporin?
Everything increased Fluid BP Hair Potassium Gums Glucose
Which acetylcholinesterase inhibitors are recommended by nice for mild to moderate AD?
Donepezil
Galantamine
Rivastigmine
Which drug is used for moderate to severe AD?
Memantine (NMDA antagonist)
What are side effects of EPO?
Accelerated HTN leading to encephalopathy and seizures Bone aches Flu like symptoms Skin rash Urticaria Pure red cell aplasia Raised PCV increases risk of thrombosis Iron deficiency
What is the most common cause of drug induced angioedema?
ACE inhibitors
What change in eGFR and creatinine is acceptable when starting an ACE inhibitor?
Decrease in eGFR up to 25%
Rise in creatinine up to 30%
How does a dose of Azathioprine change if a patient is on allopurinol?
2mg/kg starting dose - but if on allopurinol - give 25% dose
What monitoring and counselling should be given to a patient before starting them on Azathioprine?
TPMT (thiopurine methyltransferase): if no activity, can’t break down AZA
Blood tests - weekly for 4/52, then 3/12
Myelosuppression signs and symptoms: sore throat, unexplained bruising / bleeding
Immunosuppressant hence recommend to avoid any live vaccines, but recommend annual flu vaccine
Sun exposure – limited or high factor sunscreen
What are prescribing options for IBD?
Mesalazine (5ASA) suppository/enema Steroids Azathioprine 6 mercaptopurine Methotrexate (crohns only) Infliximab Surgery
Why are aminosalicylate drugs best given as local preparations for UC?
Absorbed very quickly in small bowel so need mechanism to get it to large bowel
Why is sulfasalazine useful for treating UC?
Anti inflammatory
5-ASA attached to Sulphapyridine with a diazo bond
Bacteria hydrolyse the diazo bond
Means that it isnt broken down so quickly in small bowel so can get to site of action
What 2 forms of mesalazine are available?
Coated with Eudragit-S, pH dependent release: Asacol acts from TI onwards
Microparticles coated with ethylcellulose: Pentasa acts from duodenum onwards
What is the mechanism of action of mesalazine?
Inhibits both cyclo-oxygenase and 5- lipo-oxygenase pathways of arachidonic acid metabolism
Reduces inflammatory prostaglandin production and the formation of other chemotactic substances
What cautions should be applied when prescribing mesalazine?
Renal impairment
Pregnancy and breast feeding
Blood disorders can occur: Patients must be advised to report any unexplained bleeding, bruising, purpura, sore throat, fever or
malaise during treatment
Elderly- risk of serious renal toxicity with oral preparations, test renal function initially and every 3 months for first year, then every 6 months for next 4 years and annually thereafter
What are contraindications to mesalazine prescription?
Avoid in salicylate hypersensitivity
Severe hepatic impairment
Which drugs may interact with mesalazine?
Possible increased risk of leucopenia when aminosalicylates are given with azathioprine or mercaptopurine
Preparations that lower stool pH (e.g. lactulose) may prevent release of mesalazine
What are some side effects of aminosalicylates?
Nausea Diarrhoea Abdominal pain Headache Hepatitis Agranulocytosis Interstitial nephritis Asthma in the salicylate sensitive
What is the first line immunosuppressant in UC and crohns?
Azathioprine
What is the mechanism of action of Azathioprine?
Cytotoxic, antiproliferative immunosuppressant
Metabolised to 6-Mercaptopurine (6MP
Works by inhibiting purine production (decrease leucocytes)
What are side effects of Azathioprine?
Hypersensitivity reactions (including malaise, dizziness, vomiting, diarrhoea, fever, rigors, myalgia, arthralgia, rash, hypotension and interstitial nephrosis) require immediate
withdrawal
Other main SE seen in 2-3% = hepatitis, pancreatitis, pneumonitis
What cautions should be used when prescribing Azathioprine?
Hepatic impairment: may need to reduce dose
Renal impairment: may need to reduce dose
Reduce dose in elderly
Pregnancy: treatment should not be started during pregnancy, but safe to continue treatment during pregnancy if already on it
What are contraindications to Azathioprine prescription?
Hypersensitivity to azathioprine or mercaptopurine
Breast feeding
Which drugs does Azathioprine interact with?
Allopurinol: enhances effect and toxicity of azathioprine, Reduce dose of AZA when allopurinol is given concurrently
Aminosalicylates: possible increased risk of leucopenia
Anticoagulants: reduces anticoagulant effects of coumarins
Antibacterials: risk of toxicity of azathioprine is enhanced with
rifampicin, co- trimoxazole and trimethoprim
What are long term risks with use of 6 mercaptopurine?
Lymphoma
Non melanotic skin cancers- Use of suncreams
What is the mechanism of action of methotrexate?
Anti-metabolite folic acid inhibitor
Prevents DNA synthesis and cell division by preventing synthesis of purines and thymydilate. As rapidly dividing cells require thymydilate to synthesise DNA, MTX halts division
Suppression of immune system, improving disease
Immunosuppressant and anti-inflammatory activity
What are side effects of methotrexate?
Nausea Diarrhoea Stomatitis Leucopenia Pneumonitis Hepatitis Liver fibrosis
What monitoring needs doing when on methotrexate?
Monitor FBC, U+E’s and LFT’s at baseline and every 2-4 weeks until treatment stabilised
What are some cautions and contraindications for methotrexate use?
liver and renal disease alcohol obesity diabetes infections pregnancy breast feeding
Who is eligible for biologic drugs according to nice guidelines?
Severe active Crohn’s disease / UC AND Refractory to immunomodulatory drugs / can nottolerate side effects / experienced toxicity AND Surgery inappropriate (UC) Very good drugs for fistulising disease
What is TNF alpha?
Pro-inflammatory cytokine
Binds to TNF-alpha receptors on target cells inducing variety of local and systemic effects
TNF Causes local Inflammation in GI tract: diarrhoea, malabsorption
Presumed to be CD4 subset of T cells mediating disease
What are side effects of infliximab infusion?
Human anti-chimeric Ab formation can develop
Acute hypersensitivity reactions can occur
Symptoms – fever, chills, pruritus, urticaria, chest pain, hypo/hypertension, dyspnoea
Each infusion requires P & BP every 30 mins and access to resuscitation equipment
If mild reaction – slow down / temporarily stop infusion, If severe – stop and give IV hydrocortisone
Delayed hypersensitivity reactions can occur: Fever, rash, myalgia, arthralgia, Up to 2 weeks post infusion
More likely if >12 weeks between infusions
Antibody formation can lead to reduced response to infliximab
Why is adalimumab usually better tolerated by younger patients than infliximab?
Can be given subcut rather than infusion
What are possible complications of biologic drugs for IBD?
Possible risk of lymphoma and malignancy: Increased if pt on other immunosuppressants
Infectious complications (VZV, candida): Serious in 3%
TB reactivation (PPD (purified protein derivative) and CXR required prior to treatment)
Interactions tacrolimus / live vaccines
What are contraindications to biologic therapy?
Sepsis Significantly raised LFTs (x3) Hypersensitivity to infliximab Active TB Pregnancy, avoid for 6 months after Breast Feeding, stopping treatment
What cautions should be applied in prescribing biologic therapy?
Previous TB Hepatic Impairment Renal Impairment Heart Failure Mouse allergies > 14 weeks since last infusion
Which drugs can cause SIADH?
Carbamazepine
Sulphonylureas
SSRIs
TCAs
When should calcichew be prescribed if being used as a phosphate binder?
With meals
How should EPO be prescribed?
By brand
What is a key pharmacodynamic parameter in dosing of aminoglycosides?
Cmax: minimum inhibitory concentration ratio
Therefore once daily dosing is appropriate as it keeps this ratio high enough for longer than multiple lower doses
What is the key pharmacodynamic parameter in dosing beta lactam antibiotics?
Time antibiotic concentration remains above the MIC of organism expressed as T > MIC
So aim is to maximise duration of exposure
Where are bugs located that aminoglycosides are good at killing?
Circulating microorganisms
Where are bugs located that beta lactams are good at killing?
Soft tissue
Bone and joints
Lungs
CSF
Which graph is used to look at gentamicin levels?
Hartford Nomogram
When should gentamicin levels be checked? What level is required for further dose to be given?
24 hours post dose
Pre dose level 1mg/L or less
Why might a patient’s gent levels be high?
Blood collected too early
Patient not clearing Gentamicin
Blood collected from lumen used to infuse Gentamicin earlier on
Which bugs are targeted by vancomycin?
Gram-positive bacteria including MRSA
What vancomycin levels are required for monitoring?
Collect serum specimen 30 minutes or less before next dose
Frequency of collection: First level at steady state (3rd - 5th dose)– Subsequent levels once or twice/week
More frequently if renal function changing or concurrent nephrotoxic drugs
Which are the safest drugs in renal and liver failure?
Beta lactams
Which antibiotic drugs are cell wall synthesis inhibitors?
Beta Lactam agents: Penicillins, Cephalosporins, Carbapenems, Beta-lactamase inhibitors
Glycopeptides
What is a minimum inhibitory concentration?
Lowest concentration of antimicrobial required to prevent visible growth after overnight incubation
What is the minimum bactericidal concentration?
Lowest concentration of antimicrobial required to kill bacteria
Which antibiotic drugs are protein synthesis inhibitors?
Aminoglycoside: Blocks binding of amino acid charged t-RNA to acceptor site; Miss reading of m-RNA
Tetracycline: Blocks binding of amino acid charged t-RNA to acceptor site
Chloramphenicol: Block growth of peptide chain by interfering with peptidyl transferase
Macrolides: Interfere with translocation of t-RNA on bacterial ribosome preventing further peptide elongation
What are aminoglycosides mainly used for? (Gent, streptomycin)
Used primarily to treat infections with Gram negative bacilli or in synergic combination with cell wall active antimicrobial agents against some resistant Gram positive bacteria
What are features of aminoglycoside antibiotics?
Bactericidal
Poorly absorbed orally, so only parenteral (and topical)
Penetrates poorly into CSF, bone, eye, prostate, lung, biliary tract even in inflammation
Toxicity to VIII nerve (irreversible, occur even after discontinuation, cumulative with repeated courses) Gentamicin mainly vestibular, Amikacin mainly auditory and kidney (reversible)
How can bugs become resistant to antibiotics?
Enzymatic inactivation /destruction of drug: beta lactamase, Penicillinase, Carbapenemase
Modification/bypass of target site
Drug efflux
What is the mechanism of action of mirtazapine?
Blocks alpha 2 adrenergic receptors which increases release of neurotransmitters - noradrenaline and serotonin
What are 2 important side effects of mirtazepine that can be used for benefit?
Sedation
Increased appetite
In a patient on aspirin/nsaid, what else needs adding if they are to be started on an SSRI?
Add PPI to reduce GI bleed risk
How does amiodarone cause hyper and hypothyroidism?
Hypothyroidism: interferes with conversion of T4 to T3
Hyperthyroidism: thyroiditis, donation of iodine
What does highly active anti retroviral therapy involve?
Combination of at least 3 drugs Usually 2 nucleoside reverse transcriptase inhibitors and either a protease inhibitor or a non nucleoside reverse transcriptase inhibitor NRTI: zidovudine, lamivudine NNRTI: nevirapine, efavirenz Protease inhibitor: ritonavir, indinavir
What are side effects of NRTIs?
Peripheral neuropathy
Zidovudine: anaemia, myopathy, black nails
Didanosine: pancreatitis
What are side effects of NNRTIs?
P450 enzyme interaction - inducer
Rash
What are side effects of protease inhibitors?
Diabetes Hyperlipidaemia Buffalo hump Central obesity P450 enzyme inhibition
Who should receive statins?
All people with established CV disease (stroke, TIA, IHD, peripheral arterial disease)
10 year CV risk 10% or more including type 2 diabetics
Type 1 diabetics diagnosed more than 10 years ago or aged over 40 or have established nephropathy
What are major side effects of anti malarial medications?
Atovaquone and proguanil (malarone): GI upset
Chloroquine: headache, contraindicated in epilepsy
Doxycycline: photosensitivity, oesophagitis
Mefloquine: dizziness, neuropsychiatric disturbance, contraindicated in epilepsy
What are pharmacological management options for postural hypotension?
Fludrocortisone
Midodrine