Drugs Flashcards
D2 receptor antagonist antiemetics
I: 1 M A: 2 W: 2C/I, 1 caution I: 2 E: 2
Indication (1):
- N/V prophylaxis and tx (esp in reduced gut motility)
Mechanism:
- N/V triggered by gut irritation, drugs, motion and vestibular disorders and higher stimuli (sights/smells/emotions)
- D2 receptor is is main receptor in the chemoreceptor trigger zone (CTZ) - senses emotogenic substances in the blood
- Dopamine antagonists inhibits these receptors and promote gastric emptying
Adverse effects (2):
- Diarrhoea
- EPSEs via same mech as anti-psychotics (inc. oculogyric crisis)
- Domperidone doesn’t cause extrapyramidal syndromes as it doesn’t cross BBB
Warnings (2C/I, 1 caution):
- GI obstruction (C/I)
- Perforation (C/I)
- Avoid use in children/young adults increased risk of EPSEs
Interactions (2):
- Metoclopramide: don’t co-prescribe dopaminergic agents for Parkinson’s; also, risk of EPSEs increase when metoclopramide is prescribed with antipyschotics.
- Domperidone: these interactions don’t apply
Example drugs (2): Metoclopramide, domperidone
Quinolones
I: 4 M A: 6 W: 2 cautions I: 5 E: 3
Indications (4):
Only use second or third line (rapid resistance and C. diff association)
- UTIs
- Severe GI infections (e.g. Shigella, Campylobacter)
- LRTIs (only moxifloxacin and levofloxacin )
- Pseudomona aeruginosa (only ciprofloxacin)
Mechanism:
- Inhibit DNA synthesis to kill bacteria, especially aerobic gram -ve
- Moxifloxacin and levofloxacin are newer, they can work on gram +ve and gram -ve so can treat LRTIs
- Rapid resistance develops as bacteria either increase efflux of quinolones, reduce permeability to them or develop mutations against target enzymes of them
- Quinolone resistant genes are spread horizontally
Adverse effects (6):
- Mostly well tolerated
- GI upset
- Immediate and delayed hypersensitivity reactions
- Neuro effects
- Inflammation and rupture of muscle tendons
- Prolong QT interval
- Promote C. diff colitis
Warnings (2):
- People with risk of seizure
- QT prolongation
Interactions (5):
- Reduced absorption of quinolones if taken with drugs containing divalent cations e.g. calcium antacids
- Other drugs that prolong the QT interval or cause arrhythmias (amiodarone, antipsychotics, quinolones, macrolides, SSRIs)
- NSAIDs also increase risk of seizures
- Prednisolone also increases risk of tendon rupture.
- Ciprofloxacin inhibits some cytochrome P450 enzymes so risk of toxicity of drugs e.g. theophylline.
Example drugs (3): Ciprofloxacin, moxifloxacin, levofloxacin
Azathioprine
I: 3 M A: 12 W: 2C/I, 4 cautions I: 3
Indication (3):
- IBD remission maintainance (Crohn’s / UC)
- Rheumatoid Arthritis (DMARD)
- Organ transplant (reduces rejection risk)
Mechanism:
- Azathioprine is a pro-drug > metabolised to 6-Mercaptopurine
- Inhibits RNA replication (by inhibiting purine synthesis)
- Most cells can scavenge and recycle purines and continue functioning
- Lymphocytes cannot and are far more affected
- Metabolism of Azathioprine dependant on xanthine oxidase and thiopurine methyltransferase (TPMT)
- TPMT activity is reduced or absent in some people
Adverse effects (12):
- Bone marrow suppression > Leukopenia > risk of infection
- Nausea (divide daily dose > improves)
- Allergy
- D/V
- Rash
- Fever
- Myalgia
- Hypotension
- Pancreatitis
- Hepatotoxicity
- Veno-occlusive crisis
- Increased risk of Lymphomas (and some other tumors)
Warnings (6):
- Absent TPMT activity (C/I)
- Allergy - (C/I)
- Reduced TPMT activity (caution)
- Renal impairment (dose reduce)
- Hepatic Impairment (dose reduce)
- Pregnancy (do not start but might continue treatment if benefits outweigh risk)
Interactions (3):
- Allopurinol (+ other Xanthine oxidase inhibitors) > ++ toxicity
- Trimethoprim (+ other drugs that effect purine synthesis) > ++leukopenia
- Warfarin (increase warfarin dose as it reduces effect)
Methotrexate
I: 3 M A: 5 W: 2C/Is, 1 caution I: 3
Indication (3):
- RA DMARD
- Chemotherapy for many cancers including leukaemia, lymphoma and some solid tumours
- Treatment resistant psoriasis (including psoriatic arthritis)
Mechanism:
- Inhibits dihydrofolate reductase (converts dietary folic acid to FH4 - required for DNA / protein synthesis)
- This, therefore, prevents cellular replication
- Actively dividing cells are particularly sensitive to these effects, thus it works for cancers
- Also has anti-inflammatory and immunosuppressive effects (RA and psoriasis tx)
Adverse effects (5):
- Mucosal damage (sore mouth, GI upset)
- Bone marrow suppression (pancytopenia -> increased infection risk)
- Rare hypersensitivity reactions
- Long term use can cause hepatic cirrhosis or pulmonary fibrosis
- Risk of overdose with inappropriate regime
Warnings (3):
- Teratogenic, so avoid in pregnancy (and contraception during and for 3 months post tx)
- Severe renal impairment (C/I)
- Avoid in pts with abnormal liver function, as it can cause hepatotoxicity
Interactions (3):
- Drugs that ↓renal excretion > methotrexate toxicity (penicillins, ACE-I, ARB)
- Folate antagonists (increase risk of harm abs) - trimethoprim, phenytoin)
- Clozapine - increased neutropenia risk
Nicotine replacement
I: 1 M A: 2, V = 6, B = 5 W: 3 I: 2 E: 3
Indication:
- Smoking cessation, controls withdrawal symptoms
Mechanism
- Activates nicotinic acetylcholine receptors to prevent withdrawal symptoms
- Varenicline - partial agonist of nicotinic receptor, thus reducing withdrawal symptoms by agonising the receptor, and also the reward effects of smoking by only partially agonising the receptor.
- Bupropion - NA and dopamine reuptake inhibitor, so increased amounts in synaptic cleft
Adverse effects (4):
- Local irritation (patches, nasal spray).
- GI upset (oral nicotine) - nausea
- Headache
- Varenicline - insomnia, abnormal dreams, rarely suicidal ideation
- Bupropion - dry mouth, dizziness, psych (insomnia, depression, agitation), hypersensitivity reaction
Warnings (3):
- NRT - caution in haemodynamically unstable pts
- Bupropion & Varenicline - lowers seizure threshold, careful with psych conditions
- All of above - caution in hepatic/renal impairment
Interactions (2):
- Bupropion metabolised by CP450
- Bupropion + MAO-i or tricyclic antidepressants = increased risk of adverse effects
Example drugs (3): Nicotine, varenicline, bupropion
Alginates and antacids
I: 2 M A: 2 W: 3 I: 3 E: 2
Indication (2):
- GORD symptomatic relief
- Dyspepsia short-term relief
Mechanism:
- These drugs are most often taken as a combo: 1x alginates + 2 or more x antacids (i.e. Sodium bicarbonate, calcium carbonate, magnesium or aluminium salts)
- Antacids buffer stomach acids
- Alginates increase the viscosity of the stomach contents
- They may also inhibit pepsin production. Antacids alone can be used for short-term relief of dyspepsia.
Adverse effects (2):
- Magnesium salts can cause diarrhoea
- Aluminium salts can cause constipation.
Warnings (3):
- Caution paeds
- Na- and K- containing preps should be used with caution in patients w/ fluid overload or hyperkalaemia (i.e. renal failure)
- Some preps contain sucrose, which can worsen hyperglycaemia in DM
Interactions (3):
- Divalent cations in compound alginates can bind to other drugs»_space; decrease their absorption
- Antacids can reduce serum conc of many drugs»_space; effects dosage - applies to ACEI, some ABx (i.e. cephalosporins, ciprofloxacin, tetracyclines), bisphosphonates, digoxin, levothyroxine, and PPIs)
- By increasing alkalinity of urine, antacids can increase the excretions of aspirin and lithium
Example drugs (2): Gaviscon, peptac
Amiodarone
I: 1 M A: 1 ac, 5 chr W: 3 I: 3
Indication (1):
- Management of a wide range of tachycaridas, incl atrial Fib (AF), supraventricular tachycardia (SVT), ventricular tachycardia (VT) and refractory ventricular tachycardia (VF). It is generally used only when other therapeutic options (i.e. other drugs or electrical cardioconversion) are ineffective/inappropriate.
Mechanism:
- Amiodarone has many effects on myocardial cells, incl: blockade of Na, Ca and K channels; and antagonism of A- and B- adrenoceptors. These effects reduce spontaneous depolarisation (automaticity), slow conduction velocity and increase resistance to depolarisation (refractoriness), incl the AV node »_space; reduces ventricular rate in AF and atrial flutter
- Through other (unspecified) effects it may also increase chance of cardioversion to - and maintenance of - sinus rhythm. In SVT, Amiodarone may break re-entry circuit and restore sinus rhythm
- Amiodarone’s role in reducing automaticity makes it an option for prevention and treatment of VT and VF (although little clinical trials evidence for the latter)
Adverse effects (1 ac, 5 chr):
- In acute use, amiodarone causes relatively little myocardial depression though can cause hypotension if given via IV infusion
- In chronic use, it has many, often serious, side effects, inc: pneumonitis (lungs), bradycardia/AV block (heart), hepatitis (liver) and photosensitivity/grey discolouration (skin). Due to iodine content and structural similarities to thyroid hormone, it can cause thyroid abnormalities (hypo- and hyper-). Amiodarone has a v long half-life so takes months to be completely eliminated.
Warning (2):
- Severe hypotension (C/I)
- Heart block (C/I)
- Active thyroid disease (caution)
Interactions (3):
- Digoxin
- Diltiazem
- Verapamil
5 alpha reductase inhibitors
I: 1 M A: 3 W: 1 I: 0 E: 1
Indications (1):
- Second line for BPH, LUTs
Mechanism:
- 5α-reductase converts testosterone into the more active metabolite dihydrotesosterine, which stimulates prostatic growth
- Therefore the prostate gland is reduced by inhibiting intracellular 5α-reductase
- This can take several months so α-blockers are prefered initially
Adverse effects (3):
- Anti-androgen action: transient impotence and reduced libido, breast tenderness and gynaecomasia
- Reduced hair growth can help male pattern baldness
- Breast cancer has been reported
Warnings (1):
- Pregnant women should avoid as can lead to abnormal genitalia in male foetus (e.g. by exposure to semen in unprotected sex).
Interactions:
None
Example drugs (1): Finasteride
K sparing aldosterone antagonists
I: 3 M A: 4 W: 3C/I, 1 caution I: 2 E: 2
Indications (3):
- Ascites and oedema due to liver cirrhosis
- Chronic heart failure
- Primary hyperaldosteronism
Mechanism:
- Aldosterone acts on mineralocorticoid receptors in renal DCT to increase reabsorption of Na at expense of K. Aldosterone antagonists inhibit this by competitively bind to the receptors»_space; increased Na and water excretion; increase in K retention
- Effect greatest in primary hyperaldosteronism or when circulating aldosterone is increased (i.e. cirrhosis)
Adverse effects (4):
- Hyperkalaemia»_space; muscle weakness, arrhythmias and even cardiac arrest
- Can cause liver impairment and jaundice
- Stevens-Johnson syndrome
- Spironolactone causes gynaecomastia (?patient adherence)
Warnings (3C/I, 1 caution):
- Severe renal impairment (C/I)
- Hyperkalaemia (C/I)
- Addison’s disease (C/I)
- Aldosterone antagonists can X the placenta/appear in breast milk so should be avoided if pos in pregnant or lactating women
Interactions (2):
- Combo of aldosterone antagonist w/ other K-elevating drugs (i.e. ACEI and ARB) increases risk of hyperkalaemia - though can be effective v heart failure if monitored
- Aldosterone antagonists shouldn’t be combined w/ K supplements except in specialist practice
Example drugs (2): Spironolactone, epleronone
K sparing diuretics
I: 1 M A: 1 solo, 4 combined W: 3 C/I I: 3 E: 1, 2 combinations
Indication (1):
- Hypokalaemia - part of a combination therapy, for hypokalaemia due to loop or thiazide diuretics
Mechanism:
- Relatively weak diuretics alone, but in combination they can counteract potassium loss and enhance diuresis.
- Amilioride acts on the the DCT, inhibiting reabsorption of sodium by epithelial sodium channels (ENaC), leading to sodium and water excretion, and retention of potassium.
Adverse effects (1 solo, 4 combined): - GI upset When used with other diuretics - Dizziness - Hypotension - Urinary symptoms - Could still cause electrolyte abnormalities
Warnings (3):
- Severe renal impairment (C/I)
- Hyperkalaemia (C/I)
- Volume depletion (C/I)
Interactions (3):
- Don’t use with other potassium elevating drugs (Potassium supplements, aldosterone antagonists)
- Renal clearance of other drugs may be altered
- Digoxin and lithium should have doses adjusted
Example drugs (1, with 2 combinations): Amiloride is available individually, but often used as a combination tablet, with furosemide or hydrochlorothiazide. - Amiloride - Co- amilofruse - Co - amilozide
Triptans - 5-HT (serotonin) receptor agonists
I: 1 M A: 7 W: 4C/I I: 4 E: 1
Indication (1):
1) Acute migraine (+/- Aura), reduces duration and severity
Mechanism:
- Constrict cranial blood vessels (dilation believed to be important in migrane)
- Reduce neurotransmission along Trigeminal nerve / trigeminocervical complex
Adverse effects (7):
- Throat pain / discomfort
- Chest pain / discomfort
- Myocardial infarction (reported - rare)
- N/V
- Tiredness
- Dizziness
- Transient HTN
Warnings (4):
- Coronary Artery Disease (C/I)
- Cerebrovascular disease (C/I)
- Hemiplegic migraine (C/I)
- Basilar migraine (C/I)
Interactions (4): - MAOIs - Tramadol - SSRI - Tricyclics Note: Co-prescription increases risk of Serotonin toxicity / serotonin syndrome
Example drugs (1): Sumatriptan
Loop diuretics
I: 3 M A: 5 W: 2C/I, 4 cautions I: 3 E: 2
Indication (3):
- Acute pulmonary oedema - relief of breathlessness
- Chronic HF fluid overload
- Other Oedematous states - Symptomatic treatment of fluid overload, e.g. renal/liver failure
Mechanism:
- Act on the loop of Henle, where they inhibit the Na+/K+/2Cl- Co-transporter
- All three of these are being transported from lumen to epithelial cells - water follows, so inhibiting inhibits the water uptake
- Loop diuretics also have a direct effect on blood vessels, causing dilation of capacitance veins - reduces preload, and improves function of over-stretched heart muscles in heart failure
Adverse effects (5):
- Dehydration
- Hypotension
- Low almost any electrolyte (Hyponatremia, Hypokalemia, Hypochloraemia, Hypocalcemia, Hypomagnesaemia, metabolic alkalosis)
- They can act on a similar Na+/K+/2Cl- Co-transporter in the ear, so at high doses, loop diuretics can cause problems here, causing hearing loss and tinnitus
Warnings (2 C/I, 4 cautions):
- Hypovolemia (C/I)
- Dehydration (C/I)
- Hepatic encephalopathy (caution)
- Hypokalaemia (caution)
- Hyponatraemia (caution)
- Can worsen gout (caution)
Interactions (3):
- Renally excreted drugs (e.g. lithium)
- Digoxin toxicitiy may be increased, due to antidiurectic associated hypokalaemia
- It can also increase ototoxicity and nephrotoxicity of aminoglycosides
Example drugs (2): Furosemide, bumetanide
Dipeptidylpeptidase-4 (DPP4) Inhibitors
I: 2 M A: 2 W: 2 C/I, 6 cautions I: 4 E: 3
Indications (2):
- T2DM monotherapy (metformin contraindicated / not tolerated)
- T2DM as 2nd / 3rd agent where metformin +/- sulphonylurea are contraindicated, not tolerated or inadequate
Mechanism:
- Incretins (GLP-1 and GIP) are released in the gut
- Promote insulin release and supress glucagon release > lowering blood glucose
- Incretins are rapidly deactivated by Dipeptidylpeptidase-4 (DPP-4)
- Blood glucose is reduced by inhibiting DPP4
- Glucose dependant > doesn’t work at normal glucose levels
Adverse effects (2):
- Hypoglycaemia (but lower risk than SU or insulin)
- Pancreatitis (abdo pain > withdraw drug)
Warnings (2C/I, 6 cautions)
- Pregnancy (C/I)
- Breast Feeding (C/I)
- Elderly (>80)
- Pancreatitis
- Past Allergy
- Ketoacidosis
- Renal Impairment (mod-severe) > toxicity
Interactions (4) Risk of Hypoglycaemia increased by: - Alcohol - Beta Blockers Efficacy reduced by: - Thiazide Diuretics - Loop Diuretics
Example drugs (3) Sitagliptin, linagliptin, saxagliptin
SNRI antidepressants
I: 2 M A: 8 W: 3 I: 1 E: 2
Indication (2):
- Major depression where SSRIs aren’t tolerated
- Generalised anxiety disorder (venlafaxine)
Mechanism:
- Venlafaxine is a serotonin and NA reuptake inhibitors (SNRI) in the synaptic cleft
- Venlafaxine is a weaker antagonist of muscarinic and H1 receptors than tricyclic antidepressants
- Mirtazapine is an antagonist of the inhibitory pre-synaptic A2-adrenoceptor
- Mirtazapine is a potent antagonist of H1 but not muscarinic receptors
Adverse effects (8):
- GI upset (i.e. dry mouth, nausea, weight change, diarrhoea and constipation)
- CNS effects (i.e. headache, abnormal dreams, insomnia, confusion, convulsion and sedation (Mirtazapine))
- Hyponatraemia
- Serotonin syndrome
- Increase in suicidal thoughts/behaviours.
- Venlafaxine prolongs QT interval and can increase risk of ventricular arrhythmias
- Sudden withdrawal: GI upset, neurological, ‘flu-like symptoms and sleep disturbance
- Venlafaxine is associated w/ greater risk of withdrawal effects versus other antidepressants
Warnings (3):
- Elderly at higher risk of adverse effects
- Consider dose reduction hepatic/renal impairment
- Venlafaxine - CVD (caution)
Interactions (1):
- Combo of these and other antidepressants can increase risk of adverse effects and should, generally, be avoided
Example drugs (2): Venlafaxine, mirtazapine
Tetracyclines
I: 4 M A: 5 W: 3 I: 2 E: 2
Indications (4):
- Acne vulgaris (esp. if there are inflamed papules, pustules and/or cysts)
- Lower resp tract infections including infective exacerbations of COPD, pneumonia and atypical pneumonia
- Chlamydial infections including PID
- Typhoid, anthrax, malaria and Lyme disease
Mechanism:
- Inhibit bacterial protein synthesis
- Bind to ribosomal 30s subunit
- Prevents binding of transfer RNA to messenger RNA - prevents amino acids being made
- Therefore they are bacteriostatic, which enables the immune system to kill and remove
- Broad spectrum, resistance often due to an efflux pump preventing accumulation in bacteria
Adverse effects (5):
- GI upset
- Hypersensitivity reaction
- Oesophageal irritation, ulceration and dysphagia
- Exaggerated sunburn, discolouration and/or hypoplasia of tooth enamel in children
- Intracranial hypertension.
Warnings (3):
- Pregnant, breastfeeding
- Under age 12
- Avoid if renal impairment as anti-anabolic effects can raise plasma urea
Interactions (2):
- Tetracyclines bind to divalent cations. They should therefore not be given within 2 hours of calcium, antacids or iron, which will prevent antibiotic absorption
- Tetracyclines can enhance the anticoagulant effect of warfarin by killing normal gut flora that synthesise vitamin K
Example drugs (2): Doxycycline, lymecycline
Adrenaline
I: 2 M A: 3 W: 2 I: 1
Indications (2):
- Cardiac arrest
- Anaphylaxis immediate management
Mechanism:
- Adrenaline is a potent agonist of A1, A2, B1 and B2 adrenoreceptors»_space; multitude of sympathetic/parasympathetic effects
- A1: vasoconstriction of vessels supplying skin, mucosa and abdo viscera
- B1: Increases HR, force of contraction and myocardial excitability
- B2: Vasodilation of vessels supplying heart (use in cardiac arrest) and skeletal muscles; bronchodilatation and suppression of inflammatory mediator release from mast cells
Adverse effects (3):
- After use in cardiac arrest, often followed by adrenaline-induced hypotension
- After use in anaphylaxis, often causes anxiety, tremor, headache and palpitations
- Also, angina, MI and arrhythmias (particularly in patients w/ existing heart disease)
Warnings (2)
- Local vasoconstriction in HD (caution)
- Combo adrenaline-anaesthetic preps C/I in areas supplied by an end-artery (i.e. fingers/toes).
Interactions (1):
- In patients receiving B-blockers, adrenaline may cause widespread vasoconstriction (as A1 vasoconstriction not opposed by B2 vasodilation)
Example drugs (1) Adrenaline/Epinephrine
Beta 2 agonists
I: 3 M A: 7 W: 2 I: 1 E: 4
Indications (3):
- Asthma - short acting β2 agonists used to relieve breathlessness, Long acting β2 used as ‘step 3’ treatment (alwas given with corticosteroids)
- COPD - short-acting β2 agonists are used to relieve breathlessness, Long acting β2 used for second line therapy of COPD
- Hyperkalaemia - nebulised salbutamol used as an additional treatment
Mechanisms:
- β2 - receptors found in smooth muscle of the bronchi, GI, uterus, blood vessels
- Stimulation –> smooth muscle relaxation –> improves air flow
- Stimulate Na+/K+ -ATPase pumps on cell surface membranes, causing K+ from extracellular to intracellular compartment - makes it useful adjunct in hyperkalemia (especially if IV access difficult)
Adverse effects (7):
- Activation of β2 receptors in other tissues causes tachycardia, palpitations, anxiety, and tremor
- Promote glycogenolysis that can increase serum glucose concentration
- At high doses serum lactate levels may rise
- Long acting β2 - agonists can cause muscle cramps
Warnings:
- LABA should only be used in asthma when inhaled corticosterioids is also part of therapy - without a steroid LABAs associated with increased asthma deaths
- Be careful when prescribe for patients with CVD, especially in hyperkalaemia where high doses may be needed
Interactions (1)
- Beta blockers decrease effect
Examples (4)
Short acting: Salbutamol, terbutaline
Long acting: Salmeterol, formoterol
Phosphodiesterase (type 5 inhibitors)
I: 2 M A: 9 W: 5 I: 5 E: 2
Indication (2):
- Erectile dysfunction
- Primary Pulmonary hypertension
Mechanism:
- Selective inhibition of PDE5
- It is found primarily in the corpus cavernosum of penis and arteries of the lung
- For erection to occur, sexual stimulation is required.
- Releases NO which causes cGMP production, causing smooth muscle relaxation
- PDE5 causes breakdown of cGMP and this increases blood flow
- A simular mechanism is found in the pulmonary vasculature
Adverse effects (9): Resulting from vasodilation: - Flushing - Headache - Dizziness - Nasal congestion Progressing to: - Hypotension - Tachycardia - Palpitations - Priapism - Visual disorders (e.g. colour distortion) = prompt medical review
Warnings (5):
- Stroke
- Acute coronary syndrome
- Significant cardiovascular disease
- Severe Renal Impairment (lower dose)
- Severe hepatic impairment (lower dose)
Interactions (5): Drugs that increase NO: - Nitrates - Nicorandil Caution with other vasodilatiors - a-blockers - Calcium channel blockers. - Cytochrome p450 inhibitors
Example drugs (2) Slidenafil aka Viagra® (erectile disfunction) Revatio® (Pulmonary hypertension)
Trimethoprim
I: 2 M A: 6 W: 1 C/I, 3 cautions I: 3
Indications (2):
- Uncomplicated UTIs
- Co-trimoxazole (trimethoprim combined with sulfamethoxazole) to treat and prevent pneumocystis pneumonia in people with immunosuppression
Mechanism:
- Trimethoprim inhibits bacterial folate synthesis, slowing growth (bactiriostatic)
- Broad spectrum, Gram +ve and -ve, especially enterobacteria such as E, coli
- Widespread resistance (reduced intracellular accumulation and reduced sensitivity of target enzymes)
- When used with sulfonamides they work in synergy so there is complete inhibition of folate synthesis so bactericidal
Adverse effects (6):
- GI
- Skin rash (3-7%)
- Severe hypersensitivity reactions (more common with sulfonamides)
- Haemotological disorders
- Hyperkalamia
- High creatinine
Warnings (1 C/I, 3 cautions):
- First trimester (C/I)
- Folate def (caution)
- Renal impairment (caution)
- Dose reduction in neonates, elderly, HIV
Interactions (3):
- Potassium-elevating drugs (e.g. aldosterone antagonists, ACE inhibitors, angiotensin receptor blockers) predisposes to hyperkalaemia
- Use with other folate antagonists (e.g. methotrexate)
and drugs that increase folate metabolism (e.g. phenytoin) increases risk of adverse haematological effects
- Can enhance the anticoagulant effect of warfarin by killing normal gut flora that synthesise vitamin K
Adenosine
I: 1 M A: 2 W: (4 C/I, 2 caution) I: 4
Indication (1):
- 1st line diagnostic and therapeutic agent in supraventricular tachycardia (SVT)
Mechanism:
- Binds to heart adenosine receptors (G protein coupled)
- Decreased frequency of spontaneous depolarisations (automaticity) and increasing resistance to depolarisation (refractoriness)
- This slows sinus rate, conduction velocity and increases AV node refractoriness
- Many forms of SVT arise from re-entry circuits w/in the AV node. Increasing the AV node refractoriness breaks the re-entry circuit allowing normal SA node depolarisations to re-assert control (“cardioversion”)
- If the re-entry circuit does not involve the AV node, admin of adenosine at least blocks conduction to ventricles (i.e. in Atrial flutter), allowing closer inspection of atrial rhythm on ECG - may reveal true diagnosis
- Adenosine half-line in blood <10sec
Adverse effects (2):
- Bradycardia and even asystole (by interfering w/ SA and AV node conduction)
- Induces ‘impending doom’/sinking feeling/breathlessness sensation
Warnings (4 C/I, 2 caution):
- Hypotension (C/I)
- Coronary ischaemia (C/I)
- Decompensated HF (C/I)
- Bronchospasm (C/I)
- COPD (caution)
- Heart transplant (caution)
Interactions (4):
- Dipyridamole blocks cellular uptake of adenosine > prolongs + potentiates its effect»_space; dose should be halved
- Theophylline, aminophylline and caffeine are competitive antagonists of adenosine receptors»_space; reduce its effect»_space; patients may need higher doses
Thyroid hormones
I: 2 M A: 1 W: 2 I: 3 E: 2
Indications (2):
- Primary hypothyroidism
- Hypothyroidism secondary to hypopituitarism
Mechanism:
- Thyroid gland produces T4 which is converted into more active T3 in target tissues
- Levothyroxine is synthetic T4, it is usually given as a long term replacement of thyroid hormones
- Liothyronine is synthetic T3, it is usually reserved for emergences as it has a shorter half life and quicker onset and offset
Adverse effects (1): - Excessive doses lead to hyperthyroid symptoms (GI, cardiac and neuro)
Warnings (2):
- Cardiac ischaemia on those with coronary artery disease
- Addisonian crisis can occur in those with hypopituitarism if thyroid hormones are not preceded by corticosteroid therapy
Interactions (3):
- Antacids, calcium and iron salts reduce absorption so must not be given within same 4 hour window
- Higher dose may be needed if taking cytochrome P450 inducers, e.g. phenytoin, carbamazepine.
- Levothyroxine-induced changes in metabolism can
increase insulin or oral hypoglycaemic requirements in diabetes mellitus and enhance the effects of warfarin
Example drugs (2): Levothyroxine, liothyronine
Phenothiazine antiemetics
I: 2 M A: 4 W: 3 I: 7 E: 2
Indications (2):
- Prophylaxis and treatment of N/V, inc vertigo
- Schizophrenia, used as first generation (typical) antipsychotics
Mechanism:
- Antiemetic properties come from blocking D2 receptors in CTZ, and gut
- To a lesser extent histamine A1 and Ach (Mus) receptors in the vomiting centre and vestibular system
Adverse effects (4):
- Drowsiness and postural hypotension
- EPSEs (oculogyric crisis)
- In long term: (more likely in antipsychotic use) other extrapyramidal syndromes such as tardive dyskinesia may occur
- Like all antipsychotics, phenothiazines can cause QT- interval
Warnings (3):
- Hepatotoxic (avoid in liver disease)
- Should be avoided in patients susceptible to ACh side effects such as those in prostatic hypertrophy
- Reduce dose in elderly
Interactions (7):
- QT prolonging drugs
- Antipsychotics
- Amiodarone
- Ciprofloxacin
- Macrolides
- Quinine
- SSRIs
Example drugs (2): Prochlorperazine, chlorpromazine
Calcium channel blockers
I: 3 M A: A/N: 3, V: 4, D: mix W: V/D: 2, A/N: 1, 1 I: 1 E: 2, 2
Indications (3):
- Amlodipine used as second line treatment of HTN
- All Ca channel blockers can be used to control symptoms in stable angina
- Diltiazem and verapamil used to control cardiac rate in people with supraventricualr arrhythmias (inc. supraventricular tachycardia, atrial flutter, and a. fib)
Mechanism:
- Decrease Ca2+ entry into vascular and cardia cells, decreasing intracellular Ca –> relaxation and vasodilaiton in arterial smooth muscle –> lower arterial pressure
- Supress cardiac conduction across AV node, slowing ventricular rate
- Reduced cardiac rate, and contractility and afterload decrease myocardial oxygen demand, preventing angina
Two types:
- Dihydropyridines - amlodipine and nifedipine are relatively selective for vasculature
- Non-dihydropyridines - more selective of heart - verapamil (most selective), and diltiazem
Adverse effects (many):
- Amlodipine/Nifedipine - ankle swelling, flushing, palpitations
- Verapamil - constipation, rarely bradycardia, heart block, and heart failure
- Diltiazem - mixed vascular and cardiac actions so can cause all the above
Warnings (4):
- Verapamil/diltiazem - caution if poor left ventricular function, or AV nodal delay
- Amlodipine/nifedine - avoid in unstable angina as vasodilation causes reflex increase in contractility and tachycardia which increases myocardial oxygen demand.
- Avoid in aortic stenosis –> collapse
Interactions (1):
- Beta blockers - can cause heart failure, bradycardia, andasystole
Examples (2,2):
- Dihydropyridines - amlodipine and nifedipine
- Non-dihydropyridines - verapamil and diltiazem
Digoxin
I: 2 M A: 7 W: I: 3 C/I, 3 caution
Indication (2):
- In atrial fibrillation and atrial flutter, it’s used to reduce the ventricular rate
- In severe heart failure, it’s used as a third line treatment in those already taking an ACE inhibitor, Beta blocker, and either an aldosterone antagonist or ARB
Mechanism:
- It’s negatively chronotropic (reduces heart rate)
- It’s positively inotropic (Increases force of contraction)
- In atrial fibrillation and flutter it increases parasympathetic tone, which reduces conduction at the AV node, which reduces the ventricular rate
- In heart failure, it acts on the myocytes via inhibition of of the NaK ATPase pumps, causing Na+ to acculmulate in the cells. Removal of Ca2+ requires low intracellular Na+ so elevation of Na+ causes Ca2+, which increase contractile force
Adverse effects (7):
- Bradycardia
- GI disturbance
- Rash
- Dizziness
- Visual disturbance (blurry or yellow vision)
- Can cause digoxin toxicity which will cause arrhythmias
- Theraputic index is low, meaning a slightly incorrect dose is bad
Warnings (3 C/I, 3 caution):
- Second degree heart block (C/I)
- Intermittent complete heart block (C/I)
- Patients at risk or with ventricular arrhymias (C/I)
- Dose should be reduced in renal failure as eliminated by the kidneys.
- Electrolyte abnormalities increase risk of digoxin toxicity, including hypokalemia, hypomagnesaemia, hypercalcaemia
Hypokalemia is the most important of these, as digoxin competes with potassium for the NaK ATPase pump. If potassum is low, competition is reduced, and digoxin’s effects are enhanced.
Interactions:
Loop and thiazide diuretics can increase risk of digoxin toxicity by causing hypokalemia.
Amiodorone, calcium channel blockers, spironolactone, and quinine can all increase the plasma concentration of digoxin.
Atypical antipsychotics
I: 4 M A: 6 W: 3 I: 3 E: 4
Indications (4):
- Urgent psychomotor agitation causing dangerous or violent behaviour
- Schizophrenia - when the first generation extrapyramidal (or other) SE are problematic
- Bipolar disorder - in acute episodes of mania or hypomania
- N/V
Mechanism:
- Block post-synaptic dopamine D2 receptors
- 3 main dopaminergic pathways in CNS: mesolimbic (midbrain and limbic system/ frontal system), nigrostriatal pathway (substantia nigra with corpus striatum of the basal ganglia), tuberohypophyseal pathway (hypothalamus with the pituitary)
- Antipsychotic effect probably comes from action in mesolimbic system
Features differentiating second generation
- Improved efficacy in treatement resistant schizophrenia, and against negative symptoms
- Lower risk of extrapyramidal symptoms
- Mechanisms for these differencce include a higher affinity to other receptors (particularly 5-HT2A), and looser binding to D2 receptors
Adverse effects (6):
- Sedation
- EPSEs (not as common as in 1st gen)
- Metabolic disturbance - weight gain, DM, lipid changes
- QT- interval elongation (–> arrhythmias)
- Risperidone - effects tuberohypophyseal, effecting prolactin secretion –> breast symptoms, and sexual dysfunction
- Clozapine - 1% of patients get deficiency of neutrophils, and rarely MI
Warnings (3):
- Caution in CVD
- Do not use clozapine in those with severe heart disease or Hx of neutropenia
Interactions (3):
- Sedation increased when other sedating drugs used
- Dopamine blocking anti-emetics
- Drugs that prolong the QT interval (e.g.amiodarone and macrolides)
Examples (4):
Quetiapine, olanzapine, risperidone, clozapine
Topical corticosteroids
I: 1 M A: 8 W: 2C/I I: 1 E: 2
Indication (1):
- Inflammatory skin conditions, such as eczema
Mechanism (3 classes of action):
- Immunosuppressive
- Metabolic
- Mineralocorticoid
Topically most effect is local, but can get systemic effects with potent or prolonged use .
Adverse effects (8):
- Skin thinning
- Striae
- Telangiectasia
- Contact Dermatitis
- Derioral dermatitis
- Exacerbate acne
- Rebound worsening (on withdrawl)
- Adrenal suppression
Warnings (2 C/Is):
- Infection (C/I)
- Facial lesions (C/I)
Interactions (1) :
- If using several topical agents, space out to allow absorption
Example drugs (2): Hydrocortisone, betamethasone
Antimuscarinics - CVS, GI uses
I: 3 M A: 6 W: 1 C/I, 1 caution I: 1 E: 3
Indications (3)
- Atropine - first line in severe symptomatic bradycardia to increase HR
- IBS - for there antispasmodic effect
- Palliative - reduce copious respiratory secretions
Mechanism:
- Bind to mus receptor, where competitively inhibits acetylcholine –> decreases PSNS
- Increase heart rate and conduction
- Reduce smooth muscle tone and the peristaltic contraction; including in gut and urinary tract
- Reduce secretions from glands in the respiratory tract and gut
- In eye cause relaxation of pupillary constrictor and cilary muscles –> causing pupillary dilation and preventing accommodation
Adverse effects (6):
- PSNS: tachycardia, dry mouth, constipation
- Reducing detrusor muscle activity can cause urinary retention in patients with BPH
- Blurred vision
- Some antimuscarinics (inc atropine) have central effects –> drowsiness and confusion
Warnings (1 C/I, 1 caution):
- Arrhythmia (C/I) unless bradycardia
- Angle-closure glaucoma (caution)
Interactions (1)
- Adverse effects more pronounced when with other drugs with antimus efffects e.g tricyclics
Examples (3)
Atropine - bradycardia
Hyoscine butylbromide - IBS, palliative
Glycopyrronium
Statins
I: 3 M A: 4 W: 4 I: 2 E: 4
Indications (3):
- Primary prevention of CVS events
- Secondary prevention alongside lifestyle changes
- Treating hyperlipidaemia
Mechanism:
- Reduce serum cholesterol levels by inhibiting HMG CoA reductase - reduces production by liver and increases LDLs
- They indirectly reduce triglyceride and increase HDL levels
- These effects slow and sometimes reverse atherosclerosis
Adverse effects (4)
- Headaches
- GI
- Muscle issues (aches, myopathy, rhabdomyolysis)
- Raised ALT –> drug induced hepatitis
Warnings (4):
- Hepatic impairment
- Renal impairment
- Breastfeeding
- Pregnancy (cholesterol needed in fetal development)
Interactions (2):
- Metabolism is reduced by cytochrome P450 inhibitors (amiodarone, diltiazem, itraconazole, macrolides and protease inhibitors)
- Metabolism is also reduced by Amlodipine.
Example drugs (4): Simvastatin, atorvastatin, pravastatin, rosuvastatin
Quinine
I: 2 M A: 8 W: 3 I: 2
Indications (2):
- Preventing leg cramp
- First line treatment for Plasmodium falciparum malaria
Mechanism:
- Lower excitability of the motor end plate in response to acetylcholine –> fewer muscle contractions
- Rapid killing of schizont stage P. falciparum parasites in the blood
Adverse effects (8):
- Tinnitus
- Deafness
- Blindness
- GI upset
- Hypersensitivity reactions
- Longer QT interval
- Potentially fatal in overdose
- Hypoglycemia, which can also occour in malaria so more problematic
Warnings (3):
- Hearing or visual loss
- First trimester of pregnancy (teratogenic)
- G6PD deficiency (haemolysis)
Interactions (2):
- Other drugs that prolong the QT interval or cause arrhythmias (amidarone, antipsychotics, quinolones, macrolides
- SSRIs
Aminosalicylates
I: 2 M A: 4 both, 2 S W: 1 I: 2 E: 2
Indication (2):
- Ulcerative colitis - mesalazine
- RA - sulfasalazine = DMARD
Mechanism:
Ulcerative Collitis:
- Aminosalicylates therapeutic effect achieved by releasing 5-aminosalicylic acid (5-ASA)
- Precise MOA of 5-ASA unknown but it has both anti-inflammatory and immunosuppressive effects
- Appears to act topically rather than systemically
- 5-ASA preps are designed to delay delivery of active ingredient until reaching colon
- Sulfasalazine - 5-ASA bound to sulfapyridine** which is catabolised by bacterial enzymes in the gut).
Rheumatoid Arthritis
- Sulfapyridine (bound to Sulfasalazine) has therapeutic effect (MOA unknown), but Mesalazine has not therapeutic effect in RA.
Adverse effects (4 both, 2 sulfasalazine):
Both:
- GI upset (i.e. nausea, dyspepsia)
- headache
- Rare but serious blood abnormalities (i.e. leucopenia, thrombocytopenia)
- Renal impairment.
Sulfasalazine only:
- Reversible decrease in the number of sperm (oligospermia)
- serious hypersensity reaction (incl pyrexia, rash and liver abnormalities).
Warnings (1)
- Aspirin allergies (all are salicylates)
Interactions (2):
- Drugs that alter gut pH = Mesalazine tablets with a pH-sensitive coating (.e. Asacol MR)= PPI»_space; increase gastric pH»_space; tablet coating broken down prematurely
- Lactulose lowers stool pH and may prevent 5-ASA release in the colon
Example drugs (2): Mesalazine, sulfasalazine
Iron
I: 2 M A: 3 W: 2 I: 1 E: 2
Indication (2):
- Iron deficiency anaemia
- Prophylaxis of iron deficiency anaemia
Mechanism:
- Replenishes iron stores, which are stored as ferratin in the liver, bone marrow, spleen and skeletal muscle.
Adverse effects (3):
- GI upset - nausea, epigastric pain, constipation, diarrhoea
- Black poo
- Rarely hypersensitivity reactions if given IV (eg anaphylaxis)
Warnings (2):
- May exacerbate bowel Sx in pts with intestinal disease (eg IBD, diverticular disease)
- Caution giving IV iron in atopic pts
Interactions (1):
- Oral iron can reduce absorption of drugs such as levothyroxine and bisphosphonates, so therefore they should be taken >2 hrs before iron
Example drugs (2): Ferrous fumarate, ferrous sulfate
Warfarin
I: 3 M A: 1 W: 3 I: 5
Indications (4):
- Prevent clot extension and recurrence in deep vein thrombosis and pulmonary embolism (collectively, venous thromboembolism [VTE])
- Prevent embolic complications (e.g. stroke) in atrial fibrillation.
- Prevent embolic complications (e.g. stroke) after heart valve replacement (short term after tissue valve replacement, lifelong for mechanical valve replacement)
- Warfarin is not used to prevent arterial thrombosis (e.g. myocardial infarction, thrombotic stroke) - as this is driven by platelet aggregation, it is prevented by antiplatelet agents, such as aspirin and clopidogrel.
Mechanism:
- Warfarin inhibits hepatic production of vitamin K-dependent coagulation factors and cofactors
- Vitamin K must be in its reduced form for synthesis of coagulation factors. It is then oxidised during the synthetic process.
- An enzyme called vitamin K epoxide reductase reactivates oxidised vitamin K
- Warfarin inhibits vitamin K epoxide reductase, preventing reactivation of vitamin K and coagulation factor synthesis
Adverse effects (1): - Bleeding
Warnings (3):
- Risk of haemorrhage
- Liver disease
- Pregnancy (fetal abnormalities in first trimester, risk of bleeding towards term)
Interactions (5):
- Low therapeutic index
- Small changes in hepatic warfarin metabolism by cytochrome P450 enzymes can cause clinically significant changes in anticoagulation.
- Cytochrome P450 inhibitors (e.g. fluconazole,
macrolides, protease inhibitors) decrease warfarin metabolism and increase bleeding risk.
- Cytochrome P450 inducers (e.g. phenytoin,
carbamazepine, rifampicin) increase warfarin metabolism and risk of clots.
- Antibiotics can increase anticoagulation in patients on warfarin by killing gut flora which synthesise vitamin K.
Acetylcholinesterase inhibitors
I: 2 M A: 5 W: 2C/Is, 4 cautions I: 4 E: 2
Indication (2):
1) Mild-moderate Alzheimer’s disease
2) Mild-moderate dementia in Parkinsons disease (rivastigmine)
Mechanism (7):
- Acetylcholine is an important Neurotransmitter in CNS, essential for learning and memory
- Key in Alzheimer’s/ dementia in Parkinsons (where Acetylcholine declines) - increases ACh availability
- Improves cognitive function and reduces rate of decline
Adverse effects (5)
- Asthma
- COPD
- Peptic ulcers/bleeding
- Neuroleptic malignant syndrome (NMS)
- EPSEs
Warnings (2C/Is, 4 cautions):
- Sick Sinus Syndrome (C/I)
- Heart block (C/I)
- Asthma (caution)
- COPD (caution)
- Peptic Ulcers (caution)
- Parkinsons (caution)
Interactions (4):
- NSAIDs
- Corticosteroids
- Antipsychotics (increased risk of NMS)
- Beta- blockers (and other rate-limiting medications > bradycardia / heart block)
Example drugs (2): Donepezil, rivastigmine
SSRIs
I: 4 M A: 10 W: 4 I: 4 E: 4
Indication (4):
- Mod-severe depression (1st line)
- Also in mild depression if psych treatments fail
- Pain disorder
- OCD
Mechanism:
- SSRIs preferentially inhibiting neurone reuptake of serotonin (5-HT) from the synaptic cleft»_space; increasing its availability for neurotransmission
- SSRIs differ from tricyclic-antidepressants as they do not inhibit NA uptake and cause less blockade of other receptors
- Efficacy of both drug classes v depression is similar, but SSRIs have few adverse effects so preferred
Adverse effects (10):
- GI upset
- Appetite and weight disturbance
- Hypersensitivity reactions
- Hyponatraemia
- Suicidal thoughts/behaviours may increase
- Lower seizure threshold
- Prolong the QT interval (i.e. citalopram) and can predispose to arrhythmias
- Increased risk of bleeding
- At high doses, or in combo w/ other antidepressants, can cause ‘serotonin syndrome’ - autonomic hyperactivity, altered mental state and neuromuscular exciting
- Sudden withdrawal of SSRIs –> GI upset, neurological symptoms, ‘flu-like symptoms and sleep disturbance
Warnings (4):
- Epilepsy (caution)
- PUD (caution)
- Young (caution)
- Hepatic impairment (caution)
Interactions (4):
- Don’t co-prescribe MAO-Is as both increase synaptic serotonin (» serotonin syndrome)
- Gastro-protection should be given when SSRIs given with aspirin/NSAIDs
- Bleeding risk also increased when anticoagulants co-prescribed
- SSRIs should not be combined w/ other drugs that prolong QT interval (i.e. antipsychotics)
Example drugs (4): Citalopram, fluoxetine, sertraline, escitalopram.
Metronidazole
I: 4 M A: 3 W: 2 I: 2
Indication (4):
Tx of infections:
- Antibiotic-associated colitis (C diff)
- Oral infections or aspiration pneumonia (Gm -ve anaerobes)
- Surgical and gynae infections (Gm -ve anaerobes)
- Protazoal infection (eg giardiasis, trichomonal vaginal infection, amoebic dysentery)
Mechanism
- Enters anaerobic bacteria by passive diffusion, where it is reduced, generating a nitro free radical, which binds to DNA, causing widespread damage, DNA degradation and cell death
- Only anaerobes and protazoa can reduces metronidazole this way, so it doesn’t work on aerobic bacteria
Adverse effects (3):
- GI upset
- Hypersensitivity reactions
- Peripheral and optic neuropathy, seizures and encephalopathy in high doses or prolonged courses
Warnings (2):
- Metabolised by CP450, so reduce dose in severe liver disease
- Do not drink alcohol while taking, as this drug inhibits acetaldehyde dehydrogenase
Interactions (2):
- It is a CP450 inhibitor (so any drug metabolised by CP450 will be have raised concentrations in serum)
- Increased risk of toxicity when taken with lithium
Lamotrigene
I: 2 M A: 9 W: 3 I: 6
Indication (2):
- Epilepsy prophylaxis - 1st mono / adjunct therapy in generalised tonic-clonic seizures, absence seizures
- Bipolar disorder as mood stabiliser (but not in mania / hypomania)
Mechanism:
- Reduces neuronal excitability and electrical conductance inhibits seizure activity
- Binds to active neurone Na channels, prolonging Na influx (preventing triggering)
- May also bind to post-synaptic AMPA receptor
Adverse effects (9)
- Headache
- Drowsiness
- Irritability
- Blurred vision
- Dizziness
- GI Upset
- Skin rash
- Steven Johnson syndrome
- Neuroleptic malignant syndrome
Warnings (3)
- Hypersensitivity to other anti-epilpetic drugs
- Hepatic Impairment (dose reduction)
- Pregnancy > use with caution + closely monitor but safe
Interactions (6)
- Metabolised by Glucuronidation (CORPS-V):
↑Glucuronidation Inducers = ↓ Reduce Lamotrigine concentration:
1) C - Carbamazepine
2) O - Oestrogens
3) R - Rifampicin
4) P - Phenytoin
5) S - Simeprevir and other Protease Inhibitors
↓ Glucuronidation Inducers = ↑ Increases Lamotrigine concentration:
6) V - Valproate
Vancomycin
I: 2 M A: 5 W: 1 I: 3
Indications (2):
- Treating gram + infection e.g. endocarditis if severe and/or penicillins cannot be used due to resistance
- Treating antibiotic associated colitis caused by C. diff
Mechanism:
- Specific to gram + aerobic or anaerobic bacteria
- Inhibits growth and cross linking of peptidoglycan chains, preventing synthesis of the cell wall of gram + bacteria
- Resistance is increasing, partly due to modification of cell wall to prevent vanc binding
Adverse effects (5):
- Thrombophlebitis (pain and inflammation of the vein at infusion site
- ‘Red man syndrome’ (erythema, hypotension, bronchospasm) or other anaphylactoid reactions, especially if infused too quickly
- True allergies can also occour (immidiate or delayed)
- Nephroxocity, ototoxicity
- Blood disorders
Warnings (1):
- Careful monitoring of plasma concentrations to avoid toxicity (esp in renal failure)
Interactions (3):
- Higher risk of oto and nephro toxicity when prescribed with aminoglycosides, loop diuretics or ciclosporin
Allopurinol
I: 3 M A: 3 W: 2C/I, 1 caution I: 3
Indication (3):
- Prevent gout
- Prevent uric acid and calcium oxalate renal stones.
- To prevent hyperuricaemia and tumour lysis syndrome associated w/ chemotherapy
Mechanism
- Xanthine oxidate metabolises xanthine (produced from purines) to uric acid
- Allopurinol is a xanthine oxidase inhibitor, therefore it lowers plasma uric acid conc and reduces precipitation of uric acid in joints/kidneys
Adverse effects (3):
- Most common side effect is a skin rash (mild up to severe
- Drug hypersensitivity is a rare, life-threatening side effect that can incl pyrexia, eosinophilia, lymphadenopathy
- Starting allopurinol can trigger/worsen an acute attack of gout
Warnings (2C/I, 1 caution):
- Acute attacks of gout (C/I)
- Recurrent skin rashes or more severe hypersensitivity (C/I)
- Severe renal/hepatic impairment (caution)
Interactions (3):
- Cytotoxic drug mercaptopurine - and its pro-drug azathioprine - require xanthine oxidate for metabolism
- Co-prescription: w/ amoxicillin, increases the risk of skin rash
- ACEI/thiazides, increases risk of hypersensitivity reactions.
Clopidogrel
I: 4 M A: 3 W: 1 C/I, 2 cautions I: 3
Indications (4):
- Acute Coronary Syndrome, where rapid inhibition of platelet aggregation can stop thrombosis
- To prevent occlusion of coronary artery stents
- Long term secondary prevention of thrombosis in cardiovascular, cerebrovascular and peripheral arterial disease
- Reduce risk of thrombus/stroke in atrial fibrillation if warfarin and NOAC is contraindicated
Mechanism:
- Prevents platelet aggregation and by irreversibly binding to ADP receptors on the surface of platelets
- Pathway is independent of COX pathway, so synergistic with aspirin
Adverse effects (3):
- Bleeding
- GI upset (Dyspepsia, abdo pain, diarrhoea)
- Thrombocytopenia
Warnings (1 C/I, 2 cautions):
- Active bleeding (C/I)
- Might need to stop 7 days before elective surgery
- Caution if renal and hepatic impairment, particularly if this is causing additional risk of increased bleeding.
Interactions (3):
- Pro-drug, needs hepatic cytochrome P450 metabolism.
Efficacy reduced by P450 inhibitors
- Other antiplatelets increase risk of bleeding
- Other anticoagulants increase risk of bleeding
Phenytoin
I: 3 M A: 5 W: 2 I: 4
Indication (2):
- Status epilepticus (after failure of benzodiazepines)
- Reduce generalised or focal seizures
Mechanism:
- Incompletely understood. Reduces neuronal excitability and electrical conductance, inhibiting seizure activity
Adverse effects (5):
- Long term = Appearance changes skin coursening, acne hirsutism, gum hypertrophy.
- Dose-related neurological effects = cerebellar toxicity (nystagmus, ataxia and discoordination)
- Haematological disorders and oesteomalacia (induces folic acid and vitamin D metabolism)
- Hypersensitivity reactions and anaphylaxis
- Phenytonin toxcity can cause cardiovascular collpase and respiritory depression
Warnings (2):
- Reduce doses in hepatic imparement becuase has low therapeutic index and metabolised by Zero-order kinetics
- Teratogenic (fetal hydantoin syndrome) - women planning pregancy must see specialist and take high dose folic acid before conception
Interactions (4):
- P450 inducer, so reduces efficacy of warfarin, oestrogen and progesterone amongst others.
- Cytochrome p450 inhibitors (SICKFACES.COM) increases effect and side effects.
- Complex interactions with other epileptic drugs.
- Efficacy reduced by drugs that lower the seizure threshold (e.g. SSRIs, Ticyclics, antipsychotics and tramadol)
5-HT receptor antagonist antiemetics
I: 1 M A: 2 W: 1 I: 1 E: 2
Indications (1):
- Prophylaxis and treatment of nausea particularly in general anaesthesia and chemotherapy
Mechanism:
- Serotonin not involved in vestibular communication. So will have no effect on motion sickness
Adverse effects (2):
- Constipation/diarrhoea
- Headaches
Warnings (1):
- Small risk that 5-HT antagonists may prolong the QT interval, avoid in those with long QT interval
Interactions (1):
- Avoid in those using other drugs that prolong the QT interval; antipsychotics, quinine, SSRIs
Examples (2):
Ondansetron, granisetron
H2 receptor antagonists
I: 2 M A: 3 W: 2 I: 0 E: 1
Indication (2):
- Peptic ulcer disease - for treatment of gastric and duodenal ulcers, and NSAID associated ulcers,
- GORD and Dyspepsia symptom relief
Mechanism:
- Histamine H2 Receptor blockers reduce gastric acid secretion.
- Acid is normally produced by the proton pump of the gastric parietal cell, which secretes H+ into the the stomach lumen in exchange for drawing K+ into the cell.
- Proton pump is regulated by histamine, released by local cells, and binds to the H2 receptors on the parietal cell. This activates the proton pump by a second-messenger system.
- The proton pumps can be triggered by other mechanisms, so it can’t completly stop gastric acid production, unlike PPIs, which can.
Adverse effects (3):
- Diarrhoea
- Headache
- Dizziness
Warnings (2):
- Renal impairment - reduce dose
- Like PPIs, they can disguise symptoms of gastric cancer
Interactions (0)
Example drugs (1): Ranitidine
Bisphosphonates
I: 4 M A: 4 W: 4 C/I I: 1 E: 3
Indications (4):
- Alendronic acid for those at risk of osteoporotic fractures
- Pamidronate and zoledronic acid for severe hypercalcaemia of malignancy
- Pamidronate and zoledronic acid - myeloma, and breast cancer with bone metastases, decrease fractures, cord compression and need for readiotherapy or surgery
- First line in active Paget’s disease (to reduce bone turnover)
Mechanism:
- Reduce bone turnover by inhibiting osteoclasts
- Bisphosphonates have similar structure to naturally occuring pyrophosphate so are incorporated into bone
- As bone resorbed, bisphosphonates accumulate in the osteoclasts and inhibit activity and promote apoptosis –> reducing bone loss and improving bone mass
Adverse effects (4):
- Oesophagitis
- Hypophosphataemia
- Osteonecrosis of jaw (rare, more likely if IV, good dental care decreases this)
- Atypical femoral fracture (in long term treatment)
Warnings (4C/I):
- Severe renal impairment (C/I)
- Hypocalcaemia (C/I)
- Upper GI issue (C/I)
- Dental disease, smoking (C/I)
Interactions (1):
- Binds ca, so reduced absorption if taken with ca salts (i.e. milk), as well as antacids and iron salts
Examples (3):
Alendronic acid - osteoporosis
Disodium pamidronate
Zoledronic acid - hypercalcaemia and bone mets