Drugs Flashcards

1
Q

D2 receptor antagonist antiemetics

I: 1
M
A: 2
W: 2C/I, 1 caution
I: 2
E: 2
A

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
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2
Q

Quinolones

I: 4
M
A: 6
W: 2 cautions
I: 5
E: 3
A

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
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3
Q

Azathioprine

I: 3
M
A: 12
W: 2C/I, 4 cautions
I: 3
A

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)
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4
Q

Methotrexate

I: 3
M
A: 5
W: 2C/Is, 1 caution
I: 3
A

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
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5
Q

Nicotine replacement

I: 1
M
A: 2, V = 6, B = 5
W: 3
I: 2
E: 3
A

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
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6
Q

Alginates and antacids

I: 2
M
A: 2
W: 3
I: 3
E: 2
A

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&raquo_space; decrease their absorption
  • Antacids can reduce serum conc of many drugs&raquo_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
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7
Q

Amiodarone

I: 1
M
A: 1 ac, 5 chr
W: 3
I: 3
A

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 &raquo_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
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8
Q

5 alpha reductase inhibitors

I: 1
M
A: 3
W: 1
I: 0
E: 1
A

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
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9
Q

K sparing aldosterone antagonists

I: 3
M
A: 4
W: 3C/I, 1 caution
I: 2
E: 2
A

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&raquo_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&raquo_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
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10
Q

K sparing diuretics

I: 1
M
A: 1 solo, 4 combined
W: 3 C/I
I: 3
E: 1, 2 combinations
A

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
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11
Q

Triptans - 5-HT (serotonin) receptor agonists

I: 1
M
A: 7
W: 4C/I
I: 4
E: 1
A

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
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12
Q

Loop diuretics

I: 3
M
A: 5
W: 2C/I, 4 cautions
I: 3
E: 2
A

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
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13
Q

Dipeptidylpeptidase-4 (DPP4) Inhibitors

I: 2
M
A: 2
W: 2 C/I, 6 cautions
I: 4
E: 3
A

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
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14
Q

SNRI antidepressants

I: 2
M
A: 8
W: 3
I: 1
E: 2
A

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
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15
Q

Tetracyclines

I: 4
M
A: 5
W: 3
I: 2
E: 2
A

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
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16
Q

Adrenaline

I: 2
M
A: 3
W: 2
I: 1
A

Indications (2):

  • Cardiac arrest
  • Anaphylaxis immediate management

Mechanism:

  • Adrenaline is a potent agonist of A1, A2, B1 and B2 adrenoreceptors&raquo_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
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17
Q

Beta 2 agonists

I: 3
M
A: 7
W: 2
I: 1
E: 4
A

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

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18
Q

Phosphodiesterase (type 5 inhibitors)

I: 2
M
A: 9
W: 5
I: 5
E: 2
A

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)
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19
Q

Trimethoprim

I: 2
M
A: 6
W: 1 C/I, 3 cautions
I: 3
A

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

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20
Q

Adenosine

I: 1
M
A: 2
W: (4 C/I, 2 caution)
I: 4
A

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&raquo_space; dose should be halved
  • Theophylline, aminophylline and caffeine are competitive antagonists of adenosine receptors&raquo_space; reduce its effect&raquo_space; patients may need higher doses
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21
Q

Thyroid hormones

I: 2
M
A: 1
W: 2
I: 3
E: 2
A

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
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22
Q

Phenothiazine antiemetics

I: 2
M
A: 4
W: 3
I: 7
E: 2
A

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
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23
Q

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
A

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
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24
Q

Digoxin

I: 2
M
A: 7
W:
I: 3 C/I, 3 caution
A

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.

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25
Q

Atypical antipsychotics

I: 4
M
A: 6
W: 3
I: 3
E: 4
A

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

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26
Q

Topical corticosteroids

I: 1
M
A: 8
W: 2C/I
I: 1
E: 2
A

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
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27
Q

Antimuscarinics - CVS, GI uses

I: 3
M
A: 6
W: 1 C/I, 1 caution
I: 1
E: 3
A

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

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28
Q

Statins

I: 3
M
A: 4
W: 4
I: 2
E: 4
A

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
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29
Q

Quinine

I: 2
M
A: 8
W: 3
I: 2
A

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
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30
Q

Aminosalicylates

I: 2
M
A: 4 both, 2 S
W: 1
I: 2
E: 2
A

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&raquo_space; increase gastric pH&raquo_space; tablet coating broken down prematurely
  • Lactulose lowers stool pH and may prevent 5-ASA release in the colon
Example drugs (2):
Mesalazine, sulfasalazine
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31
Q

Iron

I: 2
M
A: 3
W: 2
I: 1
E: 2
A

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
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32
Q

Warfarin

I: 3
M
A: 1
W: 3
I: 5
A

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.

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33
Q

Acetylcholinesterase inhibitors

I: 2
M
A: 5
W: 2C/Is, 4 cautions
I: 4
E: 2
A

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
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34
Q

SSRIs

I: 4
M
A: 10
W: 4
I: 4
E: 4
A

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&raquo_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.
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35
Q

Metronidazole

I: 4
M
A: 3
W: 2
I: 2
A

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
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36
Q

Lamotrigene

I: 2
M
A: 9
W: 3
I: 6
A

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

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37
Q

Vancomycin

I: 2
M
A: 5
W: 1
I: 3
A

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

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38
Q

Allopurinol

I: 3
M
A: 3
W: 2C/I, 1 caution
I: 3
A

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.
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39
Q

Clopidogrel

I: 4
M
A: 3
W: 1 C/I, 2 cautions
I: 3
A

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

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40
Q

Phenytoin

I: 3
M
A: 5
W: 2
I: 4
A

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)
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41
Q

5-HT receptor antagonist antiemetics

I: 1
M
A: 2
W: 1
I: 1
E: 2
A

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

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42
Q

H2 receptor antagonists

I: 2
M
A: 3
W: 2
I: 0
E: 1
A

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
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43
Q

Bisphosphonates

I: 4
M
A: 4
W: 4 C/I
I: 1
E: 3
A

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

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44
Q

Antimotility drugs

I: 2
M
A: 3
W: 3C/I, 1 caution
I: 0
E: 2
A

Indication (1):
- Diarrhoea (IBS or gastroenteritis)

Mechanism:
- Loperamide is an opioid like pethidine, but does not penetrate CNS so no analgesic effects
- Agonist of opioid μ-receptors in the GI tract
- Increases non-propulsive contractions of the gut smooth muscle
- Reduces propulsive contractions (peristaltic)
- Slows transit time and increases anal sphincter tone.
- Slower time –> more water absorbed –> harder stool
Other opioids have similar effects (but also are analgesics)

Adverse effects (3):

  • Constipation
  • Cramping
  • Flatulence

Warnings (2C/I, 1 caution):

  • Acute UC (C/I)
  • C. diff (C/I)
  • Acute bloody diarrhoea (dysentry) = bacterial infection - esp. E. Coli as can cause haemolytic-uraemic syndrome (HUS)

Interactions (0)

Example drugs (2):
Loperamide, codeine phosphate
45
Q

Aspirin

I: 4
M
A: 8
W: 3 C/I, 1 caution
I: 1
A

Indications (4):

  • Acute coronary syndrome, acute ischaemic stroke - inhibit platelet aggregation can prevent of limit arterial thrombosis
  • Long-term secondary prevention of thrombotic arterial events in patients with cardio and cerebro vascular and peripheral arterial disease
  • Reduce intracardiac thrombus and stroke in a. fib (if warfarin and NOACs CI)
  • Mild to moderate pain

Mechanism:

  • Irreversibly inhibits COX –> reducing thromboxane and arachidonic acid which are pro-aggregatory factors –> decreased platelet aggregation —> decrease risk of arterial occlusion
  • Antiplatelet effect occurs at low doses
  • Antiplatelet effect lasts the life time of the platelet - so wears off as new platelets are made

Adverse effects (8):

  • GI irritation, can become ulceration and haemorrhage
  • Hypersensitivity –> bronchospasm
  • High dose –> tinnitus
  • OD: hyperventilation, hearing changes, metabolic acidosis and confusion, convulsions, cardiovascular collapse, respiratory arrest.

Warnings (3C/I, 1 caution)

  • Reye’s syndrome risk in under 16s (C/I)
  • Hypersensitivity (C/I)
  • third trimester as could prematurely close ductus arteriosus (C/I)
  • Peptic ulceration (prescribe protection), or gout (caution)

Interactions (1):
- Synergistic with other antiplatelets, can be therapeutically beneficial, but increases bleeding risk

46
Q

Antihistamines (H1-receptor antagonists)

I: 3
M
A: 2
W: 1 C/I
I: 0
E: 4
A

Indications (3):

  • Allergies
  • Itch relief (pruritus) and hives (urticaria)
  • Adjunctive treatment in anaphylaxis (after adrenaline)

Mechanism:

  • H1 receptor antagonist - histamine released from storage granules in mast cells when Ag binds to IgE. Mainly via H1 receptors
  • Histamine induces Type I hypersensitivity; increased cap permeability causing oedema, vasodilation causing erythema, and itch due to sensory nerve stimulation
  • Antihistamines block histamine effect by blocking H1

Adverse effects (2):

  • First generation (chlorphenamine) - cause sedation, as histamine maintains wakefulness
  • Second generation (loratadine, cetirizine and fexofenadine) - can’t cross BBB so don’t cause sedation

Warnings (1 C/I):
- Severe liver disease (C/I)

Interactions (0)

Examples (3):
First generation: chlorphenamine
Second generation: loratadine, cetirizine and fexofenadine

47
Q

Antimuscarinics - genitourinary uses

I: 1
M
A: 5
W: 3C/I, 2 cautions
I: 1
E: 3
A

Indications (1):
- Reduce urinary frequency, urgency, and urge incontinence in overactive bladder (first line pharmacological tx)

Mechanism:

  • Bind to mus receptor - competitively inhibits acetylcholine –> decreases PSNS
  • Reduced detrusor contraction –> bladder relaxation –> increased capacity
  • Antimuscarinics for overactive bladder selective for the M3 receptor which is the main subtype in the bladder

Adverse effects (5):

  • Dry mouth
  • Tachycardia
  • Constipation
  • Blurred vision
  • Urinary retention can occur if bladder outflow obstruction

Warnings (3C/I, 2 cautions):

  • UTI (C/I)
  • Arrhythmia (C/I)
  • Urinary retention risk (C/I)
  • Elderly and dementia (caution)
  • Angle-closure glaucoma (caution)

Interactions (1)
- Adverse effects more pronounced when with other drugs with antimus efffects e.g tricyclics

Examples (3):
Oxybutynin, tolterodine, solifenacin

48
Q

Antifungal drugs

I: 1
M
A: 8 
W: 3
I: 4
E: 3
A

Indications (1):
- Local fungal infections

Mechanism: 3 types:

  • Ergosterol found in fungal cell membranes
  • Polyene antifungals- bind to ergosterol in fungal cell membranes, creating polar pore which allows intracellular ions to leak out of the cell - kills or slows growth of funghi
  • Imidazole and Triazole antifungals :- inhibit ergosterol synthesis, impairing cell membrane synthesis, cell growth and and replicaiton.

Adverse effects (8)

  • Local irritation
  • Oral: GI upset, headache, hepatitis, hypersensitivity
  • Rare: severe hepatic toxicity, prolonged QT interval predisposing to arrhythmias

Warnings (3):

  • F - liver disease (caution)
  • Moderate renal impairment - dose reduction
  • Teratogenic

Interactions (4):

  • None with nystatin or clotriamazole.
  • Fluconazole inhibits cP450 causing increase in plasma concentrations when prescribed with drugs that are metabolised by P450 enzymes (i.e. carbamazepine, warfarin, simvastatin)
  • Reduces affect of clopidogrel as it is a prodrug that gets activated in liver metabolism.
  • Increases risk of serious arrhythmias if prescribed with drugs that prolong the long QT (amiodarone, antipsychotics, macrolides, SSRIs etc)

Examples:
Topical:
- Nystatin - mouth thrush candidiasis
- Lotrimazole - skin and genital fungus inc. athlete’s foot, ring worm and thrush

Oral:
- Fluconazole, one of dose for vaginal candidiasis

49
Q

Nicorandil

I: 1
M
A: 8
W: 3C/I
I: 1
A

Indication (1):
- Prevention and treatment of chest pain in stable angina

Mechanism:

  • Causes arterial and venous vasodilation
  • Converted to nitric oxide, increasing cGMP and thus reducing intracellular Ca2+ in vascular smooth muscle cells, causing them to relax - reduces cardiac preload and L ventricular filling, reducing cardiac work and oxygen demand, thus relieving angina
  • Also activates K+-ATP channels, leading to hyperpolarisation of cell membrane, resulting in inactivation of voltage-gated Ca2+ channels, leading to further vasodilation

Adverse effects (8)

  • Flushing
  • Dizziness
  • Headache
  • Nausea, vomiting
  • Hypotension
  • Rarely; GI, skin, mucosal laceration.

Warnings (3C/I):

  • Poor L ventricle function (C/I)
  • Hypotension (C/I)
  • Pulmonary oedema (C/I)

Interactions (1):
- Phosphodiesterase inhibitors (eg sildenafil) significantly enhance nicorandil’s hypotensive effects

50
Q

Thiazolidinediones

I: 1
M:
A: 7
W: 2 C/I, 4 cautions
I: 1
E: 1
A

Indications:
- Treating type 2 DM as a single agent where metformin is contraindicated or not tolerated

Mechanism:

  • Insulin sensitiser
  • Activate PPARγ
  • Induce genes which enhance insulin action in muscle, adipose tissue and liver, increase glucose uptake and utilisation and reduce hepatic gluconeogenesis
  • Do not stimulate pancreatic insulin secretion so no risk of hypoglycaemia

Cause weight gain leading to insulin resistance.

Adverse effects (7):

  • Anaemia
  • Minor neuro symptoms (dizziness, headache, vision)
  • Oedema and cardiac failure (with insulin)
  • Weight gain
  • Small increased risk of bladder cancer and bone fracture in women.
  • Severe liver toxicity

Warnings (2C/I, 4 cautions:

  • Heart failure (C/I)
  • Bladder cancer (C/I)
  • CVS disease (caution)
  • RFs for bladder cancer (caution)
  • Hepatic impairment (caution)
  • Elderly (caution)

Interactions (1):
- Combinations of diabetic drugs can increase risk of hypoglycemia and cardiac failure

Example drugs:
Pioglitazone

51
Q

Systemic corticosteroids

I: 4
M 
A: 13
W: 2 cautions
I: 4
E: 3
A

Indication (4 classes of disease, 2 examples of each):

  • Treat allergy or inflammatory diseases (anaphylaxis, asthma)
  • Suppression of autoimmune diseases (inflammatory diseases)
  • Cancer chemotherapy (Myeloma/lymphoma/breast cancer)
  • Hormone replacement in adrenal insufficency or hypopituitarism

Mechanism:

  • They bind to cytosolic glucocorticoid receptors, which translocate to the nucleus and regulate gene expression
  • Upregulate anti-inflammatory genes
  • Downregulate pro-inflammatory genes
  • Metabolic changes, like gluconeogenesis, and increase catabolism, increasing circulating amino and fatty acids
  • Mineralocorticoid effects, stimulating Na+ and water retention, and K+ excretion

Adverse effects (5):

  • Immunosuppression, increasing risk of infection
  • Metabolic effects can cause diabetes and osteoporosis
  • Increased catabolism causes proxymal muscle weakness, skin thinning, bruising and gastritis
  • Behavioural changes, including insomnia, psychosis, and suicidal ideas
  • Hypertension, hypokalaemia, and oedema, from mineralocorticoid actions

Warnings (2 cautions):

  • Infection (caution)
  • Children (caution)

Interactions (4):

  • Increased risk of Peptic ulcers and GI bleeding when used with NSAIDs
  • Enhance hypokalemia in patients taking B2 agonists, theophylline, loop or thiazide diuretics
  • Efficacy may be reduced by p450 inducers
  • Will reduce immune response to vaccines
Example drugs (3)
Prednisolone, ydrocortisone, dexamethasone
52
Q

Benzodiazepines

I: 5
M
A: 5
W: 1C/I, 2 cautions
I: 2
E: 5
A

Indications (5)

  • First line for seizures and status epilepticcus
  • First line management of alcohol withdrawal
  • Sedation for interventional procedures
  • Short term for anxiety
  • Short term for insomnia

Mechanism:

  • Target of benzos is the γ-aminobutyric acid type A (GABAA) receptor
  • GABAA receptor is a chloride channel that opens in response to GABA binding - the main inhibitory NT in the brain.
  • Opening the channel allows Cl to flow into cell making cell more resistant to depolarisation
  • Benzodiazepines facilitate and enhance binding of GABA to the GABAA receptor –> depressing synaptic transmission
  • ETOH acts on GABAA, and in excessive use the patient becomes tolerant, so abrupt cessation provokes the excitatory state of alcohol withdrawal - so give a benzo and remove in controlled way

Adverse effects (5):

  • Drowsiness
  • Sedation
  • Coma
  • Little cardioresp depression in benzo od (compared to opioid), but loss of airway reflexes –> obstruction –> death
  • More than a few weeks use can cause dependance - with withdrawal reaction when removed

Warnings (1C/I, 2 cautions):

  • Respiratory impairment/neuromuscular dysfunction (C/I)
  • Give lower dose in elderly
  • Liver failure (caution)

Interactions (2):

  • Additive to other sedating drugs (inc. alcohol and opioids)
  • Most depend on cP450 for elimination - so cP450 inhibitors (e.g. amiodarone, diltiazem, macrolides, fluconazole) increase their effect

Examples (5):
Diazepam, temazepam, lorazepam, midazolam, chlordiazepoxide

53
Q

Dopaminergic Parkinsons drugs

I: 3
M
A: 6
W: 3 cautions
I: 3
E: 3
A

Indication (3)

  • For early Parkinson’s, when dopamine agonists (ropinirole) may be preferred over levodopa
  • In later Parkinson’s disease levadopa is intergral, while dopamine is an option for add-on therapy.
  • Levodopa and dopamine agonists are options for secondary parkinsonism, although first try to identify primary cause.

Mechanism:

  • In parkinsons there’s a deficiency of dopamine in the nigrostriatal pathway between the substantia nigra in the midbrain to the corpus striatum in the basal ganglia
  • It’s not possible to give dopamine itself, because it doesn’t cross the blood-brain barrier
  • L-dopa is a precursor of dopamine, which can enter the brain by a membrane transporter
  • Ropinirole and pramipexol are relatively selective agonists for the D2 receptor, which predominates in the striatum.

Adverse effects (6):

  • Nausea
  • Drowsiness
  • Confusion
  • Hallucinations
  • Hypotension
  • Major issue is the wearing off effect, where the patients symptoms worsen towards the end of dosage interval

Warnings (3 cautions)

  • Elderly (caution)
  • Cognitive/psychiatric disorder (caution)
  • CVS disease (caution)

Interactions (3):

  • Levadopa is always given with a peripheral dopa-decarboxylase inhibitor, in order to reduce its conversion to dopamine outside the brain
  • Dopaminergic agents should not be combined with antipsychotics, metaclopromide
Example drugs (3):
Levadopa (as co-careldopa or co-beneldopa), ropinirole, pramipexol
54
Q

Beta blockers

I: 5
M
A: 6
W: 3C/I, 3 cautions
I: 1
E: 5
A

Indications (5):

  • Ischaemic heart disease: first line option to improve symptoms and prognosis associated with angina and acute coronary syndrome
  • CHF
  • A. Fib - decreases ventricular rate, and in paroxysmal a fib, to maintain sinus rhythm
  • Supraventricular tachycardia (SVT) - restore sinus rhythm
  • Hypertension - used when Ca channel blockers, ACE inhibitors, and thiazide diuretics are insufficient

Mechanism:

  • β1 adrenoreceptors are located mainly in the heart
  • β2 adrenoreceptors are located mostly in smooth muscle of blood vessels and airways
  • Via β1 -receptor, β-blockers reduce force and speed of contraction
  • Relieves Myocardial ischaemia by decreasing work and oxygen demand, and increasing myocardial perfusion
  • Improve prognosis in heart failure by protecting the heart from effects of chronic sympathetic stimulation
  • Slow the ventricular rate in a. fib. by prolonging refractory period of the AV node.
  • SVT often has ‘re-entry’ circuits that takes in the AV node; β blockers break this circuit thus restoring sinus rhythm
  • In HTN, β blockers work in a few ways, including decreasing renin secretion.

Adverse effects (6):

  • Fatigue
  • Cold extremities
  • Headache
  • Nausea
  • Sleep disturbance and nightmares
  • Impotence in men

Warnings (3C/I, 3 cautions)

  • Heart block (C/I)
  • In asthma β-blockers cause life threatening bronchospasm (C/I)
  • Haemodynamic instability (C/I)
  • Usuallly safe in COPD but prudent to choose a β-blocker that is β1 selective (caution)
  • In HF start at low dose and increase slowly, as can impair cardiac function at first (caution)
  • Decrease dose in hepatic failure (caution)

Interactions (1):
- Do not use with non-dihydropyridine ca channel blockers (e.g. verapamil, diltiazem) - cause heart failure, bradycardia and even asystole

Examples
Bisoprolol, atenolol, ropanolol, metoprolol

55
Q

Sulphonylureas

I: 1
M
A: 3
W: 2
I: 2
E: 1
A

Indications (1):
- Treating type 2 diabetes. Used as a single agent to control blood glucose if metformin is contraindicated or not tolerated

Mechanism:

  • Stimulate pancreatic insulin secretion
  • Block ATP dependent K+ channels in the pancreas beta cell membrane
  • Depolarisation and opening of voltage gated Ca2+ channels
  • Higher intracellular Ca2+ leads to more insulin secretion
  • Residual pancreatic function required
  • Anabolic hormone release -> weight gain -> insulin resistance -> :(

Adverse effects (3):

  • GI
  • Hypoglycaemia
  • Rare hypersensitivity reactions (hepatic toxicity, drug hypersensitivty syndrome, haematological abnormalites).

Warnings (2):

  • Metabilised in the liver, metabolites excreted in the urine, half life 10-12 hrs so dose reduction in patients with liver or renal impairment
  • Increased risk of hypoglycemia if liver impairment, malnutrition, adrenal or pituitary insufficiency and in the elderly

Interactions (2):

  • Other diabetic drugs (hypoglycemia more likely)
  • Efficacy reduced with drugs that elevate blood glucose (prednisolone, thiazide and loop diuretics)
Example drugs (1):
Gliclazide
56
Q

Cephalosporins and carbapenems

I: 2
M
A: 4
W: 1 C/I, 3 cautions
I: 3
E: 4
A

Indications (2):

  • Oral Cephalosporins are 2nd and 3rd line for urinary and respiratory tract infections
  • IV cephalosporins and carbapenems are broad spectrum so can be used for most indications, but are reserved for tricky infections (very severe, complicated)

Mechanism -

  • Have a Beta-Lactam ring, so inhibit cross-linking peptidoglycans in cell wall
  • The cell then swells, lyses, and dies
  • Broad spectrum
  • More resistant to Beta-Lactamases than penicillins are

Adverse effects (4):

  • GI upset (nausea and diarrhoea)
  • Antibiotic associated colitis (C.diff) Can cause colonic perforation
  • Hypersensitivity, both immediate and delayed, likely to occur if allergic to penicillin
  • Risk of CNS toxicity, and can cause seizures, particularly with renal impairment

Warnings (1 C/I, 3 cautions):

  • Penicillin allergy (C/I)
  • Epilepsy (caution)
  • C diff risk (caution)
  • Reduce dose in renal impairment (caution)

Interactions (3):
- Enhance anticoagulant effect of warfarin, by killing normal gut flora, which synthesise vitamin K
- Cephalosporins may increase nephrotoxicity of aminoglycosides
- Carbapenems reduce plasma concentration and
efficacy of valproate

Example drugs:
Cefalexin, cefotaxime, meropenem, ertapenem

57
Q

Prostaglandin analogue eye drops

I: 1
M
A: 5
W: 1
I: 0
E: 2
A

Indication (1):
- Open-angle glaucoma and ocular hypertension (few side effects than topical β-blockers

Mechanism:
- Analogues of prostaglandin F2α reduce intraocular pressure by increasing outflow of aqueous humour via the uveoscleral pathway

Adverse effects (5):

  • Blurred vision
  • Conjunctival reddening
  • Ocular irritation
  • Pain
  • May cause permanent change in eye colour by increasing melanin

Warnings (1):
- Caution if lens is absent (aphakia) or artificial (pseudophakia) and patients at risk of iritis, uveitis and macular oedema

Example drugs:
Latanoprost, bimatoprost

58
Q

Dipyridamole

I: 2
M
A: 6
W: 2
I: 2
A

Indication (2):

  • Secondary prevention of stroke (combine with aspirin)
  • To induce tachycardia during a myocardial perfusion scan in the diagnosis of ischemic heart disease.

Mechanism:

  • Antiplatelet, causing increase in intra-platelet cAMP, which inhibits platelet aggregation
  • Vasodilation, by blocking cellular uptake of adenosine, which prolongs its effect on blood vessels, causing vasodilation

Adverse effects (6):

  • Headache
  • Flushing
  • Dizziness
  • GI symptoms
  • Increased risk of bleeding
  • Thrombocytopenia (rare, normally just affects function, not number)

Warnings (2):

  • Because it causes vasodilation and tachycardia, it can cause problems in (IHD, aortic stenosis, HF)
  • The effect is used in a myocardial perfusion scan to see if tachycardia causes ischaemia

Interactions (2):

  • Dipryidamole inhibits uptake up adenosine, which could cause cardiac arrest
  • There’s increase risk of bleeding if combined with other antiplatelets, or with anticoagulants
59
Q

Macrolides

I: 3
M
A: 6
W: 2C/I, 1 caution
I: 2
A

Indications (3):

  • Respiratory and skin/soft tissue infections, where penicillins are contraindicated by allergy
  • Severe pneumonia, in addition to penicillin, to cover atypical orgamisms (eg leigionella, mycoplasma pneumoniae)
  • Eradication of H. pylori (for example, causing peptic ulcer disease) in combination with PPI and either amoxicillin or metronidazole

Mechanism:

  • Inhibit bacterial protein synthesis (50S subunit on ribosome, blocking translocation)
  • Has a bacteriostatic effect (stopping bacterial growth, but not killing it)
  • Broad spectrum
  • Erythromycin - mostly gram +ve & some -ve
  • Synthetic macrolides (eg clarithromycin/azithromycin) increased activity vs gram -ve (eg haemophilus influenzae)

Adverse effects (6):

  • Allergic reactions
  • Nausea, vomiting, abdo pain & diarrhoea
  • Antibiotic-associated colitis
  • Liver abnormalities
  • Prolonged QT interval (predisposing to arrhythmias)
  • Ototoxicity at high doses

Warnings (2C/I, 1 caution)

  • Macrolide hypersensitivity (C/I)
  • Severe hepatic impairment (C/I)
  • Reduce dose in severe renal impairment (caution)

Interactions (2):

  • Erythromycin and clarithromycin are both CP450 inhibitors, therefore they interact with any drug metabolised by CP450 (notably warfarin & statins).
  • Caution in pts taking drugs that cause arrhytmias or prolong QT interval (amioderone, antipsychotics, quinines, quinolone abx, SSRI)
60
Q

Nitrofurantoin

I: 1
M
A: 5
W: 2 C/I, 1 caution
I: 0
A

Indication (1):
First line abx for uncomplicated lower UTI

Mechanism:

  • Reduced in bacterial cells by nitrofuran reductase to an active metabolite which damages bacterial DNA and causes cell death
  • Active vs gram+ (eg staphylococcus saprophyticus) and gram- (e.coli) organisms which commonly cause UTIs
  • Klebsiella and proteus species have intrinsic resistance to nitrofurantoin

Adverse effects (5)

  • GI upset (nausea and diarrhoea)
  • Hypersensitivity reactions
  • Turns urine brown
  • Rarely can cause chronic pulmonary reactions (eg fibrosis), hepatitis and peripheral neuropathy from prolonged administration
  • Haemolytic anaemia in neonates

Warnings (2C/I, 1 caution)

  • Pregnancy (C/I)
  • Renal impairment (C/I)
  • Caution in long term use for UTI prophylaxis, as this increases risks of adverse effects
61
Q

Sex hormone antagonists for breast cancer

I: 2
M
A: 5 both, T2
W: 3C/I
I: 3
E: 3
A

Indication (2):

  • ER positive positive breast cancer (early / locally advanced) - adjuvant treatment post-surgery to reduce risk or recurrance
  • Advanced ER positive positive breast cancer (if HER2 negative and pre-menopausal) to slow progression
  • Note: Not used in HER2 positive cases as other treatments availible.
  • Note: Aromatase inhibitors used if post-menopausal (if contraindicated > Tamoxifen)

Mechanism:

  • 2/3 breast cancers are ER positive
  • Oestrogen promotes growth of these cancers
  • Tamoxifen = Selective Estrogen Receptor Modulator (SERM) > prevents oestrogen binding
  • Aromatase inhibitors interfere with Androgen > Oestrogen conversion outside the ovary (thus reducing ER stimulation)
  • Note: Aromatase inhibitors have almost no effect on ovarian Oestrogen production (ineffective in Pre-menopause)
Adverse effects (5 both, T2):
Tamoxifen / Aromatase Inhibitors induce symptoms of Menopause: 
- Vaginal dryness
- Hot flushes 
- Osteoporosis 
- Agranulacytosis (rare) 
- Liver failure (rare) 

Tamoxifen Only:

  • Increased VTE risk
  • Increased endometerial cancer risk

Warnings (3C/I):

  • Pregnancy - miscarriage risk (Tamoxifen C/I)
  • Breast Feeding (Tamoxifen C/I)
  • Pre-menopausal (Aromatase C/I)

Interactions (3):

  • Tamoxifen = ↓CYP450 inhibitor (CRAP GPs BS) > ↑ bleeding Warfarin
  • Fluoxetine (inhibit Tamoxifen activation)
  • Paroxetine (inhibit Tamoxifen activation)
Example drugs (3):
Tamoxifen, anastrozol, letrozole
62
Q

Penicillins

I: 3
M
A:
W: 2
I: 1
E: 2
A

Indications (3):

  • Streptococcal infection (+ macrolide if severe), endocarditis and skin and soft tissue infections (added to flucloxacillin if severe)
  • Clostridial infection (e.g. tetanus)
  • Meningococcal infection (e.g. meningitis, septicaemia)

Mechanism:

  • β-lactam ring tragets enzymes responsible for cross-linking of peptidoglycans in bacterial cell walls, resulting in cells swelling, lysis and death
  • Bacteria can become resistant by various mechanisms, including β-lactamase

Warnings (2)

  • Renal impairment
  • Penicillin allergy

Interactions (1):
- Reduces renal excretion of methotrexate increasing risks of toxicity

Example drugs (2):
Benzylpenicillin, phenoxymethylpenicillin
63
Q

Thiazide diuretics

I: 2
M
A: 6
W: 2C/I, 1 caution
I: 2
E: 3
A

Indication (2):

  • Alternative first line for hypertension where a calcium channel blocker would be unsuitable e.g. due to oedema, or symptoms of heart failure
  • Add on treatment for hypertension, in patients where the BP isn’t controlled by a CCB and ACE inhibitor or ARB

Mechanism:

  • Inhibit the Na+/Cl- Co-transporter in the DCT. Prevents the reabsorption of sodium and water
  • Inital fall in extracellular fluid, but after awhile the RAAS system reverses this, at least in part
  • Long term antihypertensive effect is probably mediated by vasodilation

Adverse effects (6):

  • Hyponatraemia, although rarely problematic
  • Hypokalaemia
  • Cardiac arrythmias (from hypokalaemia)
  • May increase plasma glucose (and unmask diabetes)
  • May increase LDL- Cholesterol and Triglycerides
  • Impotence in men

Warnings (2 C/I, 1 caution):

  • Hypokalaemia (C/I)
  • Hyponatraemia (C/I)
  • May cause gout, due to reduction in uric acid excretion

Interactions (2):

  • Effectiveness reduced by NSAIDs
  • Avoid other drugs that lower potassium, like loop diuretics
Example drugs (3):
Bendroflumethiazide, indapamide, chlortalidone
64
Q

Bulk forming laxatives

I: 2
M
A: 3
W: 1C/I
I: 0
E: 3
A

Indications (2):

  • Constipation and faecal impaction (particularly in patients who cannot increase their dietary fibre intake)
  • Mild chronic diarrhoea associated with IBS or diverticular disease

Mechanism:

  • Contains a hydrophilic substance which is not absorbed or broken down in the gut
  • This attracts water into the stool (like dietary fibre), and increases its mass (so these laxatives won’t work without adequate fluid intake)
  • Increased stool bulk stimulates peristalsis, helping to relieve constipation & help with diarrhoea

Adverse effects (3)

  • Mild abdo distension
  • Flatulence
  • Rarely - can cause faecal impactation and GI obstruction

Warnings (1C/I):
- Do not use in pts with intestinal obstruction, faecal impactation, ileus (failure of peristalsis), or recent abdo surgery (at risk of paralytic ileus from anaesthetic)

Example drugs (3):
Ispaghula husk, methylcellulose, sterculia
65
Q

Acetylcysteine (NAC)

I: 3
M
A: 3
W: 0
I: 0
A

Indication (3):

  • Paracetamol poisoning antidote
  • Contrast nephropathy - help prevent renal injury due to radiographic contrast material
  • To reduce the viscosity of respiratory secretions (acting as a mucolytic).

Mechanism:

  • Paracetamol poisoning antidote. At therapeutic doses Paracetamol is metabolised mainly be conjugation w/ glucuronic acid and sulfate with a small amount converted to N-acetyl-p-benzoquinone (NAPQI) which is hepatotoxic
  • Normally, this is detoxified by conjugation w/ gluthione but in paracetamol glutathione is overwhelmed&raquo_space; free NAPQI causes liver damage
  • Acetylcysteine replenishes the body’s supply of glutathione

Adverse effects (3):

  • In large doses, via IV, can cause “anaphylactoid reaction” - similar to anaphylaxis (nause, tachycardia, rash, wheeze) but involves IgE-independent histamine release
  • Therefore once reaction has settled (by stopping acetylcysteine + antihistamines + bronchodilator), it is safe to restart acetylcysteine albeit at lower dose
  • When administered as mucolytic, acetylcysteine can cause bronchospasm - therefore bronchodilator (i.e. salbutamol) should be given immediately beforehand
66
Q

Fibrinolytic drugs

I: 3
M
A: 4 normal, 4 requiring treatment cessation
W: many
I: 3
E: 2
A

Indication (3):

  • Acute Ischaemic Stroke - Alteplase increases the chance of living independently if given within 4.5 hours of the onset of stroke
  • Acute ST elevation Myocardial Infarction - Alteplase and streptokinase can reduce mortality when given within 12 hours of symptoms, when given antiplatelets and anticoagulants. Primary PCI has generally superseded fibrinolytics in this context
  • Massive PE with Heamodynamic Instability - Fibrinolytic drugs reduce clot size, and pulmonary arterial pressures, but no evidence that they improve mortality

Mechanism:
- Catalyse the conversion of plasminogen to plasmin, which dissolves fibrinous clots, and re-canalise occluded vessels. This allows reperfusion.

Adverse effects (4 normal, 4 requiring treatment cessation):
- Nausea 
- Vomiting 
- Brusing around injection site 
- Hypotension 
Treatment should be stopped if 
- Serious bleeding 
- Allergic reaction 
- Cardiogenic shock 
- Cardiac arrest 

Warnings (1 current medical condition, 1 precaution in stoke, 1 past drug history precaution):

Predisposition to bleeding

  • Recent haemorrhage
  • Recent trauma
  • Bleeding disorders
  • Severe hypertension
  • Peptic ulcers

In acute stoke intercranial haemorrhage must be excluded with CT scan before treatment

Previous streptokinase is a contraindication to repeated streptokinase, due to production of anti-steptokinase antibodies.

Interactions (3):
Increased risk of haemorrhage in patients taking
- Anticoagulants
- Antiplatelets
- Ace inhibitors also increase anaphylactoid reactions.

Example drugs (2)
Alteplase, streptokinase
67
Q

Gabapentin

I: 6
M
A: 3
W: 1
I: 1
E: 2
A

Indication (6):

  • Focal epilepsies
  • Neuropathic Pain
  • Second-line option in diabetic neuropathy (after duloxetine)
  • First line in other painful neuropathies
  • Migraine prophylaxis (Gabapentin)
  • Generalised Anxiety Disorder (Pregabalin)

Mechanism:

  • Binds with Voltage-Sensitive Calcium Channels, where it prevents inflow of calcium channels
  • This inhibits neurotransmitter release, which reduces neuronal excitability
  • Gabapentin is closely related to GABA, the major inhibitory neurotransmitter. It’s mechanism however seems unrelated to GABA

Adverse effects (3):

  • Drowsiness
  • Dizziness
  • Ataxia

Warnings (1):
- Renally eliminated, so doses should be reduced in renal impairment

Interactions (1):
- Sedative effects are enhanced when combined with other sedating drugs, such as benzodiazepines

Example drugs (2):
Gabapentin, pregabalin
68
Q

Nitrates

I: 3
M
A: 1
W: 3C/I
I: 2
E: 2
A

Indication (3):

  • Short acting (glyceryl trinitrate (GTN)) - acute angina and chest pain associated with acute coronary syndrome (ACS)
  • Long acting (isosorbide mononitrate) - prophylaxis of angina where a beta-blocker and/or calcium channel blocker are insufficient
  • IV - tx of pulmonary oedema in combination with forusemide and oxygen

Mechanism:

  • Converted to nitric oxide, which increases cGMP thus reducing intracellular Ca2+ in vascular smooth muscle cells, causing vasodilation
  • This reduces preload and L ventricle filling, reducing cardiac work and oxygen demand, thus relieving angina and cardiac failure
Adverse effects (1):
- Vasodilatory effects (flushing, headaches, light headedness, hypotension)

Warnings (3C/I)

  • Aortic stenosis (C/I)
  • Haemodynamic instability (C/I)
  • Hypotension (C/I)

Interactions (2):

  • Don’t use with phosphodiesterase inhibitors (eg sildenafil) as they enhance and prolong the hypotensive effect of nitrates
  • Caution with antihypertensive medications (ACE/ARB/beta-blocker/CCB/thiazide-like dieuretic)
Example drugs (2):
Isosorbide mononitrate, glyceryl trinitrate (GTN)
69
Q

NSAIDs

I: 2
M
A: 5
W: 4C/I, 4 cautions
I: 4
E: 3
Extra: 3
A

Indication (2)

  • Mild-to-moderate pain, as an alternative or addition to paracetamol (paracetamol has less adverse effects, and a similar analgesic effect)
  • Regular treatment for inflammatory pain, particularly of the MSK system (eg RA, severe OA, acute gout)

Mechanism

  • Inhibits COX, which normally catalyses the conversion of arachidonic acid to prostaglandins (PG)
  • COX-1 acts to stimulate production of PGs that do things like preserve integrity of GI mucosa and maintain renal perfusion (by dilating afferent arteriole in glomerulus)
  • COX-2 acts to stimulate production of PGs that cause inflammation and pain
  • Aspirin also inhibits the production of thromboxanes, which help form blood clots. Giving it it’s antiplatelet effect

Adverse effects (5)

  • GI toxicity
  • Renal impairment
  • Increased risk of MI and stroke
  • Hypersensitivity reactions (eg bronchospasm, angioedema)
  • Fluid retention

Warnings (4C/I, 4 cautions)

  • Severe renal impairment (C/I)
  • Heart failure (C/I)
  • Liver failure (C/I)
  • Known NSAID hypersensitivity (C/I)
  • Reduce dose in PUD, GI bleeding, CVS disease, renal impairment (caution)

Interactions (4):
Increased risk of:
- GI ulceration - aspirin, corticosteroids
- GI bleeding - antcoagulants, SSRIs, venlafaxine
- Renal impairment - ACE-i/ARB, diuretics

Warfarin - increased bleeding risk
- Antihypertensives and diuretics have reduced efficacy

Example drugs (3)
Naproxen, ibuprofen, etoricoxib

Extras (3)

  • Oral NSAIDs should be taken with food to minimise GI upset
  • Consider GI protection (PPI - lansoprazole) in pts at risk of GI complications
  • Selective COX-2 only inhibitors have decreased risk of GI problems but increased risk of CV events
70
Q

TCAs

I: 2
M
A: 4 receptors, OD, withdrawal
W: 6 cautions
I: 2
E: 2
A

Indications (2):

  • Mod-severe depression where 1st line SSRIs are ineffective
  • Neuropathic pain (unlicensed)

Mechanism:

  • Symptom relief appears to be due to tricyclic antidepressants inhibiting neuronal reuptake of serotonin (5-HT) and NA from the synaptic cleft&raquo_space; increasing their availability for transmission
  • Tricyclic antidepressants also block loads of other receptors incl: muscarinic, histamine (H1), A-adrenergic (A1 + A2) and dopamine (D2) receptors - accounts for extensive adverse effects…

Adverse effects (4 receptors, OD, withdrawal):

  • Anti-muscarinic: dry mouth, constipation, urinary retention and blurred vision
  • H1 + A1: sedation and hypotension
  • Dopamine: breast changes, sexual dysfunction and, rarely, extrapyramidal symptoms (tremor and dyskinesia)
  • Other/combined receptor blockade - cardiac adverse changes (incl arrhythmias and ECG changes - incl prolonged QT and QRS durations); convulsion, hallucinations and mania
  • OD: tricyclics are v dangerous, causing severe hypotension, arrhythmias, convulsions, coma and respiratory failure (can be fatal)
  • Sudden withdrawal: GI upset, neurological, ‘flu-like symptoms and sleep disturbance.

Warnings (6 cautions):

  • Elderly (caution)
  • Epileptics (caution)
  • CVD (caution)
  • Constipation (caution)
  • Prostatic hypertrophy (caution)
  • Raised intraocular pressure (caution)

Interactions:

  • Tricyclic antidepressants shouldn’t be given w/ monoamine oxidase inhibitors as both drug classes increase serotonin and NA levels at synapse (» hypertension +/- hyperthermia +/- serotonin syndrome)
  • Tricyclic antidepressants can augment antimuscarinic, sedative or hypotensive adverse effects of other drugs

Example drugs:
Amitriptyline, lofepramine.

71
Q

Antivirals

I: 2
M
A: 5
W: 3 cautions
I: 0
A

Indication (2):

  • Acute Herpesvirus infections
  • Suppression of recurrant herpesvirus infections

Mechanism:
- Herpesvirus family are double stranded DNA viruses

Adverse effects (5):

  • Dizziness
  • GI disturbance
  • Rash
  • Phlebitis (if given IV)
  • AKI (in high doses > crystal induced AKI - hydrate to reduce risk

Warnings (3 cautions):

  • Pregnancy (caution - often benfit outweighs risk)
  • Breastfeeding (caution - often benefit outweighs risk)
  • Severe Renal Impairment > Toxicity (renally excreted)
72
Q

Valproate

I: 2
A: 5
I: 2

A

Indications (2):

  • Bipolar - acute management of manic episodes, prophylaxis
  • Epilepsy: first choice for absence seizures and an option for focal seizures

Adverse effects (5):

  • GI upset, diarrhoea
  • Tremors
  • Fatigue
  • Weight gain
  • Thinning hair

Interactions (2):

  • CYP450 inhibitor (SICKFACES.COM) > ↑Warfarin ↑ bleeding + other epilepsy drugs
  • Aspirin = displaces it from binding sites = increased adverse effects
73
Q

Proton pump inhibitors

I: 3
M
A: 3
W: 2
I: 2
E: 3
A

Indication (3):

  • Peptic Ulcer disease (including NSAID associated)
  • Dyspepsia and GORD symptom releif
  • H.pylori (with combination antibiotics)

Mechanism:
- Reduce acid secretion by irreversibly inhibiting H+/K+ATPase in gastric parietal cells

Adverse effects (3):

  • Gastrointestinal disturbances and headache
  • Increased C.diff infection risk
  • Prolonged treatment can cause hypomagnesaemia (can lead to tetany and ventricular arrhythmia)

Warnings (2)

  • May disguise symptoms of gastric cancer - inquire about red flags
  • Can increase risk of fracture in elderly and osteoporosis

Interactions (2)

  • Reduce antiplatelet effect of clopidogrel (particularly omeprazole) by decreasing it’s activation by cytochrome P450 enzymes
  • Lansoprazole and pantoprazole appear to have less effect
Example drugs (3): 
Lansoprazole, omeprazole, pantoprazole
74
Q

Alpha blockers

I: 2
M
A: 3
W: 1C/I
I: 2
E: 3
A

Indication (2):

  • Benign prostatic hyperplasia - 1st line med option to improve symptoms
  • Resistant hypertension add-on treatment, when other medicine is insufficient

Mechanism:

  • Most drugs in this class (incl doxazosin, tamsulosin and alfuzosin) are highly selective for A1 adrenoceptors - mainly found in smooth muscles (blood vessels and urinary tract - especially bladder neck and prostate). Stimulation induces contraction and vv
  • A-blockers therefore cause vasodilation (»decrease in BP) and reduced resistance to bladder outflow

Adverse effects (3):

  • Postural hypotension
  • Dizziness
  • Syncope

Warnings (1C/I):
- Existing postural hypotension (C/I)

Interactions (2):

  • Caution when introducing A-blockers to other antihypertensive drugs - may be prudent to omit one of these when 1st dose of A-blocker is taken
  • Particularly with regards to B-blockers which inhibit the reflex tachycardia which forms part of compensatory mech to vasodilation
Example drugs (3):
Doxazosin, tamsulosin, alfuzosin
75
Q

Metformin

I: 1
M
A: 3
W: 3 C/I, 3 cautions
I: 3
A

Indication:
- First line for control of blood glucose in T2DM

Mechanism

  • Lowers blood glucose by increasing sensitivity to insulin
  • Suppresses hepatic glucose production, increases glucose uptake and utilisation by skeletal muscle, and suppresses intestinal glucose absorption
  • Does not stimulate pancreatic insulin secretion, thus it does not cause hypoglycaemia
  • Reduces weight gain and can induce weight loss, thus preventing worsening of insulin resistance

Adverse effects (3):

  • GI upset (n&v, taste disturbance, anorexia, diarrhoea)
  • These effects may contribute to weight loss
  • Rarely lactic acidosis (precipitated by illness that causes metformin accumulation (eg renal impairment))

Warnings (3 C/I, 3 caution):

  • Severe renal impairment (C/I)
  • AKI (C/I)
  • Sepsis, shock, dehydration, severe tissue hypoxia (C/I)
  • Hepatic impairment (caution)
  • Alcohol intoxication, may precipitate lactic acidosis (caution)
  • Chronic alcohol overuse (caution)

Interactions (3):

  • Withold before and 48 hrs after injection of IV contrast, when increased risk of renal impairment
  • Other drugs with potential to impair renal function (eg ACE-i, NSAIDs, diuretics) should also be used with caution
  • Prednisolone, thiazide and loop diuretics elevate blood glucose, hence reducing efficacy of metformin
76
Q

Leukotriene receptor antagonists

I: 1
M
A: 4
W: 2
I: 0
E: 1
A

Indications (1):
- Asthma

Adverse effects (4):
- Headache (common / mild)
- Abdominal pain (common / mild)
- Increased rate of upper respiritory tract infections (URTI)
vHyperactivity / reduced ability to concentrate (rare)
- ?EGPA (Eosinophilic granulomatosis with polyangiitis [aka Churg-Strauss]) - poor evidence

Warnings (2):

  • Only prescribe if not controlled with ICS
  • Pregnancy = caution - no evidence but safe to continue if already taking
Example drugs (1) 
Montelukast
77
Q

Calcium and vitamin D

I: 5
M
A: 2
W: 1
I: 2
E: 4
A

Indications (5):

  • Osteoporosis
  • CKD to treat secondary hyperparathyroidism and renal osteodystrophy
  • Calcium (as calcium gluconate) with hyperkalaemia
  • Hypocalcaemia that is symptomatic (paraesthesia, tetany, seizures)
  • Vit D in deficiency - rickets, osteomalacia

Mechanisms:

  • Ca needed for normal function of muscle, nerve, bone and clotting
  • Ca homeostasis controlled by PTH and vit D, which increase serum Ca levels and bone mineralisation, and calcitonin which reduces serum Ca levels
  • In osteoporosis there is Ca deficiency - administering Ca and vit D may reduce the rate of bone loss - if this means less fractures is unclear
  • CKD reduced phosphate excretion and reduced vit D activation causes hyperphosphataemia and hypocalcaemia —> hyperparathyroidism which causes range of bone problems (osteodystrophy) - treatment may includ oral Ca supplements to bind phosphate in gut, and alfa calcidol to provide vit d that is not dependent on renal activation.
  • In hyperkalaemia Ca raises the myocardial threshold potential reducing risk of arrhythmias

Adverse effects (2):

  • Dyspepsia
  • Constipation

Warnings (1):
- Don’t give Ca and Vit D in hypercalcaemia

Interactions (2):

  • Reduces absorption of other drugs, Fe, bisphosphonates, tetracyclines, levothyroxine
  • IV; don’t let it mix with sodium bicarb as can precipitate

Examples (4):
Calcium carbonate, calcium gluconate, cholecalciferol, alfacalcidol

78
Q

Oral potassium

I: 1
M
A: 8
W: 2
I: 1
E: 2
A

Indication (1):
- Treatment and prevention of hypokalaemia

Mechanism

  • Normally tops up depleted potassium
  • Thiazide and loop diuretics excrete potassium, so potassium spacing are preferred
  • Redistributive hypokalaemia is where there is normal total potassium but low serum potassium (i.e. it’s in the cells)

Adverse effects (8):

  • Unpalatable
  • N/V
  • Diarrhoea
  • Flatulence
  • GI obstruction
  • Ulceration
  • Bleeding
  • HyperK –> arrhythmia

Warnings (2 cautions):

  • Renal impairment (caution)
  • Severe renal impairment (caution)

Interactions (1):
- Caution when used with potassium elevating drugs (e.g. IV potassium chloride, aldosterone antagonists, potassium sparing diuretics, ACEI, ARBs

Example drugs (2):
Potassium chloride, potassium bicarbonate
79
Q

Penicillinase resistant penicillins

I: 3
M
A: 4
W: 2C/I, 1 caution
I: 1
E: 1
A

Indication:

  • Skin and soft tissue infections - e.g. cellulitis (in combination with benzylpenicillin)
  • Osteomyelitis and septic arthritis
  • Endocarditis

Mechanism:

  • β-lactam ring inhibits enzymes responsible for cross-linking peptidoglycans, which weakens cell walls leading to swelling, lysis and death
  • Altered acyl side chain protectes the β-lactam ring, making it effective agains β-lactamase producing staphylococci (but not MRSA, obvs which reduces penicillin binding affinity)

Adverse effects (4)

  • Anaphylaxis
  • Minor gastrointestinal upset
  • Liver toxicity (Cholestasis and hepatitis - rare)
  • CNS toxicity with high dose and severe renal impairment

Warnings (2C/I, 1 caution)

  • Penicillin allergy (C/I)
  • Hepatotoxicity (C/I)
  • Reduce dose in those with severe renal impairment (caution)

Interactions (1):
- Reduces renal excretion of methotrexate (increasing toxicity)

Example drugs:
Flucloxacillin

80
Q

Activated charcoal

I: 2
M
A: 3
W: 1 C/1, 2 cautions
I: 1
A

Indications (2):

  • Reduce absorption of certain poisons (incl some drugs) from gut - single dose
  • To increase elimination of certain poisons - multiple doses

Mechanism

  • Molecules are aDsorbed* onto the surface of the charcoal as it travels through the gut, reducing their aBsoprtion into the gut
  • However, the affinity of charcoal for the poison (its efficacy) is dependent on the poison: weakly ionic and hydrophobic substances (i.e. benzos, methotrexate) are well adsorbed by the charcoal, whereas as strongly ionic and hydrophillic substances (i.e. strong acids/bases, alcohols, lithium and iron) are not
  • Multiple doses are used where the poison diffuses readily into the gut
  • The multiple doses maintains a steep poison conc gradient (high in blood circulation, low in GI lumen) so ensure higher adsorption to the charcoal

Adverse effects (3):

  • Black stool and vomiting
  • Aspiration of activated charcoal: pneumonitis, bronchospasm and airway obstruction
  • It can also precipitate intestinal obstruction

Warnings (1C/I, 2 cautions):

  • Reduced LOC (C/I) without airway protection
  • Persistent vomiting (caution)
  • Reduce in increased risk of intestinal obstruction (caution)

Interactions:
-Prevents absorption of many drugs taken therapeutically as well as those taken in overdose

81
Q

Carbamazepine

I: 3
M
A: 6
W: 2C/I, 3 cautions
I: 5
A

Indications (3):

  • Epilepsy - 1st choice for focal seizures, with and without secondary generalisation, and for primary generalised seizures
  • Trigeminal neuralgia - 1st choice to control pain, reduce frequency and severity of attacks
  • Bipolar disorder - prophylaxis in patients resistant/intolerant of other medications

Mechanism:

  • Not fully understood
  • Inhibits neuronal sodium channels, reducing neuronal excitability. (same MOA as Phenytoin)
  • This reduces electrical ‘kindling, in the temporal lobe and limbic system

Adverse effects (6):

  • GI upset, nausea and vomiting
  • Neuro effects, dizziness and ataxia
  • 10% will get a hypersensitivity effect, often a maculopapular rash
  • Rare effect (1/5000) is Antiepileptic hypersensitivity syndrome, usually within 2 months. Presents with severe skin reaction, fever, lyphadenopathy and systemic illness
  • Mortality of 10%
  • Can cause oedema and hyponatremia, due to diuretic effect

Warnings (2C/I, 3 cautions):

  • Pregnancy - can cause problems (take folic acid)
  • Prior antiepileptic hypersensitivity syndrome (C/I)
  • Hepatic disease (caution)
  • Renal disease (caution)
  • Cardiac disease (caution)
Interactions (5):
- Carbamazepine induces Cytochrome P450 enzymes, meaning that you need to give more of drugs that are metabolised by this, like: 
- Warfarin 
- Oestrogen
- Progestogen
- Other antiepileptics
Efficacy reduced by drugs which lower seizure threshold
- SSRIs 
- Tricyclics 
- Antipsychotics 
- Tramadol
82
Q

Heparins and fondaparinux

I: 2
M
A: 3
W: 3
I: 1
E: 4
Extra: 3
A

Indication (2):

  • VTE - low molecular weight heparin (LMWH) is 1st line for VTE prophylaxis, initial tx for DVT and PE
  • Acute coronary syndrome (ACS) - LMWH or fondaparinux are part of 1st line therapy to improve revascularisation and prevent thrombus progression

Mechanism:

  • Unfractionated heparin (UFH) - inhibits thrombin and factor Xa
  • LMWH - Inhibits factor Xa preferentially over thrombin
  • Fondaparinux - inhibits factor Xa only

Adverse effects (3):

  • Bleeding
  • Injection site reactions (as with all injections)
  • Rarely heparin-induced thrombocytopenia, caused by a low platelet count and thrombosis. It is an immune reaction and is more likely to happen with UFH

Warnings (3):

  • Use with caution in pts with increased risk of bleeding
  • Invasive procedures (Avoid around time of proceedure)
  • Renal Impairment - Lower dose of fondaparinux or LMWH - or use UFH instead

Interactions (1):
- Antithrombotic drugs (increased bleeding risk = avoid unless good reason (eg using LMWH while initiating warfarin tx, or combining LMWH with antiplatelet drugs (aspirin/clopidogrel) in ACS tx

Example drugs (4):
Enoxaparin (LMWH), dalteparin (LMWH), fondaparinux, unfractionated heparin

Extras

  • LMWH and fondaparinux have more predictable effects than UFH, and thus do not usually require laboratory monitoring, whereas UFH requires aPTT test.
  • Protamine sulfate can reverse anticoagulation from UFH. Less effective for LMWH. Ineffective for fondaparinux
  • The trade name for dalteparin is “Fragmin”, which is what is used on the wards at George’s
83
Q

Levetiracetam

I: 2
M
A: 6
W: 2
I: 1
A

Indication (2):

  • Seizure Prophylaxis (focal, myoclonic, generalised)
  • Established convulsive status epilepticus if has not responded to benzodiazepines (selected cases)

Mechanism:

  • Synaptic vesicle protein 2A (SV2A) are present in synapse NT vesicles
  • Vesicle exocytosis releases \NTs into the synaptic cleft
  • ?? Mechanism - alters vesicle exocytosis > modulating neuronal exciticity

Adverse effects (6):

  • Drowsiness (10%)
  • Headache
  • Dizziness
  • Weakness
  • Mood Disturbance / Psychiatric disturbance (rare - withdraw drug)
  • severe Hypersensitivity reaction (rare)

Warnings (2 cautions)

  • Renal Impairment (caution)
  • Pregnancy (caution)

Interactions (1):
- Few, unlike other epileptic medications (which is it’s main advantage

84
Q

Inhaled corticosteroids

I: 2
M
A: 3
W: 1
I: 0
E: 3
A

Indication (2):

  • Asthma (step 2)
  • COPD - where severe airway obstruction or recurrent exacerbations. Normally with LABA or Long acting antimuscarinic bronchodilator

Mechanism:

  • They pass through the plasma membrane, and interact with receptors in the cytoplasm. They move to the nucleus to modify gene transcription
  • Pro-inflammatory Interlukins and other mediators are downregulated
  • Anti-inflammatory proteins are upregulated
  • Reduces mucosal inflammation
  • Widens the airways
  • Reduces mucus secretion.

Adverse effects (3):

  • Oral candiditis (thrush)
  • Hoarse voice
  • Some evidence of increased risk of pneumonia in COPD

Warnings (1):
- High dose inhaled corticosteroids should be used with caution in COPD patients with a history of pneumonia, and

Example drugs (3):
Beclometasone, budesonide, fluticasone
85
Q

B2 agonist corticosteroid compound inhalers

I: 2
M
A: 6 steroids, 3 LABAs
W: 2 steroids, 1 LABA
I: 0
E: 2
A

Indication (2):

  • Asthma - To controls symptoms and prevents exacerbation, at steps 3 and 4
  • COPD - To control symptoms and prevent exacerbation, in patients who have severe airflow obstruction or recurrent exacerbations

Mechanism:

  • Corticosteroids suppress inflammation
  • Long acting B2 agonists stimulate bronchodilation
Adverse effects (Steroids= 6, LABAs = 3)
Inhaled corticosteroids can cause 
- Oral thrush 
- Hoarse voice
- Might cause pneumonia in COPD 
- Adrenal suppression (at high doses for long time)
- Growth retardation (high doses for long time in kids)
- Osteoporosis 

LABAs can cause

  • Tremor
  • Tachycardia
  • Arrhythmia
  • Muscle Cramps

Warnings (Steroids= 2, LABAs = 1):
Inhaled corticosteroids should be used in caution with
- COPD patients with history of pneumonia
- Children (Growth suppression)
LABAs should be used in cation with
- Cardiovascular disease, where tachycardia may cause angina or arrhythmia.

Interactions (0)

Example drugs (2):
Seretide, symbicort
86
Q

Aminoglycosides

I: 5
M
A: 3
W: 2
I: 2
E: 2
A

Indication (5):

  • Severe infection, particularly those caused by Gram -ve aerobes (incl P. Aeruginosa)
  • Severe sepsis
  • Pyelonephritis + complicated UTI
  • Biliary and other intra-abdominal sepsis
  • Endocarditis

Mechanism:

  • Spectrum of action incl: Gram -ve aerobic bacteria, staph and mycobacteria
  • Aminoglycosides bind irreversibly to bacterial ribosomes (30S subunit)&raquo_space; inhibit protein synthesis and are bactericidal
  • Aminoglycosides enter bacterial cell via an oxygen-dependent transport system
  • Bacterial resistance: Innate - strep and anaerobes don’t have this transport system; Acquired - other bacteria have reduced cell membrane permeability or have enzymes that modify aminoglycosides to prevent them reaching ribosomes
  • Penicillins weaken bacterial cell walls so can enhance aminoglycoside take up

Adverse effects (3):

  • Nephrotoxicity and ototoxicity due to aminoglycoside accumulation in renal tubular epithelial cells and cochlear/vestibular cells respectively
  • Nephrotoxicity presents as decreased urine output and increased serum creatinine/urea; potentially reversible
  • Ototoxicity is often not noticed until after resolution of the acute infection when patient complains of hearing loss, tinnitus and/or vertigo; potentially irreversible

Warnings (2):

  • Aminoglycosides are renally excreted - monitoring plasma drug conc is essential to prevent nephrotoxicity/ototoxicity, especially in neonates/the elderly and in the renally impaired
  • Aminoglycosides can impair neuromuscular transmission so shouldn’t be given to patients w/ myasthenia gravis until absolutely necessary

Interactions (2):

  • Ototoxicity is more likely if co-prescribed w/ loop diuretics (i.e. furosemide) or vancomycin
  • Nephrotoxicity is more likely id co-prescribed w/ ciclosporin, platinum chemotherapy, cephalosporins or vancomycin

Example drugs:
Gentamicin, amikacin

87
Q

Strong opioids

I: 4
M
A: 6
W: 3
I: 1
E: 2
A

Indication (4):

  • Severe acute pain
  • Chronic pain
  • Breathlessness (end of life care)
  • With O2, Furosemide + nirates for Breathlessness and anxiety (acute pulmonary oedema)

Mechanism:
- CNS: activation of opioid µ-receptors > reduction in neuronal excitibility and pain transmission
- Medulla: Reduce respiritory drive and breathlessness.
Reduce sympathetic activity (in MI = reduce heart rate and O2 demands)

Adverse effects (6):

  • Respiratory and neurological depression
  • Nausea and vomiting
  • Pupil constriction
  • Constipation
  • Itching
  • Heavy use = tolerance, dependance and withdrawal

Warnings (3):

  • Doses should be reduced in the elderly, hepatic and renal failure.
  • Avoid in respiritory failure
  • Avoid in biliary colic

Interactions (1):
- Other sedating agents (antipsychotics, benzodiazepines and tricyclic antidepressants)

Example drugs (2):
Morphine, oxycodone
88
Q

Typical antipsychotics

I: 4
M
A: 8
W: 2C/I, 1 caution
I: 1
E: 3
A

Indications (4):

  • Urgent psychomotor agitation causing dangerous or violent behaviour
  • Schizophrenia - when the second generation metabolic SE are problematic
  • Bipolar disorder - in acute episodes of mania or hypomania
  • Nausea and vomiting

Mechanism:

  • Block post-synaptic dopamine D2 receptors
  • 3 main dopaminergic pathways in the 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
  • D2 also in CTZ - explaining the anti nausea/vomiting effects

Adverse effects (8):

  • Sedation
  • Extrapyramidal effects (from blocking nigrostriatal pathway); acute dystonic (Parkinsonian movements), akathisia (inner restlessness), neuroleptic malignant syndrome (rare but life-threatening SE, rigidity, confusion, autonomic dysregulation and pyrexia)
  • Tardive dyskinesia (tardive = late, occurs months post therapy), (pointless involuntary movement)
  • Drowsiness
  • Hypotension
  • QT- interval elongation (–> arrhythmias)
  • Erectile dysfunction
  • Hyperprolactinaemia symptoms due to tuberohypophyseal D2 blockade (e.g. menstrual disturbance, galactorrhoea, breast pain)

Warnings (2C/I, 1 caution):

  • Dementia (C/I)
  • Parkinson’s (C/I)
  • Elderly patients need lower dose (caution)

Interactions (1):
- Drugs that prolong the QT interval (e.g.amiodarone and macrolides)

Examples (3):
Haloperidol, chlorpromazine, prochlorperazine

89
Q

Compound opioid preparations

I: 1
M
A: 3, 3OD
W: 4 cautions
I: 1
E: 2
A

Indication (1):
- Mild-to-moderate pain, secondary to simple analgesics

Mechanism:

  • Paracetamol poorly understood ?COX inhibition
  • Codeine and dihydrocodeine are weak opiods and are metabolised by Cytochrome p450 to mophine, and are agonists of opioid µ-receptors

Adverse effects (3, 3 OD):

  • Nausea
  • Constipation
  • Drowsiness
  • OD - hepatotoxicity, neuro/resp depression

Warnings (4):

  • Severe respiratory disease (caution)
  • Elderly (caution)
  • Hepatic impairment (caution)
  • Renal impairment (caution)

Interactions (1):
- Other sedating drugs (anipsychotics, benzodiazepines or tricyclic antibiotics

Example drugs (2):
Co-codamol, co-dydramol
90
Q

Antipseudomonal penicillins

I: 5
M
W: 1 C/I, 2 cautions
I: 2
E: 1
A

Indications (5):

  • Severe infections, broad specturm of potential pathogens (including p. aeruginosa)
  • Where antibiotic resistance is likely
  • Immunocompromise
  • Commonly prescribed for LRI UTIs
  • Intra-abdominal sepsis of skin/soft tissue infections

Mechanism:

  • Inhibit enzymes responsible for cross-linking peptidoglycans in bacterial cell wall
  • β-lactam ring has been modified to be more effective, particularly against p.aeruginosa
  • Combination with tazobactam inhibits β-lactamase producing bacteria (S.aureus/ Gram-negative anaerobes)

Warnings (1 C/I, 2 cautions):
- Penicillin allergy (C/I)
- Risk of C diff (caution)
- Reduced dosage with moderate/severe renal impairment (caution)
Contraindicated with Penicillin allergy; Caution with people ar tisk of C.diff; Reduce doseage in patients with moderate/severe renal impairment

Interactions (2):

  • Reduces excretion of Methotrexate (increasing toxicity)
  • Enhances anticoagulant effect of warfarin (killing bacteria involved in vit K metabolism)
Example drugs (1):
IV Pipercillin in combination with Tazobactam aka. Tazocin
91
Q

Antimuscarinics as bronchodilators

I: 2
M
A: 2
W: 2
E: 3
A

Indications (2):

  • COPD - short-acting antimuscarinics are used to relive breathlessness, long acting antimuscarinics are used to prevent breathlessness and exacerbations.
  • Asthma - short-acting antimuscarinics are used as adjuvant tx in acute exacerbations. Long acting antimuscarinics are (added to corticosteroids, and Long acting B2 agonists,) at step 4 of the asthma scale

Mechanism:

  • Binds to muscarinic receptor, competitively inhibits acetylcholine - therefore blocks the parasympathetic
  • So increase heart rate and conduction; reduce smooth muscle tone - including in resp tract; reduces secretions from glands in respiratory and GI.
  • In the eye cause relaxation of the pupillary constrictor and ciliary muscles –> pupillary dilation and stops accommodation.

Adverse effects (2):

  • When anti-mus brochodilators taken by inhalation there is relatively little systemic absorption so uncommon to have side effects
  • Dry mouth may happen

Warnings (2):

  • In angle-closure glaucoma can cause raised intraocular pressure
  • Be cautious if risk of arrhythmias

Examples (3):
Ipratropium, tiotropium, glycopyrronium

92
Q

Angiotensin converting enzyme inhibitors (ACEI)

I: 4
M
A: 5
W: 1C/I, 2 cautions
I: 3
E: 3
A

Indications (4):

  • Hypertension 1st of 2nd line treatment
  • Chronic heart failure - 1st line treatment of all grades - to improve symptoms and prognosis
  • Ischaemic heart disease - reduce risk of subsequent CV events, incl MI and stroke
  • Diabetic nephropathy and CKD w/ proteinuria

Mechanism:

  • ACEI block action of ACE to prevent conversion of angiotensin I to angiotensin II (stimulates vasoconstriction and aldosterone secretion)&raquo_space; reduces peripheral vascular resistance (afterload)&raquo_space; lowers BP
  • It particularly dilates the efferent glomerular arteriole&raquo_space; reduces intraglomerular pressure&raquo_space; slows progression of CKD
  • Stimulation of aldosterone release&raquo_space; increased Na and water excretion&raquo_space; reduced pre-load (beneficial in heart failure)

Adverse effects (5):

  • Hypotension (especially after 1st dose)
  • Persistent dry cough (due to increased levels of bradykinin which is usually inactivated by ACE) and hyperkalaemia (low aldosterone&raquo_space; K retention)
  • ACEI can also cause/renal failure - especially in patients w/ renal artery stenosis who rely on constriction of efferent arteriole to maintain glomerular filtration
  • If detected early, these adverse effects are usually reversible on stopping the ACEI
  • Rare but important side effects of ACEI are angioedema and other anaphylactoid reactions

Warnings (1C/I, 2 cautions):

  • AKI (C/I)
  • RAS (caution)
  • Pregnancy and breastfeeding (caution)

Interactions (3):

  • Due to risk of hyperkalaemia, ACEI should be avoided in patients taking other K-elevating drugs (i.e. K supplement or K sparing diuretics) except under specialist advice for advanced heart failure
  • In combo w/ other diuretics, ACEI may be associated w/ profound 1st dose hypotension
  • Combo of NSAID + ACEI increases risk of renal failure
Example drugs (3):
Ramipril, lisinopril, perindopril
93
Q

Paracetamol

I: 2
M
W: 1C/I, 4 cautions
I: 1
E: contained in 4
A

Indications (2):

  • Analgaesic = WHO pain ladder rung
  • Antipyretic = reduce fever and associated symptoms

Mechanism

  • Poorly understood
  • Weak COX inhibitor, reducing PGE2 concentrations in the thermoregulatory region of the hypothalamus
  • Possibly Selective COX2 - hence does not effect gut mucosa

Warnings (1C/I, 4 cautions)

  • Hepatotoxicity risk (C/I)
  • Alcoholism (increased NAPQI production = caution)
  • Malnutrition (caution)
  • Underweight (caution)
  • Severe hepatic impairment (caution)

Interactions (1):
- Cytochrome p450 inducers may increase rate of NAPQI production = increased risk in OD

Example drugs (4):
Paracetamol is in Lemsip, Cocodamol, Calpol, Sudafed
94
Q

Broad spectrum penicillins

I: 4
M
A: 2
W: 1C/I, 2 cautions
I: 2
E: 2
A

Indications (4):

  • Pneumonia
  • UTI
  • Combination treatment for Hospital aquired infection of intra-abdominal sepsis (co-amoxiclav)
  • Combination treatment (co-amoxiclav) for H.pylori associated peptic ulcers

Mechanism:

  • β-lactam ring inhibits enzymes responsible for cross-linking peptidoglycans, which weakens cell walls leading to swelling, lysis and death
  • Altered side chains make it more effective against gram-negative bacteria
  • Addition of Clavulanic acid (co-amoxiclav) increases activity to β-lactamase producing bacteria (S.aureus, gram-negative anaerobes)

Adverse effects (2):

  • Anaphylaxis
  • GI upset such as antibiotic-associated colitis (due to overgrowth of C.diff)

Warnings (1 C/I, 2 cautions):

  • Penicillin allergy (C/I)
  • Risk of C diff (caution)
  • Reduce dose in severe renal impairment (caution)

Interactions (2):

  • Reduces renal excretion of methotrexate (increasing toxicity)
  • Kills off bacteria responsible for Vit.K metabolism = enhances warfarin effect
Example drugs (2):
Amoxicillin, coamoxyclav
95
Q

Insulin

I: 4
M
A: 2
W: 1
I: 2
E: 4
Extra: 5
A

Indication (4):

  • Insulin replacement in people with T1DM and control of blood glucose in people with T2DM where oral hypoglycaemic tx is inadequate.
  • Diabetic emergencies (eg DKA or hyperglycaemic hyperosmolar syndrome).
  • Perioperative glycaemic control in some patients
  • Hyperkalaemia (alongside glucose + treatment to correct the underlying cause)

Mechanism:

  • For DM - stimulates GLUT-4 transporters to go to cell membrane, allowing more glucose to get into cells
  • For hyperkalaemia - drives K+ into cells, reducing serum K+ (only works while insulin being given, the effect is reversed once insulin is discontinued)

Adverse effects (2)

  • Hypoglycaemia
  • Lipohypertrophy

Warnings (1):
- Insulin clearance is reduced in patients with renal impairment, so more insulin in serum -> increased risk of hypoglycaemia

Interactions (2):

  • Other hypoglycaemic agents will increase hypoglycaemia risk
  • Corticosteroids increase insulin requirements
Example drugs (4):
Insulin aspart, insulin glargine, biphasic insulin, soluble insulin

Extra (5):

  • Rapid acting (immediate onset, short duration) -> insulin aspart (Novorapid)
  • Short acting (early onset, short duration) -> soluble insulin (Actrapid)
  • Intermediate acting (intermediate onset and duration) -> isophane insulin (Humulin)
  • Long acting (flat profile, regular administration) -> insulin glargine (Lantus)
  • Biphasic insulin = rapid + intermediate (eg Noromix)
96
Q

Emollients - aqueous cream, liquid paraffin

I: 2
M
A: 2
W: 0
I: 1
E: 2
A

Indication (2):

  • Dry or scaling skin disorders, with or without topical corticosteroids, in treatment of eczema
  • Can also be used in psoriasis

Mechanism:

  • They replace water in dry skin
  • They reduce water loss, by reducing water evaporation from the skin surface

Adverse effects (2):

  • Can cause greasiness of skin, but this is vital to therapeutic effect
  • They can exacerbate acne vulgaris and folliculitis, by blocking pores and hair follicles

Interactions (1):
- Space applications with other topical applications, to prevent drugs like topical corticosteroids from being blocked from the skin.

Example drugs (2):
Aqueous cream, liquid paraffin
97
Q

Osmotic laxatives

I: 3
M
A: 5
W: 2
I: 1
E: 3
A

Indication (3):

  • Constipation and faecal impactation
  • Bowel prep prior to surgery or endoscopy
  • Hepatic encephalopathy

Mechanism

  • Consists of osmotically active substances (sugars or alcohols) that are not digested or absorbed, therefore remaining in gut lumen
  • They hold water in stool, maintaining its volume and stimulating peristalsis
  • Lactulose also reduces ammonia absorption, which acidifies the stool, thus inhibiting proliferation of ammonia-producing bacteria (helpful in pts with liver failure, in whom ammonia has a major role in the pathogenesis of hepatic encephalopathy)

Adverse effects (5):

  • Flatulence
  • Abdo cramps
  • Nausea
  • Diarrhoea
  • Phosphate enemas can cause local irritation and electrolyte disturbances

Warnings (2)

  • Don’t use in intestinal obstruction (risk of bowel perforation)
  • Phosphate enemas cause significant fluid shift, so caution in pts with heart failure, ascites, and electrolyte imbalances

Interactions (1):
- May increase the effect of warfarin

Example drugs (3):
Lactulose, macrogol, phosphate enema
98
Q

Vitamins
Folic acid, thiamine, hydroxocobalamin, phytomenadione.

I: 
M
A: 1
W: 2
I: 1
A

Indications (1):

  • Thiamine (vitamin B1) to treat and prevent Wernicke’s encephalopathy and Korsakoff’s psychosis
  • Folic acid (the synthetic form of folate or vitamin B9)
  • Used in megaloblastic anaemia due to folate deficiency, and in the first trimester of pregnancy to reduce the risk of neural tube defects
  • Hydroxocobalamin (a synthetic form of cobalamin or vitamin B12) is used in the treatment of megaloblastic anaemia and subacute combined degeneration of the cord due to vitamin B12 deficiency
  • Phytomenadione (the plant form of vitamin K). For all newborn babies to prevent vitamin K deficiency bleeding, and is used to reverse the anticoagulant effect of warfarin (prothrombincomplex concentrate should also be given in cases of major bleeding)

Mechanism:

  • Organic substances used in metabolic processes
  • Folic acid is involved in normal cell division, initiating cell proliferation may be how it causes neural tube closure
  • Phytomenadione reverses Warfarin by providing a supply of vitamin K for vitamin K-dependent clotting factors by the liver
Adverse effects (1):
- IV phytomenadione and high-dose thiamine may rarely
cause anaphylaxis

Warnings (2):

  • In patients with co-existing B12 and folate deficiency, you should replace both vitamins simultaneously - replacing folate acid alone may speed up subacute combined degeneration of the cord due to B12 deficiency.
  • Phytomenadione is less effective in reversing warfarin in patients with severe liver disease, as clotting factors are synthesised in the liver.

Interactions (1):
- When attempting to restart warfarin after vitamin K has been given, it may result in erratic dosingrequirements.

Example drugs
Folic acid, thiamine, hydroxocobalamin, phytomenadione.

99
Q

Angiotensin receptor blockers (ARBs)

I: 5
M
A: 3
W: 2 C/I, 1 caution
I: 3
E: 3
A

Indication (5):

  • Used when ACEI are not tolerated due to cough - same indications
  • Hypertension - 1st of 2nd line treatment
  • Chronic heart failure - 1st line treatment of all grades - to improve symptoms and prognosis
  • Ischaemic heart disease - reduce risk of subsequent CV events, incl MI and stroke
  • Diabetic nephropathy and CKD w/ proteinuria

Mechanism

  • ARBs block the action of angiotensin II on the AT1 receptor&raquo_space; vasodilation&raquo_space; reduced peripheral vascular resistance (afterload)
  • It particularly dilates efferent glomerular arterioles&raquo_space; reduced intraglomerular pressure&raquo_space; slows progression of CKD
  • By blocking angiotensin stimulatory effect on release of Aldosterone - promotes Na and water excretion

Adverse effects (3):

  • Hypotension (particularly after 1st dose)
  • Hyperkalaemia and renal failure (patients w/ renal artery stenosis are particularly at risk as they rely on constriction of efferent arterioles to maintain GFR)
  • Less likely to cause dry cough and angioedema as ACEI (no impact on bradykinin metabolism)

Warnings (2C/I, 1 caution):

  • Renal artery stenosis (C/I)
  • AKI (C/I)
  • Breastfeeding/pregnancy (caution)

Interactions (3):

  • Due to risk of hyperkalaemia, ARBs should be avoided in patients taking other K-elevating drugs (i.e. K supplement or K sparing diuretics) except under specialist advice for advanced heart failure
  • In combo w/ other diuretics, ARBs may be associated w/ profound 1st dose hypotension
  • Combo of NSAID + ARBs increases risk of renal failure
Example drugs (3):
Losartan, candesartan, irbesartan
100
Q

Ocular lubricants - artificial tears

I: 1
M
A: 0
W: 0
I: 0
E: 3
A

Indication (1):
- Dry eye conditions such as keratoconjunctivitis sicca or Sjögren’s syndrome

Mechanism:

  • Sooth, lubricate and protect the eye from abrasive damage
  • Usually made of electolyte solution with a viscosity agent (which enables it to stay in the eye for longer) Oinments are highly viscous, longer lasting but blur vision

Example drugs:
Hypromellose, carbomers, liquid and white soft paraffin

101
Q

Stimulant laxatives

I: 2
M
A: 2
W: 1 C/I, 1 caution
I: 0
E: 4
A

Indications (2):

  • Constipation
  • Suppositories for faecal impactation

Mechanism:

  • Increases water and electrolyte secretion from colonic mucosa, thereby increasing volume of colonic content and stimulating peristalsis.
  • Metabolism of Senna in particular in intestines produces metabolites that further stimulate peristalsis.

Adverse effects (2):

  • Abdo pain & diarrhoea
  • Melanosis coli (reversible pigmentation of intestinal wall) can occur in prolonged use

Warnings (1 C/I, 1 caution):

  • Intestinal obstruction –> perforation (C/I)
  • Haemorrhoids or anal fissures (caution)
Example drugs (4)
Senna, bisacodyl, glycerol suppositories, docusate sodium
102
Q

Weak opioids

I: 1
M
A: 6
W: 1C/I, 2 cautions
I: 2
E: 3
A

Indication (1):
- Mild to moderate pain

Mechanism:

  • Metabolised to form small amounts of morphine or dihydromorphine = agonists of opioid µ-receptors in CNS
  • Tramadol also effects serotonergic and adrenergic pathway (like SNRIs)

Adverse effects (6):

  • Nausea
  • Constipation
  • Dizziness
  • Drowsiness
  • OD = neurological and respiritory depression
  • Never give IV = causes anaphylaxis like reaction

Warnings (1C/I, 2 cautions):

  • Epilepsy (C/I)
  • Significant respiratory disease (caution)
  • Reduce dose in renal and hepatic impairment and for elderly (caution)

Interactions (2):

  • Avoid using with other sedating drugs (antipsychotics, benzodiazipines and tricyclic antidepressants
  • Tramadol should be avoided with drugs that lower seizure threshold SSRIs, tricyclics.
Example drugs (3):
Tramadol, codeine, dihydrocodeine
103
Q

Vaccines

I: 3
M
A: 3
W: 3
I: 1
A

Indications:

  • Childhood schedule
  • Influenza vaccine annually for at risk groups
  • Pneumacoccal vaccine once for at risk groups

Mechanism:

  • Introduce an antigen to lead to adaptive immune response (usually memory B cells)
  • May be inactivated, live but attenuated, a specific peptide or protein component or a detoxified exotoxin

Adverse effects (3):

  • Local reactions and mild systemic effects
  • Severe hypersensitivity
  • MMR can cause measles like or mumps like illness

Warnings (3):

  • Anaphylactic reaction to past dose or one of its constituents
  • Significant immunosuppression
  • Pregnancy

Interactions (1):
- Immunosuppressive drugs

104
Q

Z drugs

I: 1
M
A: 5, OD, 1 + 1 drug specific
W: 4 caution
I: 5
E: 2
A

Indications (1):
- Short term treatment of debilitating or distressing insomnia.

Mechanism:

  • Similar to benzodiazepines
  • They target GABAa receptors (these are chloride channels which open when GABA binds to them)
  • This allows Chlorine to flow into the cell making it more resistant to depolarisation
  • They also increase binding of GABA to GABAa receptors with widespread inhibitory effects (e.g. reduced anxiety, sleepiness and sedation)

Adverse effects (5, OD):

  • Daytime sleepiness
  • Rebound insomnia when they are stopped
  • CNS effects (headache, confusion, nightmares, amnesia)
  • Dependance
  • Withdrawal symptoms (muscle pain, anxiety and headaches)
  • In overdose: drowsiness, coma, resp. depression
  • Zopiclone - taste distubances
  • Zolpidem - GI

Warnings (4 cautions):

  • Elderly (caution)
  • Obstructive sleep apnoea (caution)
  • Resp. muscle weakness (caution)
  • Resp. depression (caution)

Interactions (5):
- Enhance the sedative effects of alcohol, antihistamines and benzodiazepines
- Enhance the hypotensive effect of
antihypertensive medications
- P450 inhibitors (e.g. macrolides) can
enhance sedation, whereas P450 inducers (e.g. phenytoin, rifampicin) can impair sedation

Example drugs (2):
Zopiclone, zolpidem
105
Q

Lidocaine

I: 2
M
A: 6
W: 1
I: 1
A

Indication

  • First line local anaesthetic for many procedures (eg urinary catheterisation, suturing)
  • Uncommonly used as an antiarrhythmic in VT and VF

Mechanism:

  • Enters the cell then blocks votage-gated sodium channels on the cell membrane
  • Prevents action potentials in the area supplied by the blocked nerve fibers
  • In heart, reduces duration of action potential, slows conduction velocity and increases refractory period, helping with VT and VF

Adverse effects (6)

  • Initial stinging during administration
  • Drowsiness, restlessness, tremor, fits
  • OD causes hypotension and arrythmias

Warnings (1):
- Reduce dose in pts with a reduced cardiac output

Interactions (1):
- Co-adminstration with a vasoconstrictor (eg adrenaline) produces a desirable reaction that may prolong the anaesthetic effect (as less blood flow to the nerve to carry the lidocaine away, so it works for longer).

106
Q

Naloxone

I: 1
M
A: 6
W: 2
I: 0

Dosage

A

Indication (1):
- Opioid toxicity associated with respiratory &/or neurological depression

Mechanism:

  • Competitively antagonises opioid receptors (particularly the mu-receptor)
  • Displaces the exogenous opioid (eg morphine) from the receptor, thus reversing its effect

Adverse effects (6):

  • An opioid withdrawal reaction may be precipitated in people who are addicted
  • Present with pain (if opioid was being taken for analgesia), restlessness, nausea & vomiting, dilated pupils, cold and dry skin with piloerection (“cold-turkey”)

Warnings (2):

  • Opioid dependence (caution)
  • Lower doses used in palliative care setting, to reduce risk of complete reversal of analgesia

400-1200 micrograms IV. Administered under direct supervision, increments of 200-400 mcg every 2-3 minutes until desired effect achieved.

107
Q

Oestrogens and progesterones

I: 2
M
A: 4
W: 1C/I, 1 caution
I: 1
E: 2
A

Indication (2):

  • Highly effective and reversible hormonal contraception
  • Hormone replacement therapy for early or distressing menopausal symptoms

Mechanism:

  • Contraception: Oestrogen and progesterone provide negative feedback, suppressing LH/FSH and prevent ovulation and also effect cervix and endometrium.
  • HRT: provides replacement for naturally falling Oestrogen/progesterone

Adverse effects (4):

  • Irregular bleeding
  • Mood changes
  • Combined Pill (but not progesterone only) = increased VTE, CVD and CVA risk (careful in those with high baseline risk (worse for HRT as higher baseline risk)
  • Increased risk of Breast and cervical cancer

Warnings (1C/I, 1 caution):

  • Breast cancer (C/I)
  • Avoid in those at increased risk for VTE and CVD (caution)

Interactions (1):
- Cytochrome p450 inducers (CRAP GPs)

Example drugs (2) 
Combined ethinylestradiol products, desogestrel
108
Q

Oxygen

I: 3
M:
A: 1
W: 2
I: 0
A

Oxygen

Indications (3):

  • Hypoxaemia
  • Increasing reabsorption of pleural gas in pneumothorax
  • Reduce recovery time in carbon monoxide poisoning

Mechanism:

  • Increases oxygen delivery to tissue by saturating blood
  • Accelerates nitrogen diffusion out of the body by reducing % nitrogen in alveolar air (pneumothorax gas is mostly nitrogen)
  • High pO2 competes with carbon monoxide for haemoglobin binding = reducing half-life}
Adverse effects (1):
- Headaches

Warnings (2):

  • Chronic type 2 respiratory failure = risk of hypoxic drive (e.g. COPD)
  • Never allow near heat source or naked flames (e.g. smoking)

Interactions:
None