Top 100 Drugs Flashcards
Side Effects - Sodium Valporate
Valproate
Appetite increase, so weight gain
Liver failure (monitor LFTs during 1st 6 months)
Pancreatitis
Reversible hair loss (grows back curly, apparently)
Oedema
Ataxia
Teratogenicity, Tremor, Thrombocytopaenia
Encephalopathy (due to hyperammonaemia) / Enzyme inducer
Has the greatest risk of fetal abnormalities
Indications - Sodium Valporate
Seizure prophylaxis in epilepsy
Manic episodes in bipolar disorder - used as prophylaxis against recurrence
Contraindications - Sodium Valporate
Women of child-bearing age - especially time of conception and pregnancy
Hepatic Impairment
Renal impairment
Aminosalicylates - Indications
Mesalazine - 1st line mild/moderate UC
Sulfasalazine - Used with a DMARD in rheumatoid arthritis
Side Effects - Aminosalicylates
Nausea
Dyspepsia
Headache
Blood Abnormalities - leucopenia and thrombocytopenia (rare)
Oligospermia
Can cause severe hypersensitivity reactions
Contraindications - Aminosalicylates
Not given to those with aspirin hypersensitivity
Mesalazine - pH sensitive coating - affected by PPIs and Lactulose
PPI - Indications
Peptic ulcer disease
NSAID-associated ulcers
Symptomatic relief of dyspepsia and GORD
H. pylori infection
PPI - Mechanism
Irreversibly inhibit H+/K+ ATPase in gastric parietal cells
Suppress gastric acid production almost completely
PPI - Adverse effects
GI disturbances
Headache
Prolonged treatment - hypomagnesaemia - severe can lead to tetany
PPI - Warnings
May disguise symptoms of gastro-oesophageal cancer
Cautioned in those with osteoporosis - increased risk of fracture
PPI - Interactions
Reduce antiplatelet affect of clopidogrel by decreasing its activation of cytochrome P450 enzymes
Metronidazole - Indications
Antibiotic-associated colitis - gram-positive anaerobe Clostridium difficile
Oral Infections / Aspiration pneumonia
Surgical and gynae infections by gram-negative anaerobes
Protozoal infections - trichomonal vaginal infection, amoebic dysentery and giardiasis
Metronidazole - Mechanism
Anaerobic Bacteria - DNA degradation and cell death (bactericidal)
Metronidazole - Adverse Effects
GI upset (nausea and vomiting)
Delayed Hypersensitivity reactions -
Can cause peripheral and optic neuropathy, seizures and encephalopathy
Metronidazole - Warnings
Metabolised by P450 enzymes - reduced in people with severe liver disease
Inhibits acetaldehyde dehydrogenase - responsible for clearing alcohol metabolite
Alcohol should not be drunk while taking metronidazole
Metronidazole - Interactions
Some inhibitory effect on CYP enzymes
Reduction in warfarin metabolism and phenytoin
Cephalosporins - examples?
Ceftriaxone, Cefalexin, Meropenem, Ertapenem
Ceftriaxone - Mechanism
3rd generation cephalosporin
Broad-spectrum - long half-life
Penetrates the meninges, eyes and inner ear
Used in the treatment of bacterial infections caused by susceptible usually gram-positive
Ceftriaxone works by inhibiting the mucopeptide synthesis in the bacterial cell wall
Prevents them from maintaining an osmotic gradient leading to bacterial cell swelling and death
Has in vitro activity against gram-positive aerobic, gram-negative aerobic, and anaerobic bacteria
Bactericidal activity of ceftriaxone results from the inhibition of cell wall synthesis and is mediated through ceftriaxone binding to penicillin-binding proteins (PBPs)
Ceftriaxone is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended-spectrum beta-lactamases
Ceftriaxone - Cautions
Ceftriaxone should not be mixed with or giving in the same IV line as diluents/products containing calcium as they may cause ceftriaxone to precipitate.
In those at increased C. difficile infection
Epilepsy
Cautioned in those with renal impairment
Ceftriaxone - Adverse Effects
Ceftriaxone use may also cause biliary sludge or gallbladder pseudolithiasis.
GI upset
Antibiotic associated colitis -> can lead to bowel perforation and death
Clostridium difficile infections
Hypersensitivity -> Cross-reactivity can occur in penicillin allergic patients
Ceftriaxone - Interactions
Enhance anticoagulant effects of warfarin by killing normal gut flora that synthesise vitamin K
Increase nephrotoxicity of aminoglycosides
Reduce conc. of valproate
Methotrexate - Mechanism
DMARD for rheumatoid arthritis
Chemotherapy regimen for cancers: leukaemia, lymphoma and some solid tumours
Treatment of severe psoriasis
Mechanism of action
Folic analogue inhibits dihydrofolate reductase (which converts dietary folate to tetrahydrofolate -needed for DNA synthesis) and thymidylate synthase - reduce production of thymine needed for DNA synthesis –> prevents cellular replication
Anti-inflammatory and immunosuppressive - inhibition of inflammatory mediators IL-6, IL-8 and TNF-alpha
Reduction in methionine
Methotrexate - Adverse Effects
Mucosal damage
Bone marrow suppression (can lead to neutropenia and increased infection risk)
Hypersensitivity reactions - cutaneous reactions, hepatitis, pneumonitis
Long term can lead to hepatic cirrhosis or pulmonary fibrosis
Renal failure and hepatic toxicity
Risk of accidental overdose - treated with folinic acid which rescues normal cells from methotrexate effects along with hydration and urinary alkalinisation - enhance excretion
Methotrexate - Contraindicated
Teratogenic - avoided in pregnancy (both men and women)
Severe renal impairment
Abnormal liver function
Methotrexate - Interactions
Toxicity likely with drugs that can inhibit its renal excretion - NSAIDs, penicillins
Co-prescription with other folate antagonists (Trimethoprim and phenytoin) can lead to haematological abnormalities
Dexamethasone (Glucocorticoids - systemic corticosteroids) - Mechanism
Used to treat allergic or inflammatory disorders
Suppression of autoimmune disease
Cancer treatment as part of chemotherapy or to reduce tumour associated swelling
Hormone replacement in adrenal insufficiency or hypoparathyroidism
Mechanism of Action
Bind to the glucocorticoid receptor - inhibiting pro-inflammatory signals (cytokines and TNF-alpha) and promoting anti-inflammatory signals
Decreased vasodilation and permeability of capillaries
Suppression of circulating monocytes and eosinophils
Gluconeogenesis from increased circulating fatty acids and amino released by fat and muscle catabolism
Mineralocorticoid effect - Na+ retention and K+ excretion
Dexamethasone (Glucocorticoids - systemic corticosteroids) - Adverse Effects
Immunosuppression - increases the risk and severity of infection - alters host response
Increased catabolism - proximal muscle weakness, skin thinning with easy bruising and gastritis
Mood and behavioural changes - insomnia, confusion, psychosis
Hypertension, hypokalaemia and oedema
Suppresses ACTH production - in prolonged treatment leads to adrenal atrophy
If steroids are withdrawn too quickly - Addisonian crisis
Needs to be withdrawn slowly by can cause symptoms of chronic glucocorticoid deficiency
Cannot produce cortisol secretion in response to stress - needs to be provided artificially in acute illness (double dose)
Dexamethasone (Glucocorticoids - systemic corticosteroids) - Contraindicated
§ Those with infection
§ Children
Dexamethasone (Glucocorticoids - systemic corticosteroids) - Interactions
Peptic ulcers and GI bleeding - especially if used with NSAIDs
Hypokalaemia enhancement with those on Beta-2 agonists, theophylline (PDE inhibitor), loop and thiazide diuretics
Efficacy reduced by cytochrome P450 inducers (phenytoin, carbamazepine, rifampcin)
Calcium Gluconate - Indications
Used in beta blocker and Calcium Channel Toxicity
Severe acute hypocalcaemia or hypocalcaemic tetany
Acute severe hyperkalaemia (plasma-potassium concentration above 6.5 mmol/litre or in the presence of ECG changes)
Calcium deficiency, Mild asymptomatic hypocalcaemia
Hyperkalaemia is common among hospital inpatients
First line emergency treatment for severe hyperkalaemia associated with ECG abnormalities
Calcium Gluconate - Dosage
10mL of calcium gluconate 10% IV over 10-15 minutes
Calcium Gluconate - Mechanism of Action
○ In hyperkalaemia - calcium raises the myocardial threshold potential, reducing excitability and the risk of arrhythmias - no effect on serum potassium
Calcium Gluconate -Contraindicated
Conditions associated with hypercalcaemia (e.g. some forms of malignant disease)
Allopurinol - Indications
Prevent recurrent attacks of gout
Thiazide or loop diuretics - increases serum uric acid
Aspirin inhibits renal excretion of uric acid
Drug-induced gout C
Prevent uric acid and calcium oxalate renal stones
Prevent hyperuricaemia and tumour lysis syndrome
Allopurinol - Mechanism of Action
Xanthine oxidase inhibitor
Xanthine oxidase metabolises xanthine from purines to uric acid
Allopurinol - Adverse Effects
Initially can worsen gout attacks - can be prevented with co-prescription with an NSAIDs or colchicine during initiation of treatment
Allopurinol hypersensitivity syndrome - rare
Can cause Stevens-Johnson Syndrome or toxic epidermal necrolysis
Allopurinol - Cautions
Shouldn’t be started during acute attacks of gout but can be continued if patient is already on it
Renal and hepatic impairment
Allopurinol - Interactions
Active metabolite (mercaptopurine) - of the pro-drug azathioprine metabolised by xanthine oxidase Co-prescription with ACE inhibitors or thiazides can increase risk of hypersensitivity and with amoxicillin can increase the risk of skin rash
Rasburicase - Mechanism of Action
Recombinant form of urate-oxidase enzyme used to treat hyperuricemia following chemotherapy for leukaemias and non-Hodgkin’s lymphoma.
Rasburicase catalyzes enzymatic oxidation of uric acid into an inactive and soluble metabolite (allantoin).
The injection of rasburicase reduces levels of uric acid and mitigates the toxic effects of chemotherapy induced tumour lysis
Rasburicase - Contraindicated
G6PD deficiency
Rasburicase - Cautioned
Atopic Allergies
Rasburicase - Adverse Effects
Diarrhoea, fever, headache, nauseas, skin reactions, vomiting
Haemolytic anaemia, hypersensitivity, hypotension
Piptazobactam - Interactions
Antipseudomonal penicillins -> reserved for severe infections (antibiotic resistance or in immunocompromised (neutropenic) individuals)
Tazobactam is the beta - lactamase inhibitor (confers activity against beta-lactam producing Staphylococcus aureus and gram-negative anaerobes)
Clinical infections treated:
LRTIs
UTIs
Intraabdominal sepsis
Skin and soft tissue infections
Piptazobactam - Mechanism of Action
Responsible for cross-linking peptidoglycan in bacterial cell walls - weakens walls preventing them from maintaining their osmotic gradient
Piptazobactam - Adverse Effects
GI upset - nausea and diarrhoea
Clostridium difficile
Rare- antibiotic - associated colitis
Piptazobactam - Warnings
Cautioned in those with a C. difficile infection
Contraindicated in penicillin allergy
People with penicillin allergy would react to cephalosporins and other B-lactam antibiotics
Piptazobactam - Interactions
Pencillins reduce renal excretion of methotrexate - can increase toxicity
Enhance anticoagulant effects of warfarin by killing normal GI flora that synthesise vitamin K
Each dose of piperacillin - tazobactam contains 11mmol Na+ and is infused in 50-150mL fluid - needs to be considered when prescribing fluids in heart failure patients
Gentamicin - Aminoglycoside - Indications
Used to treat severe infections - caused by gram-negative aerobe (including pseudomonas aerunginosa):
□ Severe sepsis
□ Pyelonephritis and complicated UTIs
□ Biliary and other intraabdominal sepsis
□ Endocarditis
Topical - bacterial skin and ear infections
Gentamicin - Aminoglycoside - Warnings
Has a very narrow therapeutic index - little safety margin between clinically effective dose and toxic dose - aminoglycosides distribute through body water not fat - needs to be the basis of the dosage given
Warnings:
□ Renally excreted
□ Not be given in patients with myasthenia gravis
□ Neonates, elderly patients and those with renal impairment
Gentamicin - Aminoglycosides - Mechanism of Action
Mechanism of Action
Against gram-negative aerobic bacteria - some activity against staphylococci and mycobacteria - other agents preferred in practice
Inactive against streptococci and anaerobes - need to be combined with penicillin and/or metronidazole - when organism is unknown
Binds irreversibly to bacterial ribosomes (30S subunit) - inhibit protein synthesis -inhibit protein synthesis
Are bactericidal
As pencillins weaken bacterial cell walls - may enhance aminoglycoside - increase bacterial uptake via oxygen - dependent transport system which streptococci and anaerobic bacteria don’t have
Gentamicin - Aminoglycosides - Adverse Effects
Nephrotoxicity (reduced urine output and rising serum creatinine and urea) can be reversible and otoxicity (hearing loss, tinnitus or vertigo) is irreversible - accumulate in tubular epithelial cells and cochlear and vestibular hair cells - trigger apoptosis and cell death
Gentamicin - Aminoglycosides - Interactions
Ototoxicity more likely if co-prescribed with loop diuretics (e.g. furosemide) or vancomycin
Nephrotoxicity more likely is co-prescribed with ciclosporin, platinum chemotherapy, cephalosporins or vancomycin
Anti-muscarinics, bronchodilators - Indications
COPD - short acting muscarinics - relieve breathlessness (brought on by exercise or during exacerbations)
LAMAS - used to prevent breathlessness and exacerbations
Asthma - short-acting anti-muscarinic used to help relieve breathlessness during acute exacerbations (added to a short -acting beta-2- agonist e.g. salbutamol).
LAMAs (tiotroprium) - added to high dose inhaled corticosteroids and long-acting beta-2 agonists (LABA) as maintenance treatment - patients 1 or more severe asthma exacerbations in the past year
Anti-muscarinics, bronchodilators - Examples
Ipratropium, tiotropium, Glycopyrronium, Aclidinium
Anti-muscarinics, bronchodilators - Mechanism of action
Competitive inhibitor of acetylcholine
Reduce smooth muscle tone, including the respiratory tract and bladder and reduce secretions from the glands in the respiratory and GI tracts
Relaxation of the pupillary constrictor and ciliary muscles - pupil dilation + prevent accommodation
No advantaged in prescribing more than 4 times daily
Anti-muscarinics, bronchodilators - Adverse Effects
Inhaled - rapidly metabolised - less effects
Nasopharyngitis, sinusitis and cough, GI disturbance (including dry mouth and constipation and urinary retention, blurred vision and headaches)
Anti-muscarinics, bronchodilators - Warnings
Cautioned in patients with - angle - closure glaucoma (can cause a rise in intra-ocular pressure)
Cautioned in patients with urinary retention and arrhythmias
Beta 2 Agonists - Indications
Asthma - SABAs relieve breathlessness
LABAs used in chronic asthma when inhaled corticosteroids are insufficient - need to be given with inhaled corticosteroids
COPD - SABAs relieve breathlessness
LABAs 2nd line therapy of COPD - improve symptoms and reduce exacerbations
Hyperkalaemia - neubulised used to lower serum potassium (given along with insulin and glucose and calcium gluconate to stabilise the myocardium)
Beta 2 Agonists - Mechanism of Action
Smooth muscles relaxation - G - protein coupled receptors
Stimulate Na+/K- ATPase pumps on cell surface - K+ shifts from extracellular to intracellular compartments
Useful adjunct in hyperkalaemia - not used in isolation
Beta 2 agonist - Adverse effects
Flight or fight - tachycardia, palpitations, anxiety and tremor
Glycogenolysis - increase serum glucose
High dose - serum lactate goes up
Long term - muscle cramps
Beta 2 agonist - Warnings
LABA - only used with an inhaled corticosteroid
Cautioned in those with CVS risks - can induce tachycardias or arrhythmias
Beta 2 agonists - Interactions
Beta-blockers
High nebulised doses of beta - 2 agonists with theophylline and corticosteroids - lead to hypokalaemia - serum K+ needs to be monitored
Beta 2 agonists - Nebuliser Therapy
Indicate whether the nebuliser should be driven by oxygen or air
Oxygen should be used in asthma whereas medical air should be used in COPD - due to risk of CO2 retention
Inhaled Corticosteroids - Indications
Asthma - treat airway inflammation (usually combined with SABA)
COPD - Control symptoms and prevent exacerbations - people with severe airway obstruction on spirometry and recurrent exacerbations (usually combined with a LABA)
Inhaled Corticosteroids - Mechanisms of Action
Reduction in mucosal inflammation, widens the airways and reduced mucus secretion
Inhaled Corticosteroids - Adverse Effects
Immunosuppression - oral candidiasis - need to rinse mouth after use
Hoarse voice in COPD
High dose - release into systemic - adrenal suppression, growth retardation and osteoporosis
Inhaled Corticosteroids - Warnings
Cautioned at a high - dose in patients with a history of pneumonia and in children at risk of growth suppression
Leukotriene receptor antagonist - Montelukast - Indications
Adults: Add on if not controlled well by inhaled corticosteroids and LABAs
Children 5-12: alternative to LABAs where inhaled corticosteroids are insufficient
Children under 5 years: 1st line preventative therapy in young children with asthma who cannot take steroids
Leukotriene receptor antagonist - Montelukast - Mechanism of Action
Blocking the CysLT1 receptor and damping down the inflammatory cascade
Leukotriene receptor antagonist - Montelukast - Adverse Effects
Usually well-tolerated
Mild Headache and abdominal pain
Increased rate of URTIs
Rare- hyperactivity
Leukotriene receptor antagonist - Montelukast - Warnings
Not prescribed unless incompletely controlled with inhaled corticosteroids and LABAs
Adrenaline - Indications
Cardiac Arrest - Advanced Life Support - treatment algorithm for shockable and non-shockable rhythms
Anaphylaxis
Injected directly into tissues to induce local vasoconstriction - used in endoscopy to control mucosal bleeding - sometimes mixed with local anaesthetic to control mucosal bleeding - sometimes mixed with local anaesthetic drugs (e.g. lidocaine) to prolong local anaesthetic
Adrenaline - Adverse Effects
Restoration os cardiac output - followed by adrenaline -induced hypertension
When given to conscious patients in anaphylaxis or in an attempt to produce local vasoconstriction - often causes anxiety, tremor, headache and palpitations
Patients with existing heart problems - angina, MI and arrhythmias
Adrenaline - Warnings
None in cardiac arrest or anaphylaxis
For local vasoconstriction - should be given with caution in patients with heart disease
Adrenaline - anaesthetic preparations should not be given in areas supplied by an end-artery - fingers and toes - can cause tissue necrosis
Adrenaline - Interactions
In patients on beta-blockers - may induce widespread vasoconstriction
Adrenaline - Warnings
None in cardiac arrest or anaphylaxis
For local vasoconstriction - should be given with caution in patients with heart disease
Adrenaline - anaesthetic preparations should not be given in areas supplied by an end-artery - fingers and toes - can cause tissue necrosis
Anti-histamine - Indications
Allergy
Relief pruritis and hives (urticaria) due to insect bites, infections and drug allergies
Adjunct treatment in anaphylaxis after administration of adrenaline
Other class used in nausea and vomiting
Anti- histamine - Adverse Effects
1st generation antihistamine (e.g. chlorophenamine) cause sedation - histamine has a role in wakefulness
2nd generation antihistamine (e.g. loratadine, cetirizine and fexofenadine) do not cross the blood - brain barrier - have fewer adverse effects
Anti-histamine - Warnings
Mainly safe
Cautioned in patients with severe liver disease - may precipitate hepatic encephalopathy
Adenosine - Indications
As a first line diagnostic and therapeutic agent in supraventricular tachycardia (SVT), usually evident on the ECG as a regular, narrow - complex tachycardia
Adenosine - Mechanisms of Action
Adenosine is an agonist of adenosine receptors on cell surfaces.
In the heart, activation of these G-protein coupled receptors induces severe effects, including reducing the frequency of spontaneous depolarisation (automacity) and increasing resistance to depolarisation (refractoriness)
In turn, this transiently slows the sinus rate and conduction velocity and increases the AV node refractoriness.
Many forms of SVT arise from a self-perpetuating electrical (re-entry) circuit that takes in the AV node
Increasing refractoriness in the AV node breaks the re-entry circuit, which allows normal depolarisations from the sinoatrial (SA) node to resume control of heart rate (cardioversion).
Where the circuit does not involve the AV node (e.g. in atrial flutter), adenosine will not induce cardioversion.
However by blocking conduction to the ventricles, it allows closer inspection of the atrial rhythm on the ECG
This may reveal the diagnosis
The duration of effect of adenosine is very short because it is rapidly taken up by cells (e.g. red cells)
Its half-life in plasma is less than 10 seconds
Adenosine - Adverse Effects
Can induce bradycardia and even asystole
Deeply unpleasant sensation for the patient
Sinking feeling in the chest - accompanied by breathlessness and a ‘sense of impending doom’
Usually short-lived
Adenosine - Warnings
Should not be administered to patients that cannot tolerate its transient bradycardic effects e.g. those with hypotension, coronary ischaemia, decompensated heart failure
Adenosine may induce bronchospasm in susceptible individuals so should be avoided in patients with asthma or COPD
Patients who have had a heart transplant are very sensitive to the effects of adenosine
Adenosine - Interactions
Dipyridamole, an antiplatelet agent, blocks cellular uptake of adenosine.
This prolongs and potentiates its effect, so the dose of adenosine should be halved.
Theophylline and aminophylline (systemic bronchodilators) are competitive antagonists of adenosine receptors and reduce its effect.
Patients who have taken these drugs respond poorly and may require higher doses
Amiodarone - Indications
Used to treat a wide range of tachyarrhthymias, including atrial fibrillation (AF), atrial flutter, supraventricular tachycardia (SVT), ventricular tachycardia (VT).
Used when other therapeutic options (drugs or electrical cardioversion) are ineffective or inappropriate
Amiodarone - Mechanism of Action
Has many effects on myocardial cells, including blockade of sodium, calcium and potassium channels and antagonism of alpha and beta - adrenergic receptors.
There effects reduce spontaneous depolarisation (automaticity), slow conduction velocity and increase resistance to depolarisation (refractoriness), including in the AV node.
By interfering with AV node conduction, amiodarone reduces the ventricular rate in AF and atrial flutter.
Through its other effects it may also increase the chance of conversion to and maintenance of sinus rhythm.
In SVT involving a self-perpetuating (‘re-entry’) circuit that includes the AV node, amiodarone may break the circuit and restore sinus rhythm.
Amiodarone’s effects in suppressing spontaneous depolarisations make it an option for both treatment and prevention of VT and for improving the chance of successful defibrillation in refractory VF.
Amiodarone - Adverse Effects
In acute use, compared with other anti-arrhythmic drugs, amiodarone causes relatively little myocardial depression.
It can cause hypotension during IV infusion, although this is probably an effect of the solvent with which it is formulated, rather than the drug itself.
When taken chronically, amiodarone has many side effects, several of which are serious.
These include effects on the lungs (pneumonitis), heart (bradycardia, AV block), liver (hepatitis) and skin (photosensitivity and grey discolouration).
Due to its iodine content (amIODarone) and structural similarities to thyroid hormone, it may cause thyroid abnormalities, including hypo- and hyperthyroidism.
Amiodarone has an extremely long half-life.
After discontinuation, it may take months to be completely eliminated
Amiodarone - Warnings
Amiodarone is a potentially dangerous drug that should be used only when the risk-benefit balance justifies this.
It should generally be avoided in patients with increased severe hypotension, increased heart block, and increased active thyroid disease.
Amiodarone - Interactions
Amiodarone interacts with many drugs.
Increases the plasma concentrations of digoxin, diltiazem and verapamil.
This may increase the risk of bradycardia, AV block and heart failure.
The doses of these drugs should be halved if amiodarone is started
