Pharmacology - Pharmacology and Patient Safety Flashcards
Sources of info for dug hx
From patient or relatives From medical notes From clinic letter/ discharge summaries From computer print-out or shard care record Checking the bottle/ packets Nursing home drug charts
Drugs w/ high risk of error
Insulin and warfarin
Bivaribale doses w/ daily adjustment and its individualised (no find dose)
Cross-checking drugs
Check interactions w/ other drugs
Match against hx of allergy, or poor response to similar drugs
Suitability to individual – risk factors for adverse reaction, renal/ liver disease
Steps to choosing a drug
Identify classes of drugs
Compare the groups
Select formulation and trearment duration
Comparing groups of drugs
How they work, what level of efficacy
Safety – adverse effects, interactions
Suitability/ convenience – tablets/ injections, once daily etc
Cost
Avoiding harm
Lowest effective dose, shorter period
Deliver drug directly to site (skin creams, asthma inhalers)
Reduce risk – e.g. give bone protection if pt is on corticosteroids that cause osteoporosis
Consider non-drug options
Drugs that. may cause a haemorrhage if used together
Aspirin – knocks out platelets
Corticosteroid – thins the stomach lining
NSAIDs – dissolves stomach lining
Therapeutic effects of NSAIDs
Anti-infl
Analgesic
Antipyretic
Anti-infl effects of NSAIDs
Decreases PGE2 and PG1E (COX -1,2,3 inhibitors)
Prostacyclin
PGI2
Analgesic effects of NSAIDs
Decreased prostaglandins makes nerves less sensitive to infl mediators (bradykinin, 5-HT)
Antipyretic effects of NSAIDs
Decreased IL-1
Imprecise targets of NSAIDs
Block COX enzymes –> reduces (too many) PG
Useful/ friendly PG blocked
What happens when useful PG are blocked
Stomach – acid gets through, ulcer occurs
Platelet activity – less clotting, more bleeds
How do NSAIDs damage the stomach
Direct erosion of gastric lining
Indirect – block prostaglandins – unable to make protective mucus barrier against acid
Off target problems w/ NSAIDs
Kidney failure
Heart failure
Toxicity of corticosteroids
Little GI toxicity on their own
High risk together w/ NSAIDs
Drugs given for Gout
NSAIDs, colchicine for acute flare-ups
Allopurinol for chronic prevention
Drugs gives for osteoporosis
Bisphosphonates
Denosumab
Efficacy of NSAIDs for Gout
Moderate to good
Safety of NSAIDs for Gout
Short-term OK, but can cause GI bleed, renal failure, heart failure if high dose or longer-term
Suitability of NSAIDs for Gout
Inexpensive, easy to take, but contraindication in GI or cardiac disease
Dose of NSAIDs for Gout
Ibuprofen 400-800 mg tds
Naproxen 750 mg stat, then 250 mg tds for 7 days
Colchicine mechanism
Decreases infl by inhibition of granulocyte migration and inhibition of lymphocyte migration and division
Depolarisation of microtubules
Efficacy of colchicine for Gout
V good
Safety of colchicine for Gout
Nausea and diarrhoea very common
Bone marrow suppression and renal failure over longer term
Suitability of colchicine for Gout
Good option if cannot take NSAIDs; similar efficacy to naproxen but 2x greater diarrhoea
Colchicine prescription
Colchicine 0.5mg tds for 3-4 tds
Stop if diarrhoea/ vomiting
Shouldn’t exceed total 6mg in one course
Low dose can be used longer period e.g. colchicine 0.5mg daily for a few weeks to stop recurrent flares
Other uses of colchicine
Pericarditis (infl of lining of the heart)
Bechet’s disease (urogenital ulcers, arthritis)
Reduce infl after heart attack
Corticosteroids in gout
Anti-infl
Local injection if only single joint affected e.g. wrist
Systemic (tablets) i.e. oral prednisolone if severe
Efficacy of corticosteroids for Gout
Good
Safety of corticosteroids for Gout
Short-term is generally ok
Suitability of corticosteroids for Gout
Those who cannot have NSAIDs or colchicine (e.g. older patients w/ multiple co-morbidities)
Canakinumab
Selective inhibitor of IL-1 receptor
Subcutaneous injection, can last up to 12 weeks
For patients affected by frequent, severe acute gout that isn’t relieved by other drugs
Prevention of Gout
Reg treatment to Lowe uric acid levels
Preventative therapy
Drugs used in Gout attacks
Allopurinol
Febuxostat
Allopurinol pharmacology
Xanthine oxidase inhibitor
Reduces uric acid production and therefore lowers serum levels
Efficacy of allopurinol for Gout
Very good, adjust dose by serum levels (100 - 600 mg daily) and renal function
Safety of allopurinol for Gout
Good; on rare instances – serious allergy
Interactions w/ allopurinol
Purine analogues
Theophylline
Suitability slitty of allopurinol for Gout
First-choice drug; often given life-long
Allopurinol prescription
Allopurinol 100mg daily initially
Check uric acid in a couple of weeks
Up-titrate to desired level
Caution: dose adjustment needed in renal failure
Febuxostat
Newest drug on the marker, expensive
Non-purine xanthine oxidase inhibitor
However, increased risk of cardiovascular problems w/ febuxostat
When is febuxostat recommended by NICE
Can’t take allopurinol for medical reasons or
Side effects of allopurinol so bad that person can’t take the recommended amount
Bisphosphonates pharmacology
Analogues of pyrophosphate
Attach to bone crystals – inhibit osteoclast breakdown of bone
Efficacy of bisphosphonates for osteoporosis
Very good
Safety of bisphosphonates for osteoporosis
GI upset is main problem
Suitability of bisphosphonates for osteoporosis
Inexpensive, widely used but long-term adherence difficult
Zolendronic acid
Type of bisphosphonate
Once a year iv injection is available
Denosumab pharmacology
Monoclonal antibody – RANK Ligand inhibitor
Reduces osteoclast activation, differentiation and survival
Efficacy of denosumab for osteoporosis
V good
Suitability of denosumab for osteoporosis
Recommend by NICE if phosphonate; only need 1 subcut injection every 6 months
Less widely used NICE approved drugs
‘Oestrogen’ like molecules - rafloxifene
Teriparatide
Teriparatide
Recombinant parathyroid hormone – intermittent use activates osteoblast to deposit bone
Therapy for infl arthritis
Surgery
DMARDs e.g MTX, SSX, LFN, anti-TNF, gold
Non DMARDs e.g NSAID, paracetamol
Therapeutic targets in infl arthritis
Relieve pain, swelling and other symptoms e.g. fatigue
Avoid permanent joint damage
Reduce systemic complications of chronic infl e.g. anaemia of chronic disease, amyloidosis
When are local injection of corticosteroids suitable
Single, large joint
Toxicity w/ repeated use
Efficacy of MTX for infl arthritis
V good
Safety of MTX for infl arthritis
Major problems – immunosuppression, liver toxicity, lung damage
Folic acid given on another day – can reduce toxicity
Regular monitoring required
Suitability of MTX for infl arthritis
Avoid if liver problems
Drug interaction of MTX
Trimethoprim
Possible dosage regimens of MTX
Methotrexate on Mondays e.g. 7.5 mg once a week (oral or subcutaneous injection)
Folic acid 5 mg on Friday (this varies considerably amongst hospitals)
Check full blood count, renal and liver function within a few weeks
Can titrate up to 20 mg over some months if inadequate
Main TNF-alpha blocking agents
Infliximab
Etanerceprt
Adalimumab
Etanercept
Recombinant DNA human TNF-alpha receptor binds to TNF to stop its activity
NICE guidance of TNF-alpha inhibitors
Active RhA disease activity
Tried at least 2 DMARDs (incl methotrexate) for >6 months
Should normally be used together w/ methotrexate
Efficacy of TNF-alpha inhibitors for infl arthritis
V good
Safety of TNF-alpha inhibitors for infl arthritis
Injection reactions, immunosuppression
Suitability of TNF-alpha inhibitors for infl arthritis
Expensive, needs infusion or injection
If TNF-alpha inhibitors fail
• Lots of drugs directed at other targets
CD20 – rituximab
IL-6 – tocilizumab
Janus Kinase (JAK) – tofacitinib, baricitinib (these can be given orally, so more convenient for patients)
Drugs in Ankylosing Spondylitis (AS)
Adalimumab or etanercept
Drugs in PsA
Adalimumab or etanercept or infliximab
Drugs in juvenile idiopathic arthritis
Etanercept and newer agents e.g. golimumab and tocilizumab
Drugs in SLE
Belimumab (inhibits B-cell activating factor), hydroxychloroquine, corticosteroid
Steroid local injections in rheumatology
Triamcinolone
Methylprednisolone
Steroid oral tablets in rheumatology
Prednisolone; e.g. 30 mg daily for 2 weeks in acute flares
Intravenous forms of steroid in rheumatology
Hydrocortisone
Methylprednisolone (e.g. 1 g a day for 3 days)
Topical steroid in rheumatology
Multiple formulations of different strength
Major safety problems w/ corticosteroids
Cushing’s disease - tapering of steroid is too slow
Addison’s disease - tapering of steroids is too fast
Medication errors
Errors of omission
Errors of commission
Errors of omission
Omitted dose or failure to adequately monitor
Errors of commission
Errors in wrong medication or wrong dosage
Factors contributing to drug errors
Distractions in environment
Training and eduction
Medication products and packaging
Inability to read drug administration chart
How prescribers can reduce errors
Write legibly Checking of computer-generated prescriptions Check the dosage and frequency Confirm the route Consider drug interactions Identify drug allergies
When is diclofenac prescribed
Post-op, good for acute pain, but not long term as increases risks of cardiovascular event
Apply topically
Routes of administering NSAIDs
Orally
Topically
s/l
Per rectum