Passmed pharmacology revision Flashcards
Key side effects of colchicine
NSAIDs and colchicine are 1st line in the management of gout.
Key SE of colchicine is diarrhoea.
Azathioprine
MOA
Adverse effects
Interaction
Safe in pregnancy?
MOA - azathioprine is a purine analogue that inhibits purine synthesis. It is metabolised to active compound mercaptopurine.
Thiopurine methyltransferase test may be needed to look for individual’s prone to azathioprine toxicity.
Adverse effects include:
- bone marrow depression
- N& V
- Pancreatitis
- increased risk non melanoma skin cancer
Significant interaction occurs with allopurinol.
Generally considered safe in prengnacy.
Rheumatic drugs and pregnancy:
Methotrexate
Patients using methotrexate need effective contraception during and for at least 6 months after tx has stopped before conceiving.
Methotrexate :
MOA
Indication
Adverse effects
Pregnancy rules
When is it taken?
Monitoring required?
Interactions and toxicity?
MOA: inhibits dihydrofolate reductase (enzymes needed for synthesis of purines and pyrimidines).
Indicated in: inflammatory arthritis especially RA, psoriasis, chemo in ALL.
Adverse effects:
Mucositis (oral ulcers)
Myelosuppression
Pneumonitis
Pulmonary fibrosis
Liver fibrosis
Pregnancy –> avoid pregnancy for at least 6 months after tx stopped.
Methotrexate is taken weekly not daily.
FBC, U&Es and LFTs need to be monitored before starting treatment, then weekly until stabilised, then every 3 months.
Folic acid 5mg should be co- prescribed, taken 24 hours after methotrexate.
Starting dose of methotrexate is 7.5mg weekly. Only one strength of methotrexate tablet should be prescribed 2.5mg.
Trimethoprim & cotrimoxazole –> increased risk bone marrow aplasia.
High dose aspirin increases risk methotrexate toxicity.
Which electrolyte abnormality is most likely in chronic alcoholism?
What are other causes of this electrolyte abormality?
How may it present?
What is the treatment?
Hypomagnesaemia often caused by chronic alcoholism.
Other causes of low magnesium:
- diuretics
- PPIs
- -total parental nutrition
- diarrhoea
- -alcohol
- hypokalaemia
- hypercalcaemia - secondary to hyperparathyroidism =, calcium and magnesium functionally compete for transport
Presents similar to hypocalcaemia:
- paraesthesia
- tetany
- seizures
- arrythmias
- decreased PTH secretion –> hypocalcaemia
- ECG features of hypokalaemia (U waves)
- exacerbates digoxin toxicity
under 0.4 mmol/L with tetany, seizures or arrythmia then IV magnesium replacement commonly given
over 0.4 mmol then oral magnesium salts (10-200 mmol orally per day, note diarrhoea can occur with oral magnesium salts).
poisonings and treatment:
Ethylene glycol
Ethylene glycol is in antifreeze/ coolants. When ingested toxicity is divided into 3 stages:
stage 1 - alcohol intoxication symptoms - confusion, slurred speech, dizziness
stage 2 - metabolic acidosis, tachycardia hypertension
stage 3 - AKI
Treated with fomepizole - inhibits alcohol dehydrogenase
Treatment for overdose with:
Benzodiazepine
Paracetamol
Opiod
Carbon monoxide
Benzodiazepine - flumazenil
paracetamol - N acetylcysteine
Opiod - Naloxone
Carbone monoxide - hyperbaric oxygen
Drugs causing lung fibrosis
amiodarone
Antirheumatoid - methotrexate, sulfasalazine
cytotoxic agents - bleomycin
nitrofurantoin
dopamine receptor agonists - bromocriptine, cabergoline
Digoxin - MOA and uses?
Digoxin toxicity:
Presentation
Causes
Digoxin - cardiac glycoside, used in rate control in AF and sometimes for improving symptoms in heart failure.
MOA- decreases conduction via AVN slowing ventricular rate in AF & flutter. Increases force of cardiac muscle contraction by inhibition of Na/KATPase pump
Digoxin has a narrow therapeutic index - toxicity can occur even if the concentration is in the therapeutic range therefore digoxin level not monitored routinely, except in suspected toxicity.
Likelihood of toxicity increases progressively from 1.5-3 mcg/l
Presentation:
- lethargy, N&V, anorexia, confusion, yellow green vision
- arrythmias
- gynaecomastia
Causes:
- hypokalaemia - as digoxin competes with K+ for binding on Na/K ATPase, therefore lower K+ increases digoxin activity
- increasing age
- renal failure
- The hypos - hypoMg, hypoalbuminaemia, hypothermia, hypothyroidism
- The hypers - Ca / Na
- Other drugs: amiodarone, CCB verapamil and diltiazem, spironolactone, thiazides and loop diuretics (by causing hypokalaemia).
Phosphodiesterase V inhibitors
names
uses
SE
contraindications / interactions
- PDE inhibitors are used in the treatment of ED (and pulmonary hypertension)
- they cause vasodilation through an increase in cGMP leading to smooth muscle relaxation in blood vessels supplying the corpus cavernosum
Examples:
Sildenafil (viagra), tadalafil (cialis), vardenafil (levitra)
Contraindications:
- Patients taking nitrates and related drugs e.g. nicorandil
- hypotension
- recent stroke or MI (wait for 6 months)
SE:
- visual disturbances - the BLUE pill (viagra) causes blue discoloration of vision
- headache
- flushing
- nasal congestion
- priapism
- GI side effects
Serotonin syndrome
Causes
Features
MX
- Causes:
- SSRI
- St johns wort interacts with SSRI
- Triptans
- ectasy
- amphetamines
- SSRI
- Features:
- neuromuscular excitation –> hyperreflexia, myoclonus, rigidity
- ANS excitation –> hyperthermia, sweating
- altered mental state –> confusion
- Mx:
- IV fluids
- benzodiazepines
- more severe cases are managed using serotonin antagonists - cyproheptadine and chlorpromazine
TB medications and SE?
RIPE - rifampicin, Isoniazid, pyrazinamide, ethambutol
- Rifampicin:
- potent liver enzyme inducer
- hepatitis
- orange secretion
- flu like symptoms
- Isoniazid
- liver enzyme inhibitor
- peripheral neuropathy - prevent with pyridoxine (Vitamin B6)
- hepatitis
- agranulocytosis
- Pyrazinamide:
- hyperuricaemia - gout
- arthralgia, myalgia
- hepatitis
- Ethambutol:
- optic neuritis - check visual acuity before and during treatment
- dose adjusted with renal impairment
Allopurinol
MOA & uses
When is it recommended to start treatment?
SEs
Interactions
Allopurinol is used in the prevention of gout, by inhibiting xanthine oxidase - therefore prevents formation of uric acid.
Allopurinol should be started after the attack has settled down to allow a patient to make the decision to start urate lowering therapy when not in pain.
- urate lowering therapy should be offered to all patients after their first attack of gout. Especially if:
- > 2 attacks in past 12 months
- tophi
- renal disease
- urci acid renal stones
- prophylaxis if on cytotoxics or diuretics
Adverse effects –> Rashes!
- severe cutaneous adverse reaction (SCAR), SJS, Drug reaction with esoniophilia nad systemic symptoms (DRESS).
Interactions:
Azathioprine (normally metabolised to active compound 6 mercaptopurine, then metabolised by xanthine oxidase. Allopurinol can lead to high levels of active azathioprine. This can lead to neutropenic sepsis & excessive myelosuppresion.
Cyclophosphamide - (cytotoxic drug) - allopurinol reduces renal clearnace therefore may lead to bone marrow suppresion
Theophylline - allopurinol can cause increase in plasma concentraion of theophylline, inhibiting its breakdown
Which NSAID is known for increased risk of CV events?
what are the contraindications to its use?
Diclofenac is associated with increased risk of CV events compared to other NSAIDS.
Diclofenac is contraindicated in patients with:
- IHD
- Peripheral arterial disease
- Cerebrovascular disease
- congestive heart failure
patients should be switched from diclofenac to other NSAIDs e.g. naproxen or ibuprofen
What are the signs of TCA overdose?
on ECG?
Management?
- Early features –> dry mouth, dilated pupils, agitation, sinus tachycardia, blurred vision
- severe poisoning:
- arrythmia
- seizures
- metabolic acidosis
- coma
- ECG changes:
- sinus tachycardia
- widened QRS
- prolonged QT interval
- Management:
- IV bicarbonate -
- TCA overdose –> acts as potent Na channel blocker. Leads to widening or QRS. Can degenerate into VT, therefore to prevent this need to alkanise the serum with IV Sodium bicarbonate.
- first line for hypotension or arrhythmia
- indications are widened QRS interval > 100 msec or ventricular arrythmia
