Pharmacology and prescribing Flashcards
how can you find out what drugs a patient takes?
- from patient or relatives
- from medical notes
- from clinic letters / discharge summaries
- from the GP (shared care records)
what are the 2 mechanisms in which NSAIDs can damage the stomach?
- direct: erosion of gastric lining
- indirect: blocks COX enzymes so decreased lvls of prostaglandins, therefore unable to make protective gastric mucus barrier against acid
what can be given to reduce the risk of a GI bleed in a patient who takes drugs which increases their risk (eg. patient takes NSAID+aspirin+prednisolone)
Give a gastroprotective agent:
- Proton pump inhibitor (PPI) or H2 antagonist to reduce gastric acid
- Misoprostol: prostaglandin analogue that increases gastric mucus to protect stomach
what are the 2 main drugs used to treat osteoporosis?
- bisphosphonates
- denosumab
what is gout and what causes crystals to form, and what class of drugs are a risk factor for gout?
- gout is monosodium urate crystals
- can also get gouty tophi in soft tissues
Crystals form with rise in uric acid concentrations…
- Overproduction (diet, genetic factors)
- Reduced ability of kidney to get rid of uric acid
- Influence of drugs (eg. Thiazide diuretics used in treatment of high BP)
what are some side effects of NSAIDs?
short term OK, longer term and higher doses…
- peptic ulcers, cause GI bleeding
- renal failure
- heart failure
what are some side effects of colchicine?
- common: nausea, diarrhoea, abdo pain
- longer term: bone marrow suppression
how does allopurinol work to reduce uric acid production?
- inhibits xanthine oxidase which reduces serum levels of uric acid
how do bisphosphonates work? (and give 2 examples)
- attach to bone crystals, inhibit osteoclast activity
- eg. alendronic acid, zolendronic acid (once a year IV injection)
how does denosumab work?
- monoclonal antibody: RANKL inhibitor
- therefore reduces osteoclast activity
what are some side effects of methotrexate?
- immunosuppression (can make patient susceptible to infections)
- liver toxicity
- lung damage
- teratogenicity
what drug should not be taken with methotrexate (hint: the drug is commonly used to treat UTIs)
- trimethoprim
what corticosteroids are taken as oral tablets and what corticosteroids are given intravenously?
- oral tablets: prednisolone
- IV: hydrocortisone, methylprednisolone, dexamethasone
What is Cushing’s disease?
Too much steroids (caused by tapering of steroids being too slow)
- symptoms: osteoporosis, obesity, hypertension, hyperglycemia
What is Addison’s disease and what is the emergency condition that can occur?
Too little steroids ( (body doesn’t have enough cortisol): caused by tapering of steroids being too fast
- symptoms: nausea, headaches, fever, hypotension, hypoglycaemia
what is the chemical name for heroin?
- 3, 6-diacetylmorphine or diamorphine
What is the chemical name for codeine?
- 3-methylmorphine
Is the half-life of morphine short or long, how does this affect how often it is needed to be taken?
- short (3-6 hrs usually)
- therefore most morphine derivatives have to be given multiple times a day (or synthetic patches given which is slow release)
Where is morphine metabolised and excreted?
- metabolised in liver
- excreted in urine
If giving a morphine derivative IV or IM, should you choose a lower or higher dose compared to oral?
- lower dose
What is the main opioid receptor antagonist? (eg. you would give this if somebody overdosed on morphine or another opioid)
- Naloxone
- given IV/SC in acute opioid toxicity (eg. drowsy patient with small pupils and poor respiration)
What is the most important opioid for severe pain?
- Morphine
What drugs are often given alongside morphine?
- anti-emetics (for the vomiting): eg. metoclopramide, ondansetron
- laxatives (if long term use): eg. lactulose
When is diamorphine typically used?
- palliative care
What is a prodrug?
- a medication that after intake is metabolised into a pharmacologically active drug
Codeine is a prodrug, what is it metabolised into in the liver?
- morphine
Which drug is used in substitution therapy to reduce IV drug use?
- methadone (orally)
Would you prescribe opioids for neuropathic pain?
- no
Would you prescribe opioids for migraine or tension-headaches?
- no
How would you deal with opioid tolerance?
- starting dose of morphine (5-10mg in most patients, higher if no response)
- with regular use, review dose every few days, and increase by 30-50% if pain recurs
What is meant by pharmacodynamics?
- pharmacodynamics = drug action in humans
What are the 4 important sites of drug action?
- receptors
- enzymes
- ion channels
- transporters
What is the difference between an agonist and an antagonist regarding drugs?
- agonist (right key for right lock): drug that binds to receptor site and elicits a response (eg. morphine)
- antagonist (right key for right lock, but doesn’t work/blocks it): drug that binds to receptor site and does not elicit a response/blocks agonist from working (eg. naloxone)
What is meant by the term pharmacokinetics?
- pharmacokinetics = what the body does to the drug
What are some factors that affect drug concentrations (ie. how the drug passes through the body)?
- bioavailability: proportion of drug that passes into systemic circulation (eg. absorption from stomach affects this)
- then first-pass metabolism (eg. activation or breakdown by liver enzymes)
- clearance/excretion (metabolism and elimination through urine)
What is meant by the term half-life?
- half-life = time taken for drug concentration to fall to half its initial value (tells us how long the drug is in body)
Name 4 ways in which a drug can be administrated.
- oral
- injection
- rectal
- topical
- sub-lingual (under tongue)
- inhaled
What is meant by the term receptor?
- receptor = protein molecule in or on cells whose function is to interact with the bodies endogenous chemical messengers and initiate a physiological response
- (basically when a “drug” binds to receptor, it initiates a physiological response)
What are the 4 types of receptors?
- ligand gates (ion channels)
- G protein coupled receptors
- kinase linked receptors
- nuclear receptors
What is meant by the term affinity and why is it important?
- affinity = how well a drug binds to a receptor
- if we know how much drug we need to occupy our receptor site we begin to understand how much drug we need for therapeutic response
Describe how paracetamol helps to reduce fever
- Paracetamol is a COX enzyme inhibitor (thought to be selective for COX-3)
- (COX enzymes stimulate the production of prostaglandins)
- In fever, the temperature set point is elevated by the production of PGE2
- Paracetamol helps to prevent PGE2 synthesis, PGE2 is the main compound that alters the homeostatic temperature set point in the hypothalamic neurons that regulate body temperature
- PGE2 synthesis is stimulated by cytokines (IL-1, TNF-alpha) which are produced by the action of bacteria/viruses on the immune system
- By blocking PGE2 synthesis, paracetamol brings down the temperature set point to normal
During his last few months of life the patient was prescribed morphine. Describe how morphine works
- Morphine attaches to opioid receptors (Mu)
- Morphine reduces membrane excitability and hence action potential firing frequency
- (Opioids act on the dorsal horn as well as the peripheral terminals of nociceptive afferents neurons)
- Thus preventing pain signals travelling up the spinal column
- Morphine also increases release of enkephalins and 5-HT (serotonin) onto dorsal horn neurons via stimulation of the periaqueductal grey matter (PAG) and the raphe nucleus
How might the side effects of morphine undermine the quality of life in end stage cancer treatment?
- Undermines physical wellbeing
- side effects: constipation, nausea, confusion, sedation
What class of hormone is cortisol?
- Steroid hormone
In which anatomical structure is cortisol synthesised and what is the precursor molecule from which it is made?
- Synthesised in the zona fasciculata (ZF) of adrenal cortex/gland
- Precursor molecule is cholesterol
Hormones act by binding to receptors to transduce their signal into cells, describe how cortisol transduces its signal
- It is a lipid soluble hormone which diffuses into cells
- binds to its receptor inside the cell in the cytoplasm
- receptor/hormone complex moves into the nucleus to bind to DNA and activates or repress gene expression
Name two other important issues, other than drug interactions, which need to be addressed for patients prescribed methotrexate
- Need for folic acid to reduce side effects and regular bloods to monitor
- Common side effects: nausea, increased risk of infection
- Avoid pregnancy / alcohol
Name four routes of administration or forms of drug, apart from oral, which should be considered in a full drug history
- Rectal (eg. Suppositories)
- Sublingual (eg. Spray, dissolvable tablet)
- Topical (eg. Spray, cream)
- Inhaled/nebuliser
- Eye drops
what are the effects of old age on prescribing?
- metabolism slower (liver enzymes slower)
- kidneys: excretion of medications slower (drugs spend more time in the body)
- medications have different effects (eg. need lower dose of diazepam in elderly)
- polypharmacy due to multiple diseases / interactions of medications
where are glucocorticoids secreted from?
- from the cortex within adrenal glands (ZF)
what are the 3 main types of opioid receptors and their functions?
- Mu (for morphine): analgesia, euphoria (but also constipation, respiratory depression)
- Kappa (for ketcyclazocine): analgesic at periphery (but also dysphoria, hallucinations)
- Delta for vas Deferens: analgesic effects at spinal cord
what are the effects and side effects of morphine, and then what are 2 things that you need to be aware of with long-term opioid use?
EFFECTS:
- analgesia, euphoria, sedation, pupil constriction
SIDE EFFECTS:
- nausea and vomiting (chemoreceptor trigger zone in medulla)
- constipation (from reduced motility and muscle tightening)
- respiratory depression (inhibits respiratory centres in brainstem)
- suppressed cough reflex
- tolerance: with recurrent use: desensitisation of Mu receptors, dose has to be increased
- dependence: physical (restless, aggression, runny nose, shivering) and psychological (cravings may persist for months and years)
where are opioids metabolised and excreted?
- metabolised in liver
- excreted in urine
what are some considerations to take into account when prescribing morphine?
- most morphine derivatives have a short half-life so have to be given several times a day
- IV/IM morphine: choose lower dose as compared to oral
- synthetic opioid patches go on releasing the drug for days and days so check and remove if toxicity is suspected, or if change in drug/dose is needed
what pathways do NSAIDs and aspirin block?
- cyclooxygenase (COX enzymes)
- COX 1, COX 2, COX 3
what pathways do corticosteroids block?
- they block the conversion of phospholipids to arachidonic acid
why do NSAIDs have anti-inflammatory, analgesic, and antipyretic effects?
- Anti-inflammatory: decreases lvls of prostaglandin E2 and prostacyclin
- Analgesic: decreases lvls of prostaglandins which makes nerves less sensitive to inflammatory mediators (eg. bradykinin)
- Anti-pyretic: decreases lvls of IL-1
what drugs can be given to reduce the risk of GI problems?
- Proton pump inhibitor (PPI) or H2 antagonist: to reduce gastric acid
- Misoprostol: prostaglandin analogue that increases gastric mucus to protect stomach
what pathway does methotrexate target and mechanism of methotrexate?
- folate pathway
- methotrexate is an antimetabolite that inhibits dihydrofolate reductase
what drug should be taken with methotrexate, when should you not give methotrexate, and what drug should you not give methotrexate with?
- folic acid should be given (on another day) to reduce toxicity
- avoid if patient has liver problems, avoid in pregnancy
- do not give methotrexate and trimethoprim together
how much and when should methotrexate be prescribed, and folic acid, and what should be monitored?
- methotrexate 7.5mg once a week (oral or subcutaneous injection)
- folic acid 5mg once a week (on a different day to methotrexate)
- do FBC, renal, and liver function tests regularly
what are the main anti-TNF biologics?
- Infliximab
- Entanercept
- Adalimumab
when should anti-TNF biologics be prescribed according to NICE guidance and what is the issue with anti-TNFs?
- patient has active RA disease activity
- tried at least 2 DMARDs (including methotrexate) for >6 months
- anti-TNFs should usually be used together with methotrexate
- problem with anti-TNFs: expensive, have to be given by injection or infusion
what should be prescribed if anti-TNF biologics do not work?
- Rituximab: targets CD20
- Tocilizumab: targets IL-6
which corticosteroids are given in what forms?
- oral tablets: prednisolone (eg. 30mg daily for 2 weeks in acute flares)
- IV: hydrocortisone, methylprednisolone, dexamethasone (eg. 1g a day for 3 days)
what drugs are prescribed for acute gout flare-ups?
- NSAIDs (ibuprofen, naproxen)
- colchicine
- corticosteroid (local injection or oral)
what drugs are prescribed for chronic gout (prevention)?
- allopurinol
- (or febuxostat)
what is the mechanism by which colchicine works?
- inhibits granulocyte migration
- this causes depolarisation of microtubules
- this causes inhibition of lymphocyte migration and division
- results in decrease in inflammation
when should corticosteroids be given in gout?
- local injection should be given if only single joint affected
- (this is better than patient taking naproxen for eg. for 2 weeks)
what is the mechanism by which bisphosphonates work?
- pyrophopshate analogue
- attach to bone crystals and inhibit osteoclast breakdown of bone
what are the main side effects of bisphosphonates and what should the patient be told to do regarding taking the medication to help reduce side effects?
- oesophageal problems (eg. dyspahgia), upper GI problems
- rarer: osteonecrosis of the jaw, hypocalcaemia
- take on an empty stomach at least 30 minutes before breakfast or any other oral medicines
- after taking, patients should remain sat or stood upright for at least 30 minutes
how does Denosumab work?
- monoclonal antibody: RANK ligand inhibitor
- reduces osteoclast activation, differentiation, and survival
- used if patients cannot have bisphosphonates, 1 injection every 6 months
What enzyme is required to generate arachidonic acid from membrane phospholipids and what drug class can stop this reaction?
- Phospholipase A2
- steroids
What enzymes are required to generate Prostaglandins from Arachidonic acid and name 2 drugs which can block these enzymes?
- Cyclooxygenase 1+2 (COX 1+2)
- Aspirin/Non-steroidal anti-inflammatory drugs
Mechanism of action of NSAIDs.
- NSAIDs inhibit cyclooxygenase/COX (which is responsible for converting the arachidonic acid into endoperoxidase)
- Reduction of COX enzymes decreases prostaglandin production, therefore reducing inflammation and pain sensation (as well as decreasing thromboxane A2 and prostacyclin production)
Side effects of corticosteroids.
- central obesity, moon face
- acne, thinned skin
- immunosuppression
WHO analgesic ladder…
A patient is taking methotrexate for RA, they are planning on being pregnant in the next year, what should be done for this patient?
- a washout at least 3 months before conception
- methotrexate should be avoided during pregnancy due to the risk of teratogenicity
What are the side effects of hydroxychloroquine?
- retinopathy, rash
