Flashcards in Pharmacology Deck (68):
List the different classes of lipid lowering drugs ( 5 in total)
What is usually the first line treatment for lowering lipid levels? If this is contraindicated what is normally second line?
How does treatment for hyperlipidaemia differ in primary and secondary prevention
Primary - 40mg simvistatin daily
Secondary to diabetes: 40 mg simvistatin and if no response change to atorvastin 40mg daily
Secondary to MI: 80mg atorvastin daily
Familial hyperlipidaemia - start with simvastatin and work up to atorvastin if no change
How do statins work?
Inhibit HMG co A reductase in the liver to reduce cholesterol synthesis and thus LDL and vLDL synthesis.
This reduces the plasma levels of LDL and leads to increased LDL receptor expression meaning further removal of LDL
HDLs also increase
How does nicotinic acid work ?
Inhibits the synthesis of lipoprotein A therefore reducing vLDL and increasing LDL
How do fibrates work?
Agonists of PPARa and thus have a number of effects on gene expression. One of these is the increase in lipoprotein lipase and thus triglycerides are broken down into FFAs and glycerol
Therefore mainly act by reducing triglyceride levels
How does ezetimibe work?
Inhibits NPL1L which is a transporter on the intestinal brushborder
This means less cholesterol enters the enterohepatic circulation and thus less cholesterol reaches the liver
The reduction in LDL in plasma leads to increase in LDL receptor level
How do resins work?
Bile acid sequestrants - less cholesterol reabsorbed
Results in increased LDL receptor activity
Name a resin
What are the ADRs of statins
Raised transaminase levels (however this is reversible so not thought to be linked to chronic liver disease)
Myopathy/ rhabdomyolysis - raised CK levels and muscle pain
When are statins contraindicated?
Pregnancy / lactation
Need to be cautious if porphyria , people susceptible to rhabdomylosis, if hypothyroid (correct this first), renal disease, high alcohol intake
How are patients on statins monitored and advised?
- lipid levels - check it's working
- CK before and when symptomatic
- TFTs before to check for hypothyroid
- LFTs. Before and throughout
- take with food
- diet advice to help lower lipids
- reduce alcohol
- warn of myopathy side effects
What are the drug drug interactions of statins ?
Grapefruit and verapamil are cyp450 inhibitors and so increase statins and thus risk of myopathy
Amiodarone , clarithromycin, antifungals, cyclosporin, colchine , gemfibrozil and nicotinic acid all increase risk of myopathy
St. John's wort and rifampicin are cyp450 inducers and so reduce statin levels
What are the ADRs of fibrates?
When are fibrates mainly indicated?
Patients with hypertriglyceridaemias or combined hyperlipidaemia
What are the contraindications of fibrates?
Liver , renal or pre-existing gall bladder disease
What are the DDIs of fibrates?
Rosiglitazone and gemfibrozil means the dose of rosiglitazone is increased
Repaglipide and gemfibrozil means there is an increased risk of hypoglycaemia
What are the ADRs of nicotinic acid
Hyperglycaemia and insulin sensitivity
Due to this nicotinic acid is not used often
Contraindications to using nicotinic acid
What are the ADRs of ezetimibe ?
Diarrhoea and abdo pain
What are the DDIs of ezetimibe?
Cyclosporin and ezetimibe - conc of both drugs increases
Increased risk of myopathy with lipid lowering drugs
What are the ADRs of resins ?
Constipation , diarrhoea , nausea, vomiting, bloating
What are DDIs of resins?
Affect absorption of other drugs e.g. Thiazides, fat soluble vitamins , thyroid hormones, digoxin
What happens if a patient on statins is complaining of muscle ache and their CK is raised
Stop statins therapy immediately
What are the uses and problems of using combination therapy for lipid lowering
Good because more effective at lowering lipid levels however increases the risk of myopathy
List some drugs that can alter an individuals lipid profile
Testosterone, oestrogen and progesterone
Ciclosporin and tacrolimus
What life style advice would you give to someone with hypercholestrolamia
Reduce saturated fats
Increase fish oils and vit c/e
Aim for good BMI and blood pressure
Alcohol in moderation
What are the biological therapies used in rheumatology?
Anti B cell
What is the action of glucocorticoids in rheumatology?
Inhibit gene expression of IL1 and IL6 therefore inhibit T cell activation. This leads to immunosupression
What are the ADRs of corticosteroids?
Increased risk of glaucoma
What are the contraindications / cautions that need to be considered when prescribing glucocorticoids?
If patient is on antihypertensive medication - Try to avoid corticosteroids because these will counteract the medication
Patients on warfarin need to be taken with caution because corticosteroids increases anticoagulant affect of warfarin
What is the mechanism of action of methotrexate ?
In cancer cells it inhibits DHFR, inhibiting the conversion of dihydrofolate to tetrahydrofolate. Therefore inhibits s phase to kill rapidly dividing cells
In non cancer cells it inhibits purine metabolism , adenosine accumulates and suppresses T cells
How is methotrexate administered ?
Orally, IM or SC but mainly IM because better bioavailability
Given once a week because active metabolite has a long half life
What are the ADRs of methotrexate?
Hepatitis and cirrhosis
Bone marrow suppression - increased infection risk, cancer and anaemia
People on immunosuppressive medication, need additional care , what may this consist of?
Vaccines due to increased infection risk
Regular monitoring of cancer
FBC for bone marrow suppression etc
What are the DDIs of methotrexate?
Therapeutic with other DMards and steroids
NSAIDs displace plasma protein binding sites
What monitoring is needed for patients on methotrexate ?
What is hydroxychloroquine?
Antimalarial that can be used as a DMARD because it inhibits TLR and therefore reduces inflammation
Used for RA and SLE skin and joint disease
Safe and well tolerated in pregnancy
What 2 metabolites does sulphasalazine consist of?
5ASA - active anti inflammation component.
sulfapyramide - helps get to target site and fight infection
How does sulphasalazine work ?
Inhibits T cell proliferation , il2 production, neutrophil chemotaxis and degranulation
Why is sulphasalazine especially good in IBD?
It is poorly absorbed and in fact not absorped until lower GI tract by cleavage from bacteria and therefore remains mainly in GI tract
What are the ADRs of sulphasalazine ?
Common : nausea, fatigue , abdo pain and headaches
Uncommon: myelosupression, hepatitis, rash
Which DMARDs are safe in pregnancy ?
How does cyclophosphamide work?
Metabolites of this drug cross link DNA and prevent replication
What are the ADRs of cyclophosphamide
Quite serious side effects
Bladder cancer - metabolite is toxic to the epithelium
Leukaemia / lymphoma
Infertility / teratogen
Because of this only really used in life threatening lupus or vasculitis
How can the toxicity of cyclophosphamide be reduced?
Drink lots of water
Take Mensa - binds to toxins
How does azothioprine work?
Metabolised to 6MP (purine analogue) and therefore inhibits DNA/ RNA synthesis
How is azothioprine eliminated and what precautions should be taken ?
By TPMT enzyme
There is genetic polymorphism in expression of this
Need to find level of expression before administering safe dose
What are the ADRs of azothioprine?
Bone marrow suppression - infection , malignancy
How does mycophenolate work?
It's metabolite inhibits an enzyme responsible for guanine synthesis
This enzyme is particularly important in B and T cells and so other dividing cells are sparred
What are the ADRs of mycophenolate?
Myelosupression --> infection
Nausea, vomiting and diarrhoea
Who else may mycophenolate be used in other than rheumatology patients?
Name 2 calcineurin inhibitors
How do calcineurin inhibitors work ?
Inhibit calcineurin leading to inhibition of t helper cell and IL2
What are the ADRs of calcineurin inhibitors ?
Increase glucose and cholesterol
No effect on bone marrow
What are the DDIs of calcineurin inhibitors?
NSAIDs due to renal toxicity
What regular checks need to be done on someone taking calcineurin inhibitors?
Name 3 anti - TNFs
When are anti TNFs indicated ?
When methotrexate and one other dmard have been tried and there is still evidence of active RA
What are the ADRs of anti TNF?
Increased risk of infection, TB reactivation and malignancy
What are the contraindications of anti TNF ?
Women who are pregnant / breast feeding
Malignancy in last 10 years
Risk of infection: leg ulcers, latent TB
Give the name of a type of anti B cell drug?
Rituximab - monoclonal anti CD20 Ab
How is rituximab given?
Pair of infusions every 6 to 12 months
When is rituximab indicated?
Given in RA when anti TNF has failed
Main indication is non hodgekins lymphoma
How does rituximab work?
Apoptosis of CD20 positive B cells
Therefore spares memory cells - risk of infection is low
Name an IL6 antagonist
what advice should be given for taking statins?
eat night - cholesterol synthesis occurs at night so most effective this way.
take up right on empty stomach