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Flashcards in Pharmacology Deck (68):
1

List the different classes of lipid lowering drugs ( 5 in total)

Statins
Fibrates
Nicotinic acid
Ezetimibe
Resins

2

What is usually the first line treatment for lowering lipid levels? If this is contraindicated what is normally second line?

Statins
Ezetimibe

3

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

4

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

5

How does nicotinic acid work ?

Inhibits the synthesis of lipoprotein A therefore reducing vLDL and increasing LDL

6

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

7

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

8

How do resins work?

Bile acid sequestrants - less cholesterol reabsorbed

Results in increased LDL receptor activity

9

Name a resin

Cholestyramine

10

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

GI complaints
Headache
Arthralgia

11

When are statins contraindicated?

Liver disease
Pregnancy / lactation
Hypersensitivity reaction

Need to be cautious if porphyria , people susceptible to rhabdomylosis, if hypothyroid (correct this first), renal disease, high alcohol intake

12

How are patients on statins monitored and advised?

Monitoring :
- lipid levels - check it's working
- CK before and when symptomatic
- TFTs before to check for hypothyroid
- LFTs. Before and throughout

Advice:
- take with food
- diet advice to help lower lipids
- reduce alcohol
- warn of myopathy side effects

13

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

14

What are the ADRs of fibrates?

GI upset
Cholelithiasis
Myositis

15

When are fibrates mainly indicated?

Patients with hypertriglyceridaemias or combined hyperlipidaemia

16

What are the contraindications of fibrates?

Liver , renal or pre-existing gall bladder disease

17

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

18

What are the ADRs of nicotinic acid

Flushing
Itching
Headaches
Hepatotoxic
Peptic ulcer
Hyperglycaemia and insulin sensitivity

Due to this nicotinic acid is not used often

19

Contraindications to using nicotinic acid

Peptic ulcer
Liver disease

20

What are the ADRs of ezetimibe ?

Headache
Diarrhoea and abdo pain
Myalgia
Hypersensitivity

21

What are the DDIs of ezetimibe?

Cyclosporin and ezetimibe - conc of both drugs increases
Increased risk of myopathy with lipid lowering drugs

22

What are the ADRs of resins ?

Constipation , diarrhoea , nausea, vomiting, bloating

23

What are DDIs of resins?

Affect absorption of other drugs e.g. Thiazides, fat soluble vitamins , thyroid hormones, digoxin

24

What happens if a patient on statins is complaining of muscle ache and their CK is raised

Stop statins therapy immediately

25

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

26

List some drugs that can alter an individuals lipid profile

Thiazides
B blockers
Testosterone, oestrogen and progesterone
Ciclosporin and tacrolimus
Glucocorticoids

27

What life style advice would you give to someone with hypercholestrolamia

Stop smoking
Reduce saturated fats
Increase fish oils and vit c/e
Aim for good BMI and blood pressure
Exercise
Alcohol in moderation

28

What are the biological therapies used in rheumatology?

Anti TNF
Anti B cell
IL6 antagonist

29

What is the action of glucocorticoids in rheumatology?

Inhibit gene expression of IL1 and IL6 therefore inhibit T cell activation. This leads to immunosupression

30

What are the ADRs of corticosteroids?

Weight gain
Osteoporosis
Glucose intolerance
Heart disease
Infections
Bruising
Increased risk of glaucoma

31

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

32

What is the mechanism of action of methotrexate ?

Folate analogue
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

33

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

34

What are the ADRs of methotrexate?

Mucositis
Pneumonitis
Hepatitis and cirrhosis
Bone marrow suppression - increased infection risk, cancer and anaemia
Teratogenic--> abortion

35

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

36

What are the DDIs of methotrexate?

Therapeutic with other DMards and steroids
NSAIDs displace plasma protein binding sites

37

What monitoring is needed for patients on methotrexate ?

CXR
FBC
LFTs
U&e

38

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

39

What 2 metabolites does sulphasalazine consist of?

5ASA - active anti inflammation component.
sulfapyramide - helps get to target site and fight infection

40

How does sulphasalazine work ?

Inhibits T cell proliferation , il2 production, neutrophil chemotaxis and degranulation

41

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

42

What are the ADRs of sulphasalazine ?

Common : nausea, fatigue , abdo pain and headaches
DIARRHOEA
Uncommon: myelosupression, hepatitis, rash

43

Which DMARDs are safe in pregnancy ?

Sulphasalazine
Hydroxychloroquine

44

How does cyclophosphamide work?

Metabolites of this drug cross link DNA and prevent replication

45

What are the ADRs of cyclophosphamide

Quite serious side effects

Haemorrhagic cystitis
Bladder cancer - metabolite is toxic to the epithelium
Leukaemia / lymphoma
Infertility / teratogen

Because of this only really used in life threatening lupus or vasculitis

46

How can the toxicity of cyclophosphamide be reduced?

Drink lots of water
Take Mensa - binds to toxins

47

How does azothioprine work?

Metabolised to 6MP (purine analogue) and therefore inhibits DNA/ RNA synthesis

48

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

49

What are the ADRs of azothioprine?

Bone marrow suppression - infection , malignancy
Hepatitis

50

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

51

What are the ADRs of mycophenolate?

Myelosupression --> infection
Nausea, vomiting and diarrhoea

52

Who else may mycophenolate be used in other than rheumatology patients?

Transplant patients

53

Name 2 calcineurin inhibitors

Tacrolimus
Cyclosporine

54

How do calcineurin inhibitors work ?

Inhibit calcineurin leading to inhibition of t helper cell and IL2

55

What are the ADRs of calcineurin inhibitors ?

Nephrotoxins
Increase BP
Increase glucose and cholesterol
Increase uricaemia

No effect on bone marrow

56

What are the DDIs of calcineurin inhibitors?

NSAIDs due to renal toxicity

57

What regular checks need to be done on someone taking calcineurin inhibitors?

U&e's
Glucose
Blood pressure
EGFR

58

Name 3 anti - TNFs

Etanercept
Infliximab
Adalimumab

59

When are anti TNFs indicated ?

When methotrexate and one other dmard have been tried and there is still evidence of active RA

60

What are the ADRs of anti TNF?

Increased risk of infection, TB reactivation and malignancy

61

What are the contraindications of anti TNF ?

Women who are pregnant / breast feeding
Malignancy in last 10 years
MS
Active infection
Risk of infection: leg ulcers, latent TB

62

Give the name of a type of anti B cell drug?

Rituximab - monoclonal anti CD20 Ab

63

How is rituximab given?

Pair of infusions every 6 to 12 months

64

When is rituximab indicated?

Given in RA when anti TNF has failed
Main indication is non hodgekins lymphoma

65

How does rituximab work?

Apoptosis of CD20 positive B cells
Therefore spares memory cells - risk of infection is low

66

Name an IL6 antagonist

Tocilizumab

67

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

68

what screening should be carried out prior to anti-TNF treatment?

TB latency
previous malignancy