MP428 Workshops

what are the three mouse models used in IBD research?

chemically induced ; T-cell transfer ; genetically modified

what are chemically induced mouse models used for in IBD?

study of the histoligical/immunological changes that happen in the gut in humans BUT are very poor predictorsof drug efficacy in humans

what is DSS in reference to chemically induced mouse models for IBD?

damages eputherlial cells which causes innate immune cells to release pro-inflammatory cytokines, and so show how the innate immune system in involved in maintaining and reestablishing intestinal integrity

what is TNRS in reference to chemically induced mouse models for IBD?

this induces the TH1 respose and can mimic Crohn's Disease

"what is a ""T-cell transfer mouse model?"""

transfer of naive T-cells into mice which are Treg deficient which results in pancolitis and small bowel inflammation

what is T-cell transfer model used for in IBD research?

investigating immunological mechanisms that drive/regulate disease - can recapitulate pathologic of CD or UC

"what are ""genetically modified"" mice models in IBD?"

mice that are IL-10 deficient will spontaneously develop colitis

what are genetically modified mice models used for in IBD?

investigating immune mechanisms as well as how Tregs perform when they can't make IL-10

what mouse model is used for MS?

experimental autoimmune encephalomelitis (EAE)

what does the EAE model involve?

immunisisation of mice with a myelin antigen (peptide of MOG)

what is EAE used for?

pathogenesis of MS ; MoA of exisiting treatments (interferon-beta) ; development of new treatments

why aren't there many mouse models for psoriasis?

too many substantial differences in human and mice skin

how are mouse models of psoriasis made?

transplantation of psoriatic skin onto immunodeficient mice (Xenographic models)

what is the flaky skin mouse?

a spontaneous mouse mutation that can give rise to psoriasis BUT absence of T-cells means psoriasis treatment will not work as in humans psoriasis is a T-cell mediated disease

what are the two rheumatoid arthritis mouse models?

collegen-induced arthritis (CIA) ; collage-antibody arthritis

what is collagen-induced arthritis (CIA)?

RA mouse model htat recaptulates many feators of human RA incluiding the presence of rheumatoid factor and anti-citrullinated peptide antibody

what is the main use of mouse models in Sjorgen's Syndrome (SS)

indentifying the role of individual molecules in disease pathogenesis - BAFF and IL-17 for example

what is an example of a mouse model in Grave's Disease?

mice that are imunised using plasmid or adenovirus with the extracellular a suunit og the thyroptropin receptor (TSHR)

what is the main model used for Hashimoto's Thyroiditis?

experimental autoimmune thyroiditis induced by thyroglobulin

What is Hashimoto's Thyroiditis?

autoimmune disease characterised by persitant high levels of antibody against thyroid specific antigens which recruit NK cells to the thyroid, leading to damage and inflammation

what is Grave's Disease?

autoimmune disease in which antibodies against the thyroid stimulating hormone (TSH) receptor cause overproduction of thyroid hormone and thus causes hyperthyrodism

what is the purpose of a product recall?

helps to minimise the hazard to patients aurusing from the distribution of defective medicines either in quality, efficacy, or safety

what is the manufacturer's responsibilty within the supply chain?

initiating any recall that is necessary and maintaining a system capable of recalling a product effectively

what is the pharamcist's responsibility within the supply chain?

should abide by recalls and report any product that seems to be a counterfiet, or has a quality defect

what is the patient's responsibility within the supply chain?

report any ADRs and report any products that appear to be counterfit, or has a quality defect

what is a class 1 recall?

where there is a life-threatening or otherwise serious risk to patient health and requires immediate action

what is a class 2 recall?

where the affected product may cause mistreatment or harm (that is not life threatening) to the patient and requires action within 48 hours

what is a class 3 recall?

where the product is unlikely to cause harm and requires action within 5 days

what is a class 4 recall?

otherwise known as a 'caution in use,' there is no threat to the patient and usually means tht there is a typo within the PIL

"what is an ""unlicensed indication"""

use of a medication in a way that the MHRA has not authorised

"what is an ""orphan drug"""

drugs with a very samll patient population as they treat rare diseases -\> the MHRA makes them more lucrative to produce

"what is an ""off-lablel use"""

prescibing a medicine in a way that is different from it's licence -\> i.e. at a higher dose, in a different patient population, for a different illness

"what is an ""unlicenced medication"""

a drug that has no MHRA marketing authorisation but has an EU licence

what is IDIS Pharmaceuticals?

a supplier that sources/makes unlicenced/off-label medicines (specials)

what does GUISE stand for and why is it used?

Group Untreated/Unneccessary Interactions Side efects Evidence used for clinically chekcing pt medication within hospital setting

what are the main considerations before administrating drugs via a feeding tube?

need for medication ; doses and timing of administration ; review of appropriate formulas (licenced vs. unlicenced) ; monitor patient and increase/decrease based on effect ; identify any ADRs

how can drugs bind to the feeding tube?

by chemisorption (chemical bonds) or physisorption (van der waals)

how can drugs binding to tubing be overcome?

alternate drugs ; washing the tube ; diluting formulation where possibe with equal volume deionised water ; consider alternate routes of administration

what type of drugs are more likely to bind to the tubing of an EF tube?

very lipophilic ; acidic ; delocalised electrons e.g. carbamezapine, phenytoin, diazepam

why do some drugs interact with feed?

some drugs have high protein binding and feed will contian protein

what types of drugs have higher protein binding?

lipophilic, chiral, acidic drugs - chorpenamine and promethazine

how can drug-feed interactions be overcome?

alternate drugs ; alternate routes ; adjusting feeding regimen ; diluting drug ; flushing tube ; larger diametre tube

how is a blockage within the tube as a result of drug-feed interactions dealt with?

flushing with war,/carbonated water

how can drug-feed interactions cause reduced/variable absorption?

drugs can chelate with metal ions present in feed (larger MW and charged) ; high protein binding (not available to be absorbed)

how can foods requiring an empty stomach be administered while on a feeding tube?

via tube with food withheld for two hours before nad two hours after ; alternate route of administration (tube in jejunum or IV) ; flush tube with ~50mL of water

how to over come drug-drug interactions while on feeding tube

alter drug timings so they are not given together ; anternate route for one of the drugs

what is a NFA-VPS?

a non-food animal category of medicines that can be supplied by a vet, pharmacist or suitably qualafied person. written rx not needed

what is a POM-V?

prescription only medicines that can only be prescribed by a vet surgeon and supplied by a vet or pharmacist with a written Rx

what is a POM-VPS?

prescription only medicines that can be prescribed and supplied by a vet pharmacist and suitably qualified person with an oral or written Rx

what i san AVM-GSL?

an authorised veterinary medicine available on general sale

when should the Vet's RCVS registration number be on the Rx?

when prescribing a Sch 2 or 3 CD

"when should ""prescribed unber the veterinary cascade"" be written on the Rx?"

when the item does not have a GB or UK-wide marketing authroisation for the indicated for the species and condition in the

what words must be written on a veterinary dispensing label?

"""for animal treatment only"" ; ""keep out of reach of children"""

when is a dispensing label not legally required in veterinary pharmacy?

when the item is outwith the Cascade and the product is in original packaging

what legal categories require record keeping in veterinary pharmacy?

POM-V and POM-VPS

how long should records of POM-V and POM-VPS supplies be kept?

5 years

what are the main counselling points for administering a rectal foam/enema dose?

medicine goes in the rectum ; wash hands ; empy bowels before hand ; lie on left had sand to assist with distribution ; dose adminsitered when releasing after depressing the top ; try not to empty your bowels before the morning

"what is ""topping and tailing"""

a method for managing particularly bad IBD flare ups - includes an oral formualtion and rectal formulation

when swapping brands for IBD tx, what should be checked?

should stay on same brand if needing to change, a brand with very similar release profiles and excipients though pt should check for any changes in their symptoms for the first 3-4 weeks

what are the S/E of 5-ASA treatment?

nausea, headaches, diarrhoea, vomiting, abdo pain, exacerbation of colitis

what blood monitoring is required in 5-ASA tx?

FBC, U&Es, LFTs - pt should also be checking for unexplained bruising or bleeding or feeling poorly, if they do they need to contact the IBD team.

what monitoring is required for azathioprine?

U&Es, LFTs, FBC (weeksly for 4 weeks then...) 3 monthly. 6TGN/MMPN every 4 weeks. Risk of neuropenia and liver injury

how to manage nausea/vomiting in azzthiopurine tx?

divided daily dosage, taking with or after food. can switch to mercaptopurine tx

what is the link between smoking and Crohn's Disease?

crohn's is more common in smokers thank non-smokers -\> cessation will decrease chance and severity of flare ups

what blood results would show a flare up of colitis?

low haem and albumin, and increased CRP and platelets

what is proclitis?

colitis of the rectum

what is proctosigmoiditis?

colitis of the recum and sigmoid

what is distal colitis?

colitias of the distal colon

what is pancolitis?

colitis of the large colon

what is the most common location for gout to present?

50% of gout sufferes will have it in their big toe

what are the symptoms of gout?

inflamed and red shiny skin, tender and severely painful joints

what are the risk factors of gout?

obesity ; diurectics ; ACE-I ; alcohol use ; inc. cholesterol ; inc. BP ; kidney issues ; OA ; DM ; rcent surgery or trauma

Tx of gout?

colchicine, NSAIDs, steroids

what is gout brought on by?

too much purine intake with not enough excretion of uric acid

where doe sallopurinol fit in gout tx?

a long term preventative tx started after attack settles

what is osteroarthritis?

usually symmetrical, OA is the product of wear and tear on the joint -\> mechanical erosion of cartelige

what is the tx of OA?

1st - topical anti-inflammatories (TDS application) 2nd - oral anti-inflammatories 3rd - paracetamol non-pharmacological \= RICE and mechanical rubbing of affected joint

what is the MoA of GC steroids?

binds to GR making GC/GR complex with tanslocates into the nucleus adn binds to the GRE in the promoter region of genes to reduce expression of pro-inflammatory cytokines, chemokines, adhesion molecules, and InkapaBalpha and therefore serves as an importer regulator of the pro-inflammatory process tha is initiated through NF-kapaB signalling

what are the basic structural features of a neffective steroid?

C17 - differentiates between steroid classes ; C3 - usually a carbonyl attached to make a keytone ; C1-C2 + C3-C4 have unsaturated double bonds to fix the structure and have no chirality

what happens if you stop long term/high dose steroids abruptly

pt can expierence adrenal crisis and reoccurance of original sx

what is an adrenal crisis characterised as?

low cardiac output ; poor resonse to adrenaline ; CV collapse

what factors should be considered relating to safety when Rxing steroids?

method of admin (local/topical preferred) ; weakest potency used? ; smallest dose ; shortest duration possible ; consider age of pt ; mane single dosing with or just after food ; steroid card for high doses and long term tx

why should steroid tx be tapered down?

to allow the adrenal gland to kick back in and avoid adrenal crisis as well as preventing reoccurance of symtpoms

what is a side effect of topical steroids?

thinning of the skin due to reduced keratinocyte proliferation adn decreased collagen synthesis and lypolysis

general s/e of systemic steroids?

moodswings, steroid induced psychosis, steroid iduced euphoraia, increased appetite/weight, muscle wastage, osteoporosis, heartburn where taking tabs, growth restriction, acne, immunosuppression, diabetes, HBP, ulcer agravation, moonface

why does clobetasol have higher potency?

better binding with GR -\> higher logP and affinity

what is used a an inflammatory marker that can also be used as an infection marker?

CRP

how is MTX metabolised and what everday product is contraindiacted in its use?

hepatically and alcohol

how dosage regimen of analgesic should a RA pt be on?

regular para and adjuvant NOT prn

how will smoking cessation help with RA tx?

smoking increases anti-CCP ehich makes disease more erosive

what happens when a MTX pt gets an infection?

MTX should be withheld to allow tx with antibiotics, restart after infection has passed

what ways are available to combat MTX enduced nausea?

switch to IM/SC injection ; switch oral dosing to noche ; add anti-emetics for day of and day after MTX dose

how is RA treated?

1st line - MTX, sulfasalazine, or leflunomide monotherapy with hydroxychlorquine used if pt cannot tolerate any 2nd line - after increasing doses, addition of other cDMARD biologics only given to people with sufficient disease score

what isthe sufficient DAS28 score for NHS to allow tx with biologics?

5.3

what is Epidemiology?

study of the distribution and determinants of disease in populations and the application of this stidu to control a health problem

what is clinical pharamcology?

study of the effects fo drugs in humans

what is Pharmacoepidemiology?

study of the use of and the effects of drugs in large numbers of people

what are the basic principles of pharmacoepidemiology?

desceription of distribution of disease ; indetification of determinants (risk factors) of diease ; intervention to control disease ; formulation of effective health policy

what is an 'exposure'?

anything that might influence the risk of disease