Drug Safety And Drug Side Effects

Front 1

what is an adverse drug reaction (ADR)

Back 1

an undesirableeffect of a drug beyond its anticipated therapeutic effects.

The WHO define itas a noxious and unintentional drug effect.

Front 2

what are type A drug reactions

Back 2

heseare ADRs that are predictable from knowledge of the drugs pharmacodynamics andpharmacokinetics.

so the ADR is a consequence of the drugs action

- areoften dose-dependent

- generally not fatal

- generallystop the ADR by lowering the dose or withholding the treatment

- drug reactionsare generally picked up and understood during the drug testing and are notthought to be severe enough to withdraw the drug from the market

Front 3

what are type B drug reactions

Back 3

unpredicted side effects of a drug.

effectsare independent of dose + unrelated to the knownpharmacology of the drug.

often involvethe immune system/some sort of genetic abnormality

- reactions can befatal

- needto withdraw the drug and not use it again.

- unlikelyto be picked up during the drug testing

Front 4

what are the type A ADR of NSAIDS (+ why)

Back 4

GI bleeds,peptic ulcers, renal impairment and bronchospasm.

mechanism in COXinhibition, reduce prostaglandins

.'. less protective effects of PG in the gut .'. GI bleeds likely.

.'. less bronchodilator effects of PG .'. bronchospasm esp in asthmatics

.'. poor renal dilation .'. lower kidney blood flow so renal issues.

Front 5

what are the type A ADR of diuretics (+ why)

Back 5

Hypotension, dehydration, electrolyte changes

diuretics increase fluid excretion and vasodilation so explains the side effects

Front 6

what are the type A ADR of opioids (+ why)

Back 6

vomiting,confusion, constipation, urinary retention, respiratory depression (overdose)

This isdue to stimulation of opiate receptors, so too much stimulation can cause theseeffects

Front 7

why can TYPE B ADRs be fatal

Back 7

can lead to anaphalactic shock.

- in anaphylacticshock a huge amount of histamine is released resulting in bronchospasm andconstriction.

It can also cause a huge drop in BP.

Together this means you can’tperfuse your vital organs (e.g. brain) properly leading to death

Front 8

what is steven johnson syndrome?

Back 8

very severe,very rare and very difficult to predict

linked togenetics + the infection a person may have at the time and/or poor livermetabolism of drug metabolites

Starts withflu-like symptoms and high fever, the immune system gets initiated which startsattacking cells causing blistering of the skin and mucous membranes.The skin getsattacked and the epidermis gets separated from the dermis, so the skinessentially falls off.

Front 9

Howdo drugs induce hypersensitivity reactions

Back 9

unknown for definite.

Drugs tend to besmall molecular weight substances, we want this so they can get past our immunesystem.

So when developingdrugs we try keep them small.

But penicillin(which has a low molecular weight) can bind to plasma proteins and when it doesthis it increases its molecular weight and we have a much larger thing goingaround.

This is called ahapten which is immunogenic, this means the immune system sees it as a foreignbody and therefore triggers an immune response.

Front 10

under which category do ADRs for chronic drug administrations fall under?

(eg thinning of skin, buffalo hump, osteoporosis)

Back 10

type A reactions

Front 11

Options forReducing and Avoiding ADRs

Back 11

minor type A reactions may be tolerable (eg indigestion with NSAIDS)

OR continue using the drug and treat the ADR with another drug.

OR simply “accept”more severe ADRs based on the risk-reward balance.

Front 12

what must healthcare proffessionals be mindful of to try and minise ADRs

Back 12

- aware ofvulnerable groups of people

- aware of drugs that are likely to cause interactions

- must know thepharmacology, the mechanisms of drugs and signaling pathways involved.

(e.g. those with comorbidities, the elderly, the young).

- Gettinga good drug history is essential, to find out if there have been any previousdrug reactions

- HCPsmust also keep up to date with drug information (e.g. via the BNF), this may bebeing updated all the time especially if it is being monitored

Front 13

what is pharmacovigilance

Back 13

the practice of monitoring the effects of medical drugs after they have been licensed for use, especially in order to identify and evaluate previously unreported adverse reactions

Itenables the clinician/patient to balance risk and reward. Benefit should alwaysexceed risk

Front 14

what are the potential results of pharmacovigilance

Back 14

- A drug may be withdrawn fromthe market

- Contraindications identified,so no longer give this drug to people with x,y,z

- Warnings may be given

- There can be dose changes,these would be seen in the BNF

Front 15

why was Nicobrevin withdrawn + when

Back 15

2011

relieved thesymptoms of smoking but thought to have too little benefit

Front 16

why was Rosiglitazone withdrawn + when

Back 16

2010

antidiabetic drug, but found to increase MI risk

Front 17

why was Rofecoxib withdrawn + when

Back 17

2004

COX2 selective inhibitor but found to increase risk of MI and stroke

Front 18

why was thalidomide withdrawn + when

Back 18

1961

usedto treat morning sickness in pregnant women

link between womentaking thalidomide having children with physical abnormalities like polydactyl(more than 5 digits), syndactyl (fusion of 2 or more digits) and phocomelia(short arm/leg bones)

Front 19

how do we report ARDs in the UK

Back 19

using the three tier system of:

- Yellow card

- Black triangle

- Green form

Front 20

what are yellow cards

(in pharmacovigilance)

Back 20

mainmethod of post-marketing surveillance

is a yellow form that may be filled out by doctors OR patients.

only gives us the number of ARDs for a particular drug, no info on the prevalence of the ARDs in the general population.

Front 21

what are black triangles

(in pharmacovigilance )

Back 21

drugs new to the market have a black triangle on them.

special caution should be taken when prescribing the new drug.

close monitoring of the new drug.

bc trials may not have picked up the rarer side effects

Front 22

what is the green form system

(in pharmacovilgilance)

Back 22

anyone who istaking a new drug you may set up a green form for them

so if any medical problems arise whilst the person is on the drug, it must be reported.

gives potential to find rare and unusual side effects that may otherwise be missed/ignored by individual doctors.

+ve: allows us to see all the possible side effects and the prevalence of these side effects.

-ve: return of the green forms is often poor.

Front 23

why may grapefruit contraindicate with drugs

Back 23

- grapefruit inhibits CYP450.

CYP450 important in phase I of drug metabolism.

- grapefruit inhibits P-glycoproteintransporters (@ intestine)

these transporters important in secretion on the drug into intestine for faeces.

SO thedrug concentration will increase. thus more ARDs may occur.

Front 24

why may diuretics contraindicate with lithium

Back 24

Diuretics areused for heart failure, hypertension etc. and work by blocking exchangers inthe kidney.

They also interfere with excretion of lithium which is used totreat bipolar disorder.

This can lead tolithium toxicity.

Front 25

why wouldnt we prescribe beta-blockerto an asthmatic treated with salbutamol

Back 25

beta blocker mayblock beta2 receptors in the bronchi.

inhibit normal bronchodilation so can incite an asthma attack

Front 26

why may an individual taking warfarin be advised against eating broccoli or cranberry juice

Back 26

they are high invitamin K.

Warfarin usually blocks vitamin K recycling, so too much vit K willstop warfarin working.

Dose will be increased and then you stop eating as muchbroccoli and the dose becomes too high and you bleed.