drug to drug interactions

Question 1

Drug interaction is the modification of one drugs action by another durg
Need to consider drugs to include - prescribing drugs and herbal remedies, OTC medications and dietary factors such as grapefruit juice and certain vegetables ( metabolism of certain medication) and also lifestyle factors such as nicotine and alcohol
Drugs also interact with disease

Answer 1

imagine as swim lanes

Question 2

Variability in the effect of a drug can occur in different individuals or the same individual on a different occasion and can lead to

Answer 2

Loss of efficacy
Unexpected side effects or toxicity

Types of variability are
Different concentration of drug reaching the site of action ( pharmacokinetic)
Different degree of response to the same drug conc ( pharmacodynamic)
Different unpredictable response

Question 3

effects of age on drugs
is drug metabolism slower due to immature organ function and failing organ function

renal excretion is less efficient and drug sensitivity will change due to receptor numbers
body fat to mass changes

Answer 3

yes

Question 4

pharmacogenetics

Answer 4

Pharmacogenetics - how different individual genotypes relate to different drug response

Question 5

pharmacogenomics

Answer 5

pharmaco-genetics applied to the whole human genome

Question 6

what enzyme breaks down medications - changing function and increasing toxicity or change the effectiveness

Answer 6

Cytochrome C P450 - has loads of isoforms

CYP 2D6 - beta blockers - adverse reaction is excessive bradycardia

Question 7

what isoform of cryotchrome c affect warfarin ( anticoagulant ) by cause bleeding

Answer 7

CYP 2C9

Question 8

Harmful drug interactions - 15% of adverse drug reactions - certain group at high risk

Answer 8

Elderly
Hepatic or renal disease
Those of multiple durg - polypharmacy
Patients taking drugs with narrow therapeutic ranges eg phenytoin

Question 9

where do drug interactions occur

Answer 9

at pharmaceutical level - chemical interaction when drugs are mixed
at pharmacokinetic level 1 - drugs might interfere with each others absorption or alter distritution
at the pharmacokinetic level 2 - drugs may affect the metabolism or excretion of other drugs
at the pharmacodynamic level - drugs may interfere with others at the site of action - receptors, enzymes etc

Question 10

opiates and atropine slow gut down what drugs speed it up

Answer 10

metoclopramide

Question 11

Interactions with warfarin
56yr on warfarin who has epilepsy and DVT
Carbaemezepine started he is on warfarin 6mg
Several weeks later has swollen left leg
His INR ( internal northernised ratio- blood test, warfarin affects prothrombin time) 1.2 and warfarin level and INR have been well maintained in past

Answer 11

Carbamazepine cause liver enzyme induction - normally these enzymes break warfarin down into metabolites - enzyme inducing AED such as C - therefore increase activity of cytochrome P450 so warfarin metabolised quicker - so patient had developed further thromboembolism in from of DVT so therefore have treatment failure

Drugs that induce CYP450 - increase metabolism of certain other drugs and may increase their own subsequent metabolism

Carbamazepine induces CYP 3A4
Warfarin ( anticoagulant) is metaoblsied by this enzyme
Carbamazepine may therefore cause faster clearance of warfarin, reduced anticoagulant activity, failure of therapy and higher doses of warfarin required for a therapeutic effect

Question 12

antibiotics and warfarin - all antibiotics kill bacteria so what happens

Answer 12

vitamin K synthesis falls
increase anticoagulant effect
increased INR ( prothrombin time- how long it takes blood to clot)

Question 13

CYP 450 inhibiton is a relatively quick onset and related to half life and clearance of affected rugs and plasma conc of time of interaction
what is the usual effect is reduces metabolism of drugs increasing what

Answer 13

effect and toxicity

examples
anti-arrhythmics
antibiotics 
anti-ulcer 
anti-depressants 
HIV drugs 
Statins 
others - sodium valproate

Question 14

23 yr widespread rash , gp gives anti fungal cream with no effect so gives oral ketoconazole
te pruritus becomes intolerable and she sees another member of the practice. Then found dead what happened

Answer 14

like an f appearance of EECG
QTc lengthened by drug causing long QT

anti-arrhyiscs 
antiboits 
anti fungals - ketoconazole 
antihistamines lie terfenadine
psychotropic drugs

Question 15

grapefruit juice inhibits several CYP450 isoenzymes this does what

Answer 15

decreases clearance of many drug including simvastin and statins

Question 16

cranberry judice inhibts CYP2C9 think decreases the clearance of what drug

Answer 16

warfarin - enhances anticoagulant effect increasing risk of haemorrhage