Drug interactions

Question 1

What is a drug interaction

Answer 1

Clinically meaningful alteration in effect of one drug as a result of co-administration of another drug, food or chemical (precipitant)

Question 2

What types of durug interactions increase effect

Answer 2

Summative
Synergistic

Question 3

When are drug interactions only clinically relevant often

Answer 3

When narrow therapeutic index

Question 4

How common are drug interactions

Answer 4

15-65% potnetial
Actually around 6%
hospital admission 4-8%
Reduced efficacy 8%

Question 5

How does polypharmacy increase DDI

Answer 5

2 drugs - 13%
4 drugs - 38%
>7 drugs - 82%

Question 6

What is a pharmacodynamic interaction

Answer 6

Drugs act on same target site of clinical effect

Question 7

What are pharmacokinetic DDIs

Answer 7

Altered drug concentration at target site of clinical effect eg ADME

Question 8

What is pharmacodynamic DDI causes resp depression

Answer 8

opiates and benzos

Question 9

What pharmacokinetic DDI causes COCP failure

Answer 9

Antibiotics

Question 10

How can synergistic DDIs be beneficial

Answer 10

Increase effect eg antimicrobial efect of rifampacin and isoniazid at mycobacterim TB

Question 11

What effect does alcohol and benzos have

Answer 11

Increased action at GABA - sedative effect on CNS

Question 12

What drug antagonises salbutamol

Answer 12

atenolol - bronchoconstrictor - beta adrenoreceptors

Question 13

How does naloxone work

Answer 13

Antagonist at opioid receptor (which morphine is endogenous agonist) - reverses sedative effect of morphine

Question 14

What is danger os sildenail and isosorbide mononitrate

Answer 14

Markedly increased hypotnesion = can be extermely dangerous esp if cardiac problems/IHD

Question 15

Mechanisms which can alter rate and extent of absorption

Answer 15

pH
Gastric emptying and intestinal motility
Physio-chemical interaction

Question 16

What happens to absorption when pH lowered eg antacid

Answer 16

Reduced absorption - more ionisation, can’t cross membrane of cell

Question 17

What happens to drug absorption if pH of stomach increased

Answer 17

eg alcohol
Less ionisation and faster absorption

Question 18

What drugs delay gastric emptrying

Answer 18

opiate analgesics - morphine, pethidine
Antimuscarinics eg atropine, propantheline
TCAs eg impiramine - side effect

Question 19

What drugs increase rate of gastric emptying

Answer 19

Metoclopramide
Muscarinic agents eg bethanechol

Question 20

What is the clinical significance of decreased gastric emptying

Answer 20

Lower peak concentration
BUT prolonged duration

Question 21

What drugs do antacids make insoluble therefore reduce absorption

Answer 21

Tetracyclines
Quinolones
Iron
Bisphosphonates

Question 22

What drug can be used to reduce absorption of acidic drugs in overdose

Answer 22

Cholestyramine

Question 23

Examples of acidic drugs that overdoses can be treated with cholestyramine if uick

Answer 23

Digoxin, warfarin

Question 24

How does activated charcoal stop absorption

Answer 24

Adsorbs toxins to surface, not absorbed by digestive system so excreted in faeces

Question 25

What are distribution interactions

Answer 25

Displacement of plasma protein bound drugs by another drug - increased free drug conversion Danger is from toxicity

Question 26

What drugs have high protein binding

Answer 26

Warfarin, statins, amiodarone, diazepam, NSAIDs, heparin, furosemide tolbutamide, phenytoin, sulphonamides

Question 27

When does distribution DDI become significant

Answer 27

normally minor - compensation increase in metabolism and excretion free drug IF 2nd mechanism eg drug also inhibits metabolism of old drug Produces toxicitiy

Question 28

What drug interacts with phenytoin in distribution interaction

Answer 28

Valproate Also inhibits metabolism

Question 29

What two cardiac drugs can interact distibutionally causing toxicity

Answer 29

Digoixin and quinidine/verapamil/amiodarone

Question 30

mechanism of digoxin toxicity when given with quindien

Answer 30

Quinidine displaces digoxin from cardiac receptors Increase plasma concentration of digoxin -> toxiciity ALSO decreases excretion of digoxin

Question 31

Effect of CYP450 inducers vs inhibitors on effect of drugs

Answer 31

Inducers increase metabolism -> reduce effect of drug INhibitors slow metabolism -> enhanced effect

Question 32

Why does induction OF cyp450 take days to weeks?

Answer 32

Need an increase in actual enzymes - liver grows and blood flow increases, increased clearance of everything

Question 33

Why is inhibition immediate of CYP450

Answer 33

Blocking exisitng CYP450s - dont need more time

Question 34

Examples of CYP450 inducers

Answer 34

CRAPGP Phenytoin Carbamazepine Barbituatesn(phenobarbitone) Rifampicin Alcohol - chronic St johns wort Grisefolun

Question 35

Exmaples of CYP450 inhibitors

Answer 35

Cimetidine Erythromycin/clarithromycin Ciprofloxacin Sulphonamides Isoniazids Verapamil Metronidazole Omeprazole Grapefruit juice Alcohol - acutely Amiodarone Antifungals

Question 36

What drug can baribituates induce

Answer 36

Warfarin (reduced effect)

Question 36

What drug can rifampacin induce (reduce effect)

Answer 36

Theophylline

Question 37

What drug can phenytoin induce

Answer 37

COCP

Question 38

What need to watch for when stopping medication

Answer 38

If its a CYP450 inducer - may increase effect of other drug

Question 39

How can wtihdrawal of carbamazepine affect warfarin

Answer 39

Higher dose of warfarin due to inductino by carbamazepine (normal blood levels as increased clearnace) If carbamazepine stopped acutely + reaplced by valproate (inhibitor) warfarin clearance falls, blood levels above therapeutic index -> haemorrhage

Question 40

What drugs will st johns wort interfere with

Answer 40

CYP450 inducer - makes below less effective Warfarin COCP SSRI - serotonin syndrome Ciclosporin - transplant failure Theophylline Digoxin Carbamazepine Phenytoin

Question 41

What enzyme do grapefruit and cranberry juice block

Answer 41

CYP3A4 in gut wall and liver

Question 42

What drugs do grapefruit and cranberry juice interact with

Answer 42

Drugs metbaolised by CYP3A4 CCBs Benzos Simastatin - myopathy

Question 43

Why can COCP be less effective with antibiotics

Answer 43

Enterohepatic recycling - oestrogen from liver -> gut in bile -> free oestrogen by bacteria Antibiotics reduce bacteria and therefore amount of free oestrogen released from the gut

Question 44

Precautions with COCP and antibiotics

Answer 44

None if antibiotic not inducer and no N/V - short course Long course - gut recolonised

Question 45

What drug can inhibit active tubular secretion of acidic drugs

Answer 45

Penicillin, methotrexate

Question 46

What drugs inhibit tubular secretion about digoxin

Answer 46

Quinidine and verapamil

Question 47

What does interaction between lithium and thiazide diuretics?

Answer 47

Lithium retained in tubules -> increased and potnetial toxicity

Question 48

What can NaCl and spirinolactone cause

Answer 48

Hyperkalaemia Potassium sparing and adding potassium

Question 49

What effect do some antibiotics (ciprofloxacin, clarith/erythromycin) have on theophylline

Answer 49

CYP450 inducers -> theophylline toxicity

Question 50

Theophylline toxicity symptoms

Answer 50

Dizziness, hypotension Seizures, cardiac arrhtyhmias, death

Question 51

What enzyme causes interaction between methotrexate and trimethoprim and what do they cause

Answer 51

Dihydrofolate reductase enzyme inhibitors folate deficiency (bone marrow supression)

Question 52

Steps when DDI

Answer 52

Understand pharmacolgoy Avoid combination - alternative Adjust dose Monitor therapy - clinical (signs), therapeutic eg drug conc, measure marker for interaction eg U+Es Continue medication

Question 53

What antibiotics increase effect of warfarin and shld be avoided

Answer 53

Erythromycin Metronidazole

Question 54

What drugs that increase bleeding risk (GI) avoid with warfarin

Answer 54

Aspirin or NSAIDs PPI cover

Question 55

What antibiotics increase effect of CBZ and what do when given

Answer 55

Erythromycin, clarithromycin, fluconazole

Question 56

What do you do when NSAID/diuretic is prescribed with lithium and why

Answer 56

Decrease lithium dose by 50% They increase Li levels in blood (confuse with sodium in tubules and retain)

Question 57

What drugs avoid with COCP as makes ineffective

Answer 57

Carbamazepine Rifampacin Can increase dose of

Question 58

What drugs can interact with SSRIs and cause serotonin syndrome or hypertensive crisis

Answer 58

St Johns Wort Triptans MAOI