1
Q
Name the enzyme inhibitors (SICKFACES.COM)
A
Sodium valproate Isoniazid / itraconazole Cimetidine Ketoconazole Fluconazole / fluoxetine Alcohol (acute, binge) / Amiodarone Chloramphenicol Erythromycin + clarithromycin Sulphonamides (co-trimoxazole) Ciprofloxacin Omeprazole Metronidazole
Also:
Grapefruit juice
2
Q
Name the enzyme inducers (SCRAP GPSS)
A
Sulphonylureas Carbamazepine Rifampicin Alcohol (chronic) Phenytoin
Griseofulvin
Phenobarbital
St John’s Wort
Smoking
3
Q
What are the main interactions with amiodarone? WARFARIN BETA BLOCKERS LITHIUM DIGOXIN
A
- Amiodarone inhibits warfarin metabolism- enhanced anticoagulant effect
- Increased risk of bradycardia, AV block, myocardial depression with beta blockers
- Risk of ventricular arrhythmias with lithium; both prolong QT
- Plasma concentration of digoxin increased by amiodarone. half dose of digoxin if used concurrently.
Amiodarone has a very long half life so there is potential for drug interactions to occur weeks/months after stopping treatment.
4
Q
What are the common interactions with digoxin? Amiodarone Erythromycin Rifampicin St John's wort Loop/Thiazide diuretics CCBs
A
- Plasma conc of digoxin increased by amiodarone (enzyme inhibitor)
- Plasma conc of digoxin increased by erythromycin (enzyme inhibitor)
- Plasma conc of digoxin reduced by rifampicin (enzyme inducer)
- Plasma conc of digoxin reduced by St John’s Worst (enzyme inducer)
- Increased toxicity of digoxin if hypokalaemia occurs with loop and thiazide diuretics
- Plasma conc of digoxin increased by CCBs
5
Q
What are the common interactions with lithium? ACEi NSAIDs Loop/Thiazide diuretics Amiodarone
A
- Risk of lithium toxicity with ACEi (kidney excretion reduced)
- Risk of lithium toxicity with NSAIDs (excretion reduced)
- Sodium depletion with loop and thiazide diuretics (excretion of lithium reduced)
- Risk of ventricular arrhythmias with amiodarone; prolong QT interval
Therapeutic dose: 0.4 - 1 mmol/L measured 12 hrs after dose. tests BMI, eGFT, TFTs, U&Es done every 6 months.
brand specific
overdose; n+v, diarrhoea, polyuria, fine tremor
6
Q
What are the common interactions with methotrexate? Vaccines PPIs Penicillins Trimethoprim NSAIDs alcohol + doxycycline carbamazepine + clozapine
A
- ^risk of infection with vaccines
- PPIs at ^doses reduce clearance of MTX = increasing risk of toxicity
- Penicillins increases risk of MTX toxicity
- Trimethoprim- both folate antagonists, increased risk of side effects and nephrotoxicity
- NSAIDs; inhibit renal excretion = ^MTX
- alcohol = hepatotoxicity
- doxycycline = hepatotoxicity
- carbamazepine = myelosuppression
- clozapine = myelosuppresion
7
Q
What are the common interactions with phenytoin? NSAIDs Amiodarone Warfarin Fluoxetine Cimetidine St John's wort Ciprofloxacin Contraceptive pill NOACs
A
- NSAIDs enhance phenytoin
- Amiodarone = ^ phenytoin SE
- Phenytoin = accelerates metabolism of warfarin
- Cimetidine = inhibitor ^ phenytoin
- Fluoxetine = inhibitor ^ phenytoin
- St John’s Wort = inducer low phenytoin
- Ciprofloxacin =inducer low phenytoin
- Decreases efficacy of COC pill
- Phenytoin decreases exposure to NOACS
Enzyme inducers: CRAPGPSS Carbamazepine Rifampicin Alcohol Phenobarbitol Griseofulvin Phenytoin St Johns Wort Sulphonylureas
Enzyme inhibitors: SICKFACES.COM Sodium valproate Itraconazole + Isoniazid Cimetidine Fluconazole + Fluoxetine Alcohol, Amiodarone Ciprofloxacin Erythromycin Sulphonamides . Grapefruit juice Chloramphenicol Omeprazole Metronidazole
8
Q
What are the common interactions with theophylline? Quinolones St Johns Wort Rifampicin Cimetidine Fluconazole Smoking St John's Wort
A
- Increased !! CONVULSIONS !! with quinolones e.g. ciprofloxacin
- Plasma [theophylline] reduced by St John’s Wort (inducer)
- Plasma [theophylline] reduced by rifampicin (inducer)
- Plasma [theophylline] increased by cimetidine (inhibitor)
- Plasma [theophylline] increased by fluconazole (inhibitor)
- Smoking can increase theophylline clearance and increased doses of theophylline are therefore required
9
Q
What are the common interactions with warfarin? ▪︎NSAIDs ▪︎fluconazole ▪︎statins ▪︎ciprofloxacin erythromycin metronidazole ▪︎griseofulvin ▪︎alcohol ▪︎vitamin K ▪︎cranberry juice ▪︎antiepileptics
A
- Anticoagulant effect increased by NSAIDs
- Anticoagulant effect increased by fluconazole
- Anticoagulant effect increased by statins
- Anticoagulant effect increased by ciprofloxacin, erythromycin, metronidazole
- Anticoagulant effect reduced by griseofulvin
- Anticoagulant effect reduced by antiepileptics
- Alcohol effects anticoagulant control
- Anticoagulant effect antagonised by Vitamin K
- Anticoagulant effect enhanced by cranberry juice
10
Q
What is the risk of consuming tyramine based food and drink e.g. cheese if on MAOIs?
A
Hypertensive crisis
11
Q
How does alcohol interact with TCAs and mirtazapine?
Alcohol x TCAs / Mirtazepine
Alcohol x Metrondiazole / chloramphenicol
A
Increased sedative effect - TCAs / mirtazepine
A disulfiram-like drug is a drug that causes an ADR to alcohol = n+v, flushing, dizziness, throbbing headache, chest and abdominal discomfort, and general hangover-like symptoms among others.
12
Q
What are the main interactions with combined oral contraceptives?
A
- Enzyme inducing drugs ^ metabolism of COC. Additional contraceptive precautions should be taken for 4-8 weeks after stopping treatment.
- Some antibiotics may reduce efficacy by impairing bacterial flora responsible for recycling ethinylestradiol e.g. ampicillin, amoxicillin, doxycycline. Additional precautions are required for duration of treatment and for 7 days after stopping
13
Q
What are the main interactions with progesterone only contraceptives?
A
Efficacy reduced by enzyme inducers
SCRAPGPSS
Additional protection is needed for duration of treatment and 4 weeks after
14
Q
What are the main interactions with sympathomimetics e.g. pseudoephedrine?
A
- MAOI- hypertensive crisis
- Beta blockers- hypertension risk
15
Q
What are the main interactions with Orlistat? Amiodarone Anticoagulants Acarbose Ciclosporin
A
- Orlistat reduces plasma conc of amiodarone
- Anticoagulants- monitor as bleeding more easily, reduce absorption fat soluble vit (K)
- Acarbose for DB due to its GI effects
- Reduces absorption of ciclosporin
Orlistat might affect the absorption of concurrently administered drugs—consider separating administration. Particular care should be taken with AED, antiretrovirals, and narrow therapeutic index drhgs.
16
Q
What is a pharmacokinetic interaction?
A
When drug alters the absorption, distribution, metabolism, or excretion (ADME) of another drug, thus increasing or reducing the amount of drug available to produce its pharmacological effects.
- Sickfaces.com inhibitors
- Scrapgpss inducers
17
Q
What is a pharmacodynamic interaction?
A
This is where effects of one drug are changed by the presence of another drug at its pharmacological site of action.
e.g. electrolyte imbalance, combined toxicity, antagonising effects
18
Q
What PPI does clopidogrel interact with and what would be an alternative?
A
Omeprazole and esomeprazole = reduces the inhibition of platelet aggregation, whether the two medicines are given simultaneously or 12 hours apart.
Lansoprazole would be an alternative
19
Q
What drug can cause blue vision and which drug can cause yellow vision in overdose
A
Blue vision can be cause by sildenafil and yellow vision is a sign of digoxin toxicity alongside n+v
20
Q
Which SGLT is not licensed to be used with pioglitazone for triple therapy
A
Dapagflozin
21
Q
10 interactions you should know
- Fluoxetine and Phenelzine
- Digoxin and Quinidine
- Sildenafil and Isosorbide Mononitrate
- Potassium Chloride and Spironolactone
- Clonidine and Propranolol
- Warfarin and Diflunisal
- Theophylline and Ciprofloxacin
- Pimozide and Ketoconazole
- Methotrexate and Probenecid
- Bromocriptine and Pseudoephedrine
A
- Fluoxetine + Phenelzine:
- serotonin syndrome: mental changes, agitation, sweating, tachycardia, death.
- SS = any MAOI (tranylcypromine) + any drug that ^serotonin lvls, e.g. dextromethorphan, meperidine, other SSRIs.
- Stop Fluox. 5 weeks b4 MAOI.
- Stop MAOI 2 weeks b4 SSRI. - Digoxin + Quinidine:
- dec. VoD => dig tox <24 hrs.
- dec. renal/nonrenal excretion dig
- Avg ^x2; n+v - death.
- Digoxin half dose. - Sildenafil + ISMN:
- ^ hypotensive effects of ISMN. PDE5 inhibitors + nitrates can cause intense ^ cGMP & BP drop.
- Pts taking ISMN/nitrate, incl. nitroglycerin, should not take sildenafil. - KCl + Spironolactone:
- Hyperkalaemia => cardiac failure/death.
- Renal impairment pt at risk.
- Spiron. = comp. antag. of mineral corticoids (aldosterone) in distal portion of nephron => excretion of Na+ while saving K+ ions. Pts with K-depleting diuretics eg amiloride or triamterene, may also hv this interaction. Severe hyperK is dangerous: monitor serum [K+] - Clonidine + Propranolol:
- HTN unrelated to individual pharmacology.
- sudden withdrawal of clonidine from combo therapy => fatal rebound HTN.
- Clonidine = a-2 agonist: suppresses sympathetic NS from the brain = decrease in NE in the synaptic cleft => Alpha-1 rec become ^sensitized. When clonidine is suddenly withdrawn = sudden ^NE => sensitized a-1 rec stimulated => exaggerated vasoconstriction. The body cannot compensate because the b-2 rec are blocked by propranolol. 24 to 72 hours = dramatic rebound hypertension - Warfarin + Diflunisal:
- NSAID (diflunisal) ^risk GI bleeding & anticoagulant response
- In most patients, indomethacin has little effect on hypothrombinemic response.
- Paracetamol is alternative of choice but if NSAID; nonacetylated salicylates e.g. Mg salicylate are safer: min effects on platelets and gastric mucosa. - Theophylline + Ciprofloxacin;
- Ciproflox CYP1A2 enz inhibitor
- Alt; levofloxacin/ofloxacin
- Signs of theophylline toxicity: headache, dizziness, hypotension, hallucinations, tachycardia, and seizures - Pimozide + Ketoconazole:
- Pimozide alone = prolong QT interval, and linked with ventricular arrhythmias (TdP).
- Pimozide = CYP3A4 substrate, ketoconazole = potent CYP3A4 inhibitor
- Other: itraconazole, clarithromycin, erythromycin, diltiazem, and nefazodone = also potent CYP3A4 inhibitors.
- Fluconazole weaker but inhibits in larger doses. Terbinafine safer choice - does not affect CYP3A4. - MTX and Probenecid:
- 2 to 3-fold ^MTX = diarrhoea, n+v, diaphoresis, renal failure, death.
- Probenecid acts as active tubular secretion inhibitor and prevents MTX excretion.
- Also with penicillins and salicylates.
- low-dose MTX (arthritis) is lower risk; in fact, NSAIDs in combo with low-dose MTX are often prescribed purposely.
- Alt: paracetamol, Celecoxib does not affect MTX pharmacokinetics. However, rofecoxib produces some ^ in [MTX] - Bromocriptine and Pseudoephedrine;
- severe peripheral vasoconstriction, ventricular tachycardia, seizures, death
- Bromocriptine = ergot-derived dopamine agonist [antiparkinsonian therapy].
- SE: thickening of bronchial secretions and nasal congestion. Sig as pt on bromocriptine likely to self medicate OTC decongestant such as pseudoephedrine.
- Patients receiving bromocriptine should be advised to avoid all sympathomime-tics.
22
Q
Clarithromycin X Amitryptyline
A
Prolong QT interval
- amitryptyline [TCA]
- amiodarone [class III anitarrhythmic]
- amisulpride [antipsychotic]
- chlorpromazine [schizophrenic drug]
- haloperidol [antipsychotic, 3A4 inhibitor]
- olanzapine [atypical antipsychotic]
- quetiapine [atypical antipsychotic]
23
Q
Isocarboxid x Amitriptyline
MAOI x TCA
A
Amitriptyline increases risk of severe toxic rxn with isocarboxazid. Wait 2 weeks after discontinuing MAOIs before starting SSRIs.
Examples of MAOIs - rasagiline (Azilect), selegiline (Eldepryl, Zelapar), isocarboxazid (Marplan), phenelzine (Nardil), tranylcypromine (Parnate).
24
Q
Simvastatin x amlodipine
A
Amlodipine => ^ blood levels ofsimvastatin.
In practice, effect is x2 that compared to uninhibitedsimvastatin.
- patients onamlo10mg + simvastatin20mg, = effect of having simvastatin40mg alone. Limit to 20mg.
25
PD interactions arise when one drug changes the response of target or non-target tissues to another drug:
• Synergism
– Penicillin-Streptomycin
Penicillin-Streptomycin Solution is a dual antibiotic solution used as a supplement to cell culture media to control bacterial contamination
– Digoxin toxicity with diuretic induced potassium loss
26
PD interactions arise when one drug changes the response of target or non-target tissues to another drug:
• Antagonism
– Beta blockers diminish the effectiveness of beta agonists such as salbutamol
– Antidote: agents with a specific action against the activity or effect of drugs involved in poisoning cases
27
PK absorption eg. Altered pH; non-ionized form of a drug is more lipid soluble and readily absorbed from GIT > ionized form.
-Eg:, antacids (Al or Mg hydroxide) increase the pH and reduce absorption of acidic drugs such as?
```
Acidic drugs:
digoxin (heart conditions),
phenytoin (epilepsy),
chlorpromazine (schizophrenia)
isoniazid (tuberculosis)
```
Therefore, these drugs must be separated by at least 2h in the time of administration of both.
28
PK absorption eg H2 antagonists increase the pH and Reduce absorption of acidic drugs:
digoxin (heart conditions),
phenytoin (epilepsy),
chlorpromazine (schizophrenia)
isoniazid (tuberculosis)
Therefore, these drugs must be separated by at least 2h in the time of administration of both.
29
Altered motility: Atropine (non-selective muscarinic blocker) Increase absorption of cyclosporin due to the increase of stomach emptying time and increases the toxicity of cyclosporine. This is an example of
- PD
- PK absorption
- PK excretion
- PK metabolism
- PK distribution
PK absorption
30
```
Chelation - Iron may chelate ciprofloxacin, resulting in decreased absorption
example of
- PD
- PK absorption
- PK excretion
- PK metabolism
- PK distribution
```
PK absorption
| decreased ciprofloxacin exposure
31
PK interactions (2): Distribution
• Drugs in bloodstream often bound to plasma proteins;
• Only unbound drugs can leave blood to affect target organs;
• Low albumin levels can increase availability of drugs and potentiate their effects;
• Competitive: drugs with higher affinity to albumin are capable to displace others, leading to increase concentration of free
drug (therefore yield more drug response):
Phenytoin (90%)
Tolbutamide (96%)
Warfarin (99%)
Aspirin (80-90%)
Sulfonamides
Phenylbutazone
32
PK interaction (3):Metabolism
the most drug-drug interactions are metabolism based (diagram)
Phase I metabolism: involves oxidative metabolism via the Cytochrome P450 (CYP) family of enzymes
33
Enzymatic induction
Inducer: Drug that will increase the synthesis of CYP450 enzymes
e.g. barbiturates, bzd, hydantoin antiepileptics, glucocorticoids, rifampicin, griseofulvin, St. John´s wort, smoking, grilled meat, chronic alcohol
intake – increase
SCRAP GPSS
-Decrease the effect of several drugs, e.g.
cardiotonics, steroid hormones, coumarin
anticoagulants
N.B enzyme induction involves protein synthesis. Therefore, it needs time up to 3 weeks to reach a maximal effect
34
Enzymatic inhibition
SICKFACES.COM
Inhibitor: Drug that will decrease the metabolism of a substrate
e.g. some macrolides, quinolones, sulfonamides, some antimycotics (e.g. ketoconazole, fluconazole), isoniazid, metronidazole, chloramphenicol,
amiodarone, verapamil, diltiazem, quinidine, SSRI, proton pump inhibitors, cimetidine, garlic, ginkgo, grapefruit juice
-Increase the effect of several drugs
Inhibition of the enzyme may be due to the competition on its binding sites , so the onset of action is short may be within 24h.
35
When an enzyme inducer (e.g.carbamazepine) is administered with an inhibitor (verapamil) -> the effect of the __________ will be predominant
inhibitor
36
```
Omeprazole Inhibits oxidative metabolism of
A. aspirin
B. diazepam
C. sertraline
D. clarithromycin
```
B. diazepam
Omeprazole has actual adverse influences on the pharmacokinetics of medications such as diazepam, carbamazepine, clozapine, indinavir, methotrexate, tacrolimus, mycophenolate mofetil, clopidogrel, digoxin, itraconazole, posaconazole, and oral iron supplementation.
37
PK interaction (4): Excretion
Drugs are eliminated from the body as an unchanged drug or metabolite
– Renal excretion is the major route of elimination;
– affected by renal function and urinary pH
38
Drug-Food
| interactions
Tetracycline x Milk (Ca2+ ) -> Unabsorpable complex
MAOI x matured tyramine cheeses => acute attack hypertension
Warfarin (diagram)
Vitamin K-containing foods
39
Drug-Disease interactions
HEART : b1 adrenergic receptors - Heart rate & Contractility
SMOOTH MUSCLE -airway & vasculature:
b2 adrenergic receptors -> Relaxation & dilation
Drug ADR: homologous targets
•Non-selective b antagonists, e.g. Propranolol, are contraindicated in patients with asthma
40
Drug-Disease interactions:
| Contraindications of atropine
1- Patients with angle closure glaucoma
2- Patients with shallow anterior chamber
3- Senile hyperplasia of the prostate
4- Patients with gastric ulcer
(increase symptoms due to slowing gastric emptying)
41
Changes in absorption
| Alteration -GI motility
Alteration/ action
GI motility - Increased GI motility caused by metoclopramide may decrease cefprozil absorption (2nd gen cephalosporin)
42
```
GI alkalinization by omeprazole may decrease absorption of
A. amantadine
B. dapsone
C. metronidazole
D. ketoconazole
```
D. ketoconazole
| changes in absorption PK
43
GI flora - Decreased GI bacterial flora caused by an antibiotic admin could decrease bacterial production of vitamin K augmenting anticoagulant effect of
warfarin
44
Changes in absorption
| Alteration -Drug metabolism in wall of intestine
```
Drug metabolism in wall of intestine -
certain antidepressants (TCAs and MAOI) + phenylephrine could potentiate a spike in BP; HTN crisis
MAO = enz in GIT that breaks down neurotransmitters like NE (& dopamine & serotonin); thus, MAOIs act to increase these chemicals in our synapses. NE = main neurotransmitter of SNS works to imm. ^BP. Thus, a sympathomimetic like phenylephrine + MAOI, which is also stimulating the sympathetic system, has the potential to elevate BP into a hypertensive crisis.
```
45
Incidentally, MOA is involved in other body processes including the breakdown of tyramine, an amino acid involved in BP regulation. Tyramine helps release more NE. Thus, to prevent hypertensive crises, patients who take MAOIs should stay away from..
foods rich in tyramine like strong/aged cheeses, cured meats, yeasts, beers and dried fruits.
46
Phase II metabolism
conjugates the previously oxidized molecule with a water soluble weak acid (glucouronic acid, tauric acid, etc) enhancing overall water solubility
47
How to do drug-drug interactions occur
Drug-drug interaction always due to interaction at phase I enzymes (i.e. cytochrome P450)
48
Passive tubular reabsorption example
Sodium bicarbonate. Increases lithium clearance and decreases its action
Antacids Increases salicylates clearance and decreases its action
49
What happens when pH increases
Ionisation doesn't occur as it only occurs at acidic pH
50
```
PK interactions: Absorption
a)
b)
c)
d)
```
a) altered pH
b) altered motility
c) altered intestinal bacteria flora
d) chelation
51
which drugs have strong affinity to protein binding
Phenytoin (90%)
Tolbutamide (96%)
Warfarin (99%)
52
which drugs have weak affinity
Aspirin
Sufonamides
Phenylbutazone
53
Non selective antimuscarinic drugs should never be used for...
ANGLE CLOSURE GLAUCOMA
Even moderate doses of drugs with antimuscarinic effects given systemically can induce acute glaucoma in patients with shallow anterior eye chambers = medical emergency.
ACID-PEPTIC DISEASE
Because anticholinergics can slow gastric emptying, they can worsen symptoms in patients with gastric ulcer
URINARY/GI INCONTINENCE
Drugs with antimuscarinic effects may reduce the contractility of bladder smooth muscle => acute urinary retention in men with BPH. Reduction of GI motility may also worsen symptoms in patients with intestinal obstruction or ileus.
54
Active tubular secretion
- In proximal tubules. Drug combines with a specific protein to pass through.
- When a drug has a competitive reactivity to the protein (active transport of another drug), this drug will reduce other drug excretion => increasing its conc. and hence its toxicity.
- Probenecid decreases tubular secretion of methotrexate.
55
Passive tubular reabsorption
- Excretion and reabsorption of drugs occur in the tubules by passive diffusion which is regulated by concentration and lipid solubility.
- N.B., Ionized drugs are reabsorbed lower than non-ionized ones
56
Pharmacokinetic drug interactions
```
• Changes in GI absorption
• Displacement from plasma protein binding
• P450 Mediated
– Enzyme inhibition
– Enzyme induction
• Decreased renal elimination
```
57
Drug-Herb interactions
```
• St John’s Wort
e.g. cyclosporin
• Ginkgo biloba
• Kava
• Garlic
```
58
Clinically significant to pharmacist perspective for interactions – what to look for
```
1. Vulnerable patient groups
– Elderly
– Multiple drug therapies (poly-pharmacy)
– Renal or hepatic impairment
– Chronic or serious illness
2. Particular groups of drugs:
• Narrow therapeutic index
• Enzyme inducers
• Enzyme inhibitors
```
59
Sirolimus & grapefruit juice
Plasma concentration of sirolimus increases by grapefruit juice
sirolimus - immunosupressant used to prevent kidney rejection
60
Clozapine & cytotoxics
Avoid use of cytotoxics with clozapine due to possible increased risk of ventricular arrhythmias
61
Theophylline & phenobarbital
Metabolism of theophylline accelerated by phenobarbital
62
Tetracyclines & zinc
Absorption of tetracyclines possibly reduced by zinc (give atleast 2-3 hours apart)
63
Lithium & metronidazole
Increased risk of lithium toxicity when given with metronidazole
SICKFACES.COM
64
Narrow therapeutic index
digoxin, theophylline, warfarin, ciclosporin, phenytoin, carbamazepine, lithium
65
```
Enzyme inducers out of the following:
A. Carbamazepine
B. Ciprofloxacin
C. Warfarin
D. Amiodarone
E. Ketoconazole
F. Phenytoin
G. Diltiazem
H. Rifampicin
```
carbamazepine
phenytoin
rifampicin
66
Enteric coated preparations are designed to breakdown in alkali (high pH) environments in the intestine.
1 - Lactulose
2 - Antacids
1 - lactulose reduces stool pH in intestine (acidic) and prevents release of active ingredient in enteric coated preparations
2 - antacids increase stomach pH (alkali) and enteric coated preparations are damaged before reaching intestine
67
Phenytoin and Amiodarone
Amiodarone increases phenytoin concentration
NB: Amiodarone is an enzyme inhibitor.
Due to amiodarones long half life: potential for interaction several months after discontinuation
68
Phenytoin and Warfarin
Phenytoin (p450 enzyme INDUCER) induces warfarins metabolism, decreases warfarin concentration, reduced anti-coagulation effect, decreases INR
69
Phenytoin and COC
Phenytoin (a p450 enzyme inducer) accelerates metabolism of Oestrogens, reducing their effectiveness
Patient should be changed to an IUD
70
Phenytoin and Fluoxetine
Fluoxetine increases phenytoin concentration
71
Phenytoin and Theophylline
phenytoin increases theophylline elimination
Patients taking phenytoin may require larger theophylline doses than recommended to achieve therapeutic blood theophylline concentrations.
72
Phenytoin and St Johns Wort
St Johns Wort decreases phenytoin concentration
| St Johns Wort is an enzyme inducer
73
Phenytoin and Fluconazole
Fluconazole increases phenytoin concentration (Fluconazole enzyme inhibitor part of SICKFACES)
74
Phenytoin and Cimetidine
Cimetidine increases phenytoin concentration (Cimetidine enzyme inhibitor part of SICKFACES)
75
Phenytoin and Diltiazem
Diltiazem increases phenytoin levels, and diltiazems own effects are decreased by phenytoin
76
Phenytoin and Rate limiting CCB's
rate limiting ccb potentially increases the concentration of phenytoin and phenytoin is predicted to decrease the exposure to the rate limiting ccb
- verapamil
- diltiazem
77
Amiodarone and Grapefruit Juice
Grapefruit Juice increases levels of Amiodarone
Grapefruit Juice is an enzyme inhibitor
78
Amiodarone and warfarin
Amiodarone increases warfarin levels
Enhances anti-coagulant effects, increased bleed risk
Amiodarone is an inhibitor of some of the CYP450 enzymes.
79
Amiodarone and Simvastatin
Increased risk of Myopathy
Max dose of Simvastatin: 20mg
This is not the same with Atorvastatin etc but still monitor for mypopathy
80
Amiodarone and beta blockers and Rate-limiting CCB's diltiazem and verapamil
Increased risk of
Bradycardia
Myocardial depression
AV block
When given with beta blockers/ rate limiting CCB
81
Amiodarone and Lithium
Increased risk of Ventricular Arrhythmias
(poss associated with QT prolongation)
Also both effect THYROID function
82
Isotetrinoin x minocycline
isotretinoin and Minocycline (tetracyclines).
- ’pseudotumour cerebri’ (benign intracranial hypertension)
- Manufacturers contraindicate with tetracyclines.
- Symptoms of intracranial hypertension: constant throbbing headache, blurred / double vision, drowsiness, n+v
83
Methotrexate x Trimethoprim
Increased risk of haematological toxicity.
Low-dose MTX and trimethoprim or co-trimoxazole = cases of severe bone marrow depression.. Full blood count should be monitored when methotrexate is used.
84
Theophylline and Quinolone antibiotics e.g. Ciprofloxaxin, Levofloxacin
Increased risk of SEIZURES
| These BOTH lower seizure threshold
85
What do diltiazem and Verapamil (rate limiting CCBs) do to Theophyllines concentration?
Increase it
| these are CYP3A4 enzyme inhibitors!
86
NSAIDs and warfarin/ phenindione
NSAIDs increase warfarin levels- increased anticoagulant effect
NSAIDs, like warfarin, have a high affinty for Albumin. They displace warfarin off the protein= more free warfarin
So remember the interaction is not because both drugs can increase bleed risk- NSAIDs actually increase the levels of warfarin
87
SSRI's and TCA's and warfarin
SSRI's and TCA's will increase warfarin levels- increased anticoagulant effect
88
Statins and warfarin
Only statin that interacts: Rosuvastatin
| Increased effects of warfarin
89
```
This black dot interaction leads to an increased risk of myopathy.
A. Simvastatin and Clarithromycin
B. Amiodarone and Clopidogrel
C. Ciprofloxacin and Clozapine
D. SSRI and NSAID
E. Rosuvastatin and Warfarin
```
Anti-coagulant effect enhance (both thin blood)- increased risk of bleeds
simvastatin x clarithromycin
90
Orlistat + Antiepileptics
Possible increased risk of convulsions- orlistat lowers seizure threshold
91
Methotrexate and Phenytoin
MTX reported as a seizure inducer and should be avoided by most on AED. Some AED have been shown to reduce how well MTX works.
Phenytoin (Dilantin, Phenytek)
Carbamazepine (Tegretol)
Valproic acid (Depakene, Stavzor, Depacon)
92
Methotrexate and Trimethoprim/ Co-trimoxazole (trimethoprim + Sulfamethoxazole)
Do not use together- both deplete folate- haematological blood toxicity risk
Sulfamethoxazole also increases methotrexate toxicity
93
Methotrexate and Ibuprofen
Methotrexate toxicity increased by NSAIDs due to decreased renal excretion
94
Methotrexate and Flucloxacillin
Methotrexate toxicity increased by all penicillins due to decreased renal excretion
95
Methotrexate and Clozapine
Neutropenia risk increased
96
PPI's and Methotrexate
Increased risk of Methotrexate toxcity as excretion decreased
97
ALOT of antibiotics interact with Methotrexate. Can you think of any?
```
Trimethoprim/ co-trimoxazole (folate depletion)
^ MTX toxicity:
Ciprofloxacin
Doxycycline
Tetracycline
Sulfonamide (Sulfamethoxazole)
```
98
If in doubt, whats that ONE DRUG that seems to have interactions with everything?!
CICLOSPORIN
| an immunosuppressant
99
Which OTC medication can possibly interact with ANTI-EPILEPTICS and increase the risk of CONVULSIONS?
ORLISTAT (Alli)
100
Carbamazepine is an enzyme inducer, but is itself metabolised by the CYP450 system. Which other enzyme inducers may reduce the concentration of carbamazepine?
Phenytoin (May also reduce phenytoins conc)
Rifabutin
St Johns Wort
101
What drugs, used in hypertension, can increase the risk of Myopathy?
Diltiazem
Verapamil
Amlodipine
Ranolazine
MAX SIMVASTATIN DOSE= 20mg for all of these!!
102
Drugs interacting with Gentamicin/ Vancomycin?
NEPHROTOXIC DRUGS:
Ciclosporin (immunosuppressant)
Tacrolimus (immunosuppressant)
Cephalosporins
```
OTOTOXICITY:
Loop diuretics (furosemide)
```
103
What kind of OTC products should patients with high BP avoid?
SOLUBLE preparations e.g. effervescent
| Due to high SODIUM content
104
Spironolactone + ACEi/ARB
Potassium sparing diuretic given with postassium elevating drugs: HYPERKALEAMIA
105
Spironolactone + Tacrolimus
Potassium sparing diuretic given with postassium elevating drug Tacrolimus: Hyperkaleamia
106
Furosemide + Vancomycin
Increased risk of Ototoxicity
107
Digoxin + Diuretics
Diuretics (thiazides and loops) can cause Hypokaleamia
Digoxin toxicity is precipitated by low potassium!!
Give potassium sparing diuretics/ potassium chloride to manage
108
Eplerenone (potassium sparing diuretic) is metabolised by the CYP450 enzyme system
Which enz inhibitors increase its conc?
Which enz inducers reduce its conc?
Its concentration is increased by clarithromycin and itraconazole only
Its concentration is reduced by all the enzyme inducers
109
What drugs may cause hypoglyceamia and therefore reduce the amount of insulin a patient needs?
ACE inhibitors!
| Other oral antidiabetics
110
NSAID + quinolone (ciprofloxacin, Levofloxacin)
Possible increased risk of seizures
111
NSAID + Diuretics
Increased risk of nephrotoxicity
NSAIDs will also antagonise the diuretic effects: Fluid retention! Can cause ankle swelling and high blood pressure with chronic use
112
NSAIDs + anti-hypertensives (beta-blockers, CCB's, ACE inhibitors, alpha-blockers [tamsulosin, doxazosin] nitrates)
NSAIDs themselves can cause high BP
| They antagonise the hypotensive effects of these drugs
113
Which opioid can enhance the anticoagulant effect of coumarins (warfarin)
Tramadol
114
Which antibiotic can reduce the effectiveness of most of the opioids, including fentanyl, morphine, codeine, methadone?
RIFAMPICIN!! (enzyme inducer)
115
Opioids can reduce BP (hypotensive)
| Their hypotensive and sedative effects are increased by alcohol. What happens if given with MAOIs?
CNS excitation or depression
Hypotension or HTN can occur
(MAOIs can cause hypotensive crisis)
116
Clopidogrel + enzyme inhibitors
Some of the enzyme inhibitors (erythromycin, cimetidine, ciprofloxacin, fluconazole, ketoconazole) actually REDUCE clopidogrels antiplatelet effect!- dont get confused in exam!
117
Clopidogrel + PPI's
Antiplatelet effect REDUCED by omeprazole and esomeprazole
Pantoprazole safest PPI to use, or H2 antagonist
118
Sotalol + loop or thiazide diuretics
risk of ventricular arrhythmias caused by sotolol is increased by diuretics due to their hypokaleamia effect
119
Lithium + ACE inhibitors
ACE inhibitors will decrease the excretion of lithium!
| Nothing to do with electrolyte disturbance
120
Ppl with DB are often at an ^ risk of liver disease and infection, and the use of MTX together with some DB meds may increase that risk. Using MTX over a long period of time has also been linked to liver conditions such as cirrhosis. Specific medications that should be avoided or used with caution include:
```
Quinapril (Accupril)
Acarbose (Precose)
Pioglitazone (Actos)
Rosiglitazone (Avandia)
Exenatide (Byetta, Bydureon)
```
121
Lithium + Aminophylline/ Theophylline
These will increase the excretion of lithium, reducing its levels
122
NSAIDs + Lithium
Excretion of lithium reduced by NSAIDs so increased risk of Lithium Toxicity!
123
Lithium + SSRIs
Increased risk of CNS effects, lithium toxicity
| think SSRI's cause hyponatreamia- sodium levels effect lithium
124
Methotrexate and Aspirin
Methotrexate toxicity increased
| As Aspirin and NSAIDs decrease methotrexate excretion
125
Doxycycline + Isotretinoin
Severe headache/ visual disturbance due to cranial (brain) hypertension
126
Atorvastatin and clarithromycin
increased risk of myopathy
127
Co-trimoxazole + Spironolactone
Increased risk of hyperkaleamia
128
Metronidazole + Mebendazole
severe skin reaction
129
Baclofen + ACE inhibitors
Baclofen enhances hypotensive effect
130
Baclofen + beta blockers
Baclofen enhances hypotensive effect
131
Alpha blockers (sildenafil) + nitrates (isosorbide mononitrate)
Enhanced hypotension effects
132
Clarithromycin x ciclosporin
Increased conc of ciclosporin
133
A patient uses simvastatin 40 mg nocte and presents with a prescription for an antibiotic.
Which of the following antibiotics may precipitate rhabdomyolosis if given concomitantly with simvastatin?
Amoxicillin
Ciprofloxacin
Co-amoxiclav
Daptomycin
Doxycycline
The correct answer was Daptomycin
Statins are predicted to increase the risk of rhabdomyolosis when given with daptomycin.
Low weighted and MISC chapter
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