Interactions Flashcards

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Name the enzyme inducers (SCRAP GPSS)

A
Sulphonylureas
Carbamazepine
Rifampicin
Alcohol (chronic)
Phenytoin

Griseofulvin
Phenobarbital
St John’s Wort
Smoking

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q
What are the main interactions with amiodarone?
WARFARIN
BETA BLOCKERS
LITHIUM
DIGOXIN
A
  1. Amiodarone inhibits warfarin metabolism- enhanced anticoagulant effect
  2. Increased risk of bradycardia, AV block, myocardial depression with beta blockers
  3. Risk of ventricular arrhythmias with lithium; both prolong QT
  4. 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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q
What are the common interactions with digoxin?
Amiodarone 
Erythromycin 
Rifampicin 
St John's wort
Loop/Thiazide diuretics 
CCBs
A
  1. Plasma conc of digoxin increased by amiodarone (enzyme inhibitor)
  2. Plasma conc of digoxin increased by erythromycin (enzyme inhibitor)
  3. Plasma conc of digoxin reduced by rifampicin (enzyme inducer)
  4. Plasma conc of digoxin reduced by St John’s Worst (enzyme inducer)
  5. Increased toxicity of digoxin if hypokalaemia occurs with loop and thiazide diuretics
  6. Plasma conc of digoxin increased by CCBs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q
What are the common interactions with lithium?
ACEi
NSAIDs
Loop/Thiazide diuretics
Amiodarone
A
  1. Risk of lithium toxicity with ACEi (kidney excretion reduced)
  2. Risk of lithium toxicity with NSAIDs (excretion reduced)
  3. Sodium depletion with loop and thiazide diuretics (excretion of lithium reduced)
  4. 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q
What are the common interactions with methotrexate?
Vaccines
PPIs
Penicillins
Trimethoprim
NSAIDs
alcohol + doxycycline
carbamazepine + clozapine
A
  1. ^risk of infection with vaccines
  2. PPIs at ^doses reduce clearance of MTX = increasing risk of toxicity
  3. Penicillins increases risk of MTX toxicity
  4. Trimethoprim- both folate antagonists, increased risk of side effects and nephrotoxicity
  5. NSAIDs; inhibit renal excretion = ^MTX
  6. alcohol = hepatotoxicity
  7. doxycycline = hepatotoxicity
  8. carbamazepine = myelosuppression
  9. clozapine = myelosuppresion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q
What are the common interactions with phenytoin?
NSAIDs
Amiodarone 
Warfarin 
Fluoxetine
Cimetidine 
St John's wort
Ciprofloxacin 
Contraceptive pill 
NOACs
A
  1. NSAIDs enhance phenytoin
  2. Amiodarone = ^ phenytoin SE
  3. Phenytoin = accelerates metabolism of warfarin
  4. Cimetidine = inhibitor ^ phenytoin
  5. Fluoxetine = inhibitor ^ phenytoin
  6. St John’s Wort = inducer low phenytoin
  7. Ciprofloxacin =inducer low phenytoin
  8. Decreases efficacy of COC pill
  9. 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q
What are the common interactions with theophylline?
Quinolones 
St Johns Wort
Rifampicin 
Cimetidine 
Fluconazole 
Smoking 
St John's Wort
A
  1. Increased !! CONVULSIONS !! with quinolones e.g. ciprofloxacin
  2. Plasma [theophylline] reduced by St John’s Wort (inducer)
  3. Plasma [theophylline] reduced by rifampicin (inducer)
  4. Plasma [theophylline] increased by cimetidine (inhibitor)
  5. Plasma [theophylline] increased by fluconazole (inhibitor)
  6. Smoking can increase theophylline clearance and increased doses of theophylline are therefore required
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q
What are the common interactions with warfarin?
▪︎NSAIDs
▪︎fluconazole 
▪︎statins
▪︎ciprofloxacin erythromycin metronidazole 
▪︎griseofulvin 
▪︎alcohol 
▪︎vitamin K
▪︎cranberry juice
▪︎antiepileptics
A
  1. Anticoagulant effect increased by NSAIDs
  2. Anticoagulant effect increased by fluconazole
  3. Anticoagulant effect increased by statins
  4. Anticoagulant effect increased by ciprofloxacin, erythromycin, metronidazole
  5. Anticoagulant effect reduced by griseofulvin
  6. Anticoagulant effect reduced by antiepileptics
  7. Alcohol effects anticoagulant control
  8. Anticoagulant effect antagonised by Vitamin K
  9. Anticoagulant effect enhanced by cranberry juice
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the risk of consuming tyramine based food and drink e.g. cheese if on MAOIs?

A

Hypertensive crisis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the main interactions with sympathomimetics e.g. pseudoephedrine?

A
  • MAOI- hypertensive crisis

- Beta blockers- hypertension risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Which SGLT is not licensed to be used with pioglitazone for triple therapy

A

Dapagflozin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

10 interactions you should know

  1. Fluoxetine and Phenelzine
  2. Digoxin and Quinidine
  3. Sildenafil and Isosorbide Mononitrate
  4. Potassium Chloride and Spironolactone
  5. Clonidine and Propranolol
  6. Warfarin and Diflunisal
  7. Theophylline and Ciprofloxacin
  8. Pimozide and Ketoconazole
  9. Methotrexate and Probenecid
  10. Bromocriptine and Pseudoephedrine
A
  1. 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.
  2. Digoxin + Quinidine:
    - dec. VoD => dig tox <24 hrs.
    - dec. renal/nonrenal excretion dig
    - Avg ^x2; n+v - death.
    - Digoxin half dose.
  3. 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.
  4. 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+]
  5. 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
  6. 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.
  7. Theophylline + Ciprofloxacin;
    - Ciproflox CYP1A2 enz inhibitor
    - Alt; levofloxacin/ofloxacin
    - Signs of theophylline toxicity: headache, dizziness, hypotension, hallucinations, tachycardia, and seizures
  8. 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.
  9. 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]
  10. 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.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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]
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

PD interactions arise when one drug changes the response of target or non-target tissues to another drug:
• Synergism

A

– 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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

PD interactions arise when one drug changes the response of target or non-target tissues to another drug:
• Antagonism

A

– 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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

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?

A
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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

PK absorption eg H2 antagonists increase the pH and Reduce absorption of acidic drugs:

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

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
A

PK absorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q
Chelation - Iron may chelate ciprofloxacin, resulting in decreased absorption
example of 
- PD 
- PK absorption
- PK excretion
- PK metabolism
- PK distribution
A

PK absorption

decreased ciprofloxacin exposure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

PK interactions (2): Distribution

A

• 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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

PK interaction (3):Metabolism

A

the most drug-drug interactions are metabolism based (diagram)
Phase I metabolism: involves oxidative metabolism via the Cytochrome P450 (CYP) family of enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Enzymatic induction

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Enzymatic inhibition

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

When an enzyme inducer (e.g.carbamazepine) is administered with an inhibitor (verapamil) -> the effect of the __________ will be predominant

A

inhibitor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q
Omeprazole Inhibits oxidative metabolism of 
A. aspirin
B. diazepam
C. sertraline
D. clarithromycin
A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

PK interaction (4): Excretion

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Drug-Food

interactions

A

Tetracycline x Milk (Ca2+ ) -> Unabsorpable complex

MAOI x matured tyramine cheeses => acute attack hypertension

Warfarin (diagram)
Vitamin K-containing foods

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Drug-Disease interactions

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Drug-Disease interactions:

Contraindications of atropine

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Changes in absorption

Alteration -GI motility

A

Alteration/ action

GI motility - Increased GI motility caused by metoclopramide may decrease cefprozil absorption (2nd gen cephalosporin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q
GI alkalinization by omeprazole may decrease absorption of 
A. amantadine
B. dapsone
C. metronidazole
D. ketoconazole
A

D. ketoconazole

changes in absorption PK

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

GI flora - Decreased GI bacterial flora caused by an antibiotic admin could decrease bacterial production of vitamin K augmenting anticoagulant effect of

A

warfarin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Changes in absorption

Alteration -Drug metabolism in wall of intestine

A
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.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

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..

A

foods rich in tyramine like strong/aged cheeses, cured meats, yeasts, beers and dried fruits.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Phase II metabolism

A

conjugates the previously oxidized molecule with a water soluble weak acid (glucouronic acid, tauric acid, etc) enhancing overall water solubility

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

How to do drug-drug interactions occur

A

Drug-drug interaction always due to interaction at phase I enzymes (i.e. cytochrome P450)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Passive tubular reabsorption example

A

Sodium bicarbonate. Increases lithium clearance and decreases its action

Antacids Increases salicylates clearance and decreases its action

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What happens when pH increases

A

Ionisation doesn’t occur as it only occurs at acidic pH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q
PK interactions: Absorption
a)
b)
c)
d)
A

a) altered pH
b) altered motility
c) altered intestinal bacteria flora
d) chelation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

which drugs have strong affinity to protein binding

A

Phenytoin (90%)
Tolbutamide (96%)
Warfarin (99%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

which drugs have weak affinity

A

Aspirin
Sufonamides
Phenylbutazone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

Non selective antimuscarinic drugs should never be used for…

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Active tubular secretion

A
  • 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
Q

Passive tubular reabsorption

A
  • 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
Q

Pharmacokinetic drug interactions

A
• Changes in GI absorption
• Displacement from plasma protein binding
• P450 Mediated
– Enzyme inhibition
– Enzyme induction
• Decreased renal elimination
57
Q

Drug-Herb interactions

A
• St John’s Wort
e.g. cyclosporin
• Ginkgo biloba
• Kava
• Garlic
58
Q

Clinically significant to pharmacist perspective for interactions – what to look for

A
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
Q

Sirolimus & grapefruit juice

A

Plasma concentration of sirolimus increases by grapefruit juice

sirolimus - immunosupressant used to prevent kidney rejection

60
Q

Clozapine & cytotoxics

A

Avoid use of cytotoxics with clozapine due to possible increased risk of ventricular arrhythmias

61
Q

Theophylline & phenobarbital

A

Metabolism of theophylline accelerated by phenobarbital

62
Q

Tetracyclines & zinc

A

Absorption of tetracyclines possibly reduced by zinc (give atleast 2-3 hours apart)

63
Q

Lithium & metronidazole

A

Increased risk of lithium toxicity when given with metronidazole
SICKFACES.COM

64
Q

Narrow therapeutic index

A

digoxin, theophylline, warfarin, ciclosporin, phenytoin, carbamazepine, lithium

65
Q
Enzyme inducers out of the following:
A. Carbamazepine
B. Ciprofloxacin
C. Warfarin
D. Amiodarone
E. Ketoconazole
F. Phenytoin
G. Diltiazem
H. Rifampicin
A

carbamazepine
phenytoin
rifampicin

66
Q

Enteric coated preparations are designed to breakdown in alkali (high pH) environments in the intestine.
1 - Lactulose
2 - Antacids

A

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
Q

Phenytoin and Amiodarone

A

Amiodarone increases phenytoin concentration

NB: Amiodarone is an enzyme inhibitor.
Due to amiodarones long half life: potential for interaction several months after discontinuation

68
Q

Phenytoin and Warfarin

A

Phenytoin (p450 enzyme INDUCER) induces warfarins metabolism, decreases warfarin concentration, reduced anti-coagulation effect, decreases INR

69
Q

Phenytoin and COC

A

Phenytoin (a p450 enzyme inducer) accelerates metabolism of Oestrogens, reducing their effectiveness

Patient should be changed to an IUD

70
Q

Phenytoin and Fluoxetine

A

Fluoxetine increases phenytoin concentration

71
Q

Phenytoin and Theophylline

A

phenytoin increases theophylline elimination
Patients taking phenytoin may require larger theophylline doses than recommended to achieve therapeutic blood theophylline concentrations.

72
Q

Phenytoin and St Johns Wort

A

St Johns Wort decreases phenytoin concentration

St Johns Wort is an enzyme inducer

73
Q

Phenytoin and Fluconazole

A

Fluconazole increases phenytoin concentration (Fluconazole enzyme inhibitor part of SICKFACES)

74
Q

Phenytoin and Cimetidine

A

Cimetidine increases phenytoin concentration (Cimetidine enzyme inhibitor part of SICKFACES)

75
Q

Phenytoin and Diltiazem

A

Diltiazem increases phenytoin levels, and diltiazems own effects are decreased by phenytoin

76
Q

Phenytoin and Rate limiting CCB’s

A

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
Q

Amiodarone and Grapefruit Juice

A

Grapefruit Juice increases levels of Amiodarone

Grapefruit Juice is an enzyme inhibitor

78
Q

Amiodarone and warfarin

A

Amiodarone increases warfarin levels
Enhances anti-coagulant effects, increased bleed risk

Amiodarone is an inhibitor of some of the CYP450 enzymes.

79
Q

Amiodarone and Simvastatin

A

Increased risk of Myopathy
Max dose of Simvastatin: 20mg

This is not the same with Atorvastatin etc but still monitor for mypopathy

80
Q

Amiodarone and beta blockers and Rate-limiting CCB’s diltiazem and verapamil

A

Increased risk of
Bradycardia
Myocardial depression
AV block

When given with beta blockers/ rate limiting CCB

81
Q

Amiodarone and Lithium

A

Increased risk of Ventricular Arrhythmias
(poss associated with QT prolongation)

Also both effect THYROID function

82
Q

Isotetrinoin x minocycline

A

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
Q

Methotrexate x Trimethoprim

A

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
Q

Theophylline and Quinolone antibiotics e.g. Ciprofloxaxin, Levofloxacin

A

Increased risk of SEIZURES

These BOTH lower seizure threshold

85
Q

What do diltiazem and Verapamil (rate limiting CCBs) do to Theophyllines concentration?

A

Increase it

these are CYP3A4 enzyme inhibitors!

86
Q

NSAIDs and warfarin/ phenindione

A

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
Q

SSRI’s and TCA’s and warfarin

A

SSRI’s and TCA’s will increase warfarin levels- increased anticoagulant effect

88
Q

Statins and warfarin

A

Only statin that interacts: Rosuvastatin

Increased effects of warfarin

89
Q
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
A

Anti-coagulant effect enhance (both thin blood)- increased risk of bleeds

simvastatin x clarithromycin

90
Q

Orlistat + Antiepileptics

A

Possible increased risk of convulsions- orlistat lowers seizure threshold

91
Q

Methotrexate and Phenytoin

A

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
Q

Methotrexate and Trimethoprim/ Co-trimoxazole (trimethoprim + Sulfamethoxazole)

A

Do not use together- both deplete folate- haematological blood toxicity risk

Sulfamethoxazole also increases methotrexate toxicity

93
Q

Methotrexate and Ibuprofen

A

Methotrexate toxicity increased by NSAIDs due to decreased renal excretion

94
Q

Methotrexate and Flucloxacillin

A

Methotrexate toxicity increased by all penicillins due to decreased renal excretion

95
Q

Methotrexate and Clozapine

A

Neutropenia risk increased

96
Q

PPI’s and Methotrexate

A

Increased risk of Methotrexate toxcity as excretion decreased

97
Q

ALOT of antibiotics interact with Methotrexate. Can you think of any?

A
Trimethoprim/ co-trimoxazole (folate depletion)
 ^ MTX toxicity:
Ciprofloxacin
Doxycycline
Tetracycline
Sulfonamide (Sulfamethoxazole)
98
Q

If in doubt, whats that ONE DRUG that seems to have interactions with everything?!

A

CICLOSPORIN

an immunosuppressant

99
Q

Which OTC medication can possibly interact with ANTI-EPILEPTICS and increase the risk of CONVULSIONS?

A

ORLISTAT (Alli)

100
Q

Carbamazepine is an enzyme inducer, but is itself metabolised by the CYP450 system. Which other enzyme inducers may reduce the concentration of carbamazepine?

A

Phenytoin (May also reduce phenytoins conc)
Rifabutin
St Johns Wort

101
Q

What drugs, used in hypertension, can increase the risk of Myopathy?

A

Diltiazem
Verapamil
Amlodipine
Ranolazine

MAX SIMVASTATIN DOSE= 20mg for all of these!!

102
Q

Drugs interacting with Gentamicin/ Vancomycin?

A

NEPHROTOXIC DRUGS:
Ciclosporin (immunosuppressant)
Tacrolimus (immunosuppressant)
Cephalosporins

OTOTOXICITY:
Loop diuretics (furosemide)
103
Q

What kind of OTC products should patients with high BP avoid?

A

SOLUBLE preparations e.g. effervescent

Due to high SODIUM content

104
Q

Spironolactone + ACEi/ARB

A

Potassium sparing diuretic given with postassium elevating drugs: HYPERKALEAMIA

105
Q

Spironolactone + Tacrolimus

A

Potassium sparing diuretic given with postassium elevating drug Tacrolimus: Hyperkaleamia

106
Q

Furosemide + Vancomycin

A

Increased risk of Ototoxicity

107
Q

Digoxin + Diuretics

A

Diuretics (thiazides and loops) can cause Hypokaleamia
Digoxin toxicity is precipitated by low potassium!!

Give potassium sparing diuretics/ potassium chloride to manage

108
Q

Eplerenone (potassium sparing diuretic) is metabolised by the CYP450 enzyme system
Which enz inhibitors increase its conc?
Which enz inducers reduce its conc?

A

Its concentration is increased by clarithromycin and itraconazole only

Its concentration is reduced by all the enzyme inducers

109
Q

What drugs may cause hypoglyceamia and therefore reduce the amount of insulin a patient needs?

A

ACE inhibitors!

Other oral antidiabetics

110
Q

NSAID + quinolone (ciprofloxacin, Levofloxacin)

A

Possible increased risk of seizures

111
Q

NSAID + Diuretics

A

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
Q

NSAIDs + anti-hypertensives (beta-blockers, CCB’s, ACE inhibitors, alpha-blockers [tamsulosin, doxazosin] nitrates)

A

NSAIDs themselves can cause high BP

They antagonise the hypotensive effects of these drugs

113
Q

Which opioid can enhance the anticoagulant effect of coumarins (warfarin)

A

Tramadol

114
Q

Which antibiotic can reduce the effectiveness of most of the opioids, including fentanyl, morphine, codeine, methadone?

A

RIFAMPICIN!! (enzyme inducer)

115
Q

Opioids can reduce BP (hypotensive)

Their hypotensive and sedative effects are increased by alcohol. What happens if given with MAOIs?

A

CNS excitation or depression
Hypotension or HTN can occur
(MAOIs can cause hypotensive crisis)

116
Q

Clopidogrel + enzyme inhibitors

A

Some of the enzyme inhibitors (erythromycin, cimetidine, ciprofloxacin, fluconazole, ketoconazole) actually REDUCE clopidogrels antiplatelet effect!- dont get confused in exam!

117
Q

Clopidogrel + PPI’s

A

Antiplatelet effect REDUCED by omeprazole and esomeprazole

Pantoprazole safest PPI to use, or H2 antagonist

118
Q

Sotalol + loop or thiazide diuretics

A

risk of ventricular arrhythmias caused by sotolol is increased by diuretics due to their hypokaleamia effect

119
Q

Lithium + ACE inhibitors

A

ACE inhibitors will decrease the excretion of lithium!

Nothing to do with electrolyte disturbance

120
Q

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:

A
Quinapril (Accupril)
Acarbose (Precose)
Pioglitazone (Actos)
Rosiglitazone (Avandia)
Exenatide (Byetta, Bydureon)
121
Q

Lithium + Aminophylline/ Theophylline

A

These will increase the excretion of lithium, reducing its levels

122
Q

NSAIDs + Lithium

A

Excretion of lithium reduced by NSAIDs so increased risk of Lithium Toxicity!

123
Q

Lithium + SSRIs

A

Increased risk of CNS effects, lithium toxicity

think SSRI’s cause hyponatreamia- sodium levels effect lithium

124
Q

Methotrexate and Aspirin

A

Methotrexate toxicity increased

As Aspirin and NSAIDs decrease methotrexate excretion

125
Q

Doxycycline + Isotretinoin

A

Severe headache/ visual disturbance due to cranial (brain) hypertension

126
Q

Atorvastatin and clarithromycin

A

increased risk of myopathy

127
Q

Co-trimoxazole + Spironolactone

A

Increased risk of hyperkaleamia

128
Q

Metronidazole + Mebendazole

A

severe skin reaction

129
Q

Baclofen + ACE inhibitors

A

Baclofen enhances hypotensive effect

130
Q

Baclofen + beta blockers

A

Baclofen enhances hypotensive effect

131
Q

Alpha blockers (sildenafil) + nitrates (isosorbide mononitrate)

A

Enhanced hypotension effects

132
Q

Clarithromycin x ciclosporin

A

Increased conc of ciclosporin

133
Q

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

A

The correct answer was Daptomycin

Statins are predicted to increase the risk of rhabdomyolosis when given with daptomycin.