Illustrated Drug interaction By Mohie Al

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Illustrated Drug interaction
By
Mohie Al-Dien Elsayed (MD)
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Definitions and Terms:
-Adverse Event (AE): untoward, unintended, Effect or Experience possibly causing harm
-ADE (AE associated with a Drug): an AE which happens in a patient taking a drug
-ADR (Adverse Drug Reaction): ADE with Drug/event suspected causal association.
-Drug Interactions: “The pharmacologic or clinical response to the administration of a drug combination
different from that anticipated from the known effects of the two agents when given alone ”. Drug
interactions represent 3–5% of preventable in-hospital ADRs.
Drug-Drug Interactions classification:
I) According to effect:
A-Harmful Effects (potentiating/antagonism)
B- Beneficial Effects (Additive or Synergistic)
II) According to site of interaction:
A) In-vitro: 1-Drug-laboratory tests interaction:
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2) Mixing 2 drugs prior injection:
B) IN-VIVO:
♣ Underlying factors; A) Patient factors:
 Old age changes: e.g. ↓ liver metabolism, kidney function, nerve transmission or the functioning of bone marrow.
↓sensation→ ↑ the chances of errors being made in the administration of drugs .
 Genetic factors: e.g enzyme genetic variability.
 Serious diseases that could worsen if the dose of the medicine is reduced.
 at High Risk for Drug Interactions e.g. Hepatic/renal diseases.;Autoimmune disorders.Cardiovascular
disease.;Gastrointestinal disease; Infection ; Psychiatric disorders; Respiratory disorders.;Seizure disorders.
pregnant women , Smoking ;Alcohol
 Diet/Nutrition ;Environment
B) Drug dependent factors:
*Polypharmacy:
*Narrow therapeutic index = LD50 (Lethal dose in 50% of animals) / ED50 (Effective dose in 50% of animals) e.g.
Aminoglycoside antibiotics (gentamicin, tobramycin) Anticoagulants (warfarin, heparins), Aspirin, Carbamazepine,
Conjugated estrogens,Cyclosporine ,Digoxin,Esterified estrogens, Hypoglycemic agents, Levo-thyroxine Na, Lithium
,Phenytoin, Procainamide, Quinidine sulfate/gluconate, Theophylline,Tricyclic antidepressants ,Valproic acid.
2-Steep dose-response curve (Phenytoin, Aminoglycoside Vancomycin): Small changes in the dosage of a drug
produce large changes in the drug's concentration in the patient’s blood plasma.
3-Saturable hepatic metabolism: In addition to dose effects the capacity to metabolize the drug is greatly decreased.
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Plasma drug concentration
Need to keep concentration of drug within
the therapeutic range
MTC
MEC
Time
MEC=Minimum effective concentration
MTC=Maximum therapeutic concentration
♣ Classified according to underlying mechanisms into:
A) Pharmacokinetic drug-drug interaction:
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1) Altered Absorption:
a) Altered pH:
*Gastric acidity: * Infection   Absorption of weak acid drugs eg Aspirin & Phenobarbitone.
* Antiacids ,H2 antagonists , PPIs, atazanavir, itraconazole (gastric alkalinity) →↓ Absorption of weak Acid
(Aspirin,barbiturate,Ketoconazole ,quinolones & fluoroquinolones , tetracyclin)& ↑ absorption of weak base .
*Intestinal Alkalinity   Absorption of weak base drugs e.g. Ephedrine
b) Altered Efflux Transporter (P-gp, MDR1) to intestinal lumen(↓ by Quinidine →↑digoxin plasma concentration .
c) Altered motility; Gastric Emptying Time,GET (stomach emptying time):
* GET ↓by food,morphine,Metoclopramide (antiemitic)→ ↑absorption of rapid dissolution drugs ( Paracetamol &
Propranolol) & ↓ absorption of delay dissolution drug( Digoxin).
*GET ↓by fasting ,antacids, opioid, antimuscarinic (propantheline atropine), antidiarrhoeal →↓ absorption of
paracetamol & ↓ bioavailability of drugs that are degraded in the intestine (levodopa) and ↑Increased bioavailability
of lipid soluble drugs .
NB: The Reverse; Laxatives will cause drugs to move through the intestine so rapidly that they are poorly absorbed.
d) Interactions during absorption.
1- Chelation : (Chelating agent forming a stable complex with a toxic metal):
*Antacids (Ca2+, Mg2+, Al3+), iron salts (Fe2+) and milk (Ca2+) inhibit the absorption of tetracyclines
*Bile acid binding resins: cholestyramine, cholestipol adsorps and inhibits the absorption of thyroxine , cardiac
glycosides (digoxin, digitoxin), warfarin, corticosteroids, thiazides .
*Kaolin-pectin decrease the absorption of digoxin
*Tetracyclines and Quinolones chelate metals and form an insoluble complex that ↓their absorption.
* EDTA chelates toxic metals such as lead and reduces toxicity.
2- Adsorption: nonspecific, physical,binding of a drug to another agent:
-Cholestyramine adsorbs dicumarol,methotrexate and digitoxin and decreases their absorption.
-Antacids decrease digoxin and iron absorption by adsorption.
d) Altered intestinal bacterial flora:
Antibiotics (Chloramphenicol, tetracyclines) kill a large number of the normal flora of the intestine,
* →↓synthesis of vit K by bacteria, →↑the efects of oral anticoagulants which compete with vit K.
* →↓ enterohepatic recycling of estrogens, → the efficacy of oral contraceptives
* →↑ absorption of drugs that are metabolized by gut bacteria e.g.digoxin.
(In 10% 0f patients receive digoxin 40% or more of the administered dose is metabolized by the intestinal flora).
e) Altered blood flow: NE with local anaesthetic
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B) Altered distribution:
1) Plasma protein (e.g. albumin acidic drugs) & a1-acid glycoprotein, basic drugs) displacement:
Depends on the affinity of the drug to plasma protein. The most likely bound drugs are capable to displace
others. It is clinically important if displaced drug is highly PP binding, with LONG T ½, small Vd, narrow
therapeutic range. The free drug is increased by displacement by another drug with higher affinity.
e.g Aspirin, Phenylbutazone, Clofibrate & Sulfa Displace:
- Oral Anti-coagulants (Dicumarol, Warfarin)  Bleeding
- Oral Hypoglycemics (Tolbutamide)  Hypoglycemia
-Bilirubin in Neonate  Jaundice & Kernictrus
2) Interactions due to disturbances in fluid and electrolyte balance:
Primary drug
-Digoxin
-Lignocaine
-Diuretics
-Tubocurarine
-Lithium
-ACEIs
Interacting drug effect
-Diuretic-induced hypokalemia
-Diuretic-induced hypokalemia
-NSAID-induced salt and water retention
-Diuretic-induced hypokalemia
-Thiazide-induced reduction in renal clearance
-Kcl and/or patassium-retaining diuretic-induced
hyperkalemia
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Result of interaction
-Digoxin toxicity
-Antagonism of antiarrhythmic
effects
-Antagonism of diuretic effects
-Prolonged paralysis
-Raised plasma lithium
-Severe hyperkalemia
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3) Altered Elimination:
A)
Altered transporters (which transport drugs to different organs):
P-gp= p-glycoprotein;MDR=multidrug resistance;;OATP=,organic anion transporting polypeptide;OCT[organic cation transporter; OAT,
organic anion transporter
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1-Altered Eflux transporter (Pgp)
B) Altered Uptake transporter
Inhibitor
Substrate
effect
↓ PCT acidic drug
excretion→↓ renal
excretion &↑systemic
toxicity
↓ hepatic uptake take
→↑systemic toxicity
OAT1
OCT1
Probencide.novobiocin
Cimitidine, desipramine,
phenoxy-benzamine,quinine
Pencillin, cephalosporones ,cidofover
amantadine, cimetidine, memantine,
Procainamide ,metformin
OATP
Gemfibrazol ,cyclosporine
squinavir ,retoniver ,squinavir
rifampicin
Statins, repaglinide, digoxin
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Competitive drug interaction in renal tubules:
Primary drug
*Penicillin
*Methotrexate
*Salicylate
*Indomethacin
*Chlorpropamide
*Digoxin
Competing drug
Effect of interaction
*Probenecid
*Increased penicillin blood level
*Salicylates
*Bone-marrow suppression
*Sulfonamides
*Salicylate toxicity
*Probenecid
*Indomethacin toxicity
*Probenecid
*Hypoglycemia
*Phenylbutazone Spironolactone
*Increased plasma digoxin
Amiodarone Verapamil
- Alkalinization of urine (NaHCO3)  Excretion of weak acid drugs e.g. Aspirin
-acidification by Vit. C Excretion of weak base drugs e.g. quinidine, amphetamine
Drugs that act as weak acids or bases :
Weak acids.:Acetylsalicylic acid ,Furosemide ,Ibuprofen ,Levodopa ,Acetazolamide ,Sulfadiazine,
Ampicillin ,Chlorothiazide ,Paracetamol ,Chloropropamide ,Cromoglicic acid ,Ethacrynic acid ,alphaMethyldopamine ,Phenobarbital ,Warfarin ,Theophylline ,Phenytoin.
Weak bases: Reserpine ,Amphetamine ,Procaine ,Ephedrine ,Atropine ,Diazepam ,Hydralazine ,Pindolol
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B) Altered Metabolism: Enzyme inhibitors/inducers
HME Inducers: Phenytoin, Phenobarbitone, Rifampicin, Testosterone & Tobacco smoking   Their own
metabolism & Other drugs.
HME Inhibitors: MAO-I, Cimetidine, Estrogen, Na Valproate & Chloramphenicol
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Cytochrome P 450 enzymes:
Common drug substrates
CYP1A2 Clozapine, clomipramine,
estrogen, fluvoxamine,
haloperidol , tacrine, theophylline,
CYP2C9 Phenytoin, warfarin, tolbutamide,
glipizide
CYP2D6 Alprenolol, bufuralol, carvedilol,
metoprolol, propranolol, timolol,
amitriptyline,clomipramine,desipr
amine, imipramine, nortriptyline
,flecainide ,mexiletine, fluoxetine,
propafenone, haloperidol , paroxetine , perphenazine, venlafaxine ,
codeine ,dextromethorphan
CYP2E1 Paracetamol, benzene, ethanol,
isoflurane,theophylline
CYP3A Diltiazem, felodipine, nifedipine,
verapamil,ciclosporin, tacrolimus,
alprazolam, midazolam,
triazolam, atorvastatin, lovastatin,
clarithromycin,erythromycin,
indinavir, nelfinavir, ritonavir,
saquinavir, losartan, sildenafil
Inhibitors
(↑drug level of substrate)
Amiodarone, cimetidine,
fluoroquinolones,
ticlopidine, Ciprofloxacin,
enoxacin,fluvoxamine
Amiodarone, fluconazole,
miconazole,phenylbutazone,
sulphinpyrazone
Clomipramine, quinidine,
fluoxetine, haloperidol,
paroxetine, Bupropion,
paroxetine, quinidine
Inducers
(↑drug level of substrate)
Polycyclic aromatic
hydrocarbons,Omeprazole
, ritonavir, phenobarbital
Disulfiram, diethyldithiocarbamate
Diltiazem, verapamil,
itraconazole, ketoconazole,
clarithromycin,
erythromycin,troleandomyci
n, Delavirdine , indinavir,
ritonavir,saquinavir,grapefru
it juice,mifepristone,
nefazodone, Amprenavir,
aprepitant,atazanavir,ciprofl
oxacin,darunavir/ritonavir, ,
fluconazole, fosamprenavir,
grapefruit juice,imatinib,
Ethanol, isoniazid
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Carbamazepine,
phenobarbital, rifampin,,
St John’s Wort
Not inducible
Rifabutin, rifampin,
rifapentine,carbamazepine,
phenobarbital, phenytoin,
topiramate, efavirenz,
nevirapine, St John’s
Wort, Avasimibe,
phenytoin, rifampin,
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II- Pharmacodynamic Drug-Drug interaction:
A) Additive, synergistic or summation interactions
Drugs
Anticholinergics + anticholinergics (anti-parkinsonian
agents, butyrophenones, phenothiazines , tricyclic
antidepressants, etc.)
Antihypertensives + drugs causing hypotension (antianginals, vasodilators, phenothiazines)
CNS depressants + CNS depressants (alcohol, antiemetics, antihistamines, hypnosedatives, etc.)
QT prolonging drugs + other QT prolonging drugs
(Amiodarone + Disopyramide)
Methotrexate + co-trimoxazole
Nephrotoxic drugs + nephrotoxic drugs (gentamicin or
tobramycin with cefalotin (cephalothin)
Neuromuscular blockers + drugs with neuromuscular
blocking effects (e.g. aminoglycoside antibacterials)
Potassium supplements + potassium-sparing diuretics
(triamterene)
Aminoglycoside +B-lactam
Result
Increased anticholinergic effects; heat stroke in hot and
humid conditions; a dynamic ileus; toxic psychoses
Increased antihypertensive effects; orthostasis
Impaired psychomotor skills, reduced alertness,
drowsiness, stupor, respiratory depression, coma, death
Additive prolongation of QT interval, increased risk of
torsade de pointes
Bone marrow megaloblastosis due to folic acid antagonism
Increased nephrotoxicity
Increased neuromuscular blockade; delayed recovery,
prolonged apnoea
Marked hyperkalaemia
Synergim
Potentiation: .
- Barbiturates (NOT analgesic) potentiate the analgesic effect of aspirin.
- Change pH:
*alkalinize urine by NaCo3  efficacy of aminoglycoside, sulphonamid
*Acidify urine by vit, C efficacy of B lactam, nitrofurantoin.
- hypokalemia digitalis toxicity
B-Antagonism:
*Chemical e.g. Heparin(Ac.) +Pr.So4(base)
*Physiological e.g. Ad& H on bronchi
*Pharmacological One Agonist + One Blocker + One Receptor.
Iatrogenic Disease:
Drug-induced disease.
- Large dose of Reserpine & Chlorpromazine (Iatrogenic Parkinsonism)
-Large dose of Cortisol (Iatrogenic Cushing’s disease)
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Drug-food interaction
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Food
High-carbohydrate meals
Acidic foods/juices and sodas (e.g., cola)
antacids (Mg , aluminium ) , iron products and
calcium in vitamin-mineral products and liquid
enteral nutritional supplements
vitamin B6 (pyridoxine) found in avocados, beans,
peas, sweet potatoes, bacon, beef liver, pork, tuna &
some nonprescription vitamin-mineral products
Avocado ;Brassicas (brussel sprouts, broccoli,
cabbage)
Grape fruit juice
Soya
Hypericum perforatum (St John’s wort)
vitamin K found in green leafy vegetables(spinach,
collard greens),, tomatoes coffee, beef liver, green
tea, , Alfalfa tablets Broccoli ,Brussels sprouts,
Cabbage, Cauliflower (raw), Green tea ,Liver, Soybean, Vegetable oils (canola, soybean) , Watercress
Consuming foods high in sodium (i.e licorice,
processed meats, canned foods)
The drug may increase appetite thus increasing
nutrient intake
The drug may decrease appetite thus decreasing
nutrient intake
Foods Containing High Amounts of Tyramine
Ale , Avocados,Bananas,Beans (lima beans, butter
beans, bean pods),Caviar, aged Cheese, Chocolate
Coffee,Figs,Fish ,meat (bologna, fermented meat,
salami, pepperoni, summer sausage),Liver (beef or
chicken), Raspberries, Raisins, Sour cream,Soy
beans or sauce, Tofu, Wines (especially red),Yeast
preparations, Yogurt
Drugs
Iron, levodopa, penicillins (most),
tetracycline, erythromycin
Ketoconazole
Fluoroquinolones (ciprofloxacin,
levofloxacin, ofloxacin,
trovafloxacin), Tetracycline
↑ absorption
↓ absorption
↓blood levels of
dopamine &antiparkinsonism effects
Enzymatic inducer
(effect↓)
levodopa,;
Oral anticoagulant
Amlodipine,nifedipine, Cyclosporine,
tacrolimus Terfenadine, astemizole
,Cisapride , Pimozide Carbamazepine,
Saquinavir, Midazolam, Alprazolam,
Triazolam
Clozapine, Haloperidol, Olanzapine,
caffeine, NSAIAs, Phenytoin,
Zafirlukast, warfarin
Warfarin, Digoxin, Theophylline,
cyclosporine, phenytoin and
antiretrovirals
Oral Anti-coagulant
Antihypertensives
effect
↓ absorption
Enzymatic
inhibition
(Toxicity)
Enzymatic
inhibition(Toxicity)
Enzymatic inductor
(CYP450)
Interfere with
efficacy
↓effectiveness of
the drug.
Cortico-steroid
Diuretic
MAOIs
acute
exacerbation of
blood pressure.
Effect of Drugs in nutrient body content
Food
Taking large amounts of these drugs will cause a loss of Vitamin C in the body.
Women who take these drugs often have low levels of folic acid and B6 in the blood.
Vitamin D and folic acid levels in the body are ↓by the taking of these types of drugs.
Ginseng
Kava (Piper methysticum)
Chamomile
Hawthorn
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drug
Aspirin
Oral contraceptives
Anticonvulsant
Warfarin, Heparin, Aspirin and NSAIA
Levodopa
Benzodiazepines, barbiturates , opioid
Beta-adrenergic antagonists, Cisapride,
Digoxin, Quinidine
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HERBALS AND DRUG INTERACTIONS
Activity
Commonly Used Herbs*
Anti-coagulant chamomile, dong quai (tang-kuei), horse chestnut
Anti-platelet
bilberry, bromelain, cayenne, feverfew, flaxseed oil, garlic, ginger, ginkgo, ginseng, green
tea, meadowsweet, motherwort, and turmeric
Pro-coagulant
goldenseal, Oregon grape root, shepherd's purse
*other anticoagulant and antiplatelet herbs, white atracytlodes, cnidium (chuanxiong), salvia, garlic,
zedoaria, pueraria, carthamus, lysimachia, cinnamon bark, tien-chi (sanqi), and capillaris (also listed: tangkuei and turmeric).
Herb
Cayenne
Some Common Uses
Possible Side Effects or Drug Interactions
External: used for muscle
spasm and soreness
Internal: GI tract disorders
External: potential for skin ulceration and blistering with
greater than 2 days of use. Internal: overuse may cause severe
hypothermia.
Echinacea
boosts the immune system & Echinacea may cause inflammation of the liver if used with
helps fight colds and flu. Aids certain other medications, such as anabolic steroids,
wound healing.
methotrexate or others.
Ephedra (MaHuang)
It is used in many over-thecounter diet aids as an
appetite suppressant. Or
used for asthma or
bronchitis.
Ephedra may interact with certain antidepressant medications
or anthypertensive medications to cause dangerous elevation in
blood pressure or heart rate. It could cause death in certain
individuals.
MAOI, central nervous system stimulants, alkaloids ergotamines
and xanthines
Feverfew ‫الينسون‬
↓migraine headaches and for
arthritis, rheumatic disease
& allergies.
Feverfew may increase bleeding, especially in patients already
taking certain anti-clotting drugs.
↓ Blood cholesterol, TG
levels and blood pressure.
Garlic may increase bleeding, especially in patients already
taking Anticoagulants ,NSAIA, acetylsalicylic acid certain.
Ginger is used for reducing
nausea, vomiting and vertigo
Ginger may ↑bleeding, potentiate anticoagulant sulfaguanidine
(enhance absorption)
↑blood circulation & oxygenation and for improving
memory and mental
alertness.
Ginkgo may increase bleeding especially in patients already
taking warfarin, Aspirin and NSAIA
Garlic
Ginger‫زنجبيل‬
Ginkgo (ginkgo
biloba) ‫الجنكة‬
‫الصينية‬
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Ginseng increases physical
stamina and mental
concentration.
warfarin (to cause bleeding or to ↓ effectiveness. It may cause
bleeding in women post- menopause . ↑ heart rate or blood
pressure. antidepressants such as phenelzine sulfate (to cause
manic episodes, headaches);); corticosteroids (potentiation);
estrogens (potentiation)
mild laxative and also
reduces inflammation.
Goldenseal may worsen swelling and/or high blood pressure.
nervousness, anxiety or
restlessness; it is also a
muscle relaxant.
↑the effects of certain anti-seizure, prolong the effects of certain
anesthetics ,↑ the effects of alcohol. It may ↑the risk of suicide
for people with certain types ofdepression.
Licorice is used for treating
stomach ulcers.
Certain licorice compounds may cause high blood pressure,
swelling or electrolyte imbalances.corticosteroids and thiazide
diuretics (potentiation); digitalis or other cardiac glycosides
(increased sensitivity)
used for enlarged prostate
and urinary inflammations.
People using saw palmetto may see effects with other hormone
therapies.
St. John's Wort is used for
mild to moderate depression
or anxiety and sleep
disorders.
prolong the effect of certain anesthetic agents. warfarin (to
cause bleeding); serotonin-uptake inhibitors (to cause mild
serotonin syndrome); indinavir (decreased bioavailability);
digitoxin, theophylline, cyclosporin, phenprocoumon, and oral
contraceptives (all with reduced bioavailability)
Mild sedative or sleep-aid. It
is also a muscle relaxant.
↑the effects of certain anti-seizure or prolong the effects of
certain anesthetic agents.
Ginseng
Goldenseal
Kava-kava
Licorice
Saw Palmetto
St. John's Wort
‫القديس‬
Valerian ‫الناردين‬
‫نبات‬
Herb
Interactions Reported or Suspected
Tang-kuei danggui
warfarin (to cause bleeding)
Salvia danshen ‫ المريمية‬,
warfarin (to cause bleeding)
‫نبات الناعمة‬
Rhubarb dahuang ‫راوند‬
↑cardiac glycosides and antiarrhythmic (by ↓K via laxative effect)
Aloe luhui ‫الصبار‬
↑cardiac glycosides and antiarrhythmic (by ↓K via laxative effect)
Ma-huang
MAO is (to cause hypertension); cardiac glycosides or halothane (to produce cardiac
arrhythmia); caffeine (to ↑cardiovascular side effects)
Astragalus huangqi ‫قتاد‬
cyclosporine, azathioprine, methotrexate (to impair intended immuno-suppressive effects).
Bupleurum chaihu
sedatives (potentiation)
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Drug
Herbal/Food
Adverse Effects/Drug Interactions Reported
Alprazolam
Kava‫فلفل كاوة‬
Synergistic CNS activity of alprazolam
Quinine
Elevated serum drug levels of amantadine and risk of toxicity (ataxia,
mental confusion)
Khat
Delayed or decreased absorption of amoxicillin and ampicillin
Grapefruit (juice)
Increased bioavailability of astemizole
Quinine
↑serum drug levels of astemizole, and↑ risk of cardiotoxicity
Buspirone
Grapefruit(juice)
Increased serum drug levels of buspirone
Dihydrop. Ca.
channel B.
Grapefruit (juice)
Increased serum drug levels: amlodipine 15%, felodipine >300%,
nifedipine 35%, nisoldipine 400%
Carbamazepine
Grapefruit(juice)
Increased serum drug levels by about 40%
Quinine
Elevated serum drug levels of carbamazepine by about 37%
Grapefruit (juice)
↑ serum drug levels and increased usual ADRs of cyclosporine
Quinine
Elevated serum digoxin levels by about 75%
Licorice
Elevates serum digoxin levels 4-fold
Amantadine
Amoxicillin ,
ampicillin
Astemizole
Cyclosporine
Digoxin
Hawthorn
‫الزعرور‬
Increased cardiac toxicity
‫البرى‬
Estrogen
Ginseng (Siberian)
Elevates serum digoxin levels by about 75%
St. John’s wort
Decreases serum digoxin concentration by 25%
Grapefruit (juice)
Increased serum drug levels by 37%
Herbal tea
Increased serum drug levels by 28%
Increased serum drug levels of lithium
Lithium
diuretic Herbs
(broom‫ الوزال‬, buchu,
dandelion ‫الهندباء‬
,juniper ‫) العرعر شجر‬
Midazolam
Grapefruit (juice)
Increased serum drug levels of midazolam
St. John’s wort
Incoherent, confused, nausea, weakness, and fatigue;
effects occurred 10 days after paroxetine was discontinued and first dose
of St. John’s wort was initiated
Ginseng (Siberian)
Insomnia, tremulousness, tension headaches, irritability, and visual
hallucinations
Phenobarbital
Quinine
Elevated serum phenobarbital levels by about 35%
Quinidine
Grapefruit (juice)
Reduced and delayed cardiac effects (QTc).
Licorice
Mineralocorticoid of licorice blocked; hypokalemia and muscle
weakness
Theophylline
St. John’s wort
Increases serum theophylline concentration by about 50%
Triazolam
Grapefruit (juice)
Increased serum drug levels of triazolam
Paroxetine and
other SSRIs
Phenelzine
Spironolactone
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Warfarin
Dashen
Increased anticoagulant activity or increased INR
Ginkgo biloba ‫ الجنكه‬,
garlic, feverfew
‫الينسون‬, and cayenne
Platelet aggregation inhibitor effects and increased risk of
bleeding/bruising
Ginseng(Siberian)
Decreased anticoagulant activity or decreased INR
Licorice
Increased anticoagulant activity or increased INR
Alfalfa ‫ فصة‬, ‫البرسيم‬
Decreased anticoagulant activity or decreased INR
Vitamin E (doses of
200 IU/day)
Increased anticoagulant activity and increased platelet aggregation
inhibition, increased risk of bleeding
Ginger ‫زنجبيل‬
↑anticoagulant activity, increased INR, prolonged bleeding
Quinine
Increased anticoagulant activity or increased INR
It may be possible to reduce or prevent ADRs by:
 Avoiding unnecessary drug use; if you don't prescribe drugs you will not get ADRs
 Consult the BNF and the BNF for Children which are useful sources of information on drug interactions.
 Read the Drug Safety Updates from the MHRA http://www.mhra.gov.uk/mhra/drugsafetyupdate
 Exercise caution when prescribing at extremes of age. These patients are at higher risk due to altered
pharmacodynamics and pharmacokinetics
 Neonates (first 30 days of life) are at risk of toxicity due to inefficient renal filtration, relative enzyme
deficiencies, differing target organ sensitivity, and inadequate detoxifying systems causing delayed excretion.
 Children; drugs are not extensively tested in this group, the drug may not be licensed at all or licensed but used
'off-label', for which the prescriber is legally responsible.
 Elderly; altered response to drugs (pharmacodynamics).
 reduced response at receptor level (beta-blockers),
 increased central nervous sensitivity (benzodiazepines)
 Reduced clotting factors (increased response to warfarin).
 Elderly; altered handling of drugs (pharmacokinetics) - see the BNF for specific dose reductions of individual
drugs.
 Absorption- may be reduced (reduced levodopa and iron absorption may be clinically significant),
 Altered distribution; generally reduced weight in the elderly with decreased body water (need to reduce loading
dose of digoxin) and increased body fat (benzodiazepines can accumulate) and decreased binding to albumin
(phenytoin).
 Metabolism- reduced blood flow (propranolol), reduced liver mass (theophylline may become toxic).
 Excretion- decreased renal excretion (digoxin, lithium).
 Identify patients with co-existing disease which may affect drug elimination
 Reduce maintenance dose of digoxin in patients with renal impairment
 Reduce dose of oral propranolol in patients with hepatic disease
 Identify drugs which pose risk and monitor carefully
 Enzyme inducers and inhibitors- flag patient's notes to remind you and others.
 Drugs with major effect on a vital process such as warfarin
 Drugs with narrow therapeutic range such as digoxin, carbamazepine, theophylline, phenytoin
 Drugs where loss of effect may lead to disease breakthrough such as chronic obstructive pulmonary disease
 Patient dependent on prophylactic action such as transplant patients taking ciclosporin
 Counsel patients on drug action and possible side-effects, provide written information and encourage patients to
report back progress and /or side-effects
 Gender – some ADRs are more prevalent in the female population. Examples of this are the increased
susceptibility of females to the toxic effects of digoxin, heparin and captopril.
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
Information for Practitioners to Relay to Patients about Interactions with Drugs.
Type of Interaction
Examples
Patient Information
Drug absorption inhibited
by binding, resulting in
low drug levels.
Tetracycline with minerals; alkaloids with
tannins; pectins, resins, and fibers may
bind several drugs.
Take herbs at least one hour apart,
preferably 1.5 hours apart from taking
drugs.
Drug absorption inhibited
by rapid transit time,
resulting in low drug
levels.
Diarrhea or frequent bowel movements
due to colitis or laxative intake speeds
transit of all materials through the
intestinal tract.
Treat diarrhea and avoid excessive use
of laxatives. Induction of diarrhea is
an intended treatment strategy in
Chinese medicine for nephritis.
Drug absorption and/or
elimination modified.
Saponins may improve absorption and
elimination of drugs, altering the blood
levels and rate of change of drug levels;
strongly acid or alkaline herbs may alter
absorption of drugs.
Take herbs at least 1.5 hours apart
from drugs; avoid herbal preparations
that have high saponin content.
Drugs metabolized too
slowly resulting in
elevated drug levels.
Grapefruit juice and herbs that inhibit
CYP enzyme system can result in much
higher levels of drugs in the bloodstream,
and longer persistence of the drugs.
Take herbs at least 1.5 hours apart
from drugs, preferably taking the
drugs first (so that drug metabolism is
already under way by the time the
herbs can inhibit enzyme systems).
Potassium decreased when
using cardiac drugs,
resulting in adverse
cardiac conditions.
Laxative and diuretic herbs may reduce
potassium; these types of herbs are often
given together for weight loss.
Avoid any strong laxative or diuretic
action while using cardiac drugs. To
compensate for mild diuretic or
laxative treatments, consume highpotassium foods.
Drug action is intensified
by similar effect of herbs.
Blood vitalizing herbs and blood thinning
drugs may prevent adequate clotting;
hypoglycemic herbs and hypoglycemic
drugs may lower blood sugar too far;
caffeine or ephedrine containing herbs and
CNS stimulants disturb nerve functions.
When the drug therapy is already
addressing a particular therapeutic
goal, avoid adding an herbal therapy
with the same goal. Intensify
monitoring of blood conditions
affected by the drugs.
Drugs cause adverse
reaction to occur when
certain substances are
ingested.
MAO inhibitors can cause hypertension
when an ordinary food component,
tyramine, is ingested; some drugs can
cause severe nausea when alcohol is
ingested.
Learn the known reactions and take
reasonable steps to avoid problematic
herbs. It may be unnecessary to have
total abstinence from an herb that
reacts with a drug.
Miscellaneous: reported
drug interactions.
St. John’s wort decreases bioavailability
of indinavir.
Learn the known reactions and avoid
using the combination.
Desired drug effect is
counteracted by herb
effect.
Immune-enhancing herbs may counteract
intended immunosuppressive action of
drugs in autoimmune disorders, including
transplant rejection reactions.
If herbs with known immuneenhancing actions are to be used, limit
the dosage to avoid counteracting the
drugs.
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