6142 M3 | [3] Dispensing - Drug Interactions

DRUG INTERACTIONS — Duplication

potentiation of effect when 2 drugs with the same active ingredient or with the same action (synergistic action) are taken at the same time.

DRUG INTERACTIONS — Antagonism

reduction of efficacy when two drugs with opposing actions are taken together.

DRUG INTERACTIONS — Alteration of Pharmacokinetic Actions - (ADME)

a second drug may increase or decrease the rate during ADME of first drug.

PHARMACODYNAMIC INTERACTIONS — ADDITION ($1+1=2$)

The effect of one drug is added to the effect of another drug (combined effect).

PHARMACODYNAMIC INTERACTIONS — ADDITION: Prazosin + Beta-blocker

Orthostatic hypertension

PHARMACODYNAMIC INTERACTIONS — ADDITION: Non-dihydropyridine calcium channel blocker + Beta-blocker

Blockade of atrioventricular node

PHARMACODYNAMIC INTERACTIONS — ADDITION: Antidepressant + Azithromycin

Cardiac arrythmias

PHARMACODYNAMIC INTERACTIONS — SYNERGISM ($1+1=3$)

The effect of one drug combined with the effect of another drug results to a pharmacologic effect which is more than what was expected.

PHARMACODYNAMIC INTERACTIONS — SYNERGISM examples

Sulfamethoxazole (SMZ) and trimethoprim (TMP); Sulfadoxine and Pyrimethamine

PHARMACODYNAMIC INTERACTIONS — ANTAGONISM ($1+1=\underline{0}$)

Common, the effect of a drug is cancelled by the presence of another drug.

PHARMACODYNAMIC INTERACTIONS — ANTAGONISM examples

Propranolol + Albuterol; OHA + Glycocorticoids; L-Dopa + Neuroleptics; Tetracycline + Penicillin

PHARMACODYNAMIC INTERACTIONS — POTENTIATION ($1+0=2$)

There is a drug with effect (1) and drug with no effect (0). The drug with no effect enhances the effect of the drug with pharmacologic activity.

PHARMACODYNAMIC INTERACTIONS — POTENTIATION: Amoxicillin + Clavulanic acid

Co-amoxiclav (amoxicillin stays longer in the body)

PHARMACODYNAMIC INTERACTIONS — POTENTIATION: Loop diuretic + Silver ear fluid imbalance

ototoxicity

ELECTROLYTE CONCENTRATION — Digoxin + Non potassium sparing diuretics

digoxin toxicity

ELECTROLYTE CONCENTRATION — Digoxin mechanism

Potassium controls the entry of digoxin in the cells through potassium channels. Lower concentration of potassium in the body may lead to digoxin toxicity.

ELECTROLYTE CONCENTRATION — Lithium + diuretics

Lithium + diuretics

PHARMACOKINETIC INTERACTIONS — Antacids advice

In general, we can advise patients taking antacids with another drug that there should be adequate spacing in dosage intake such that one drug is not affected by the other.

ABSORPTION — COMPLEXATION

Complex formation (chelates) which are not absorbable by the body.

ABSORPTION — COMPLEXATION examples

Quinolones/tetracycline + Fe, Ca, Mg, Al, Bi, Zn

ABSORPTION — ALTERATION OF MOTILITY / GER: Increase in GI motility

Faster transit time from the stomach to intestine; site of absorption is stomach = increased motility causes decreased therapeutic effect/overdosage/toxicity; site of absorption is intestine = increased motility increases therapeutic effect or overdosage/toxicity

ABSORPTION — ALTERATION OF MOTILITY / GER: Decreased intestinal tone

Stays longer in the stomach = decreased therapeutic effect since drug is disrupted/destroyed by gastric fluids (if absorption site is intestine) or leads to overdosage/toxicity (if absorption site is stomach)

ABSORPTION — ALTERATION OF MOTILITY / GER: Cathartic/laxatives

increase motility

ABSORPTION — ALTERATION OF MOTILITY / GER: GER (Gastroesophageal reflux)

tendency to have lesser absorption because the drug doesn't reach the site of absorption

ABSORPTION — ALTERATION OF MOTILITY / GER: Anticholinergic

Anticholinergic

ABSORPTION — ALTERATION OF GI FLORA

Mostly antibiotics can disrupt the GI flora.

ABSORPTION — ALTERATION OF GI FLORA: Antibiotic + Digoxin

Increase in digoxin level

ABSORPTION — ALTERATION OF GI FLORA: Antibiotic + Warfarin

Increase anticoagulation

ABSORPTION — ALTERATION OF GI FLORA: Antibiotic + OCP (Oral Contraceptive Pills)

Alters enterohepatic circulation of estrogen leading to the decrease in concentration of OCP

ABSORPTION — ALTERATION OF GI FLORA remedy

REMEDY: Have spacing and do not administer them concurrently.

DISTRIBUTION — DISPLACEMENT FROM PROTEIN BINDING SITE

Some drugs are protein-bound first before it becomes a free drug. However, if another drug is already occupying the intended receptor of the drug, it wouldn't have a binding site, making it a free drug.

DISTRIBUTION — Free drug

Increased drug concentration in the body.

DISTRIBUTION — Phenytoin + Warfarin

Increase in free phenytoin leading to gingival hyperplasia (Warfarin occupies phenytoin receptors, displacing phenytoin)

DISTRIBUTION — Tolbutamide + Sulfonamide

Hypoglycemia (Both hypoglycemic effects)

DISTRIBUTION — Epinephrine + Lidocaine

Vasoconstriction. Beneficial drug interaction for local anesthesia: First, epinephrine will constrict the blood vessels around the certain body area. Then, inject lidocaine, which will exert its effect locally instead of systemically.

DISTRIBUTION — Hypoalbuminemia

Low albumin = less proteins for drugs to bind = more free drugs

ABSORPTION — ALTERED PH

Drugs are only soluble, stable, or absorbed at a certain pH. Change in environmental pH alters a drug's stability, absorption, or solubility.

ABSORPTION — ALTERED PH examples

Ketoconazole + antacid decreased drug bioavailability; Bisacodyl + antacid. Antacids make gastric fluids less acidic and more alkaline/basic.

METABOLISM — Overview

One drug is enhancing or inhibiting/blocking the metabolism of another. The most common enzyme responsible for metabolizing drugs is cytochrome P450.

METABOLISM — CYP450 inducers

Metabolized faster = decreased therapeutic effects

METABOLISM — CYP450 inhibitors

Stay longer in the body = increased therapeutic effects; may lead to overdosage/toxicity

ENZYME INDUCER — List

Carbamazepine, Cigarette smoking, Chronic alcoholism, Griseofulvin, Rifampicin, Omeprazole, Phenobarbital, Phenytoin, St. John's Wort

ENZYME INHIBITOR — List

Cimetidine, Ciprofloxacin, Acute alcoholism, Valproic acid, Verapamil, Chloramphenicol, Erythromycin (macrolides except Azithromycin), Disulfiram, Diphenhydramine, Grapefruit, Isoniazid (INH), Metronidazole, Ketoconazole

DISULFIRAM — Function and effect

Disulfiram is used to treat chronic alcoholism. It inhibits aldehyde dehydrogenase, increasing the serum acetaldehyde concentration, which is responsible for the deleterious effect (flushing, tachycardia, hyperventilation, and hypotension). This discourages the patient to take alcohol.

DRUG-FOOD INTERACTIONS — Effects on food/drugs

Neutralize drug effects, changes in gastric emptying, drug chelation, changes in the activity of drug metabolizing enzymes, changes in splanchnic blood flow and plasma protein binding.

DRUG-FOOD INTERACTIONS — Bioavailability impact

Food reduces bioavailability.

DRUG-FOOD INTERACTIONS — Pharmacist advice

Pharmacist should give proper advice, to avoid the potential adverse drug reaction on whether to eliminate the interacting food altogether or adjust the time of intake to allow spacing between intake of food and of the drug.

EXAMPLES OF FOOD THAT SHOULD NOT BE TAKEN WITH DRUGS — Ethanol/Alcohol

Increases the risk of liver damage, increase drowsiness &/or sedation, or cause nausea

EXAMPLES OF FOOD THAT SHOULD NOT BE TAKEN WITH DRUGS — Caffeine

A CNS stimulant, alters the action of many drugs affecting the CNS depending on whether the drug is sympathetic or parasympathetic

EXAMPLES OF FOOD THAT SHOULD NOT BE TAKEN WITH DRUGS — Grapefruit

Causes enzyme induction whereby the biotransformation of some drugs are hastened OR causes enzyme inhibition whereby the biotransformation of some drugs are altered/deterred

EXAMPLES OF FOOD THAT SHOULD NOT BE TAKEN WITH DRUGS — Milk

Dairy product or any product containing Ca, Fe, Mg, Al, and other heavy metals (like antacids & multivitamins), forms a chelate with the drug rendering both the drug & the heavy metal non-usable by the body

EXAMPLES OF FOOD THAT SHOULD NOT BE TAKEN WITH DRUGS — Drug that causes gastric irritation

Patients are advised to take the medication with milk or crackers or with a full stomach

EXAMPLES OF FOOD THAT SHOULD NOT BE TAKEN WITH DRUGS — Antibiotics

Can alter/disrupt the GI flora. Almost always taken with an empty stomach unless the patient complains of gastric irritation. If the patient complains of GI irritation, advise them to take a light meal such as crackers/biscuits

DRUG-FOOD INTERACTIONS — Specific food pairings: Biphosphates + food

Decrease BA

DRUG-FOOD INTERACTIONS — Specific food pairings: Anti-infectives + any food

May decrease BA except Penicillin and Tetracycline which should be taken 2 hrs. a.c. (before meals)

DRUG-FOOD INTERACTIONS — Specific food pairings: Erythromycin stearate

Taken before meals

DRUG-FOOD INTERACTIONS — Specific food pairings: Erythromycin ethyl succinate

Taken before or after meals

DRUG-FOOD INTERACTIONS — Specific food pairings: Digoxin + oatmeal

Fiber interfere with its absorption

DRUG-FOOD INTERACTIONS — Specific food pairings: MAOI's + cheese, tyramine, yogurt, sour cream, cured meat, liver, caviar, dried fish, avocado, banana, red wine

HTN due to increase in catecholamine

DRUG-FOOD INTERACTIONS — Specific food pairings: Warfarin + broccoli, spinach, kale, vitamin K

Decrease anticoagulant effect

DRUG-FOOD INTERACTIONS — Specific food pairings: Metronidazole + alcohol

Disulfiram-like effect

DRUG-FOOD INTERACTIONS — Specific food pairings: Griseofulvin/Phenytoin + fatty foods

Increase BA

EXCRETION — Mechanism

One drug is enhancing or inhibiting/blocking the excretion of another drug.

EXCRETION — pH effect

pH: ionized compounds (acidic) are more readily excreted.

EXCRETION — Amoxicillin + Clavulanic acid

Clavulanic acid inhibits excretion of amoxicillin -> Co-amoxiclav (amoxicillin stays longer in the body)

EXCRETION — Methamphetamine + Vitamin C

Methamphetamine (weak base) + Vitamin C = faster excretion of methamphetamine

DIETARY SUPPLEMENTS OR FOOD SUPPLEMENTS — Definition

Alternative therapy most commonly used, includes medicinal herbs or herbal drugs, nutraceuticals, natural substances that include certain herbs, such products as cholesterol-lowering margarines, psyllium-fortified products.

DIETARY SUPPLEMENTS OR FOOD SUPPLEMENTS — Regulation

Therapeutic claims not scientifically studied & evaluated by the FDA ("No approved therapeutic claims" = walang bisa). Food supplements may act as drugs, but they do not have approved therapeutic claims because they did not undergo clinical trials. Should they undergo clinical trials and passed, they become drugs.

DRUG-MEDICINAL HERBS INTERACTIONS — Overview

May intensify or reduce the efficacy of a drug or cause a serious side effect. Avoided by consulting the doctor before taking supplements.

DRUG-MEDICINAL HERBS INTERACTIONS — Chamomile + Warfarin/Other anticoagulants

Increases risk of bleeding

DRUG-MEDICINAL HERBS INTERACTIONS — Chamomile + Phenobarbital/Other barbiturates/Other sedatives

Intensifies or prolongs the sedative effect

DRUG-MEDICINAL HERBS INTERACTIONS — Chamomile + Iron

Reduces iron absorption

DRUG-MEDICINAL HERBS INTERACTIONS — Echinacea + Hepatotoxic drugs (Anabolic steroids, Amiodarone, Methotrexate, Ketoconazole, Immunosuppressants, Corticosteroids, Cyclosporine)

Prolonged use of Echinacea may cause liver damage. When taken with other hepatotoxic drugs, the risk of liver damage may be increased.

DRUG-MEDICINAL HERBS INTERACTIONS — Echinacea + Immunosuppressants

Antagonistic effect since Echinacea is an immune system stimulant

DRUG-MEDICINAL HERBS INTERACTIONS — Echinacea + Warfarin/Other anticoagulants

Increases risk of bleeding

DRUG-MEDICINAL HERBS INTERACTIONS — Feverfew + Iron

Reduces iron absorption

DRUG-MEDICINAL HERBS INTERACTIONS — Feverfew + Ergotamine/Other migraine drugs

Increases heart rate and blood pressure

DRUG-MEDICINAL HERBS INTERACTIONS — Feverfew + NSAIDs

NSAIDs reduces effect of feverfew

DRUG-MEDICINAL HERBS INTERACTIONS — Feverfew + Warfarin/Other anticoagulants

Increases risk of bleeding

DRUG-MEDICINAL HERBS INTERACTIONS — Garlic/Garlic capsules + Insulin/Glipizide/Other hypoglycemic drugs

Intensifies hypoglycemic effect

DRUG-MEDICINAL HERBS INTERACTIONS — Garlic/Garlic capsules + Saquinavir/Antiretroviral

Decreases blood levels of saquinavir diminishing its effect

DRUG-MEDICINAL HERBS INTERACTIONS — Ginger + Warfarin/Other anticoagulants

Increases risk of bleeding

DRUG-MEDICINAL HERBS INTERACTIONS — Ginkgo + Warfarin/Other anticoagulants/Aspirin/NSAIDs

Increases risk of bleeding

DRUG-MEDICINAL HERBS INTERACTIONS — Ginkgo + Phenytoin/Other anticonvulsants

Reduces effectiveness as anticonvulsant

DRUG-MEDICINAL HERBS INTERACTIONS — Ginseng + MAO inhibitors

Intensifies antidepressant effect and increases risk of side effects such as headaches, tremors, and manic episodes

DRUG-MEDICINAL HERBS INTERACTIONS — Ginseng + Warfarin/Other anticoagulants/Aspirin/NSAIDs

Increases risk of bleeding

DRUG-MEDICINAL HERBS INTERACTIONS — Ginseng + Hypoglycemic drugs

Intensifies hypoglycemic effect

DRUG-MEDICINAL HERBS INTERACTIONS — Ginseng + Corticosteroids

Intensifies side effects

DRUG-MEDICINAL HERBS INTERACTIONS — Goldenseal + Digoxin/Estrogen Replacement Therapy

Increases blood levels of digoxin

DRUG-MEDICINAL HERBS INTERACTIONS — Goldenseal + MAO Inhibitors

Increases risk of side effects such as headaches, tremors, and manic episodes

DRUG-MEDICINAL HERBS INTERACTIONS — Goldenseal + Opium and derivatives

Reduces effectiveness

DRUG-MEDICINAL HERBS INTERACTIONS — Goldenseal + Warfarin/Other anticoagulants

Antagonizes anticoagulant effect and increases risk of blood clots

DRUG-MEDICINAL HERBS INTERACTIONS — Grapefruit + Most drugs

Grapefruit is an enzyme inducer reducing effectiveness of most drugs

DRUG-MEDICINAL HERBS INTERACTIONS — Licorice + Antiarrhythmics/Digoxin

Negates antiarrhythmic effect by increasing risk of abnormal heart rhythms; increases risk of digoxin toxicity by lowering potassium levels through increased urine formation

DRUG-MEDICINAL HERBS INTERACTIONS — Licorice + Diuretics

Intensifies diuretic effect causing rapid loss of potassium

DRUG-MEDICINAL HERBS INTERACTIONS — Licorice + Potassium sparing diuretics

Negates effectiveness of potassium sparing diuretics

DRUG-MEDICINAL HERBS INTERACTIONS — Licorice + MAO inhibitors

Intensifies antidepressant effect and increases risk of side effects such as headaches, tremors, and manic episodes

DRUG-MEDICINAL HERBS INTERACTIONS — Milk Thistle + Hypoglycemic drugs

Intensifies hypoglycemic effect

DRUG-MEDICINAL HERBS INTERACTIONS — Milk Thistle + Saquinavir

Decreases blood levels of saquinavir diminishing tis effect

DRUG-MEDICINAL HERBS INTERACTIONS — Saw Palmetto + Estrogen Replacement Therapy/Oral contraceptives

Intensifies effects of estrogen