1- Farmacodynamics

1.1 Pharmacology receivings

1.1.1. Competitive effect

1.1.2 Additive effect

1.1.3. Antagonism

1.2 Organ or physiological system

2- Farmacocinetics

2.1 Absorption

2.1.1 Gastrointestinal tract absorption

2.1.2 Gastric motility alteration

2.1.3 Gastric pH alteration

2.1.4 Gastric enzymatic alteration

2.1.5 Intestinal flora alteration

2.2 Distribution

2.2.1 Plasmatic protein union-points displacement

2.2.2 Tissular union point displacement

2.3. Metabolism

2.3.1 Enzymatic induction

2.3.2 Enzymatic inhibition

2.4 Excretion

2.4.1 Renal excretion

1. Farmacodynamics

Due to modifications that experiment two or more drugs action over the same effect or organ, causing antagonisms or potentiations.

1.1 Pharmacological receivings

1.1.1 Competitive effects

Guanethidine + mixed sympathicomimetic drugs (ephedrine): Both compete in the adrenergic neuron point of entry. Guanethidine decreases or makes void the ephedrine effect.

1.1.2 Additive Effect

MAOI + mixed sympathicomimetic drugs: Addition of effects by secreted noradrenaline excess.

MAOI + tricyclic antidepressants: Addition of effects by no-recapted noradrenaline.

Tricyclic antidepressants + noradrenaline: Addition of effects by no-recapted noradrenaline. Beware of dental operations.

1.1.3 Antagonism

Salbutamol + betablockers

Salbutamol is a beta-stimulant and its effect is antagonized by betablockers.

Take care about betablockers dispensed for asthmatics who take jointly both drugs, because it's possible that unchains an asthmatic crisis.

1.2 Organ or Physiological system

Aminoglycosides antibiotics + diuretics:
ototoxicity increase

Alcohol + CNS sedatives:
hazard in drivers

Chlorpromazine: antipsychotic + trihexyphenidyl:
Avoids extrapyramidal effects + amitriptyline: Avoids depression.

Increases anticholinergics effects: dryness mouth, visual alterations, urinary retention, constipation.

If it appears in old-men patients: dryness mouth, bad use of denture, wrong mastication, denutrition.

2. Farmacocinetics

2.1 Absorption

2.1.1 Gastrointestinal tract absorption

Tetracyclines + (Fe, Al, Ca, Mg, milk):
Tetracyclines are absorbed and do not act. Let 2-3 hours between both drugs.

Colestyramine or Colestipol + (thyroid hormones, warfarin, digitalis glycosides, thiazides):

Colestyramine or colestipol reduces the absorption. Kaolin + Pectin + (dioxin, tetracyclin, lincomycin):
Kaolin + Pectin reduces the absorption.

Penicillamine + (Fe, Al):
Penicillamine absorbs less.

2.1.2 Gastric motility alteration

Cathartics: Increase transit speed. Less absorption.

Anticholinergics: Decrease transit speed. More absorption.

Metoclopramide + acetaminophen, levodopa, tetracyclines: metoclopramide increases the absorption speed.

Aluminous gel + isoniazid: isoniazid it absorbs slowly.

2.1.3 Gastric pH alterations

The ionized drug form is more soluble and more absorbable.

Ketoconazole + (antacids, anticholinergics, H2 antagonists): The ketoconazole is less absorbed.

Bisacodyl + (antacids). Irritations. Vomits. Bisacodyl takes enteric covering.

2.1.4. Gastric enzymatic alteration

The folic acid, in food, is like polyglutamate. Phenytoin inhibits the enzima that turns into monoglutamate that is the absorbable form, causing anaemia.

2.1.5. Intestinal flora modification

Anticoagulants + antibiotics There is a modification of the intestinal flora and less production of K vitamin. Increased anticoagulant effect.

Digoxin + Antibiotics: A 10% of patients metabolize digoxin through the intestinal flora. By decreasing the flora by action of antibiotic, it increases the circulating digoxin.

Oral contraceptives + ampicillin The ampicillin decreases the intestinal flora and break off the contraceptive entero-hepatic circulation, decreasing its efficiency.

2.2 Distribution

2.2.1 Plasmatic protein union-points displacement

Fixed Drug (not active)

Free Drug (active)

Phenylbutazone displaces warfarin: hazard of hemorrhage Naproxen displaces warfarin: hazard of hemorrhage Sulfamides displace bilirubin: hazard of quernicterus

(last days of pregnancy)

(in just borned)

2.2.2. Tissular union-points displacement

Quinidine increases its digoxin plasmatic concentrations because it displaces from the tissular union-points.
Increased digoxin effect.

2.3 Metabolism

2.3.1. Enzymatic induction

Increased activity of hepatic microsomal biotransforming enzymas.
Phenytoin + corticosteroids: increased corticosteroids elimination (hazard in Adison disease, in rheumatic arthritis).
Rifampicin + oral contraceptives: hazard of pregnancy.
Enzymatic inductor elements:

Chronic alcoholism Spironolactone Barbiturates Phenytoin Carbamazepine Rifampicin

Griseofulvin Primidone Tobacco

2.3.1. Enzymatic inhibition

Decreased activity of hepatic microsomal biotransforming enzymas.
Alcohol + disulfiram (aldehyde dehydrogenase inhibition)
Alcohol + Methronidazole (antabus type reaction)
Alcohol + Cephalosporins (antabus type reaction)
Cimetidine + (diazepam, chlordiazepoxide, theophylline, labetalol, propanolol): increased media-life of the second.
Verapamil + Carbamazepine: increased carbamazepine levels.
Enzymatic inhibitor substances:

2.4 Excretion

2.4.1 Urinary pH alteration


Amphetamines + bicarbonate (to high dose):
Less amphetamine urinary excretion.
Urinary excretion alteration.

Acetohexamide + Phenylbutazone: less acetohexamide excretion

Probenecid + penicillins: beneficial interaction

Lithium + thiazides: increased lithium toxicity.

Terapeutical or Pharmacological Groups with bigger risks:

Antiarrhytmics
Oral anticoagulants
Oral antidiabetics
Antiepileptics
Antihypertensives H2
Antagonists
Corticosteroids
Digitalis glycosides

Patients with higher risk

Asthma
Cardiopathy
Diabetes
Epilepsy
Glaucoma
Hepatopathy
Nephropathy
Elder patients with digitalis glycosides therapy
Psychotropic agents

Alteración pH urinario:

anfetaminas + bicarbonato a dosis elevadas:
Menor excreción urinaria de anfetaminas
Alteración excreción urinaria

Acetohexamida + fenilbutazona : menor excreción acetohexamida

Probenecid + penicilinas: interacción beneficiosa.

Litio + tiazidas : aumento de la toxicidad del litio.

Grupos Terapéuticos o Farmacológicos con mayor riesgo

Antiarrítmicos
Anticoagulantes orales
Antidiabéticos orales
Antiepilépticos
Antihipertensívos
Antihistamínicos H2
Corticosteroides
Glucosidos Digitálicos
 
Pacientes con riesgo más elevado. Pacientes con:

Asma
Cardiopatía
Diabétes
Epilépsia
Glaucoma
Hepatopatía
Nefropatía
Pacientes ancianos bajo tratamiento con glucosidos digitálicos.
Psicotrópos

Interactions risk reduction

1- Identify risk factors for the patient

A) Age
B) Pathological status (hypertensive, diabetes, cardiopathy, nephropaty, hepatopathy, glaucoma)
C) Dietetical customs
D) Alcoholism
E) Tobaccoism

2- Join complete drugs antecedents

A) Prescribed drugs (one or more doctors)
B) Not prescribed drugs (OTC)

3- Learn to the patient

A) Establish dose and takings
B) establish types of handled secondary effects
C) Indicate to inform about rare effects
D) Breathe to inquire about treatment

4- Knowing dispensed drugs

A) Know pharmacology
B) Know interactions
C) Take care about drug groups with higher risk

5- Dispose quickly and responsible information

A) Drugint(c) interactions software
B) Dispose of handly bibliography to enlarge