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Therapeutic Incompatibility, Study notes of Pharmacy

Therapeutic incompatibility refers to a situation where two or more medications or treatments are not compatible or interact negatively with each other when used together. This can result in reduced effectiveness, altered pharmacokinetics, increased toxicity, or adverse effects.

Typology: Study notes

2017/2018

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Available from 06/19/2023

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Download Therapeutic Incompatibility and more Study notes Pharmacy in PDF only on Docsity! 1 FACTORS THAT MAY AFFECT THERAPEUTIC MECHANISM OF THERAPEUTIC Ex1., antiacidsincrease the pH Ex2., H2 antagonists ↑pH Decrease the tablet dissolution of Ketoconazole (acidic) Antibiotics kill a large number of the normal flora of the intestine Increase digoxin concentration and increase its toxicity Ex1., Tetracycline interacts with iron preparations or Ex2., Antacid (aluminum or magnesium) hydroxide Decrease absorption of ciprofloxacin by 85% due to chelation Unabsorbable complexMilk (𝐂𝐚𝟐+) THERAPEUTIC INCOMPATIBILITY  It is the modification of the therapeutic effect of one drug by the prior concomitant administration of another. o It is also called drug interactions  It may be as a result of prescribing certain drugs to a patient with the intention to produce a specific degree of pharmacological action, but have restore or intensity of the action produced is different room that intended by the prescriber 1. Pharmacokinetics of the drug 2. Pharmacodynamic property of the drug 3. Insufficient study of the patient 4. Prescription writing errors 5. Trademark or nomenclature error Divided into two groups: PHARMACOKINETICS  interaction that alters the kinetics of the drug which involves its o Absorption o Distribution o Metabolism o Excretion PHARMACODYNAMICS  related to the pharmacological activity of the interacting drugs o Addition o Synergism o Potentiation o Antagonism o Altered cellular transport o Effect on the receptor site o PHARMACOKINETIC INTERACTIONS 1. DRUG ABSORPTION INTERACTIONS a) Changes in gastrointestinal pH (altered pH) o The non-ionized form of a drug is more lipid soluble and more readily absorbed from GIT than the ionized form does Therefore, these drugs must be separated by at least 2h in the time of administration of both o Acidic drugs will be absorbed in acidic environment, same as through with basic drugs it will absorbed in basic environment o E.g., Ketoconazole and antacid- reduced absorption of ketoconazole (separate by at least 2h in the same administration of both) b) Altered intestinal bacterial flora o In 10% of patients receive digoxin… 40% or more of the administered dose is metabolized by intestinal flora o E.g., antibiotics + digoxin-dec digoxin concentration and inc toxicity c) Complexation or chelation o E.g., tetracycline + iron o tetracycline + milk (Ca)- unabsorbable complex o Antacid+ ciprofloxacin - dec absorption of cipro by 85% by chelation o tetracycline with metals (vit and min)- reduced absorption of tetracycline through chelation of of metals o Digoxin + cholestyramine- reduced absorption of digoxin due to complexation with THERAPEUTIC INCOMPATIBILITY 2 cholestyramine o Kaolin and charcoal and any drug-kaolin and charcoal act as adsorbent which will prevent absorption of any drug 5  Probenecid  Sulphinpyrazone  Phenylbutazone  Aspirin  Thiazide diuretics  Indomethacin  Penicillin  Azidothymidine  Indomethacin 3  Verapamil  Amiodarone  Quinidine  Digoxin  Diuretics  Lithium  Indomethacin  Furosemide  Aspirin  NSAIDS  Methotrexate b) Alteration of urine flow and pH o Excretion and reabsorption (Passive tubular reabsorption) of drugs occur in the tubules by the passive diffusion which is regulated by concentration and lipid solubility o Ionized drugs are reabsorbed lower than non- ionized one o Loop and thiazide diuretics indirectly increase proximal tubular reabsorption of Li+ (which is handed in a similar way as Na +) and this can cause Li+ toxicity in patient treated with lithium carbonate for mood disorders o Changes in active kidney tubule excretion o Probenecid and penicillin- probenecid competes in the kidney tubule for excretion causing prolonged penicillin activity o Furosemide and salicylates- salicylate toxicity due to furosemide competing for excretion o Urinary pH o The effect of urinary pH on the excretion of weak acids and bases is put to use in the treatment of poisoning, but is not a cause of accidental interactions o Changes in urinary pH- Generally drugs in polar form are excreted favorably as to non-polar or lipophilic. Excretion of basic drugs is promoted by acidifying the urinary pH urinary pH and vice versa o Salicylates + NaHCO3- inc pH promoting excretion of salicylates o Quinidine+ HCl= Decrease pH promoting quinidine excretion o Salicylates+ acidifying agents- Toxicity of salicylates EFFECT OF FOOD ON KINETICS  Delayed absorption of drugs  Total amount of drugs absorbed may be reduced  Slowing Gastric emptying 4  Binding with drugs  Alters dissolution rate of drugs  Alters pH of the GIT PHARMACODYNAMIC INTERACTIONS ADDITION/ADDITIVE EFFECT  occurs when two or more drugs having the same effect are combined and the result is the sum of the individual effects relative to the doses used. This additive effect may be beneficial or harmful to the client.  Interaction of drugs with similar pharmacological effects in which the total action of both when combined can be predicted o Ibuprofen and paracetamol o Ephedrine and Aminophylline o Verapamil and Propranolol  ADDITIVE MEANS 1+1 = 2 SYNERGISM/SYNERGISTIC EFFECT  occurs when two or more drugs, with or without the same overt effect, are used together to yield a combined effect that has an outcome greater than the sum of the single drugs active components alone  Interaction of drugs in which the total action of both when combined is greater than predicted  They may not have similar pharmacological actions o Alcohol and sedatives o Probenecid- prolong activity of penicillin o Sulfamethoxazole and trimethoprim o Ampicillin and Sulbactam o Ephedrine and Aminophylline  Synergism of side effects o NSAIDS, warfarin, clopidogrel–inc risk of bleeding o ACE inhibitors, K sparing diuretics-inc risk of hyperkalemia o Verapamil and Beta- adrenergic antagonist-inc bradycardia o Antidepressant and antihistamine- increase drowsiness  SYNERGISM MEANS 1+1 = 3 POTENTIATION  describes a particular type of synergistic effect – a drug interaction in which only one of two drugs exerts the action that is made greater by the presence of the second drug.  Interaction of drugs in which the action of one drug is increase by concurrent administration of another drug  They may not have similar pharmacologic actions o ampicillin and sulbactam o Levodopa and carbidopa o Enzyme inhibitors and any drug THERAPEUTIC INCOMPATIBILITY OCCURS DUE TO FOLLOWING REASONS 7  Multiple Pharmacological effects-more than 1 potent drug  Multiple prescribers  Use of non-prescription drugs  Patient Noncompliance o Patient feel better or asymptomatic before finishing the therapy o Patient does not understand medication orders o Patient may not explain the regimen thoroughly o Cost of medication o Patient Finds the treatment Inconvenient or a threat to life because of the side effects of the drug o Poor communication between health care professionals and the patient  Drug abuse/misuse of drug A. Error in dosage B. Wrong dose or dosage form C. Contra-indicated drugs D. Synergistic and antagonistic drugs E. Drug interactions ERROR IN DOSAGE  Many therapeutic incompatibilities result from errors in writing or interpreting the prescription order. The most serious type of the dosage error in the dispensing is overdose of a medication E.g., Atropine Sulphate capsules Rx Atropine sulphate - 0.005g Phenobarbitone - 0.015g Aspirin - 0.300g Causes: In this prescription, the quantity of the atropine sulphate in each capsule is more than its recommended dose. Remedy: The prescription is referred back to the prescriber to correct the overdose of the atropine sulphate. The recommended dose of atropine for a single capsule is 0.25 to 2mg. WRONG DOSE OR DOSAGE FORM  There are certain drugs which have quite similar names and there is always a danger of dispensing the wrong drug  E.g., Prednisone and Prednisolone, Digoxin and Digitoxin  Sometimes many drugs are available in the different dosage forms and hence, if the dosage form is not clearly mentioned on theFACTORS CONTRIBUTING TO THE OCCURRENCE OF DRUG 8 prescription, it becomes necessary to seek clarification from the prescriber.  The responsibility of the pharmacist becomes to check the prescription intensively and if he finds these types of errors he should immediately consult the prescriber for the clarification. PRESCRIBING CONTRAINDICATED DRUGS  There are certain drugs which may be contra- indicated in a particular disease or a particular patient who is allergic to it  Corticosteroids are contra-indicated in the patients having peptic ulcers  The penicillin and Sulphur drugs are contra- indicated in the patients who are allergic.  Vasoconstrictors are contra-indicated in hypertensive patients.  Barbiturates and morphine should not be given to the asthmatic patients. E.g., Sulphadiazine capsules Causes: Ammonium chloride is a urinary acidifier. It causes the deposition of the Sulphonamide crystals in the kidney. Remedy: Before prescribing such substances, a doctor must be careful. If he does not, a pharmacist shows his caliber to point out such type of the doctor’s error. Such must Immediately be referred back to the concerned doctor and get corrected. PRESCRIBING SYNERGISTIC OR ANTAGONISTIC DRUGS  When two drugs are prescribed together, they tend to increase the activity of each other which is known as SYNERGISM.  When two drugs are prescribed together, they tend to decrease the activity of each other which is known as ANTAGONISM.  E.g., o A combination of aspirin and paracetamol increases the analgesic activity. o A combination of penicillin and streptomycin increases the antibacterial activity. o Amphetamines show its antagonists effect with the barbiturates. E.g., Amphetamine sulphate syrup Causes: In this prescription, there is a combination of two sympathomimetic drugs, thereby causing additive effect. Remedy: The prescription is referred back to the prescriber for necessary corrections. 9 DRUG INTERACTIONS  The effect of one drug is altered by the prior or simultaneous administration of another drug. The drug interaction can usually be corrected by the proper adjustment of dosage if the suspected interaction is detected E.g., Tetracycline capsule - 250mg capsules Direction: Take one capsule every 6 hours with milk. Causes: Tetracycline is inactivated by calcium present in milk. So, it should not be taken with milk. Remedy: In this prescription, the therapeutic incompatibility is unintentional. So, the prescription is referred back to the prescriber to change the direction.
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