أسئلة الـ 25 فارما PPPM قبل التعديل

• Drug interactions are complex interplays between pharmacological agents that impact safety and efficacy
• Drug interactions occur when one drug alters the pharmacokinetics or pharmacodynamics of another, leading to adverse effects or therapeutic failure
• DDIs can manifest at the pharmacodynamic or pharmacokinetic level

Mechanisms of DDIs

• Enzyme inhibition or induction is a mechanism of Drug-Drug interactions
• Competition for binding sites is a mechanism of Drug-Drug interactions
• Alterations in drug absorption is a mechanism of Drug-Drug interactions

Clinical Implications of DDIs

• Clinical implications range from compromised therapeutic efficacy to heightened toxicity

Synergistic Effects

• Some drugs together produce an enhanced response greater than their individual effects
• Aminoglycosides combined with penicillin enhance their bactericidal effects

Additive Effects

• Drugs with similar mechanisms produce an additive effect
• There is an increased risk of adverse effects with additive effects
• Using two anticholinergics (amitriptyline + oxybutynin) increases antimuscarinic toxicity

Antagonistic Effects

• The effects of one drug may oppose another when given concurrently
• Levothyroxine and lithium neutralize each other's therapeutic benefits

Narrow Therapeutic Index Drugs

• Even minor pharmacodynamic changes can be hazardous with narrow therapeutic index drugs
• Warfarin, Digoxin and Lithium are examples of narrow therapeutic index drugs
• Adding or discontinuing interacting drugs can lead to toxicity or treatment failure

Receptor Effects

• Drugs acting at the same receptor may compete for binding sites
• Codeine and tramadol both act at mu opioid receptors
• Combining codeine and tramadol can reduce their analgesic effects

Pharmacokinetic Interactions

• Absorption occurs from the GIT
• Distribution occurs via the bloodstream
• Metabolism occurs in the liver but can occur elsewhere
• Excretion occurs via the kidneys, biliary tract, or other routes

Chelation or Complex Formation

• Tetracyclines like doxycycline can bind to cations (calcium) in antacids
• A tetracycline-calcium complex is insoluble, decreasing doxycycline absorption
• This interaction can be avoided by separating doses of doxycycline and antacids

pH-Dependent Interactions

• Antacids increase stomach pH, which impairs ketoconazole absorption (weakly acidic drug)
• Proton pump inhibitors (omeprazole) increase gastric pH, which reduces absorption of atenolol (weak basic drug)

P-Glycoprotein Interactions

• Azole antifungals (ketoconazole) inhibit P-gp efflux transporters, increasing the absorption of other P-gp substrates, like digoxin

Changes in GI Motility

• Metoclopramide speeds up motility, decreasing the time for absorption of drugs like levothyroxine
• Opioids (morphine) slow motility, increasing the time for absorption of drugs like atenolol

Impact of Plasma protein binding

• Drugs highly bound to plasma proteins include warfarin and phenytoin
• Highly bound drugs can be displaced by other highly protein-bound drugs, increasing the free, unbound fraction and distribution
• Ibuprofen displacing warfarin enhances warfarin's anticoagulant effect and bleeding risk
• Digoxin binds extensively to tissues, and drugs that displace it from binding sites (quinidine, verapamil) can increase distribution into plasma, potentially increasing toxicity

Blood-Brain Barrier Interactions

• One drug may inhibit efflux transporters like P-glycoprotein at the blood-brain barrier
• Inhibition of P-glycoprotein enhances distribution of other substrates into the CNS
• SSRI fluoxetine inhibits P-gp, which can increase levels of drugs like methadone in the brain

Impacts of Plasma volume alterations

• Diuretics can reduce plasma volume
• Reduced plasma volume causes higher concentrations of other concomitant drugs in plasma, such as warfarin, increasing its toxicity

Impacts of Protein Alterations

• Cimetidine inhibits cytochrome P450 enzymes, decreasing the production of albumin and alpha-1 acid glycoprotein
• Decreased production of albumin and alpha-1 acid glycoprotein decreases plasma protein binding capacity for certain drugs

Drug interactions at metabolizing sites

• Drug interactions at metabolizing sites primarily occur in the liver
• Cytochrome P450 (CYP) enzymes play a crucial role in the biotransformation of drugs

Enzyme Inhibition

• One drug inhibits the activity of a metabolizing enzyme
• Decreasing the metabolism of another co-administered drug
• Fluoxetine (SSRI) inhibits CYP2D6, increasing plasma concentration of drugs metabolized by this pathway, such as beta-blocker (metoprolol)

Enzyme Induction

• One drug enhances activity of metabolic enzymes
• Enhancing metabolism of co-administered drugs
• Rifampin (Anti-TB) induces CYP3A4, affecting metabolism of numerous drugs, such as oral contraceptives
• Enzyme induction can reduce contraceptive efficacy, necessitating alternative birth control methods in patients taking rifampin

Renal Clearance Interactions

• Drugs that inhibit renal tubular secretion (probenecid) decrease urinary excretion and clearance of other drugs
• Penicillin undergoes tubular secretion, increasing its plasma levels

Glomerular filtration alterations

• Drugs that reduce glomerular filtration rate (NSAIDs) decrease urinary clearance of other drugs
• Lithium has renal excretion as a main excretion route which leads to lithium accumulation

Tubular Reabsorption Effects

• Digoxin is cleared via tubular reabsorption
• Drugs that inhibit reabsorption (quinidine) can clinically increase digoxin clearance

Plasma Protein Binding impacts on Renal Excretion

• High protein-bound drugs have decreased glomerular filtration as only free drug can be filtered
• Displacement from plasma proteins increases the fraction filtered
• Furosemide displaces aspirin, increasing renal clearance of aspirin

Urine pH Changes

• Sodium bicarbonate (Drugs alkalinize urine) reduces renal tubular reabsorption of weak acids by ion trapping
• Ammonium chloride (Drugs acidify urine) reduces renal tubular reabsorption of weak bases by ion trapping