Lecture #7 - Adverse Drug Experiances

Analgesic Interactions (ASA)

ASA: Competative COX-1 blocking means decreased antiplatelet activity. Have NSAID over 8hrs before or 30 minutes after ASA dose *NSAIDS: ASA*

Adverse DI mechanism - Distribution

Alter plasma protein binding of highly bound drugs (>90%) -Highly protein bound (*warfarin, phenytoin, sulfonylureas* (glyburide) ) -Displacing drugs: *NSAIDs* -Clinical relevance: can the bumping off of other drugs create an adverse experience? They're not sure

Antibiotic Interactions (azithro/clarithro)

Az. decreases GI flora which effects the p-glycoprotein system in GI, increasing the digoxin plasma levels to toxic. *Azithro/Clarithro - Digoxin*

Analgesic Interactions (ASA/Warfarin)

Both effect clotting and Both occupy CYP2C9. Using both increases bleeding risk. *NSAIDS: ASA - Warfarin*

Anxiolytic reaction (benzodiazepines)

additive CNS depressants would cause excess sedation as well as addative macrolide antibiotics *Benzo's - CNS depressants*

Antibiotic Interactions (Tetracycline)

no dairy, antacids,vitamins: these things chealate with antibiotic and don't allow it to absorb *Tetracycline: Antacid - Dairy - Vitamin*

where can you report an adverse reaction?

FDA online

what does the public expect of dentists to understand about the drugs we give?

-"..limited number of drugs routinely used in dental therapeutics: antibiotics, local anesthetics and vasoconstrictors, analgesics and sedative/anxiolytics. Consequently, most dental practitioners have a thorough knowledge of the indications for, contraindications of and precautions for the drugs they routinely use." -The public expects that we understand the big picture of what we prescribe and how they interact

Adverse DI mechanism - Absorption

-Antibiotic-cation complexes (antacids, Fe supplements, dairy products) - *tetracycline* (Insoluble, pass through the GI tract) -Alter gastric pH and GI bacteria: *antacids, proton pump inhibitors *

Adverse DI mechanism - Metabolism

-CYP450 enzymes -Drugs acting as substrates/inducers/inhibitors

Analgesic Interactions (SSRI)

SSRI: COX-1 inhibition and serotinin reuptake. Platelets use seretonin to aggregate meaning SSRI's cause more bleeding. (Short term OK) *NSAIDS: SSRI*

Adverse DI mechanism - Elimination

-Change urinary pH -Inhibit renal excretion - limit lithium excretion, lithium is low TI (*NSAIDs-lithium*) -P-glycoprotein efflux pump: pump drugs back into the GI tract, some drugs such as *Clarithromycin can inhibit the efflux of digoxin*

what are the "hangups" coming to a consenseous about the adverse drug interaction risk for certain drugs?

-Little agreement among drug compendia: lack of standard terminology or severity rating systems -Lack of reliable and timely data: under reporting by practitioners

what are the charecteristics of drugs commonly involved in adverse drug interactions?

-Major CYP450 substrates, inducers, or inhibitors -High protein binding -Chronic use: don't usually prescribe for long periods of time, less likely to have problems -Narrow therapeutic index (LOW NUMBER): cardiovascular drugs (digoxin, warfarin), misc drugs (cyclosporine, lithium carbonate, methotrexate, phenytoin)

Vasoconstrictor Interactions

-Possible interaction with TCA, definite interaction with meth and coke -Block of the reuptake of norepi means that patients can get increase in BP due to little distribution *EPI: Meth - Coke - TCA*

Polypharmacy in today's society

-adult Rx use 59% with any drugs and 15% with >5 drugs ->65YO use: 90% with any Rx drug, 39% with >5 Rx drugs

Antibiotic Interactions (Metronidazole)

Lithium: met. reduces renal excretion of lithium, which can cause toxic effect Alchohol: Met. inhibits acetaldehyde dehydrogenase (the enzyme metabolizing alchohol), you get disulfuram reaction and feel nausea and headache *Metronidazole - Lithium - Alchohol*

Analgesic Interactions (HTN)

NSAIDS and ACEI, diuretics, B-blockers (HTN): NSAIDS block the prostaglandin natural vasodilation mechanism which lowers the lowering of the BP *NSAIDS: ACEI - B-Blocker*

Analgesic Interactions (EtOH)

NSAIDS and EtOH: NSAIDS inhibit COx-1 protective while EtOH stimulates gastric secretion, meaning bleeding damage risk is higher *NSAIDS: EtOH*

Antibiotic Interactions (Amoxicillin)

Warfarin: Amo. alters GI flora, which lowers Vit. K production. Warfarin gets higher anticoagulant effect *Amoxicillin: Warfarin*