3.1 Flashcards
What is the pharmacodynamic method of DDI?
Drugs influence each other’s effects directly
When a drug stops another drug from acting on the body. Eg more/less potent active.
What is the pharmacokinetic method of DDI?
Drugs affect ADME affect the effective concentration at their sites of action
What are some common examples of pharmacokinetic DDI?
Eg drug a stops the absorption of drug b
Ex: Iron supplement and vitamin C absorbtion
Ex: Vanc (50% protein bound) and any drug that affects protein binding changes distribution; or warfarin (98% protein bound, narrow therapeutic index)
Ex: Metabolism: CYP 450 system many drugs inhibit/induce the whole CYP450 system all drugs using same pathway with be inhibited or induced eg statins and grapefruit juice
Ex: ETOH induces the same enzyme that breaks down APAP. So, with ETOH, APAP is metabolized faster, so a toxic metabolite is created at an accelerated rate (liver can’t handle)
In a pharmacodynamic DDI, what are the two general mechanisms that lead to the DDI?
Receptor- drugs compete at a receptor
Non-receptor- 2 drugs have similar actions through different cellular mechanisms
How does protein-binding lead to DDIs?
Highly protein-bound drugs (e.g. ASA, phenytoin, valproic acid, warfarin…) enhanced toxicity if binding sites become saturated
Pay attention to highly protein-bound drugs: If there’s any displacement on protein binding significant effects for DDI
How does receptor binding lead to DDI?
Competing at the receptor level
Ex:
Buprenorphine (Partial agonist/antagonist) binds to opioid receptors prevent euphoria from opioid drugs abuse
How do therapeutic actions of drugs lead to DDI?
Work towards the same direction. Eg ASA + Heparin: Both work on coagulation cascade increased risk of bleeding
What is an additive DDI?
A + B
Ex:
Sedatives – potentiate each other sedation effect
Alcohol – potentiate sedative effects of many drugs
What is a synergistic DDI?
AxB Combination multiply the effects Ex: Anti-infectives vancomycin and aminoglycosides Ritonavir and Atazanavir Pain therapy Amitriptylline and Morphine Gabapentin and Morphine
What is potentiation in a DDI?
A –> Bx300%
The effect of one drug is greatly increased by the intake of another drug itself without notable effect
Ex:
Amoxicillin + Clavulanate potassium enhance activities of Amoxicillin against bacteria
What is functional antagonism in DDI?
= physiological : 2 drugs produce opposite effects on same physiological function
What is chemical antagonism in DDI?
Inactivation- Rxn between the 2 drugs neutralizes their affects
What is a dispositional antagonism in DDI?
Leads to change in ADME = disposition
Why shouldn’t a pt on ASA for CAD take NSAIDs?
ASA- is an NSAID (with special properties) used in CAD to prevent platelet aggregation
Ibuprofen is non-specific. Blocks both COX-1 and COX-2. Acts as a competitive inhibitor on COC-1 and Cox-2. Give 800 of motrin x3 and 81mg of ASA once, then who wins the competition? If motirn blocks the COX-1, then the therapeutic effect of ASA is reduced = no cardiac protection from ASA. BUT- ASA binds irreverably to COX-1 (but not motrin)… therefore the anti-platelet affect is stronger with ASA.
ASA- irreversible inhibition of COX-1
Motrin- Competetiveinhibition of CoX-1 (can be overcome)
Why are NSAIDs contra-indicated with SSRIs?
2x risk of GI bleed
SSRI- stops activation of platelets.
NSAIDs- Increase risk of GI bleed by inhibiting COX-1, COX-2 When inhibited stops prostaglandin synthesis, which stimulated GI to make mucus erosion of mucus membrane in stomach
