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Pharmacology 10 and 11: Principles of Drug Interactions

Terms in this set (42)

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Pharmaceutical
-negative, gentamicin, positively
-propofol, surfactant, propofol
-Heating pads, transdermal patches
___ Interaction
Certain drugs react with each other and get inactivated if their solutions are mixed before administration.
• Ampicillin (___ charged) mixed with ___ (___ charged).
• Lidocaine and ___ (lidocaine disrupting the ___ properties of the ___ vehicle)
• ___ can increase the release of the narcotic fentanyl from ___
1) pH
2) bacterial flora
3) drug chelates or complexes
4) mucosal damage
5) GIT motility
6) Blood flow
The gastrointestinal absorption of drugs may be affected by concurrent use of agents that lead to:
1) Altered ___
2) Altered ___
3) Formation of ___
4) Drug induced ___
5) Altered ___
6) Altered ___
nonionized
Only the ___ form of a drug can readily penetrate cell membranes.
-ranitidine
-ketoconazole
The gastrointestinal absorption of drugs may be affected by concurrent use of agents that lead to:

Altered pH
Example: Acid reducing agents as ___→ ↓absorption of weak acid as ___
-Antibiotics
-estrogens, oral contraceptives
-oral anticoagulants, vit K
The gastrointestinal absorption of drugs may be affected by concurrent use of agents that lead to:

Altered intestinal bacterial flora
___ kill a large number of the normal flora of the
intestine
• Inhibit the enterohepatic recycling of ___, thus decrease the efficacy of ___
• prolonged the effects of ___ which compete with ___
-Bile acid, cholestyramine, furosemide
-Charcoal
The gastrointestinal absorption of drugs may be affected by concurrent use of agents that lead to:

Formation of drug chelates or complexes
• ___ sequestrants such as ___ adsorbs many drugs such as ___ and decreases their absorption
• ___ adsorbs some drugs to its surface so that the drug cannot be absorbed
-Antineoplastic
-cyclophosphamide
-digoxin
The gastrointestinal absorption of drugs may be affected by concurrent use of agents that lead to:

Drug-induced mucosal damage
-___ agents e.g., ___ Inhibit absorption of several drugs eg., ___
Narcotics
The gastrointestinal absorption of drugs may be affected by concurrent use of agents that lead to:

Altered gastrointestinal tract motility
___ slow the motility (movement) of substances through the intestine
-Epinephrine
-local anesthetics
The gastrointestinal absorption of drugs may be affected by concurrent use of agents that lead to:

Blood flow
-___ reduces blood flow and is used in combination with ___
Cyclosporine
-anti-rejection drug sirolimus, kidney
-St. John's wort, Pumped back out into the intestinal lumen, excreted
The gastrointestinal absorption of drugs may be affected by:

Cell transporters such as P-glycoprotein (P-gp)
___
-With P-gp inhibitor such as the ___ result in ___ damage
-With P-gp activator such as ___= ___ and ___
Pharmacokinetic
-Aspirin & Sulfa
-Tolbutamide
___ mechanism for drug interactions: Distribution
___ and ___ → Displace: Oral Hypoglycemic (___) → Hypoglycemia
-Theophylline
-Smoking
-Cimetidine & Macrolides as erythromycin
Metabolism
CYP450: CYP1A2
Substrate: ___
Inducers: ___
Inhibitors: ___
-Warfarin
-Barbiturate, carbamazepine, rifampin, & St. John's wort
-Quinidine, paroxetine
Metabolism
CYP450: CYP2C9
Substrate: ___
Inducers: ___
Inhibitors: ___
-Statin
-Barbiturate, carbamazepine, rifampin, & St. John's wort
-Ketoconazole, erythromycin, grapefruit juice
Metabolism
CYP450: CYP3A4
Substrate: ___
Inducers: ___
Inhibitors: ___
opposite of active drugs
For pro-drugs, the effects of inducers and inhibitors are ___
an inhibitor
Pro-Drug + ___
-Pro-Drug does not break down to active metabolites
-Pro-drug stays pretty much unmetabolized
an inducer
Pro-Drug + ___
-Pro-Drug breaks down to active metabolites
-Active metabolites are excessive
-Anti-gout drug probenecid
-NaHCO3, acid, Aspirin
-NH4Cl, base, Ephedrine & Amphetamine
Excretion
• ___ given with oral penicillin (they compete for the same cellular transporters in the tubule, so more penicillin is retained in the body)
• Alkalinization of urine (___) → ↑ Excretion of weak ___ drugs e.g. ___
• Acidification of urine (___) → ↑ Excretion of weak ___ drugs e.g. ___
Pharmacodynamic
-benzodiazepines plus barbiturates
___ Factors that produce drug interactions
-Additive effect of two or more drugs with similar mechanism of action eg, ___ plus ___
Pharmacodynamic
-Propranolol plus verapamil
___ Factors that produce drug interactions
Effect of two drugs with dissimilar mechanism of action
-Generally the two different agents would produce additive effects without the need for high doses of either one.
-Can result in lower incidence of adverse effects and often better tolerated, unless their adverse effect profile is similar: ___ plus ___ can cause severe bradycardia and cardiac standstill
-nitrates (e.g., nitroglycerin)
-erectile dysfunction, sildenafil (Viagra)
Synergistic DDIs
An example of an unwanted synergistic drug interaction is the combination of ___ and ___ drugs such as ___ which may cause a potentially life-threatening drop in blood pressure when taken together.
Percocet
Excedrin
Synergistic DDIs
Many pain medications use two or more analgesics
(e.g., ___ contains oxycodone and acetaminophen, ___ contains acetaminophen, aspirin, and caffeine) for greater pain relief than each individual component can provide.
naloxone (Narcan)
Antagonism
The narcotic antagonist ___ is used for narcotic overdoses
1) medications
2) alternative drug selections
3) CYP inhibitor
4) CYP inducer
5) co-administration
Strategies to avoid drug interactions
1. Find out what ___ the patient is taking
2. Find ___ that avoid or minimize the interaction
3. Reduce the dosing of one if the other is a ___
4. Increase the dosing of one if the other is a ___
5. For directly interacting agents avoid ___
1) Vitamin K
-vitamin K, vitamin K

2) Tyramine
-depression
-tyramine
-hypertensive
-norepinephrine
Food and Beverage Drug Interactions
1. Foods rich in ___ and warfarin
• Increase of ___ levels in the body can increase clotting and reduce the effectiveness of warfarin, which could result in a stroke. (Mechanistic antagonisms of warfarin by ___)

2. ___-Containing Foods and MAOIs
• Use with monoamine oxidase inhibitors (MAOIs) which treat ___ → high levels of ___ can be absorbed, resulting in a "___ crisis" due to the indirect release of ___ from nerve terminals
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