Introduction Flashcards
(25 cards)
Toxicity
- Excessive extension of therapeutic physiological effect
- e.g. bradycardia and hypotension (β blockers)
- Necrosis
- Carcinogenesis/Mutagenesis
- Teratogenesis
Pharmacokinetics (PK)-
what the body does to a drug
- Pharmacodynamics (PD)-
what the drug does to the body
- _______________determine the onset, intensity, and the duration of drug action:
Pharmacokinetics
___________ is from the site of administration permits entry of the drug (either directly or indirectly) into plasma.
- Absorption
- First, absorption
When the drug reversibly leaves the bloodstream and distributes into the interstitial
and intracellular fluids, this is called______________
- Distribution
- Second,
The drug may be biotransformed by ____________ in the liver or other tissues.
- Metabolism
- This is the third step.
The drug and its metabolites are _______________ from the body in urine, bile, or feces.
- Elimination
- This is the final process.
- Occurs in gut lumen, intestinal mucosa, portal vein, and liver before entering systemic blood circulation
Metabolism * First-Pass
- When a drug is absorbed from the GI tract, it enters the portal circulation before entering the systemic circulation.
- If the drug is rapidly metabolized in the liver or gut wall during this initial passage, the amount of unchanged drug entering the systemic circulation is decreased.
Phase when:
- Oxidation, hydrolysis, hydration, reduction
- Make drugs polar for excretion or prepare for Phase II
- Majority catalyzed by cytochrome P450 (CYP) enzymes
- Phase I
Phase when * Conjugation increases excretion
- Phase II
Kidneys cannot efficiently eliminate lipophilic drugs
• Readily cross cell membranes
• Reabsorbed in the distal convoluted tubules
• Lipid-soluble agents are first metabolized into more polar substances in the liver via two general sets of reactions:
phase I and phase II
Elimination/Excretion
• Renal → elimination in urine
• Biliary → elimination in feces
Herbal/Dietary Interference
- Dissolution/pH
- GI Motility/Gastric Emptying
- Membrane Transport
- Metabolism
Inducers
• CYP450-dependent enzymes are an important target for pharmacokinetic drug interactions.
• Drugs (or other substances) may induce the activity of these enzymes by increasing synthesis of one or more CYP isozymes.
• Causes increased biotransformation of drugs and can lead to significant decreases in plasma concentrations of drugs metabolized by these CYP isozymes
• E.g. phenobarbital, rifampin, carbamazepine, St. John’s wort
Consequences of increased drug metabolism:
- 1) decreased plasma drug concentrations
- 2) decreased drug activity if the metabolite is inactive
- 3) increased drug activity if the metabolite is active
- 4) decreased therapeutic drug effect.
Inhibitors
• Inhibition of CYP isozyme activity can lead to higher drug concentrations and/or greater potential for serious toxic effects
• Most common form of inhibition is through competition for the same isozyme.
• Some drugs can inhibit reactions for which they are not substrates, leading to drug interactions.
• E.g. erythromycin, ketoconazole, ritonavir
• Grapefruit juice inhibits CYP3A4
Signs & Symptoms
- Blood Pressure
- Heart Rate
- Level of Consciousness
- Bruising/Bleeding
- Diaphoresis
- Pain
- etc.
Lab Tests & Other Exams
- Serum/blood levels of specific agents
- INR
- CrCl
- LFTs
- EKG
- etc.
The ratio of the dose that produces toxicity in half the population (TD50) to the dose that produces a clinically desired or effective response (ED50) in half the population
- TI is a measure of a drug’s safety
- A larger value indicates a wide margin between doses that are effective and doses that are toxic
Therapeutic index (TI) of a drug
Management Plan
- Initiate/discontinue herbs
- Consult prescriber
- Recommend labs or tests
- Provide patient education
- Seek medical attention
According to the Medscape drug interaction checker, both warfarin and dang gui __________________
Increase anticoagulation
