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
- PK properties determine the onset, intensity, and the duration of drug action:
Pharmacokinetics
from the site of administration permits entry of the drug (either directly or indirectly) into plasma.
- Absorption
- First, absorption
the drug may then reversibly leave the bloodstream and distribute into the interstitial
and intracellular fluids.
- Distribution
- Second,
the drug may be biotransformed by metabolism by the liver or other tissues.
- Metabolism
- Third,
the drug and its metabolites are eliminated from the body in urine, bile, or feces.
- Elimination
- Finally,
Metabolism
* First-Pass
* Occurs in gut lumen, intestinal mucosa, portal vein, and liver before entering
systemic blood circulation
- 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.
- Oxidation, hydrolysis, hydration, reduction
- Make drugs polar for excretion or prepare for Phase II
- Majority catalyzed by cytochrome P450 (CYP) enzymes
- Phase I
- 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.
is 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
