Module 1: General Principles of Pharmacology Flashcards
Factors Influencing Drug Response
Med. prescription process:
- Diagnosis
- Therapeutic goal established
- Drug prescribed
- Drug admin.
- Concentration at site of action
- Response
- Monitor and/or adjust dose
Influencing factors:
1. Admin. issues — Drug source, med. errors, adherence
- Pharmacokinetics (PK) — Absorption, distribution, metabolism, excretion (individual variation)
- Pharmacodynamics (PD) — Drug-receptor, pt’s functional state, placebo effects (individual variation)
Pharmacokinetics
Four basic PK processes:
1. ABSORPTION — the process by which drugs enter the body and bloodstream
- DISTRIBUTION — drug goes from the blood to the interstitial and intercellular tissue
- METABOLISM — enzymatic-mediated alteration of a drug structure (most drugs are metabolized by the liver)
- EXCRETION — most drugs are eliminated via urine (also eliminated via bile by the livers)
PK Process #1: Absorption
Major routes (rate and extent of absorption varies by route) — Oral, IV, SQ, and IM (permits use of long-acting depot preparations)
Factors affecting absorption:
1. Rate of dissolution
- Rate of absorption — surface area, lipid solubility, blood flow, pH partitioning
- Completeness of absorption — changes in anatomy, drug, or food interaction
Bioavailability
Amount of active drug that reaches systemic circulation from its site of admin.
BIOEQUIVALENCE: the absence of a significant difference in the rate and extent of absorption of the active ingredient that reaches systemic circulation
Generic drugs must be bioequivalent to the brand name drug, and can usually be readily changed; Bioequivalence studies must be within +/- 20% (minimal) drug response variation
PK Process #2: Distribution
Factors affecting distribution:
1. Blood flow to tissues
- Ability of drug to exit the vascular system (brain, fat, lung, eye, etc.)
- Ability of the drug to enter cells
Blood-Brain Barrier (BBB)
Factors affecting drug movement across the BBB:
1. Lipid-soluble (non-polar) drugs: dissolve right through the lipid membrane of the BBB (i.e. drugs that treat pain or CNS disorders)
- Water-soluble (ionized or polar) drugs: CANNOT pass through the BBB; must become lipid-soluble or enter via some sort of transport system
Protein Binding
Albumin is the most prevalent protein in plasma and the most important of the proteins to which drugs bind
Only unbound (free) drug molecules can leave the vascular system; bound molecules are too large to fit through the pores in the capillary wall
i.e. A pt with hypoalbuminemia will have more free, unbound drug in their vasculature
PK Process #3: Metabolism
Types of hepatic metabolism:
1. Phase I (Non-synthetic, “P450 system”) — responsible for a larger amount of drug metabolism via oxidation, reduction, demethylation, and hydrolysis; Concerns: age, nutrition, and DDIs
- Phase II (Synthetic) — conjugation
Both metabolic processes will convert the drug into a more water-soluble (polar) compound for excretion via bodily fluids (urine or bile)
PRODRUG: a biologically inactive compound which can be metabolized in the body to produce a drug
First Pass Effect
Occurs when a drug is admin. orally, and enters the liver where it suffers extensive biotransformation to such an extent that the bioavailability is drastically reduced, thus showing subtherapeutic effects
Sublingual (SL), nasal, and parenteral routes avoid first-pass effect, thus require lower doses than oral route admin.
PK Process #4: Excretion
Drugs (i.e. anesthetics) must be water-soluble (polar) to be eliminated in urine, bile, breast milk, or expired air; lipid-soluble drugs can be reabsorbed through passive reabsorption
Drugs that are eliminated slowly require lower doses
Normal serum creatinine (0.5-1.5 mg/dl) does not necessarily mean ideal renal function and excretion; Creatinine clearance is a much better indicator of renal impairment
P glycoprotein: active transporter found in the kidneys that move compounds into the urine
Causes of impaired excretion:
1. Poor organ function (i.e. age-related)
- DDIs
- Genetic predisposition
Half Life
Time for the concentration of a particular drug to drop by one-half in a particular pt
A regular, established admin. schedule allows for drug accumulation until steady state (therapeutic range) is achieved
~5 half lives are required to reach steady state (97% concentration)
Pharmacodynamics
Dose-response relationship (the dose is compared to the intensity of the response produced)
Efficacy & potency:
1. Maximal efficacy: the maximum achievable effect of a particular drug
- Relative potency: the amount of drug necessary to attain a given effect
Drug Receptors Theory
Types of drugs:
1. Agonists: activate receptors (i.e. NE)
- Partial agonists: activate receptors less than full agonists
- Antagonists: prevent receptor activation by endogenous molecules or other drugs
Non-Receptor Mediated
Simple physical or chemical reactions in the body caused by drugs that do not require receptor activation/inhibition
i.e. Antacids, saline laxatives (retain water in the intestines by osmosis), chelation therapy (form complexes with metals for excretion), and antiseptics (precipitate proteins and bacteria)