Flashcards in W1 : Intro Deck (31):
what is definition of pharmacology?
the study of biochemical and physiological aspects of drug effects, including absorption, distribution, metabolism, elimination, toxicity, and specific mechanisms of drug action.
what is pharmacokinetics?
refers to way the body handles the drug absorption, distribution, biotransformation, and excretion.
once pharmacokinetics is determined, rational dosage regime can be initiated.
what is pharmacodynamics?
the study of biochemical and physiologic effects of drugs and their mechanism of action
what are Enteral routes of drug administration?
Oral - most common
Sublingual - doesn't go into intestines, but mouth is part of digestive system, so it is under enteral
what are Parental routes of drug administration?
Intravenous - IV
Intramuscular - IM usu in deltoid or gluteus or quadriceps muscle
Subcutaneous - SC
Intradermal - within skin, ex PPD
what are OTHER (other than Enteral and Parental) types of drug administration?
Inhalation - meant to go to LU
Intranasal - calcitonin, osteoporosis (goes to nasal mucosa)
Intrathecal / Intraventricular - subarachnoid space in spine where cerebrospinal fluids is (ex AIDs patients with fungal meningitis - goes to brain)
Topical - local action
Transdermal - patch on skin (drug goes to blood so systemic action)
what is the First Pass Effect?
the effect of liver metabolism of drug prior to reaching systemic circulation
*administration by IV, IM and sublingual routes allow drug to attain concentrations in the systemic circulation and to be distributed throughout the body prior to hepatic metabolism
**when drug administered rectally - 50% goes to LV and 50% goes to inferior vena cava and to heart to be distributed systemically
***Orally - 100% goes to LV first, what is not metabolizes in the liver (a small portion) will go to blood
a drug passes through the membranes more readily if it is ______?
thus the affects the absorption and excretion of passively diffused drug
weak acids are hydrogen ion ________.
at high pH they donate H+ and become negatively charged, but at low pH they become protonated and carry a neutral charge
weak bases are hydrogen ion ________.
at low pH, weak bases accept H+ and become positively charged, but a a high pH they are neutral because they dissociate their protons
acid drugs, such as aspirin, are better absorbed in what types of environments?
in acidic environment such as the ST with pH of 2
alkaline drugs are best absorbed in what types of environment?
in alkaline environment such as the SI, which has pH of 8
what is ion-trapping and in what conditions is it helpful to use this methods?
since the pH of urine is acidic, a weakly acidic drug can be extensively reabsorbed into the body from urine.
if pH of the urine is increased, the excretion of drug can increased.
what are factors that influence absorption of drugs?
1. more blood flow --> more absorption
2. more surface area --> more efficient absorption
3. quick mvmt of drug thru GI tract --> less absorption
what is bioavailability?
the fraction of administered drug that reaches the systemic circulation unchanged
how do you determine the bioavailability of a drug?
by plotting plasma concentration of drug versus time, area under the cure (AUC) is measured
AUC oral / AUC injected IV x 100
what affects bioavailability of drug?
1. first pass hepatic metabolism : rapid metabolism --> decreased amount of drug gaining access to blood
2. solubility of drug : extreme hydrophilic or hydrophobic results in poor absorption, so need some lipid and some liquid solubility for best absorption
3. checmial instailbity
4. natrure of drug formulation
what is drug distribution?
process by which drug reversibly leaves bloodstream and enters the intersitium and or cells
what factors affect drug distribution?
1. blood flow
2. capillary permeability : the capillaries of LV and SP have large fenestrations allowing drugs to pass. in the brain, capillaries are continuous forming the blood-brain barrier preventing many substances from entering the brain
3. drug structure : hydrophobic/philic, charged/uncharged
4. plasma protein binding of drugs mostly with albumin which acts as a drug reservoir
what is definition of Volume of Distribution (Vd)?
calculation of the parent volume in which drug is disseminated.
Vd gives a rough accounting of where the drug goes in the body. it can also be used to calculate the dose of a drug needed to achieve a desired plasma concentration.
what is equation for Vd?
VD = Dose (mg) / plasma concentration (mg/L)
what is total volume of fluids in the body?
Male : total body water 60% of body weight / 42 L
- 20% extracellular (plasma & interstitial fluid) 14 L
- 40% intracellular 28 L
drug-> plasma 4 L-> interstitial 10 L-> intercellular 28 L
what is half-life of a drug?
(t 1/2) is the period of time required for the concentration of a drug to decrease by one-half
what is the binding of drugs to plasma proteins?
drugs may bind to plasma proteins (usu albumin)
Bound drugs are INACTIVE
Unbound drugs are ACTIVE
what is binding capacity of albumin?
strongest affinity for anionic and hydrophobic drugs ; less affinity for hydrophilic drugs
in which class of drugs is the dose small, so the binding sites of albumin are in excess of available drug (bound-drug fraction is high)?
Class I drugs
in which class of drugs is the dose large, and thus greatly exeed the number of albumin binding sites (and high proportion of drugs exists in free state)?
Class 2 drugs
what is the goal of metabolism?
where is the major site of metabolism? what are some other sites?
goal is to produce metabolites that are polar or charged, and can be eliminated by the KD
major site is LV ; other sites are LU, KD, adrenals, etc.
*metabolism can also transform active drug into less active or inactive forms, or a prodrug (inactive or less active drug) into a more active drug
in which phase of drug metabolism is the drug oxidized or reduced to a more polar form?
and most of this phase uses what system of enzymes?
Phase 1 reactions
most phase 1 reactions utilize cytochrome P450 system of enzymes
in which phase of metabolism does a polar group such as glutathione is conjugated to the drug? what does this process do?
in Phase 2 reactions
this substantially increases the polarity of the drug. the highly polar drugs can then be excreted by the KD. drugs undergoing Phase 2 reaction may have already phase 1 transformations.