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Pharm intro.

Pharmacokinetics Drug movement into, within and out of the body
Pharmacodynamics Drug actions and their mechanisms what it does once it reaches its site of action
What happens if a drug becomes charged? It CANNOT pass a biological membrane
absorption transfer of drugs from site of administration to systemic circualtion
Bioavailibility fraction of an oral dose that appears in systemic circulation reduces by first pass effect altered by changes in GI motility can be reduced by other substances present in the GI tract ex: antacids will inhibit the absorption of a tetracycline
distribution transfer of drugs from systemic circulation to tissues is effected by: blood flow, pH, blood-brain barrier, and tissue factors
elimination clearance; removal of drug from the body
metabolism of drugs mainly done by? LIVER
excretion is done by? renal and/or hepatobiliary systems
First pass effect liver metabolizes a lot of drug before reaching systemic circulation if taken orally some drugs have higher first pass effect than others ex: morphine does not work orally, must be IV
Primary means by which drugs transfer across the cell membrane is? passive diffusion
Which drugs can pass through these membranes? low molecular weight both lipid and water soluble --> must be WEAK acid or base
pH = pKa then there are equal amounts of charged and uncharged particles (ideal)
pH > pKa BH+ < B favors absorption (both solutions basic) AH < A- no absorption
pH < pKa BH+ > B no absorption AH > A- favors absorption (both solutions acidic)
Filtration passage of molecules through pores or porous structures
transport mechanisms drug combines with a transport protein in the membrane and the complex can move across the membrane together usually happens with highly polar drugs or charged drugs facilitated diffusion active diffusion (requires energy)
Presystemic absorption gut and liver (oral)
Systemic absorption IM, IV, subQ, kidney, etc.
Enteral GI tract administration
paranteral needle administration
patches have loading doses and the skin becomes saturated so the patient has to move the next patch elsewhere to avoid over dosing
topical used to treat something locally
plasma protein binding protein bound drug CANNOT distribute to tissues or be eliminated becomes "pharmacologically inactive" one drug can displace another; heavily bound protein drugs have high affinity
does protein binding effect absorption? NO! binding occurs AFTER absorption but BEFORE distribution
How does edema or swelling effect anesthetics? will change blood pH and make anesthetics INEFFECTIVE
Biotransformation elimination/metabolism conversion of drug to different chemical structure
what is responsible for bio-transformation? mainly the liver via a system of enzymes called the cytochrome P450 (CYP) system these enzymes are responsible for phase 1 and phase 2 rxns
phase 1 rxn oxidation/reduction rxn by oxygenases and reductases
phase 2 rxn formation of conjugates by transferases; drugs are conjugated with a sugar, an amino acid, or a sulfate
Bio-transformation relative to parent compound metabolite is MORE water soluble may be more or less active may be inactive may be more or less toxic
prodrugs INACTIVE until converted to active form by metabolism (through bio-transformation)
Do all drugs go through both phases? NO; some may even go through the phases backwards
Hepatic elimination secretion into bile and small intestines
Enterohepatic recycling drug conjugate secreted into the bile and reconverted to parent compound by intestinal bacteria which can then be reabsorbed by the small intestines alteration of bacterial flora can affect the action of some drugs
Renal elimination glomerular filtration tubular secretion of organic acids and bases drugs can passively diffuse from tubular cells into the urine and back into the blood stream --> recycling pH of urine and pKa of drug is important
How do you increase elimination of weak acids? Alkalize the urine by administering bicarbonate or use a diuretic such as acetazolamide which increase bicarb
How do you increase elimination of weak bases? Acidify the urine by administering ammonium chloride
First order elimination VAST MAJORITY constant percentage of drug eliminated per unit time 50%/4hrs
plasma 1/2 life time necessary to reduce plasma levels of drug my one-half 4-5 half lives for therapeutic drugs and 4-5 half lives for elimination
capacity limited (zero order) elimination constant amount of drug eliminated per unit time 50mg/4hrs
Receptors regulatory proteins that interact with a drug or hormone and intiate a cellular response basis for classifying drugs: beta-2 agonists, beta antagonists, muscarinic agonists/antagonists
what type of receptor do most drugs work through? G-coupled protein receptor
Agonists affinity and efficacy can bind AND activate
Antagonists ONLY affinity can bind but CANNOT activate
Tonically active system antagonist has to constantly block an agonist for there to be an effect Ex: vasodilators and beta blockers
Full agonists can produce full response; efficacy = 1
partial agonists produce a response less than that of full agonists; efficacy > 0 but < 1
inverse agonists produce a response less than that of partial; efficacy < 0
Dose response curves interactions between agonists and receptors are typically characterized by this sigmoidal or S shaped higher effects higher dosage used to determine ED50 can also determine max respoonse
ED50 does that produces 1/2 max response
Competitive anatagonists block binding by an agonists to its receptor blockade can be overcome reduces POTENCY of agonists
NON-competitive anatagonists block binding by an agonists to its receptor blockade CANNOT be overcome reduces EFFICACY of agonists form covalent bond with receptor; must be destroyed and body needs to form new receptor
orthosteric interaction at single site
allosteric binding at one site effects the binding at another site
Indicies of safety bigger the number in the numerator, the safer the drug
biologics are composed of? vaccines, allergenics, blood and blood components, somatic cells, gene therapy, tissues, etc. can be composed of sugars, proteins, nucleic acids or complex combos of the 3
what are biologics? what do they do? genetically-engineered proteins derived from human genes most are designed to inhibit specific components of the immune system
do biologics follow the same dynamics as small molecule drugs? NO; most are anti-body based thus follow the rules of immunology
Created by: larsyy



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