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Pharm Exam 1

Pharmacodynamics What the drug does to the body
DR Drug + Receptor; usually drug bound to a protein
ED50 dose where 50% of the people would experience a therapeutic effect. Expected dose
TD50 dose where 50% of people would experience toxicity. Toxic dose
LD50 dose where 50% of patients would die. Lethal dose
Therapeutic Window (TI) Efficacy without unacceptable toxicity. The window between the therapeutic effect and the toxic effect.
How to calculate TI TD50/ED50 50% ppl with toxic/50% of ppl with therapeutic
High TI wide therapeutic window (desirable because a higher dose is needed to reach toxicity and a lower dose is needed to reach efficacy)
Low TI small therapeutic window (warfarin, lithium)
Agonists; DR* drug is bound and is eliciting a change; conformational change is depicted by the asterisk
3 types of Agonists Full, partial or mixed agonist-antagonist, Inverse
Full Agonist Elicits maximal response; stabilizes DR*, causing a full effect by activating an inactive receptor
Partial or mixed agonist-antagonist stabilizes DR (antagonist, no change) and DR* (agonist, change)
Inverse inactivates free active receptors (R*), stabilizes DR in the case of R*
Antagonists inhibition of agonist activity. Stabilizes DR and prevents DR*
3 types of antagonists competitive, noncompetitive, nonreceptor
Competitive antagonists reversible binding, active site. An agonist can bump off antagonist at the active site and cause DR*
Noncompetitive antagonists irreversible active site or allosteric site; high affinity bond, no matter how many agonists it cannot bump off the agonists; Also it will bind to an alternate site and prevent the agonist from binding or prevent the agonist from causing change
Nonreceptor: 2 types Chemical: agonist inactivation (protamine binds to heparin and inactivatess it) Physiologic: mediates opposite response of agonist (how a beta blocker acts in hyperthyroidism; the patient is tachycardic so you give a beta blocker that will counter it
Pharmacokinetics What the body does to the drug
4 topics of pharmacokinetics absorption, distribution, metabolism, and excretion.
Is the lipid core hydrophilic or hydrophobic? hydrophobic
Are the surfaces of the extracellular and intracellular membranes hydrophobic or hydrophilic? hydrophilic
How do drugs pass through the membrane? Passive diffusion (small and hydrophobic) Facilitated diffusion (hydrophilic; needs a transporter and does not use ATP) Active Transport (hydrophilic; needs a transporter and uses ATP. Endocytosis: drug is engulfed and released in the cell.
Nonionized molecules lipid soluble
Ionized molecules hydrophilic, charged, and has difficulty penetrating the membrane
pKa which equation is used to calculate it? pH at which 50% of the drug is ionized Henderson-Hasselbach equation pH + log ([HA]/[A-])
pH trapping determined by pKa and pH across membrane weakly acidic drugs (ASA); they are protonated in the stomach (nonionized) and deprotonated in plasma (ionized)
BBB has tight junctions that prevent passive diffusion. So how do drugs penetrate the CNS? They are small and hydrophobic Active transport Facilitated transport Intrathecal (bypass) this is the easiest
Absorption depends on..... the rate at which and extent to which the drug leaves its site of administration
Bioavailability extent to which the drug reaches systemic circulation; "fraction absorbed"
What is the assumption about bioavailability the site of action is reached directly from the systemic circulation
Factors that modify absorption concentration, circulation at the site of absorption, drug solubility, and surface area
2 phases of distribution Initial phase: once the drug reaches systemic circulation 2nd phase: once the drug reaches the tissues (distribution to tissues)
Volume of distribution Vd = Dose/ [Drug]plasma Volume of fluid required to contain the total amount of drug absorbed in the body at uniform concentrations equal to that in the plasma steady state.
Low Vd retained in the vascular compartment so it does not distribute well
High Vd highly distributed into non-vascular compartments; so it can pass through plasma to target organs.
what type of bond: shifting electron density in areas of a molecule, or in a molecule as a whole, results in the generation of transient (+) or (-) charges. These areas interact with transient areas of opposite charge on another molecule. Van der Waals; weakest
What type of bond: two bonding atoms share electrons covalent; strongest/irreversible
what type of bond: hydrogen atoms bound to nitrogen or oxygen become more positively polarized, allowing them to bond to more negatively polarized atoms such as oxygen, nitrogen, or sulfur hydrogen
What type of bond: Atoms with an excess of electrons (imparting an overall negative charge on the atom) are attracted to atoms with a deficiency of electrons (imparting overall positive charge on the atom) ionic
Hydrophilic or Hydrophobic: "water-loving"/water-soluble hydrophilic
Hydrophilic or Hydrophobic: Polar, usually ionized (contains a charge) hydrophilic
Hydrophilic or Hydrophobic: lipophilic hydrophobic
Hydrophilic or Hydrophobic: "fat loving"/water soluble hdrophobic
Hydrophilic or Hydrophobic: Renal excretion hydrophilic
Hydrophilic or Hydrophobic: Requires transport to cross cell membrane and BBB hydrophilic
Hydrophilic or Hydrophobic: Passively diffuses across the cell membranes and BBB hydrophobic
Hydrophilic or Hydrophobic: Forms H+ bonds hydrophilic
Hydrophilic or Hydrophobic: non-polar, usually not ionized (no charge) hydrophobic
Created by: nab81