M1: Ch1 Pharma Intro Flashcards
Important document with 700 types of drugs listed from Egypt
Ebers Papyrus
Scientific study of the origin, nature, effects & uses of drugs. Deals with how drugs interact w/in biological systems to affect function.
Pharmacology
Comprised 40 volumes describing several thousands of prescriptions by Emperor Nung
Pen Tsao (Great Herbal)
Ancient Hindu medical text describes 760 medical herbs
Susruta
Wrote Kitab Al Shifa which considered 760 drugs. Chief guide to the medical sciences.
Avicenna
Massive decline in number & quality of medical writings available.
Dark Ages
17th Century. Art of Medicine become scientific.
Age of Enlightenment
300 drugs are used by ancient people
Babylo-Assyrian Civilization
Precursor to Pharmacology. Science of drug preparation & the medical use of drugs.
Materia medica
Actions of drug on body. Determine the group in which the drug is classified. Play the major role in deciding whether that group is appropriate therapy for a particular symptom or disease.
Pharmacodynamics
Actions of body on drug. Govern absorption, distribution & elimination of drugs. Important in choice & administration of a particular drug for a particular patient.
Pharmacokinetics
Use of drugs for prevention and cure of diseases
Pharmacotherapeutics
The art & science of compounding & dispersing drugs or preparing suitable dosage forms for administration of drugs in man & animals.
Pharmacy
Study of effect of drugs on population
Pharmacoepidimiology
Study of cost effectiveness of drug treatment
Pharmacoeconomics
Science of identification of drugs
Pharmacognosy
Study of relationship of the individuals genetic make up to his response to specific drugs
Pharmacogenomics
Concerned with effects of drugs upon MO & Parasites
Chemotherapy
Branch of Pharmacology that deals with undesirable effects of chemicals on living systems, from individual cells to humans to complex ecosystems.
Toxicology
Breeding animals in which the gene for the receptor or its endogenous ligand has been knocked out (mutated so that the gene product is absent or nonfunctional)
Knocked out mice
Science of substances used to prevent, diagnose & treat disease
Medical Pharmacology
Any substance that brings about change in biologic functions through its chemical actions. Substance which is used to modify or explore physiological/pathological states for the benefit of recipients. (WHO)
Drug
Drug molecule interacts as agonist or antagonist with a specific molecule that plays a regulatory role called a
Receptor
Drug may be synthesized within the body as
Hormones
Drug in which chemical is not synthesized in the body
Xenobiotics
Physical Nature of Drugs
Solid, Liquid & Gaseous
Examples of Physical Nature of Drugs in Solid form
Aspirin & Atropine
Examples of Physical Nature of Drugs in Liquid form
Nicotine & Ethanol
Example of Physical Nature of Drugs in Gaseous form
Nitrous Oxide
Most drugs have molecular weights between
100-1000
Drug MW: is probably set by the specificity of action. Drug must be sufficiently unique in shape, charge & etc. to prevent its binding to other receptors (good fit to only one type of receptor)
Lower limit
Drug MW: is determined primarily by a requirement that drug must be able to move within the body (site of administration to the site of action)
Upper limit
Do not diffuse readily between compartments, therefore, must be administered directly.
Drugs >MW 1000
A clot dissolving enzyme. Administered directly into vascular compartment by IV or intra-arterial infusion.
Alteplase
Drug for pain
Morphine
Drug for Malaria
Quinine
Drug for heart dysrhythmias
Digoxin
Drug for Pre eclampsia
Magnesium sulfate
Drug for anemia
Magnesium trisicalate
A thrombotic agent
Streptokinase
A very strong bond and is irreversible under biologic conditions. Not readily broken.
Covalent bonds
More common than covalent bonding in drug-receptor interactions. Weaker than covalent bonds.
Electrostatic bonds
Relatively weak bond. Interactions of highly lipid-soluble drugs (cell membranes). Interaction of drugs with internal walls of receptor pockets.
Hydrophobic bonds
Drugs that bind through weak bonds to their receptors are more _______ than drugs that bind by means of very strong bonds.
Selective
Drug shape must permit binding to its receptor site via bonds
Complementary
More than half of all useful drugs are chiral molecules (can exist as enantiomer pairs)
Phenomenom of Chirality (Stereoisomerism)
Implies the ability to predict the appropriate molecular structure of a drug on the basis of information about its biologic receptor
Rational Drug Design
Most drugs must bind to this to produce effect
Receptor
Bind to & activate receptor to directly or indirectly bring about effect. Receptor activation involves a change in conformation.
Agonist drugs
Compete with and prevent binding by other molecules by binding to a receptor
Antagonist drugs
Drugs that bind to the same receptor molecule but do not prevent binding of the agonist are said to act _________ & may enhance or inhibit the action of agonist molecule.
Allosterically
Is not overcome by increasing the dose of agonist
Allosteric Inhibition
Receptor can exist in the inactive & nonfunctional form
Ri
Receptor can exist in the activated form
Ra
In the absence of any agonist, some of the receptor pool must exist in Ra form some of the time & produce the same physiologic effect as agonist-induced activity (thermodynamic considerations)
Constitutive activity
Have a much higher affinity for Ra configuration & stabilize it
Agonists
Drugs administered at concentrations sufficient to saturate the receptor pool (activate receptor-effector systems to the maximum of which it is capable) cause a shift of almost all receptor pool to the Ra-D pool.
Full agonists
Bind to the same receptors & activate them but do not evoke a great response no matter how the high the concentration is. Significant fraction of receptors exists in Ri-D pool. Have low intrinsic efficacy.
Partial agonist
Fixing the fractions of drug-bound Ri & Ra in the same relative amounts as in the absence of any drug. No change observed.
Conventional Antagonist Action
A drug has a much stronger affinity for the Ri than for Ra state & stabilizes a large fraction in the Ri-D pool; reduces any constitutive activity resulting in effects that are opposite of the effects produced by conventional agonists at that receptor.
Inverse Agonists
Presence of antagonist at the receptor site will block access of agonists to the receptor & prevent the usual agonist effect
Neutral Antagonism
For preventing excessive activation when agonist molecules continue to be present for long periods
Desensitization mechanisms
To avoid constant activation of receptor by binding of many different ligands
Selectivity
Nonregulatory molecules (plasma albumin) capable of binding to receptors which will result in no detectable change in function; not completely without significance (used to determine amount of free drug in the circulation)
Inert binding site
An inactive precursor chemical that is administered, readily absorbed, distributed & then converted to the active drug by biologic processes inside the body.
Prodrug
Passive diffusion in an aqueous or lipid medium is common. Active processes in the movement of many drugs.
Permeation
Occurs within the larger aqueous compartments of the body & across epithelial membrane tight junctions & endothelial lining of blood vessels through aqueous pores.
Aqueous Diffusion
Most important limiting factor for drug permeation. Lipid barriers separate aqueous compartments
Lipid Diffusion
Determines how readily molecule moves between aqueous & lipid media.
Lipid aqueous partition coefficient of a drug
Downhill movement and driven by concentration gradient
Aqueous diffusion
For substances that are too large or too insoluble in lipid (peptides, AA & glucose) Movement by active transport or facilitated diffusion. Are selective, saturable and inhibitable.
Special Carriers
Process by which substance is bound at a cell-surface receptor, engulfed by cell membrane, & carried into cell by pinching off of the newly formed vesicle inside the membrane; substance can then be released inside the cytosol by breakdown of the vesicle membrane.
Endocytosis
Examples of Vesicle Membrane
Vitamin B12 & Iron
Responsible for secretion of many substances from cells (neurotransmitter substances)
Exocytosis
