Introduction to Pharmacology & Its General Principles Flashcards
medyo oa
What century where reliance on observation and experimentation began to replace theorizing in physiology and clinical medicine
End of 17th Century
Origin of ancient drugs
Plants
Science of drug preparation and the medical uses of drugs and identifies receptors
Materia Medica
The precursor to Pharmacology
Materia Medica
T/F: Any real understanding of the mechanisms of action of drugs was prevented by the absence of methods for purifying active agents from the crude materials that were available
True
Who developed the methods of experimental physiology and pharmacology; which has laid the foundation needed for understanding how drugs work at the organ and tissue levels.
Francois Magendie & Claude Bernard (Maganda & Cathryn Bernardo)
Real advances in basic pharmacology during this time were accompanied by an outburst of unscientific claims that marketed worthless patent medicines
Late 18th & Early 19th Century
Information accumulated about the drug action and biologic substrate of that action
Drug Receptor (1940s & 1950s)
Receptors for which no ligand has been discovered and whose function can only be guessed.
Orphan Receptors
Receptors and effectors do not function in isolation; they are strongly influenced by other receptors and by
Companion Regulatory Proteins
The relation of the individual’s genetic makeup to his or her response to specific drugs
Pharmacogenomics
Small segments of RNA can interfere with protein synthesis with extreme selectivity has led to investigation of __________ and __________ as therapeutic agents
small interfering RNAs (siRNAs), micro-RNAs (miRNAs)
Short nucleotide chains that are synthesized to be complementary to natural RNA or DNA, can interfere with the readout of genes and the transcription of RNA.
Antisense Oligonucleotides (ANOs)
T/F: All substances do not undergo certain circumstances to be toxic.
F; can undergo
T/F: Chemicals in botanicals (herbs and plant extracts, ”nutraceuticals”) are no different from chemicals in manufactured drugs except for the much greater proportion of impurities in botanicals.
T
T/F: All dietary supplements and all therapies promoted as health-enhancing, should meet the same standards of efficacy and safety as conventional drugs and medical therapies.
T
What are the 2 nature of drugs?
Pharmacodynamics & Pharmacokinetics
Pharmacodynamics or Pharmacokinetics?
Receptor, Receptor Sites
Pharmacodynamics
Pharmacodynamics or Pharmacokinetics?
Inert Binding Sites
Pharmacodynamics
Pharmacodynamics or Pharmacokinetics?
Movement of drugs in body
Pharmacokinetics?
Pharmacodynamics or Pharmacokinetics?
Absorption
Pharmacokinetics
Pharmacodynamics or Pharmacokinetics?
Distribution
Pharmacokinetics
Pharmacodynamics or Pharmacokinetics?
Metabolism
Pharmacokinetics
Pharmacodynamics or Pharmacokinetics?
Elimination
Pharmacokinetics
Drug Development & Regulation
- Safety & Efficacy
- Animal Testing
- Clinical Trials
- Patents & Generic Drugs
Body of knowledge concerned with action of chemicals on biologic systems, especially by binding to regulatory molecules (receptors) and activating or inhibiting normal body processes
Pharmacology
Activator
Agonist
Inhibitor
Antagonist
Target molecules or regulatory molecules in biological systems
Receptor
What do you call the new large molecule drugs that can be receptors themselves and bind endogenous molecules?
Biologicals
Drugs that may interact directly with other drugs
Chemical Antagonists
Drugs that interact almost exclusively with water molecules
Osmotic Agents
Who stated “The dose makes the poison”?
Paracelsus (1493 - 1541)
Area of pharmacology concerned with the use of chemicals in the prevention, diagnosis, and treatment of disease, especially in humans.
Medical Pharmacology
Area of pharmacology concerned with the undesirable effects of chemicals on biologic systems (e.g., poison)
Toxicology
T/F: It is the dose of the drugs that makes the drug lethal or poisonous.
T
Finds the exact mechanism of actions of drugs and identifies the receptors
Pharmacogenomics
Any substance that brings about change in biologic function through chemical actions (binds to receptors)
Drug
Specific molecule in the biologic system that plays a regulatory role
Receptor
T/F:
Receptor: No binding site = There is an effect in the body
F; no effect in the body
What kind of drugs that are usually easy to eliminate?
Water-soluble drugs
No receptor
Inert Substance
Chemical components of drugs similar to the human body
- Inorganic Ions
- Nonpeptide Organic Molecules
- Small peptides & proteins
- Nucleic Acids
- Lipids
- Carbohydrates
T/F: The body can process what it doesn’t t produce.
F; the body can’t process
Drugs may be synthesized within the body
Hormones
Chemicals that are not synthesized in the body
Xenobiotics
Drugs that have almost exclusively have harmful
effects.
Poisons
Poisons of biologic origin (i.e. synthesized by plants or animals) in contrast to inorganic poisons such as lead and arsenic.
Toxin
Physical Nature of Drugs
- Solid
- Liquid
- Gaseous
T/F: To interact chemically with its receptor, a drug molecule must have the appropriate size, electrical charge, shape, and atomic composition
T
Molecular weight of Lithium
7
Molecular weight of Thrombolytic Agents
50,000
What MW entails that receptors are small and for selective binding
100 MW
What MW is easily distributed but also easily be eliminated?
100 MW
MW: Upper limit wherein drugs can traverse within the different barriers of the body
1000 MW
MW that may not reach certain areas of the body
1000 MW
MW that cannot move within the body and cannot diffuse readily between the different
compartments of the body
> 1000 MW
MW that is given directly at the site of action and must be administered where they have their effect (usually proteins)
> 1000 MW
Why does >1000 MW have difficulty in traversing different sites of the body?
They have to fit in / They are prevented by the blood-brain barrier, blood-air barrier, etc.
Stereoisomerism / Can exist as enantiomeric pairs
Chirality
Affects the potency of the drugs
Chirality
A drug that interacts with adrenoceptors, has a single chiral center and thus two enantiomers.
Carvedilol
Potent beta receptor blocker
(S)(-) isomer
Weak beta receptor blocker
(R)(+) isomer
An intravenous anesthetic and racemic mixture.
Ketamine
Ketamine: (+/-) enantiomer is a more potent anesthetic and less toxic than the (+/–) enantiomer.
+ , -
T/F: Enzymes are usually stereoselective, one drug enantiomer is often more susceptible than the other to drug-metabolizing enzymes.
T
T/F: At present, only a small percentage of the chiral drugs are clinically marketed as the racemic mixtures the rest are available only as active isomers.
F; At present, only a small percentage of the chiral drugs are clinically marketed as the active isomer the rest are available only as racemic mixtures.
Mechanism for Drug Shapes
Lock and Key Mechanism
Binds to a specific site and activates the receptor which bring out the effect
Agonist Drugs
Binds to a receptor, competes with, and prevents binding by other molecules
Pharmacologic Antagonist
Binds at a different site other than the agonist binding site and increases agonist response
Allosteric Activators
Binds at a different site other than the agonist binding site and decreases agonist response
Allosteric Inhibitors
Binds at the agonist binding site and decreases agonist response
Competitive Inhibitors
Several other binding site in receptors and for other chemicals that bind to the receptors
Allosteric Site
The presence of the antagonist at the receptor site will block access of agonists to the receptor and prevent the usual agonist effect.
Neutral Antagonism
Produce increasing effects with increasing dose (Eventually saturate all receptors and response will plateau)
Agonist alone
Agonist + Competitive Inhibitor
Require a higher dose to achieve the similar effect
Agonist + Allosteric Activators
Enhances the response/effect produced by agonist with the same dose
Agonist + Allosteric Inhibitors
Diminish the response/effect produced by agonist with the same dose
Drug Receptor Bonds
Sharing of electrons
Strongest
Electrons are shared in order to stabilize these chemicals
Covalent Bonds
Irreversible under biologic conditions / Cannot be easily dislodged
Covalent Bonds
Drug Receptor Bonds
More common (+)(-) and weaker
Electrostatic Bonds
Can we manipulate Electrostatic Bonds?
Yes
Drug Receptor Bonds
Weakest and highly lipid-soluble drugs
Hydrophobic Bonds
Interacts with lipids of cell membranes and in the interaction of drugs with the internal walls of receptors
Hydrophobic Bonds
Action of the drug in the body
Pharmacodynamics
Action of the body on the drug
Pharmacokinetics
D + Receptor-Effector → _________ → Effect
Drug-Receptor-Effector
D + R → _______ → Effector Molecule → Effect
Drug-Receptor Complex
D + R → D-R Complex → ________ → Effector Molecule → Effect
Activation of Coupling Molecule
Inhibition of metabolism of endogenous activator → _________ → Increased effect
Increased activator action on an effector molecule
Occurs in the absence of the agonist. Some of the receptor pool must exist in Ra form and may produce same physiologic effect as agonist-induced activity
Constitutive / Basal Activity
Activates receptor-effector system to the maximum extent (Ra-D pool) {activated form}
Full Agonist
Binds to the same receptors and activate them in the same way but do not evoke as great a response
Partial Agonist
Binds to a site on the receptor molecule separate from the agonist binding site
Allosteric Modulators
Modifies receptor activity without blocking agonist activity
Allosteric Modulators
May increase / decrease response to agonist and is also noncompetitive
Allosteric Modulators
Drug has a stronger affinity for the Ri pool and reduces constitutive activity
Inverse Agonist
Results in effects that are opposite of the effects produced by conventional agonists
Inverse Agonist
Binds to a receptor, compete with and prevent binding by other molecules
Antagonist
Inactive precursor and must be administered and converted to the active drug by biologic process inside the body
Prodrug
Undergoes hepatic metabolism to be come a more active form that will enable them to reach target receptors
Prodrug
Movement of molecules through the watery extracellular and intracellular spaces.
Permeation
Movement of molecules through the watery extracellular and intracellular spaces.
Aqueous Diffusion
Membranes of capillaries with small water-filled pores
Has passive processes
Aqueous Diffusion
Governed by Fick’s Law
Aqueous Diffusion & Lipid Diffusion
What diffusion?
Water-soluble drugs easily diffuse due to the presence of water intracellularly and extracellularly
Aqueous Diffusion
Movement of molecules through membranes and other lipid structures
Lipid Diffusion
Most important factor for drug permeation
Passive Process
Lipid Diffusion
Drugs transported across barriers by mechanisms that carry similar endogenous substances
Transport by Special Carriers
Its capacity is limited (limit rate of transport across membranes) and is not governed by Fick’s Law
Transport by Special Carriers
Transport by Special Carriers
Needs energy
Against a concentration gradients
Activate Transport
Transport by Special Carriers
No energy directly required
May utilize another concentration gradient of a substance / use an active receptor
Downhill
Facilitated Diffusion
Binding to specialized components (receptors) on cell membranes
Endocytosis
Internalization by infolding of the area of the membrane and contents of the vesicle are subsequently released into the cytoplasm
Endocytosis
Permits very large or very lipid-insoluble (water soluble) chemicals to enter the cell
Endocytosis
- B12 with intrinsic factor
- Iron with transferrin
Reverse process
Expulsion of membrane encapsulated material from the cell
Exocytosis
Predicts the movement of molecules across a barrier
Fick’s Law of Diffusion
Drug absorption is faster in organs with larger surface areas (e.g. small intestine) than from organs with smaller absorbing areas (e.g. stomach)
Fick’s Law of Diffusion
Fick’s Formula
Rate = C1 - C2 x Permeability Coefficient / Thickness x Area
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HHE: Higher Concentration
C1
Lower Concentration
C2
Intrinsic property of the drug; measure of the mobility of the drug in medium of the length of the diffusion path.
Permeability Coefficient
Length of the diffusion path; Thicker means harder to permeate through.
Thickness
Surface area of the membrane
Area
Greater concentration difference = ______ ; ______ proportional to the rate
Faster equilibriation ; Directly
↑ Permeability Coefficient = ___ Rate
↑
Bigger Surface Area = _________ ; ________ proportional to rate
More areas to traverse ; Directly
Is a function of the electrostatic charge (degree of ionization, polarity) of the molecule
Aqueous solubility of a drug
Water molecules are attracted to (charged/uncharged) drug
Charged
Lipid solubility of a molecule is _______ proportional to
its charge
Inversely
Lipid Diffusion
Determines the fraction of molecules charged (ionized) versus uncharged (nonionized)
pH of the medium
Fraction of molecules in the ionized state can be predicted by means of the H-H equation
Lipid Diffusion
Clinically important when it is necessary to estimate or alter the partition of drugs between compartments of different pH
Henderson-Hasselbach Equation
Formula for Henderson-Hasselbach
log (protonated) / (unprotonated) = pka - pH
T/F: The HHE applies to both acid and basic drugs.
T
T/F: In HHE, protonated means associated with a proton (a hydrogen ion / H+)
T
Neutral molecule that can form a cation (+charged) by combining with a proton (hydrogen ion)
Weak Base
Ionized, more polar, more water soluble when they are protonated
Weak Base
Neutral molecule that can reversibly dissociate into an anion (-charged) a proton (hydrogen ion)
Weak Acid
Not ionized, less polar, less water soluble when they are protonated
Weak Acid
T/F: Large number of drugs are weak acids with amine containing molecules
F; weak bases
T/F: Primary, secondary, and quarternary amines may undergo reversible protonation and vary their lipid solubility with pH, but tertiary amines are always in the poorly-lipid soluble charged form.
F
(1) Primary, secondar, tertiary
(2) but quarternary
Amount absorbed into the systemic circulation amount of drug administered
Bioavailability
Important parameter of Bioavailability
Blood Plasma - Looks into the amount of blood present in systemic circulation compared to amount of drug administered
- Maximum convenience
- Absorption maybe slower, and less complete
Oral
T/F: Some drugs have low bioavailability when given orally
T
- Instantaneous and complete absorption
- Bioavailability by definition is 100%
- Potentially more dangerous, high blood levels reached if administration is too rapid
Intravenous (IV) / Parenteral
- Absorption is often faster and more complete (higher bioavailability) than oral
- Large volumes (>5 ml into each buttock) if the drug is not irritating
Intramuscular (IM)
T/F: Heparin can be given by intramuscular route.
F; It will cause bleeding in the muscle
- Slower absorption than IM route
- Heparin can be given by this route, does not cause hematoma
Subcutaneous
- Permits absorption direct into the systemic circulation, bypassing hepatic portal circuit and first-pass metabolism
- Slow or fast depending on formulation of the product
Buccal and Sublingual
In the pouch between gums and cheeks
Buccal Route
Under the tongue
Sublingual Route
T/F: Buccal and Sublingual routes offer different features when absorbed.
F; It offers the same features
Tend to migrate upward in the rectum where absorption is partially into the portal circulation
Rectal (Suppository)
T/F: Larger amounts of unpleasant drugs are better administered rectally
T
For respiratory diseases
Inhalation
Delivery closest to the target tissue
Inhalation
Results into rapid absorption because of the rapid and thin alveolar surface area
Inhalation
Drugs that are gases at room temperature (eg, nitrous oxide), or easily volatilized (anesthetics)
Inhalation
Application to the skin or mucous membrane of the eye, nose, throat, airway, or vagina for local effect
Topical
Rate of absorption varies with the area of application and drug’s formulation and absorption is slower compared to other routes
Topical
Application to the skin for systemic effect and rate of absorption occurs very slowly
Transdermal
Influences absorption from IM, subcutaneous, and in shock
Blood Flow
T/F: High blood flow maintains a high drug depot-to-blood concentration gradient, which maximizes absorption
T
Major determinant of the rate of absorption (Fick’s law)
Concentration
Subject to first-pass effect
- Oral
First-pass effect is avoided
- Intramuscular (IM)
- Subcutaneous
- Transdermal
Partial avoidance of first-pass effect
- Rectal
Significant amount of the agent is metabolized in the gut wall, portal circulation, and liver before it reaches the systemic circulation
First-pass effect
Target of cocaine and some tricyclic antidepressants
NET
Norepinephrine reuptake from synapse
NET
Target of selective serotonin reuptake inhibitors and some tricyclic antidepressants
SERT
Serotonin reuptake from synapse
SERT
Target of reserpine and tetrabenazine
VMAT
Transport of dopamine and norepinephrine into adrenergic vesicles in nerve endings
VMAT
Transport of many xenobiotics out of cells
MDR1
Leukotriene secretion
MRP1
