Pharmacology basics Flashcards
How do drugs interact with receptors
Drug interact as a ligand with a receptor (large protein macromolecule responsible for cellular signaling). This results in activation of cellular biochemical processes by way of a transduction pathway that ultimately brings about the pharacological effect
What is a sucide substrated
A competitive inhibitor that is converted to an irreversible inhibitor at the active ste of the enzyme.
What are the general mechanisms by which drugs work
Vanderwal’s interaction: like repel each other, weak interaction;
Hydrogen bonding- weak;
Ionic- share more than one hydrogen;
Covalent- irreversible bound (aspirin)
Principle of induced fit
Also called lock and key; drug acts as a key, receptor as a lock, combination yeilds a response; Dynamic and flexible interaction
Tachyphylaxis
Rapidly decreasing response to a drug after administration of only a few doses; repeated same doses are less effective over time. Morphine addiction. Adding ketamine to fentanyl delays tachyphylaxis
Desensitized (tolerance)
Decreased response to the same dose with repeated (constant) exposure; or more drug needed to achieve same effect. Receptors don’t respond to it
Inactivation
Recptors normally results in a depression of maximal response of agonist dose-response curves; complete response
Refractory period
A total inability to respond in an effective time
Down-Regulation
tolerance/sensitivity at the cellular level may be due to a change in the number of receptors (without the appropriate subunit) due to change in stimulation. Less receptors there to respond. Example hormones
Pharmacodynamics
What happened in the process of the drug, binding one receptor; then multiple binding to a lot of receptors, which then going stimulate a local response prior to a body response
Graded dose response relationship
Constructed for responses measured on a continuous scale (hear rate). They relate the intensity of reponse to the size of the tose and hence are useful to characterize the actions of the drugs.
Quantal dose response
Constructed for drugs that elicit an all or none response (prescence or abscense of convulsions) for most drugs the doses required to produce specific quantal effect in a population are log normally distributed so that the frequence of distribution of teh responses plotted agains log dose is a guassian normal distribution curve. The percentage of the population requiring a paticular dose to exhibit the effect can be determined from these curve.
Dose response curves
Percent effect (y), drug dose (x); depicts the relationship between drug dose and magnitude of drug effect
Define Potency
The measure of the drug concentration required to elicit a particular effect; The concentration or dose (ED 50) of a drug required to produce 50% of the drug’s maximal effect as depicted by a graded dose response curve; concentration in which you get 1/2 of efficacy
Define Efficacy
The maximum effect a drug can have (full response)
Agonist
Receptor interaction with a drug that results in some level of activation
Full agonist
Results in maximal effect
Partial agonists
Results that are not maximal
Inverse agonist
an agent that binds to the same receptor as an agonist but induces a pharmacological response to that agonist; inactive a receptor that is normally on. Bind to the agonist site or elsewhere to induce a response
Antagonist
interacts selectively with receptors but it lacks intrinsic efficacy and this is able to block or reduce the action of an agonist at the receptor; Has no effect if nothing has been given that it needs to reverse
Competitive antagonist
Competitive occurs at the same recptor site- reversible (easily dissociate from the receptor) or irreversible (form a stable chemical bond with receptor (alkylation); Torb is a competitive antagonist- may have to give enough fentanyl to overcome
Non-competitive active site antagonist
binds to the active site and is irreversible or very close
Non-competitive allosteric antagonist
binds to a distinctly separate binding site from the agonist exerting their action to the receptor via the other binding site. Do not compete at the active binding site. The bound antagonists may prevent conformational changes in the receptor required for receptro activation after the agonists bindts- will decrease efficacy
What are spare receptors
Explains a maximum response beign achieved when only a fraction of the total number of receptors is occupied. Amplification of signal through G protein amplification. Binds to receptors, when it falls off it can then activate another receptor and the first receptor stays active
Therapeutic Window
The range of a drug or its concntration in a bodily system that proves safe effective therapy
Therapeutic Index
is a measure of a drug’s safety LDF50/ED 50; The higher the value the safer the drug
ADME
Absorption, distribution, metabolism, elimination/excretion; Four dynamic drug movements; plasma drug concentrations at any point in time after administration of a dose reflect the combined effects of four dynamic drug movements
Absorption- define
From the site of administration (orally, parentally) to systemic circulation; Bioavailabillity, oral absorption play a role
Distribution- define
From systemic circulation to tissues (target/nontarget) and back again. Protein binds- systems blood and lymph
Metabolism- define
breaks it down, activates, or deactivates the drug
Excretion- define
elimination of the drug from the body
What is pH trapping (ion trapping)
The build up of a higher concentration of a chemical across a cell membrane due to the pKa value of the chemical and difference of pH across the cell membrane. Move to one compartment to another then hydrogen is stuck or gives it. Weakly acidic likely to give up hydrogen ion
What drug properties favor drug entry into the CNS
Lipid Soluble, small size- low mocular weight, can use exisiting, BB protiens, deliver intratheical, non protein bound
Define bioavailability
The percentage of an administered dose of drug that reaches systemic circulation and is thus able to induce a response. Used to predict drug efficacy after different routes of administration or administration of different formulations
Explain the process of first pass metabolism
The concentration of a drug is greatly reduced before it reaches systemic circulation due to the liver (only)
Factors affecting drug absorption from oral administration
Reach systemic circulation from absorption from the small intestine; pH- favors absorption of weak acids; surface area favors SI vs. Stomach; motility;concentration of diffusible drug at the site of movement; permeability and thickness of the mucosal epithelium; and intestinal blood flow which maintains the concentration gradient across the mucosal epithelium
Explain volume of distribution
Is a constant that relates the amount of drug in the body to the plasma drug concentration, but does not necessarily correspond to any actual anatomic volume or compartment
What organs/tissues are responsivel for metabolism of drugs
Is the enzymatic conversion of one chemical compound into another. Most drug metabolism occurs in the liver, although some will occur in the gut wall, lungs, skin, or blood plasma.
What factors influence renal excretion
Host factors determine renal excretion include renal blood flow (including glomerular filtration rate), active tubular secretion, and tubular (generally passive) reabsorption. The kidney is also capable of metabolizing some drugs, although only occasionally clinical important. Glomerular filtration is a passive process
What factors influence biliary excretion
Slow; more contact with intestines leading to adverse GI reactions; chemic struction, polarity, and molecular weight, with MW being the major determinant.
How are drugs concentrated in the urinary system
Drugs excreted in the urine that do not undergo passive reabsorption will be progressively concentrated in the renal tubule. Tubular cells
Describe the process of enterohepatic recirculation
Conjugated (phase II) drugs excreted by this route may undergo enterohepatic circulation if intestinal bacteria or due to pH change unconjugate the drug or metabolite. Allowing intestinal absorption to occur. Prolongs elimination half life and further exposes gastrointestinal tract to the drug
Define Drug Clearance
Parameter used to assess the excretory capacity and thus physical well being of an organ relative to plasma concentration. Differs from elimination because it is a volume per unit of time, not a rate constatnt
Define First-order Kinetics
Decrease exponentially with time, rate of elimination is proportional to concentration, plot of log [drug] or ln [drug] versus time are linear; t1/2 is constant regardless of the [drug]; cant saturate the eliminating step
Define Zero-order kinetics
[drug] decreases linearly with time, rate of elimination is constant, rate of elimination is independent of [drug], no true t1/2; no point of CRI with zero order kinetics, as can staturate, ex. Buprenorphine
Define halflife
disappearance of drug from plasma
Define elimination half life
the time necessary for plasma or blood concentrations to decline by 50%; Should be the basis for an appropriate dosing interval
How does age affect the volume of distribution of a drug
Body composition changes as people; physiologic functions generally decline steadily with increasing ages. Energy requirements of dogs decrease as they age. Organ mass reduces in size and function by approximatly 25%
How does obesity affect the volume of distribution of a drug
Increased porportion of body fat is accompanied by a decrease in total body water and cell mass; as distribution of water solubel drugs decreased with total body water, PDCs tend to increase. The distrubution of lipid soluble drugs increase as the proportion of body increases, however which tends to decrease PDCs unless the patient is dose on mg/kg bases
How does pathologic fluid accumulations affect the volume of distribution of a drug
Edema formation and intravenous fluid administration contribute to a vast increase in total body water substantially increasing Vd of hydrophilic antimicrobials
How does cholestasis induce or inhibit cytochrome p450 enzymes
Cholestasis decrease the content or activity of cytochrome p450 drug metabolizing enzymes and thus can affect the elimination of drugs that are not secreted in bile
How does liver failure affect the volume of distribution of a drug
Decreased protein binding of drugs that may accompany liver disease. Increase hepatic clearance and thus compenasate for reduced hepatic metabolism. Further complicated by the effects of fluid, electrolyte, and acid-base imbalances, which are also likely to occur.
How does kidney failure affect the volume of distribution of a drug
Uremia induced alterations in tissue receptors or from decreased or increased PDCs caused by disease induced changes in pharmacokinetic; decreased renal blood flow which tends to parallel glomerular filtration and tubular secretion.
How does heart failure (decreased cardiac output) affect the volume of distribution
Primary or compensatory disturbances that lead to altared drug disposition include renal sodium and water retention, increased pulmonary and systemic venous pressures, and increased sympathetic nervous systme output
