COMLEX/STEP 1 Pharmacology

(114) Pharmacodynamics

What the drug does to the body and how

(114) Pharmacokinetics

What the body does to the drug and how

(114) Equilibrium dissociation constant (K_d)

the drug concentration required to saturate 50% of the receptors

(114) EC₅₀

the drug concentration that produces 50% of maximal response

(114) Intrinsic activity

The ability of a drug bound to its receptor to activate downstream effector
mechanisms

(114) Efficacy

The quantitative ability of a drug to elicit a physiologic response when it interacts with a receptor (it is related to the drug’s intrinsic activity)

(114) Potency

The concentration of drug required to produce an effect (it is related to the drug’s affinity for its target)

(114) Spare Receptors

remaining receptors that are not bound by agonist

(114) Toxicology

The branch of a science that deals with the undesirable effects of chemicals on living systems, from individual cells to humans to complex ecosystems

(114) Rational Drug Design

The development of drugs based on knowledge of the three-dimensional structure of the receptor site

(114) Pharmacogenomics

The relation of the individual’s genetic makeup to his or her response to specific drugs

(114) Partial Agonist

A drug that binds to and activates a receptor but does not evoke a maximal response, no matter how high the concentration of drug

(114) Antagonist

A drug that binds to a receptor, competes with and prevents binding by other molecules

(114) Intrinsic Efficacy

The relative ability of a drug-receptor complex to produce the maximal functional response

(114) Inverse Agonist

drug that has a much stronger affinity for the Ri than for the Ra state and stabilizes a large fraction in the R i –D pool, reducing constitutive activity

(114) Constitutive Activity

In the absence of any agonist, some of the receptor pool must exist in the activated (Ra) form some of the time and may produce the same physiologic effect as agonist-induced activity

(114) Agonist

A drug that binds to and activates the receptor in some fashion, which directly or indirectly brings about the effect

(114) Allosteric Activator

A drug that directly activates a receptor by binding to a receptor site distinct from the primary site

(114) Allosteric Inhibitor

A drug that binds a receptor at a site distinct from the primary site, inhibits the action of the agonist, and is not overcome by increasing the dose of the agonist

(115) Two-state receptor occupancy model

In the absence of a ligand, a receptor assumes two conformational states – active (Ra) and inactive (Ri)

(115) Classical receptor occupancy model

receptors in a receptor pool are inactive unless activated by a ligand

(115) Mechanism of Action of protamine sulfate

binds to negatively charged heparin in the bloodstream so heparin’s anticoagulant effect is neutralized

(115) Receptor desensitization

A decrease in the coupling efficiency of receptors – the receptor and the cell become unresponsive (insensitive) to the action of the drug, even in the continued presence of the drug

(115) Receptor downregulation

A decrease in the number of receptors by internalization followed by degradation of the receptor (and ligand)

(115) Median effective dose (ED50)

The dose of a drug required to produce a specified effect in 50% of the population

(115) Median lethal dose (LD50)

The dose of a drug that is lethal in 50% of the population

(115) Median toxic dose (TD50)

The dose of a drug that produces a specified toxic effect in 50% of the population

(115) Adverse Effects on Drug Metabolism of Antacids

reduce absorption and reduce efficacy of tetracyclines

(115) Adverse Effects on Drug Metabolism of Cholestyramine

strong cation exchange resin that forms a non-absorbable complex with many drugs, sequestering the drugs within the complex and preventing absorption of the drugs from the GI tract

(116) Nonionized Molecules Diffusion

Diffuse readily across the cell membrane

(116) Ionized Molecules Diffusion

have low lipid solubility and are less able to penetrate lipid membrane

(116) Solute Carrier (SLC) Superfamily

Facilitated diffusion down a concentration gradient, Energy not required

(116) ATP-Binding Cassette (ABC) Superfamily

ATP hydrolysis, catalyzed by ATPase, supplies energy for active transport against a concentration gradient. Active efflux of xenobiotics

(116) Function of P-glycoprotein

central channel for the ATP-dependent pumping (active efflux) of drugs from the cell

(116) Ion Trapping

Nonionized, uncharged form diffuses readily across the lipid barriers of the nephron. The ionized form does not diffuse as readily because of protonation in the blood and the urine. Reason why urine is more acidic than blood

(116) First Pass Effect

A fraction of an oral dose may be inactivated by drug-metabolizing enzymes in the GI tract and liver before reaching the systemic circulation

(116) Bioavailability

The fraction of the dose of active drug that reaches the systemic circulation

(116) Utility of IV Administration

Immediate-rapid effects, Emergency use, Dose titration readily done

(116) Utility of IM Administration

Suitable for Moderate volumes, Oily vehicles, Some irritating substances

(116) Utility of Transdermal Administration

Bypasses first-pass effect, Simple, convenient, painless, Provides sustained blood levels

(116) Utility of IO Administration

Very rapid onset, Bypass first-pass effect, Useful when trial of IV access unsuccessful in critically ill patient

(116-117) Cytochrome P450 (CYP) enzymes

Predominant enzymes involved in oxidative metabolism, inhibit or induce drugs. Abundant in liver

(117) Phase 1 Reactions

Oxidation, reduction, and hydrolysis. Unmasks a polar functional group (-OH, -COOH, -SH, -NH₂) that alters the biological properties of the drug. The drug may be inactivated (most often), activated, or unchanged

(117) Phase 2 Reactions

transfer an endogenous molecule to the substrate (i.e. drug or phase 1 product) producing a hydrophilic metabolite that is almost always inactive

(117) Function of NADPH-CYP oxidoreductase

Transfers electrons to the CYP where it can, in the presence of O2, oxidize xenobiotic substrates, many of which are hydrophobic and dissolved in the ER.

(117) UDP-Glucuronosyltransferase (UGT)

Phase 2 Transferase that transfers glucuronic acid from uridine diphosphate (UDP)-glucuronic acid

(117) Sulfotransferases (SULT)

Phase 2 Transferase that transfers sulfate from 3 ́-phosphoadenosine-5 ́-phosphosulfate (PAPS).

(117) N-Acetyltransferases (NAT)

Phase 2 Transferase that transfers acetyl moiety from acetyl coenzyme A.

(117) Glutathione-S-transferases (GST)

Phase 2 Transferase that catalyzes nucleophilic attack by glutathione (GSH) on electrophilic atoms in xenobiotics or toxic metabolites → neutralization of reactive oxygen species

(117) Methyltransferases (MT)

Transfers methyl moiety from S-adenosyl-methionine (SAMe)

(117) Function of Serum Creatinine

Can be used to estimate Glomerular Filtration Rate (GFR)/renal function

(117) β-glucuronidase

Enzyme found in intestinal bacteria that cleave drug conjugates, help with reabsorption of drug

(123) Clearance (CL)

The volume of blood from which the drug is removed per unit of time. Units: volume/time (mL/min or L/h)

(123) Volume of Distribution (V_d)

The proportionality factor that relates the amount of drug in the body to the concentration of drug in the blood or plasma. Units: Liters or Liters/kg body weight

(123) Bioavailability (F)

The fraction of the administered dose of drug that reaches the systemic circulation. Intravenous (IV) administration: F = 1 (100%)

(123) Elimination Half-Life (t½ )

The time required for the amount of drug in the body or blood to fall by 50%. For drugs eliminated by first-order kinetics, this number is a constant regardless of the concentration.

(123) Steady State

Dynamic equilibrium (first-order elimination only): the rate of drug elimination = the rate of drug administration

(123) Extraction Ratio (EH)

A measure of an organ’s intrinsic capacity for eliminating a given drug from the systemic circulation over a single pass through the organ (usually liver or kidney)

(123) Area Under the Curve (AUC)

The integration of the variation in plasma drug concentration over time after a single dose or during a single dosing interval. Reflects the actual (total) body exposure to an administered dose of a drug, irrespective of the rate of absorption.

(123) First-order Kinetics

A constant fraction of drug is eliminated per unit of time

(123) Zero-order Kinetics

A constant amount of drug is eliminated per unit of time

(123) Loading Dose

The dose of drug that promptly raises the concentration of drug in plasma to the target concentration

(123) Maintenance Dose

The dose of drug required per unit time to maintain a desired steady state plasma concentration

(123) Extraction Ratio (E)

a clearance model of an organ’s intrinsic capacity for eliminating a drug in a single pass through the organ at steady state.

(123) For drugs with high Hepatic Extraction (EH) (>0.7), Shunting of blood past the liver will:

result in substantial increases in drug availability in systemic circulation

(123) For drugs with low Hepatic Extraction (EH) (<0.3), Shunting of blood past the liver will:

cause little change in bioavailability

(123) Absolute bioavailability

comparing bioavailability of oral (or other route) to the I.V. formulation of the same drug

(123) Relative bioavailability

comparing the bioavailability of:
-Different formulations of the same drug (eg, tablet, capsule, solution), or
-The same formulation of the same drug made by different companies (eg brand and generic tablets)

(123) Initial distribution phase of Multi-compartment model

Highly-perfused organs – brain, kidney, liver, heart – receive most of the drug

(123) Multi-compartment model

Drug concentration in a sample varies over time as the drug distributes around the body

(123) Second distribution phase of Multi-compartment model

Delivery to muscle, most viscera, skin, and fat is slower

(123) Pharmaceutical equivalence

Drug products that contain the same active ingredients and are identical in strength or concentration, dosage form, and route of administration

(123) Therapeutic equivalence

Bioequivalent drug products having similar safety and efficacy profiles

(123) Interchangeable biologic product

Biosimilar product and meets additional standards for interchangeability

(123) Biosimilar

Biological product highly similar to an FDA-approved biological product and having no clinically meaningful differences in safety and effectiveness from the reference product

(123) Bioequivalence

Pharmaceutically equivalent drug products show no significant difference in the rate and extent of absorption of the active pharmaceutical ingredient

(124) The vast majority of drugs follow _____ at therapeutic doses:

First-Order Kinetics

(124) The drugs Ethanol, aspirin, and phenytoin follow _____ at therapeutic doses:

Zero-Order Kinetics

(124) Therapeutic Window

The range associated with therapeutic efficacy and a minimum of toxicity for a given agent

(124) Peak concentration

The maximum concentration (Cmax) achieved during repeated dosing cycles

(124) Trough concentration

The minimum drug concentrations achieved during repeated dosing cycles

(124) Minimum effective concentration

The minimum concentration required to produce a therapeutic effect

(124) Loading Dose (LD) Calculation:

(Vd x Cdesired)/F

(124) Maintenance Dose (MD) Calculation:

(CL x Cdesired)/F

(125) Adverse Drug Reactions

Unwanted, uncomfortable, or dangerous effects of drugs

(125) Adverse Drug Effects

Any injuries resulting from medication use, including physical/mental harm or function loss

(125) On-Target effect

results from the drug interacting with its therapeutic target in intended or unintended tissue

(125) Off-Target effect

results from the drug interacting with a target or targets other than the intended target in intended or unintended tissue

(125) Fetotoxicity

Injury to the fetus from a substance that enters the maternal and placental circulation, which may cause fetal malformations, altered growth, or in utero death

(125) Neonatal abstinence syndrome

Symptoms of withdrawal that babies can develop after birth if their mothers have taken addictive drugs during their pregnancy

(125) Haptens

Small chemicals (drugs or their metabolites) that are not reactive in their original state become immunogenic by covalent binding to host proteins on cells or in plasma complexes

(125) Biologic drugs

Protein drugs, such as monoclonal antibodies, cytokines, enzymes, and vaccines can preferentially stimulate antibody responses and some T cell responses

(125) Type I Hypersensitivity

IgE-mediated immediate hypersensitivity reactions

(125) Type II Hypersensitivity

Antibody-dependent cytotoxic reactions, delayed onset

(125) Type III Hypersensitivity

Immune complex-mediated reactions, IgG predominantly

(125) Type IV Hypersensitivity

T cell-mediated delayed-type reaction

(125) A patient with two alleles encoding for a nonfunctional protein will be a:

Poor metabolizer (PM)

(125) A patient with one functional allele will be a:

Intermediate metabolizer

(125) Individuals with two functional alleles will be a:

Extensive metabolizers (EM)

(125) A patient with Very high enzymatic activity, occasionally due to gene duplication will be a:

Ultra-rapid metabolizer