PHARMACOLOGY Lecture Notes Flashcards
PHARMACOLOGY: DEFINITION
Etymology:
Pharmakon = drug, remedy
Logos = study/logic
Scope: study of drugs including their structure, composition, chemical properties, and their biomedical and physiological effects on the body
Drugs: any chemical that will affect the body or living processes
OBJECTIVES AND PHASES OF PHARMACEUTICAL RESEARCH
PRE-CLINICAL TRIALS (DRUG DISCOVERY)
Determine drug’s toxic and pharmacological effects through in vitro (e.g., cell cultures, isolated organs) and in vivo (e.g., rodent, non-rodent animal models) studies
Purpose: establish safety and biological activity before human exposure; identify potential lead compounds
HUMAN CLINICAL EXPERIMENTATION
Phase 1: safety, pharmacokinetics, and maximum tolerated dose (MTD) in 20–80 healthy volunteers
Phase 2: effectiveness, optimal dosing, and further safety evaluation in 100–300 real patients (target population)
Phase 3: confirm safety & effectiveness in 1,000+ patients; often involves comparative studies against existing treatments and identification of less common adverse effects
Phase 4: long-term effects, optimal use, additional indications, and ongoing safety monitoring after drug approval
CORE ETHICAL PRINCIPLES INVOLVING HUMAN SUBJECTS
AUTONOMY (Self-Determination)
Patients have the right to decide in their own best interest; this involves understanding risks and benefits.
They can refuse treatments or participate in research without penalty, emphasizing voluntary participation.
BENEFICENCE
Duty to protect research subjects from harm and to maximize possible benefits while minimizing risks.
Assess potential risks and possible benefits thoroughly before and during the study.
JUSTICE
Fairness in the distribution of research benefits and burdens across social class, racial, and ethnic groups.
INFORMED CONSENT AND SAFETY MONITORING
INFORMED CONSENT
Right to be informed, voluntarily, without coercion, about all aspects of the study.
State purpose, duration, procedures, foreseeable risks & benefits, confidentiality, and alternative treatments.
PATIENT MUST: be alert, able to comprehend the information, and have the capacity to make a decision.
Inclusion/Exclusion examples (illustrative):
Inclusion: 18–65 years old; 50–100 kg; no medication for the last 3 months
Exclusion: pregnancy/nursing, sexually active considerations, abnormal lab values (illustrative examples from the transcript)
Ongoing safety monitoring and documentation: This includes continuous pharmacovigilance, collecting and reporting adverse drug reactions (ADRs) through systems like MedWatch (in the U.S.) to ensure the drug's safety profile is continuously assessed.
PHASES OF DRUG DEVELOPMENT: POST-CLINICAL INSIGHTS
Pharmaceutic phase (disintegration) → pharmacokinetic phase (absorption, distribution, metabolism, excretion) → pharmacodynamic phase (drug effects on the body)
PHARMACOKINETICS, PHARMACODYNAMICS, AND PHARMACEUTIC PHASE
PHARMACEUTIC PHASE: describes how solid forms of drugs disintegrate, become soluble, and are absorbed into the bloodstream
DISINTEGRATION: Manual breakdown of tablets into smaller particles in the GI tract.
DISSOLUTION: Dissolving of disintegrated particles in gastrointestinal fluids to form a solution that can be absorbed.
PHARMACOKINETICS: movement of a drug within the body to achieve drug action
ADME:
Absorption: movement of drug from site of administration into the blood.
Distribution: movement of drug from blood to tissues and site of action.
Metabolism: chemical alteration of drug by the body.
Excretion: removal of drug and its metabolites from the body.
PHARMACODYNAMIC PHASE: (covered under Pharmacodynamics section)
ABSORPTION AND ITS DETERMINANTS
ABSORPTION: movement of a drug from its site of administration into the blood
FACTORS AFFECTING ABSORPTION (explicit points from transcript and standard concepts)
Rate of dissolution: faster dissolution → faster absorption, as the drug needs to be in solution to cross membranes.
Surface area: larger surface area (e.g., small intestine's villi and microvilli) → faster absorption.
Blood flow: higher perfusion to the absorption site → faster absorption; poor blood flow (e.g., in shock) slows absorption.
Lipid vs water solubility:
Lipid-soluble (lipophilic) drugs cross lipid membranes more readily via passive diffusion.
Water-soluble drugs dissolve in aqueous environments but may cross lipid membranes less readily, often requiring carrier-mediated transport.
pH partitioning and ionization: ionized forms may cross membranes less readily; local pH affects absorption.
Acidic drugs are non-ionized in acidic environments (e.g., stomach) and therefore better absorbed. Basic drugs are non-ionized in basic environments (e.g., small intestine) and better absorbed.
Ionized forms are typically water-soluble and have difficulty crossing the lipid bilayer membranes due to their charge.
Drug concentration at the site of administration: higher concentration gradient generally leads to faster absorption via passive diffusion.
Drug formulation: excipients, coating, and physical form (e.g., liquid vs. tablet) significantly influence absorption rate and extent.
Additional notes: sex, exercise, age, and other physiological factors can influence absorption. For instance, age can affect gastric pH, motility, and blood flow; exercise can alter blood flow distribution.
MODES OF ABSORPTION
Passive Transport (no energy required)
Diffusion: movement from high to low concentration across membranes, driven by a concentration gradient.
Facilitated diffusion: requires specific carrier proteins to transport drugs across membranes but no direct energy expenditure, still follows a concentration gradient.
Active Transport: requires energy (ATP) to move drugs against a concentration gradient, often involving specific transport proteins.
Pinocytosis: cells engulf drug particles in vesicles for transport across the cell membrane, typically for large molecules.
BIOAVAILABILITY, DISTRIBUTION, METABOLISM, AND EXCRETION
BIOAVAILABILITY (F): percentage of administered drug that reaches systemic circulation in an unchanged form and is available for action. For IV drugs, F=100%.
DISTRIBUTION: movement from bloodstream to body compartments (interstitial and intracellular fluids, and various tissues).
Influenced by factors like cardiac output, regional blood flow (well-perfused organs receive drugs faster), membrane permeability (e.g., cell barriers), and plasma protein binding.
Plasma protein binding: Many drugs reversibly bind to plasma proteins (e.g., albumin, alpha-1 acid glycoprotein). Only the unbound or free drug is pharmacologically active, able to distribute into tissues, elicit its effect, and be eliminated.
Tissue binding: Some drugs accumulate in specific tissues (e.g., adipose tissue for highly lipid-soluble drugs, bone for tetracyclines), serving as a drug reservoir or leading to tissue-specific toxicity.
Special barriers: The Blood-Brain Barrier (BBB) and placental barrier selectively restrict drug passage, protecting the brain and fetus from many substances, typically allowing only highly lipid-soluble, small, non-ionized drugs to pass readily.
METABOLISM / BIOTRANSFORMATION: chemical modification of drugs to more excretable (usually more polar) forms.
Primary site: liver; involvement of Cytochrome P450 enzymes (CYPs) and other enzymes (e.g., esterases, glucuronosyltransferases).
Phase I reactions (Functionalization): Generally involve oxidation, reduction, and hydrolysis reactions. These reactions often introduce or expose a polar functional group (like -OH, -NH2, -SH), making the drug more water-soluble or setting it up for Phase II. They can result in active, inactive, or toxic metabolites.
Phase II reactions (Conjugation): Involve the covalent attachment of a polar, endogenous molecule (e.g., glucuronic acid, sulfate, glutathione, acetate) to the drug or its Phase I metabolite. This significantly increases water solubility and usually leads to inactive metabolites that are readily excreted.
First-pass effect (Presystemic metabolism): Extensive metabolism of an orally administered drug by the liver (and sometimes gut wall) before it reaches the systemic circulation, significantly reducing its bioavailability.
Metabolism commonly makes drugs more water-soluble and less active; however, some drugs are metabolized into more active metabolites (prodrugs) or toxic metabolites.
EXCRETION: removal of drugs and metabolites from the body via urine (kidneys are primary route), bile (frequent for large, polar molecules), sweat, breath, feces.
Other minor routes include tears, saliva, and breast milk (important consideration for nursing mothers).
HALF-LIFE AND ELIMINATION
HALF-LIFE (t_{1/2}): time required for the plasma concentration of a drug to decrease by 50% during the elimination phase.
Practical use: helps determine dosing frequency, duration of action, and time to reach/clear steady state; crucial for preventing accumulation or ensuring therapeutic levels.
PRACTICAL CALCULATIONS AND EXAMPLES
DRUG DOSAGE COMPUTATION
General formula: Volume to administer (mL) = Desired dose (mg) / Concentration (mg/mL)
Example 1: Digoxin IV ordered 0.75 mg; vial concentration = 0.5 mg/mL
Volume to administer = \frac{0.75}{0.5} = 1.5 \text{ mL}
Example 2: Suspension 125 mg/5 mL ordered 200 mg
Volume = \frac{200}{125} \times 5 = 8 \text{ mL}
Example 3: Amoxicillin 1.2 g total; capsules 400 mg each
Number of capsules = \frac{1200}{400} = 3 \text{ capsules}
Example 4: Acetaminophen 0.5 g; tablets 250 mg each
Number of tablets = \frac{500}{250} = 2 \text{ tablets}
RECONSTITUTION CALCULATION
Powder = 500 mg; to be reconstituted with 5 mL sterile water
Resulting concentration = \frac{500 \text{ mg}}{5 \text{ mL}} = 100 \text{ mg/mL}
INTRAVENOUS DRIP RATES
FLOW RATE (gtt/min) formula:
\text{Flow rate (gtt/min)} =\frac{\text{Volume (mL)} \times \text{Drop factor (gtt/mL)}}{\text{Time (min)}}
Example A: 500 mL over 4 hours with drop factor 20 gtt/mL
Time = 4 h = 240 min
Flow rate = \frac{500 \times 20}{240} \approx 41.7 \text{ gtt/min}
Flow rate (mL/hr) formula:
\text{Flow rate (mL/hr)} =\frac{\text{Volume (mL)}}{\text{Time (hr)}}
Example B: 200 mL over 2 hours
Flow = \frac{200}{2} = 100 \text{ mL/hr}
ADDITIONAL IV RATE PRACTICE
Example C: 100 mL IV over 30 minutes with drop factor 60 gtt/mL
Flow rate (gtt/min) = \frac{100 \times 60}{30} = 200 \text{ gtt/min}
Flow rate (mL/hr) = \frac{100}{0.5} = 200 \text{ mL/hr}
PHARMACODYNAMICS
DOSE-RESPONSE RELATIONSHIP: the body’s physiological response to changes in drug concentration at the site of action, typically visualized with a dose-response curve.
POTENCY: amount of drug needed to produce a given effect; a more potent drug requires a smaller dose for the same effect (shifted left on a dose-response curve).
EFFICACY: the ability of a drug to produce the desired pharmacological effect (maximum effect or E_{max}) irrespective of the dose. It reflects the intrinsic activity of the drug.
THERAPEUTIC INDEX (TI)
Definition: relationship between the therapeutic dose and toxic dose, indicating the safety margin of a drug.
Common representation: TI = \frac{TD{50}}{ED{50}} (where TD{50} is the toxic dose for 50% of the population and ED{50} is the effective dose for 50% of the population).
A higher TI indicates a wider safety margin, meaning a larger difference between effective and toxic doses; a lower TI indicates higher risk of toxicity at effective doses, requiring careful monitoring.
ONSET, PEAK, DURATION OF ACTION
ONSET: time to reach minimum effective concentration (MEC) in the plasma, initiating the therapeutic effect.
PEAK: time of maximum drug concentration in plasma, often correlating with maximum therapeutic effect.
DURATION OF ACTION: length of time the drug concentration remains above the MEC, maintaining its therapeutic effect.
THERAPEUTIC DRUG MONITORING
PURPOSE: to determine peak and trough (lowest) levels to optimize therapy, especially for drugs with a narrow therapeutic index.
PEAK DRUG LEVEL: highest plasma concentration at a specific time after administration; indicates rate of absorption and maximal exposure.
TROUGH (DRUG LEVEL): lowest plasma concentration, usually measured just before the next dose; indicates rate of elimination and helps prevent drug accumulation or sub-therapeutic levels.
APPLICATIONS: optimize dosing regimens, avoid toxicity, ensure efficacy, identify non-adherence, assess drug interactions.
RECEPTOR THEORY AND MECHANISM OF ACTION
BINDING: drug-receptor interaction determines pharmacological effect; receptors are typically proteins on cell surfaces or within cells.
Agonist: activates receptors to produce a response by mimicking an endogenous ligand.
Full agonist: produces a maximal response when all receptors are bound, with high intrinsic activity.
Partial agonist: produces a sub-maximal response even when fully saturating the receptors, having lower intrinsic activity than a full agonist.
Antagonist: blocks receptor activation by preventing agonists from binding or by interfering with their action.
Competitive antagonist: Binds reversibly to the same binding site as the agonist; can be overcome by increasing agonist concentration. This shifts the agonist dose-response curve to the right without reducing the maximal response.
Non-competitive antagonist: Binds irreversibly to the agonist binding site or to an allosteric site elsewhere on the receptor, altering the receptor's ability to respond to the agonist. Its effect cannot be fully overcome by increasing agonist concentration, generally reducing the maximal response (efficacy) of the agonist.
MECHANISM OF ACTION
What the drug does to the body and how it produces its effect at a molecular or cellular level.
Drugs can also exert their effects by interacting with molecular targets other than classical receptors, such as enzymes (e.g., enzyme inhibitors like ACE inhibitors), ion channels (e.g., channel blockers or openers like calcium channel blockers), or transport proteins (e.g., reuptake inhibitors like SSRIs).
RELATED DRUG EFFECTS & INTERACTIONS
DRUG RESPONSE CATEGORIES (Side effects / Adverse effects are secondary effects)
Primary effect: desirable therapeutic response (e.g., anti-allergic effect of cetirizine).
Secondary effects: additional effects, which may be desirable or undesirable (e.g., sedation in some antihistamines).
ALLERGIC REACTIONS/HYPERSENSITIVITY
Possible after repeated exposure; can range from mild rashes (Type I, II, III, IV hypersensitivity reactions) to severe, life-threatening responses.
Anaphylactic reaction: severe, potentially life-threatening systemic reaction characterized by rapid onset, airway compromise, hypotension, and requires urgent care (e.g., epinephrine).
TOXIC EFFECTS: unintended adverse effects that can be harmful or fatal, often dose-dependent or due to accumulation.
DRUG INTERACTIONS
Additive effects: combined effect equals sum of individual effects (1+1=2) when two drugs with similar pharmacological actions are given together.
Synergistic effects: combined effect greater than the sum of individual effects (1+1=3 or more) when two drugs enhance each other's effects.
Antagonistic effects: one drug blocks or reduces the effect of another, potentially reducing therapeutic benefit or reversing adverse effects.
Toxic interactions: combinations that raise risk of adverse outcomes, often due to altered metabolism (e.g., enzyme inhibition/induction) or increased toxicity to specific organs.
TOXICITY, TOLERANCE, AND DEPENDENCE
DRUG TOLERANCE: decreased response to a drug over time following repeated administration, requiring higher doses for the same effect. This can result from pharmacokinetic (e.g., enzyme induction) or pharmacodynamic (e.g., receptor downregulation) changes.
DRUG DEPENDENCE
Physical dependence: state where the body has adapted to a drug, and physical withdrawal symptoms (e.g., nausea, tremors, seizures) occur upon cessation or reduction of the drug.
Psychological dependence: cravings and compulsive use of a drug to experience its effects or avoid dysphoria, often leading to drug-seeking behaviors.
EXAMPLES AND CONSIDERATIONS
Some antidotes and rescue agents (e.g., Digibind in digoxin toxicity, naloxone in opioid overdose) may be used in toxicity management to neutralize the drug or block its effects.
WARNINGS ABOUT POLYPHARMACY
Use of multiple drugs, especially common in
PHARMACOLOGY: DEFINITION
Etymology:
Pharmakon = drug, remedy
Logos = study/logic
Scope: study of drugs including their structure, composition, chemical properties, and their biomedical and physiological effects on the body
Drugs: any chemical that will affect the body or living processes
OBJECTIVES AND PHASES OF PHARMACEUTICAL RESEARCH
PRE-CLINICAL TRIALS (DRUG DISCOVERY)
Determine drug’s toxic and pharmacological effects through in vitro (e.g., cell cultures, isolated organs) and in vivo (e.g., rodent, non-rodent animal models) studies
Purpose: establish safety and biological activity before human exposure; identify potential lead compounds
HUMAN CLINICAL EXPERIMENTATION
Phase 1: safety, pharmacokinetics, and maximum tolerated dose (MTD) in 20–80 healthy volunteers
Phase 2: effectiveness, optimal dosing, and further safety evaluation in 100–300 real patients (target population)
Phase 3: confirm safety & effectiveness in 1,000+ patients; often involves comparative studies against existing treatments and identification of less common adverse effects
Phase 4: long-term effects, optimal use, additional indications, and ongoing safety monitoring after drug approval
CORE ETHICAL PRINCIPLES INVOLVING HUMAN SUBJECTS
AUTONOMY (Self-Determination)
Patients have the right to decide in their own best interest; this involves understanding risks and benefits.
They can refuse treatments or participate in research without penalty, emphasizing voluntary participation.
BENEFICENCE
Duty to protect research subjects from harm and to maximize possible benefits while minimizing risks.
Assess potential risks and possible benefits thoroughly before and during the study.
JUSTICE
Fairness in the distribution of research benefits and burdens across social class, racial, and ethnic groups.
INFORMED CONSENT AND SAFETY MONITORING
INFORMED CONSENT
Right to be informed, voluntarily, without coercion, about all aspects of the study.
State purpose, duration, procedures, foreseeable risks & benefits, confidentiality, and alternative treatments.
PATIENT MUST: be alert, able to comprehend the information, and have the capacity to make a decision.
Inclusion/Exclusion examples (illustrative):
Inclusion: 18–65 years old; 50–100 kg; no medication for the last 3 months
Exclusion: pregnancy/nursing, sexually active considerations, abnormal lab values (illustrative examples from the transcript)
Ongoing safety monitoring and documentation: This includes continuous pharmacovigilance, collecting and reporting adverse drug reactions (ADRs) through systems like MedWatch (in the U.S.) to ensure the drug's safety profile is continuously assessed.
PHASES OF DRUG DEVELOPMENT: POST-CLINICAL INSIGHTS
Pharmaceutic phase (disintegration) → pharmacokinetic phase (absorption, distribution, metabolism, excretion) → pharmacodynamic phase (drug effects on the body)
PHARMACOKINETICS, PHARMACODYNAMICS, AND PHARMACEUTIC PHASE
PHARMACEUTIC PHASE: describes how solid forms of drugs disintegrate, become soluble, and are absorbed into the bloodstream
DISINTEGRATION: Manual breakdown of tablets into smaller particles in the GI tract.
DISSOLUTION: Dissolving of disintegrated particles in gastrointestinal fluids to form a solution that can be absorbed.
PHARMACOKINETICS: movement of a drug within the body to achieve drug action
ADME:
Absorption: movement of drug from site of administration into the blood.
Distribution: movement of drug from blood to tissues and site of action.
Metabolism: chemical alteration of drug by the body.
Excretion: removal of drug and its metabolites from the body.
PHARMACODYNAMIC PHASE: (covered under Pharmacodynamics section)
ABSORPTION AND ITS DETERMINANTS
ABSORPTION: movement of a drug from its site of administration into the blood
FACTORS AFFECTING ABSORPTION (explicit points from transcript and standard concepts)
Rate of dissolution: faster dissolution → faster absorption, as the drug needs to be in solution to cross membranes.
Surface area: larger surface area (e.g., small intestine's villi and microvilli) → faster absorption.
Blood flow: higher perfusion to the absorption site → faster absorption; poor blood flow (e.g., in shock) slows absorption.
Lipid vs water solubility:
Lipid-soluble (lipophilic) drugs cross lipid membranes more readily via passive diffusion.
Water-soluble drugs dissolve in aqueous environments but may cross lipid membranes less readily, often requiring carrier-mediated transport.
pH partitioning and ionization: ionized forms may cross membranes less readily; local pH affects absorption.
Acidic drugs are non-ionized in acidic environments (e.g., stomach) and therefore better absorbed. Basic drugs are non-ionized in basic environments (e.g., small intestine) and better absorbed.
Ionized forms are typically water-soluble and have difficulty crossing the lipid bilayer membranes due to their charge.
Drug concentration at the site of administration: higher concentration gradient generally leads to faster absorption via passive diffusion.
Drug formulation: excipients, coating, and physical form (e.g., liquid vs. tablet) significantly influence absorption rate and extent.
Additional notes: sex, exercise, age, and other physiological factors can influence absorption. For instance, age can affect gastric pH, motility, and blood flow; exercise can alter blood flow distribution.
MODES OF ABSORPTION
Passive Transport (no energy required)
Diffusion: movement from high to low concentration across membranes, driven by a concentration gradient.
Facilitated diffusion: requires specific carrier proteins to transport drugs across membranes but no direct energy expenditure, still follows a concentration gradient.
Active Transport: requires energy (ATP) to move drugs against a concentration gradient, often involving specific transport proteins.
Pinocytosis: cells engulf drug particles in vesicles for transport across the cell membrane, typically for large molecules.
BIOAVAILABILITY, DISTRIBUTION, METABOLISM, AND EXCRETION
BIOAVAILABILITY (F): percentage of administered drug that reaches systemic circulation in an unchanged form and is available for action. For IV drugs, F=100%.
DISTRIBUTION: movement from bloodstream to body compartments (interstitial and intracellular fluids, and various tissues).
Influenced by factors like cardiac output, regional blood flow (well-perfused organs receive drugs faster), membrane permeability (e.g., cell barriers), and plasma protein binding.
Plasma protein binding: Many drugs reversibly bind to plasma proteins (e.g., albumin, alpha-1 acid glycoprotein). Only the unbound or free drug is pharmacologically active, able to distribute into tissues, elicit its effect, and be eliminated.
Tissue binding: Some drugs accumulate in specific tissues (e.g., adipose tissue for highly lipid-soluble drugs, bone for tetracyclines), serving as a drug reservoir or leading to tissue-specific toxicity.
Special barriers: The Blood-Brain Barrier (BBB) and placental barrier selectively restrict drug passage, protecting the brain and fetus from many substances, typically allowing only highly lipid-soluble, small, non-ionized drugs to pass readily.
METABOLISM / BIOTRANSFORMATION: chemical modification of drugs to more excretable (usually more polar) forms.
Primary site: liver; involvement of Cytochrome P450 enzymes (CYPs) and other enzymes (e.g., esterases, glucuronosyltransferases).
Phase I reactions (Functionalization): Generally involve oxidation, reduction, and hydrolysis reactions. These reactions often introduce or expose a polar functional group (like -OH, -NH2, -SH), making the drug more water-soluble or setting it up for Phase II. They can result in active, inactive, or toxic metabolites.
Phase II reactions (Conjugation): Involve the covalent attachment of a polar, endogenous molecule (e.g., glucuronic acid, sulfate, glutathione, acetate) to the drug or its Phase I metabolite. This significantly increases water solubility and usually leads to inactive metabolites that are readily excreted.
First-pass effect (Presystemic metabolism): Extensive metabolism of an orally administered drug by the liver (and sometimes gut wall) before it reaches the systemic circulation, significantly reducing its bioavailability.
Metabolism commonly makes drugs more water-soluble and less active; however, some drugs are metabolized into more active metabolites (prodrugs) or toxic metabolites.
EXCRETION: removal of drugs and metabolites from the body via urine (kidneys are primary route), bile (frequent for large, polar molecules), sweat, breath, feces.
Other minor routes include tears, saliva, and breast milk (important consideration for nursing mothers).
HALF-LIFE AND ELIMINATION
HALF-LIFE (t_{1/2}): time required for the plasma concentration of a drug to decrease by 50% during the elimination phase.
Practical use: helps determine dosing frequency, duration of action, and time to reach/clear steady state; crucial for preventing accumulation or ensuring therapeutic levels.
PRACTICAL CALCULATIONS AND EXAMPLES
DRUG DOSAGE COMPUTATION
General formula: Volume to administer (mL) = Desired dose (mg) / Concentration (mg/mL)
Example 1: Digoxin IV ordered 0.75 mg; vial concentration = 0.5 mg/mL
Volume to administer = \frac{0.75}{0.5} = 1.5 \text{ mL}
Example 2: Suspension 125 mg/5 mL ordered 200 mg
Volume = \frac{200}{125} \times 5 = 8 \text{ mL}
Example 3: Amoxicillin 1.2 g total; capsules 400 mg each
Number of capsules = \frac{1200}{400} = 3 \text{ capsules}
Example 4: Acetaminophen 0.5 g; tablets 250 mg each
Number of tablets = \frac{500}{250} = 2 \text{ tablets}
RECONSTITUTION CALCULATION
Powder = 500 mg; to be reconstituted with 5 mL sterile water
Resulting concentration = \frac{500 \text{ mg}}{5 \text{ mL}} = 100 \text{ mg/mL}
INTRAVENOUS DRIP RATES
FLOW RATE (gtt/min) formula:
\text{Flow rate (gtt/min)} =\frac{\text{Volume (mL)} \times \text{Drop factor (gtt/mL)}}{\text{Time (min)}}
Example A: 500 mL over 4 hours with drop factor 20 gtt/mL
Time = 4 h = 240 min
Flow rate = \frac{500 \times 20}{240} \approx 41.7 \text{ gtt/min}
Flow rate (mL/hr) formula:
\text{Flow rate (mL/hr)} =\frac{\text{Volume (mL)}}{\text{Time (hr)}}
Example B: 200 mL over 2 hours
Flow = \frac{200}{2} = 100 \text{ mL/hr}
ADDITIONAL IV RATE PRACTICE
Example C: 100 mL IV over 30 minutes with drop factor 60 gtt/mL
Flow rate (gtt/min) = \frac{100 \times 60}{30} = 200 \text{ gtt/min}
Flow rate (mL/hr) = \frac{100}{0.5} = 200 \text{ mL/hr}
PHARMACODYNAMICS
DOSE-RESPONSE RELATIONSHIP: the body’s physiological response to changes in drug concentration at the site of action, typically visualized with a dose-response curve.
POTENCY: amount of drug needed to produce a given effect; a more potent drug requires a smaller dose for the same effect (shifted left on a dose-response curve).
EFFICACY: the ability of a drug to produce the desired pharmacological effect (maximum effect or E_{max}) irrespective of the dose. It reflects the intrinsic activity of the drug.
THERAPEUTIC INDEX (TI)
Definition: relationship between the therapeutic dose and toxic dose, indicating the safety margin of a drug.
Common representation: TI = \frac{TD_{50}}{ED_{50}} (where TD_{50} is the toxic dose for 50% of the population and ED_{50} is the effective dose for 50% of the population).
A higher TI indicates a wider safety margin, meaning a larger difference between effective and toxic doses; a lower TI indicates higher risk of toxicity at effective doses, requiring careful monitoring.
ONSET, PEAK, DURATION OF ACTION
ONSET: time to reach minimum effective concentration (MEC) in the plasma, initiating the therapeutic effect.
PEAK: time of maximum drug concentration in plasma, often correlating with maximum therapeutic effect.
DURATION OF ACTION: length of time the drug concentration remains above the MEC, maintaining its therapeutic effect.
THERAPEUTIC DRUG MONITORING
PURPOSE: to determine peak and trough (lowest) levels to optimize therapy, especially for drugs with a narrow therapeutic index.
PEAK DRUG LEVEL: highest plasma concentration at a specific time after administration; indicates rate of absorption and maximal exposure.
TROUGH (DRUG LEVEL): lowest plasma concentration, usually measured just before the next dose; indicates rate of elimination and helps prevent drug accumulation or sub-therapeutic levels.
APPLICATIONS: optimize dosing regimens, avoid toxicity, ensure efficacy, identify non-adherence, assess drug interactions.
RECEPTOR THEORY AND MECHANISM OF ACTION
BINDING: drug-receptor interaction determines pharmacological effect; receptors are typically proteins on cell surfaces or within cells.
Agonist: activates receptors to produce a response by mimicking an endogenous ligand.
Full agonist: produces a maximal response when all receptors are bound, with high intrinsic activity.
Partial agonist: produces a sub-maximal response even when fully saturating the receptors, having lower intrinsic activity than a full agonist.
Antagonist: blocks receptor activation by preventing agonists from binding or by interfering with their action.
Competitive antagonist: Binds reversibly to the same binding site as the agonist; can be overcome by increasing agonist concentration. This shifts the agonist dose-response curve to the right without reducing the maximal response.
Non-competitive antagonist: Binds irreversibly to the agonist binding site or to an allosteric site elsewhere on the receptor, altering the receptor's ability to respond to the agonist. Its effect cannot be fully overcome by increasing agonist concentration, generally reducing the maximal response (efficacy) of the agonist.
MECHANISM OF ACTION
What the drug does to the body and how it produces its effect at a molecular or cellular level.
Drugs can also exert their effects by interacting with molecular targets other than classical receptors, such as enzymes (e.g., enzyme inhibitors like ACE inhibitors), ion channels (e.g., channel blockers or openers like calcium channel blockers), or transport proteins (e.g., reuptake inhibitors like SSRIs).
RELATED DRUG EFFECTS & INTERACTIONS
DRUG RESPONSE CATEGORIES (Side effects / Adverse effects are secondary effects)
Primary effect: desirable therapeutic response (e.g., anti-allergic effect of cetirizine).
Secondary effects: additional effects, which may be desirable or undesirable (e.g., sedation in some antihistamines).
ALLERGIC REACTIONS/HYPERSENSITIVITY
Possible after repeated exposure; can range from mild rashes (Type I, II, III, IV hypersensitivity reactions) to severe, life-threatening responses.
Anaphylactic reaction: severe, potentially life-threatening systemic reaction characterized by rapid onset, airway compromise, hypotension, and requires urgent care (e.g., epinephrine).
TOXIC EFFECTS: unintended adverse effects that can be harmful or fatal, often dose-dependent or due to accumulation.
DRUG INTERACTIONS
Additive effects: combined effect equals sum of individual effects (1+1=2) when two drugs with similar pharmacological actions are given together.
Synergistic effects: combined effect greater than the sum of individual effects (1+1=3 or more) when two drugs enhance each other's effects.
Antagonistic effects: one drug blocks or reduces the effect of another, potentially reducing therapeutic benefit or reversing adverse effects.
Toxic interactions: combinations that raise risk of adverse outcomes, often due to altered metabolism (e.g., enzyme inhibition/induction) or increased toxicity to specific organs.
TOXICITY, TOLERANCE, AND DEPENDENCE
DRUG TOLERANCE: decreased response to a drug over time following repeated administration, requiring higher doses for the same effect. This can result from pharmacokinetic (e.g., enzyme induction) or pharmacodynamic (e.g., receptor downregulation) changes.
DRUG DEPENDENCE