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Fundamentals of pharmacology

Last updated: January 18, 2021

Summary

The action of a drug depends on multiple factors. Pharmacokinetics is the study of a drug's movements in the body and can be described as what the body does to the drug, while pharmacodynamics is the study of a drug's action and effects on a body and can be described as what the drug does to the body. The administration of a drug in combination with other drugs or substances can cause a variety of interactions that can synergistically or antagonistically modify the effect of those drugs (e.g., via the activation or inhibition of cytochrome P450 enzymes by certain medications). Knowledge of interactions and pharmacokinetics help determine the ideal route of administration (topical, oral, IV). Drugs that are eliminated by the liver may attain high serum concentrations when hepatic function is impaired, which increases the risk of drug toxicity. The same principle applies to drugs that are eliminated via the kidneys.

Overview

  • Pharmacokinetics
    • LADME is an acronym for the important phases of pharmacokinetics:
      • Liberation
      • Absorption
      • Distribution
      • Metabolism
      • Excretion
  • Pharmacodynamics
    • Receptor types and their interaction with the drug
    • Dose-response relationship
  • Pharmacogenetics: : deals with the effect of genetic variations on drug metabolism and drug action.
  • Clinical trials: : phases of drug development, testing, and regulatory approval (occur after preclinical studies)
Overview of clinical trial phases [1][2]
Clinical trial phase Purpose Study population
Phase 0 trial
  • Exploratory phase with no therapeutic or diagnostic intent
  • Small number of healthy individuals (∼ 10–15)
Phase I trial
  • Small number of healthy individuals or patients with a specific disease (∼ 15–30)
Phase II trial
  • Evaluate efficacy, optimal dose range, and side effects
  • Moderate number of patients with a specific disease (∼ 10–100)
Phase III trial
  • Final confirmation of safety and evaluation of efficacy against placebo or the current standard of care
  • Randomized control trial with a large number of patients with a specific disease (∼ 100–1000)
Phase IV trial
  • Postmarketing surveillance: compares the real-life efficacy to that described in research studies
  • Safety studies following approval
  • Large number of patients with a specific disease after drug approval

Before clinical trials begin, drugs are first tested in preclinical studies. Preclinical studies do not include human subjects.

LADME is an acronym for the important phases of pharmacokinetics: Liberation, Absorption, Distribution, Metabolism, Excretion.

Pharmacokinetics

Pharmacokinetics deals with drug absorption, distribution, metabolism, and excretion.

Liberation

  • The process by which the drug is released from its pharmaceutical form (e.g., capsule, tablet, suppository, etc.)
  • The most common routes of drug administration are:
    • Injection (the drug is introduced directly into the bloodstream or into tissue)
    • Inhalation
    • Peroral administration
    • Dermal administration
    • Rectal administration
  • Less common routes
    • Buccal
    • Sublingual
    • Intra-articular administration

Absorption

The process by which the drug reaches the bloodstream. The following factors affect drug absorption:

  • Bioavailability
    • Describes the rate and concentration at which a drug reaches systemic circulation
    • Expressed as a percentage of the dose that was initially administered
    • Drugs administered intravenously have a bioavailability of 100%.
    • Can be calculated using the area under curve (AUC) of the plotted graph concentration versus time: (F) = (AUCoral/AUCIV) x 100
    • Bioavailability is affected by two mechanisms:
      • Ability to pass through lipid membranes: dependent on the nature of the substance (see the table below)
      • First pass effect
  • Bioequivalence: Two proprietary preparations of a drug are said to be bioequivalent if they exhibit the same bioavailability when administered in equal doses.
Abilities of chemical compounds
Chemical nature Clinical significance Example
Lipophilic
  • Predominantly nonpolar compounds
Hydrophilic
  • Predominantly polar compounds
Amphiphilic

Distribution (pharmacology)

After the drug reaches the bloodstream, it is initially distributed in the most vascularized organs.

  • Distribution coefficient: measure of hydrophobicity/hydrophilicity of a drug
    • Corganic/ Cwater
      • Corganic = drug concentration in an organic solvent
      • Cwater = drug concentration in water
  • Volume of distribution:
    • Vd = M/Cplasma
      • Vd = volume of distribution (usually expressed in liters/kg body weight)
      • M = amount of drug in the body at a specific time
      • Cplasma = plasma concentration of the drug at a specific time
    • The theoretical volume a drug would occupy if it was distributed evenly in fluids at plasma concentration.
    • Provides information about a drug tendency to distribute in other compartments (e.g., muscle or adipose tissue) rather than in the plasma.
    • Drugs can distribute in more than one compartment.
    • The Vd of plasma protein-bound drugs may be increased in patients with renal and liver disease due to loss of plasma proteins.
Volumes of distribution
Vd Low Medium High
Drugs
Compartment
  • Extracellular fluids
  • Binding to plasma proteins: Different drugs have different affinities to bind to plasma proteins (e.g., albumin).
    • Only the unbound fraction of the drug has a pharmacological effect.
    • Different drugs may compete to bind to plasma proteins
  • Redistribution: transfer of a drug between the different compartments within the human body
    • Lipophilic substances (e.g., inhalation anesthetics) are redistributed from plasma into fat tissue initially decreased action of the applied drug
    • Drug is stored but over time is released again from fat tissue into plasma → delayed elimination and prolonged action of the specific drug ).

Renal and liver disease can increase the apparent volume of distribution of drugs bound to plasma proteins.

Metabolism (biotransformation)

Biotransformation is the chemical alteration of substances (e.g., drugs) within the body by the action of enzymes and mainly takes place in the liver. Biotransformation detoxifies drugs and facilitates their elimination.

Types of drug kinetics

  • Zero order kinetics: The rate of metabolism and/or elimination remains constant and is independent of the plasma concentration of a drug at steady state (Cp decreases linearly over time)
    • Zero-order is a capacity-limited elimination.
    • Examples include ethanol, phenytoin, aspirin (at high concentrations)
  • First order kinetics: The rate of metabolism and/or elimination is directly proportional to the plasma concentration of the drug (Cp decreases exponentially over time)
    • First-order is a flow-dependent elimination.
    • Applies to most drugs

It takes zero PHEN-tAS-E (fantasy) to remember the drugs that are eliminated by zero-order kinetics: PHENytoin, ASpirin, Ethanol.

Phases of biotransformation

  • Phase I reaction: A drug is transformed into a polar, water-soluble metabolite by cytochrome P450 via one or more of the following reactions:
    • Oxidation (most common reaction)
    • Reduction
    • Hydrolysis
  • Phase II reaction: A drug is conjugated and thereby transformed into a very polar metabolite (can be excreted renally) via one or more of the following reactions:
  • Clinical significance
    • Detoxification: In most cases, the drug is inactivated and modified into a hydrophilic metabolite, allowing excretion of the drug via the kidneys or in bile.
    • Activation: Certain drugs are transformed in the liver from their inactive prodrug state into active forms (e.g., the ACE inhibitor enalapril is transformed through ester hydrolysis into the active form enalaprilat).
    • Formation of toxic metabolites (e.g., the breakdown of paracetamol gives rise to toxic metabolites that may cause severe liver damage in large doses).
    • In the elderly population, phase I reactions will usually become impaired before phase II reactions.
    • In individuals who are slow drug acetylators, the decreased rate of metabolism increases risk of side effects (e.g., isoniazid).

In the elderly population, phase I reactions will usually become impaired before phase II reactions.

Excretion

  • Drug clearance (CL): a measure of the rate of drug elimination.
    • It is defined as the plasma volume that can be completely cleared of the drug in a given period of time (e.g., creatinine clearance).
    • CL = Vd x Ke = rate of drug elimination/plasma drug concentration
    • CL can be impaired in patients with cardiac, hepatic, or renal dysfunction.
  • Half-life (t½):
    • The time required for the plasma concentration of a drug to reach half of its initial value
    • In first-order kinetics

Defects in renal, hepatic, or cardiac function can impair drug clearance.

After 4 half-lives, more than 90% of the drug will be eliminated.

Drugs and/or their metabolites are excreted from the body in one or more of the following ways:

Loading dose

  • Definition: the amount of an initial dose of a certain drug needed to reach a target plasma concentration
  • Formula: loading dose = (Cp x Vd) / F
  • In patients with renal and/or liver dysfunction, loading dose (which does not depend on drug clearance) and time to steady-state are usually unaffected..

Maintenance dose

  • Definition: The amount of a certain drug needed to achieve a steady target plasma concentration.
  • Formula: maintenance dose = (Cp x Cl * τ) / F
    • Cp = target plasma concentration at steady state (mg/L)
    • Cl = clearance (L/h)
    • τ = dosing interval (hours)
    • F = bioavailability
  • In patients with renal and/or liver dysfunction, maintenance dose is decreased (because of impaired drug clearance) and time to steady-state is unchanged (time to steady state depends on ).

Renal or liver conditions lower the maintenance dose without affecting the loading dose.

The main factor influencing the time to steady-state is t½, not dose or administration frequency.

Pharmacodynamics

Pharmacodynamics deals with the effect of a drug at its site of action, the dose-response relationship of the drug, and the influence of other factors on the drug effect.

Types of receptors

Every functioning molecule in an organism is a potential site of action for a drug. Means through which drugs act include:

Drug-receptor interactions

Basic principles

  • Drug affinity: a measure of the tendency of a drug to bind to its receptor
    • Most drug-receptor bonds are reversible
    • Covalent drug-receptor bonds, which are less common, are almost always irreversible (e.g., the binding of aspirin to cyclooxygenase enzyme).
  • Drug efficacy (correlates with Emax): the maximum degree to which a drug activates receptors after binding and triggers a cell response
    • On an efficacy graph, the difference in efficacy of the two drugs is determined by the difference in the maximal effect exerted by each of them (shown on the y-axis); drugs with different efficacy will have different heights, with the difference in efficacy represented on the y-axis.
    • Not related to potency (drugs with a high efficacy can have a low potency)
    • Partial agonists are less efficacious than full agonists.
  • Residence time: : the lifespan of a drug‑receptor complex

Antagonists have zero efficacy, agonists have maximum efficacy, and partial agonists (see below) have submaximal efficacy.

Types of drug-receptor interactions

  • Agonist: a drug that has a similar effect to that of the endogenous receptor activator (e.g., β2 agonists)
  • Partial agonist
  • Antagonist: a drug that binds to a receptor and prevents its activation.
    • Competitive antagonist
    • Non-competitive antagonist
      • The drug binds at a site other than the agonist-binding site, changes the structure of the agonist binding site, and decreases the affinity of the agonist.
      • As a result, the efficacy of the agonist is decreased and increasing the agonist concentration does not achieve the same efficacy.
    • Functional (physiological) antagonist; : In this type of antagonism, two different molecules working through separate receptors produce physiologically opposite effects.
  • Inverse agonist: Binds to the same receptor as an agonist, but not to the same active site. It elicits a response that is opposite to the agonistic response and has a negative efficacy.
  • Allosteric regulation
    • Allosteric modulator: Binds at a different site than the agonist and initiates conformational changes that induce modulation of ligand-binding.
    • Allosteric activator
      • Binds at a site other than the agonist-binding site (also called allosteric site) and changes the structure of the active binding site to increase affinity to the substrate
      • For more information on enzyme kinetic, see also “Enzymes and biocatalysis.”
Overview of drug-receptor interactions
Competitive antagonist Noncompetitive antagonist Partial agonist
Potency
  • Decreased
  • Unchanged
  • Independent
Efficacy
  • Unchanged
  • Decreased
  • Decreased
Drug example

Dose-response relationship

The following terms are used to describe dose-response relationships:

  • Potency (EC50): The potency of a drug is measured as the concentration required to produce a pharmacological response of a specified intensity.
    • Not related to efficacy (drugs with a high potency can have a low efficacy) but dependent on affinity
    • EC50 = the effective concentration required to produce 50% of the maximum possible response (Emax)
    • A left shift of the curve is a sign of decreased EC50 and increased potency, meaning a lower concentration of the drug is needed.
    • EC50 is not to be confused with ED50; ED50 is the median effective dose that produces a desired beneficial effect in 50% of the population.
      • ED50 = 5 mg implies that administration of 5 mg of the drug achieves a desired effect in 50% of the studied population
      • The same drug may have different ED50 values based on the indication (e.g., aspirin has different ED50 values for headache and for thromboembolism prophylaxis).
  • Therapeutic index (TI): a measurement of the safety of a drug
  • Therapeutic window: the range of doses that is effective for treating a condition with a minimum of adverse effects
  • Lethal dose (LD50): The dose that is lethal for 50% of the test population in animal experiments.

TILE: Therapeutic Index: = TD50/ED50

Drug tolerance and tachyphylaxis

The effect of a drug can decrease with repeated dosing:

Pharmacogenetics

Overview

  • Pharmacogenetics deals with genetic variation in the expression of enzymes that metabolize drugs.
  • These genetic differences can cause a drug response to deviate from the expected response and/or increase the risk of side effects:
    • If the enzyme in question is responsible for the breakdown of a drug, the following effects are possible:
      • A hyperactive variant of the enzyme decreases the drug response.
      • A hypoactive variant of the enzyme can cause cumulative drug effects and thus increase the risk of side effects.
    • The reverse is true if the enzyme is responsible for the activation of a drug.

Examples of clinically relevant variations

Drug interactions and the cytochrome P450 system

Drug interactions

  • Drug interactions can cause an increase or decrease in the potency of a drug or result in additional side effects.
  • The greater the number of coadministered drugs, the greater the chance of drug interaction

Types of interactions

  • Additive: the effect of two substances interacting with each other corresponds to the sum of their individual effects
  • Synergistic: the effect produced by the interaction of two substances is greater than the sum of their individual actions
  • Potentiation: the therapeutic effect of a substance is enhanced by another substance with no therapeutic action
  • Permissive: the effect of a substance can only be achieved in the presence of another substance
  • Antagonistic: the effect produced by the interaction of two substances is smaller than the sum of their individual actions

Beers criteria (Beers list)

Beers list is a list of over 50 drugs with potentially decreased effectiveness or increased risk of side effects or interactions in the elderly population.

Cytochrome-P450 system

Basic principles

  • Overview
    • Cytochrome P450 is a superfamily of heme-containing, primarily oxidative enzymes that take part in phase 1 reactions.
    • There are 200 cytochrome P450 enzymes, which are classified into 43 subfamilies and 18 families based on the similarity of amino acid sequences.
      • Of these 200, only 12 are involved in drug metabolism.
      • They belong to the first three families:
    • The highest concentration of CYP enzymes is found within the centrilobular hepatocytes.
  • Nomenclature: the prefix "CYP" (which stands for cytochrome P450)- PLUS family number PLUS a letter representing the subfamily PLUS isoenzyme number (e.g., CYP2D6 means isoenzyme no. 6 of subfamily "D" of the 2nd main family)
  • Induction and inhibition: CYP induction increases the rate of metabolism of the substrate, while CYP inhibition decreases it.
    • The effects of drugs that are activated by CYP enzymes (e.g., prodrugs) are increased by enzyme induction and decreased by enzyme inhibition.
    • The effects of drugs that are broken down by CYP enzymes are decreased by enzyme induction and increased by enzyme inhibition.
  • Ultrarapid metabolizers
    • Activity of CYP2D6 is increased in individuals with a duplication on chromosome 22.
    • These individuals require a significantly higher dose to achieve the desired effect.
  • Role in carcinogenesis: metabolic activation of certain pro-carcinogens (e.g., aflatoxin, sterigmatocystin) → induction of cancer (e.g., hepatocellular carcinoma) [4][5][6]

Carbamazepine acts as both substrate and inducer of CYP3A4.

Rifampicin and carbamazepine are some of the strongest inducers of cytochrome P450 enzymes and can thus interact with many drugs.

Ctochrome P450 substrates, inhibitors, and inducers [7][8]
CYP Substrate
CYP 450 inhibitors CYP 450 inducers
CYP1A2
  • Smoking [9]
CYP2C CYP2C19
CYP2C9
CYP2D6
CYP2E1
  • Ethanol

CYP3A4

P450 inducers: warfarin levels (Chronic Alcoholics Steal Phen-Phen and Never Refuse Greasy Carbs): C - Chronic alcohol use, S - St. John's wort, P - Phenytoin, P - Phenobarbital, N - Nevirapine, R - Rifampin, G - Griseofulvin, C - Carbamazepine

P450 inhibitors can be remembered with “sickfaces.com group”: S - Sulfonamides, I - Isoniazid, C - Cimetidine, K - Ketoconazole, F - Fluconazole, A - Alcohol (binge drinking), C - Ciprofloxacin, E - Erythromycin, S - Sodium valproate, C - Chloramphenicol, O - Omeprazole, M - Metronidazole, G - Grapefruit juice

The P450 substrates beta-BLOCKers, THEophylline, WARfarin, STATins, ORAL contraceptives, and antiPSYCHOtics: Let's BLOCK THE WAR between STATes with ORAL and PSYCHOlogical tools.

Adverse effects

Adverse effects of substances can be classified into the following groups:

We list the most important adverse effects. The selection is not exhaustive.

Cardiovascular adverse effects

Dilated cardiomyopathy caused by Doxorubicin and Danurobicin can be prevented with Dexrazoxane.

ABCDE to recall the 5 class of drugs potentially causing torsades de pointes: antiArrhythmic, antiBiotics, antiCychotics, antiDepressants and antiEmetics.

Endocrine adverse effects

Overview of substances causing endocrine adverse effects
Endocrine adverse effects Substance Main clinical use

Adrenocortical insufficiency

  • Corticosteroids (especially when discontinued suddenly after chronic intake)
  • Acute inflammatory reactions
  • Chronic inflammatory diseases
  • Autoimmune diseases
Diabetes insipidus
Hot flashes
Hyperglycemia
  • HIV infection
  • Lipid-lowering agent
  • Acute inflammatory reactions
  • Chronic inflammatory diseases
  • Autoimmune diseases
Hyperprolactinemia
Hyperthyroidism
Hypothyroidism
  • Infections
  • Chronic inflammatory diseases
  • Diuretics
SIADH
  • Major depressive disorde

Hydrochlorotiazide, Niacin, Tacrolimus and corticoSteroids can lead to High amouNT of Sugars in your blood.

SUlfonamides, Lithium and AMiodarone may induce SUdden Lethargy And Myxedema (hypothyroidism).

If patients taking Carbamazepine, Cyclophosphamide or SSRI get SIADH, they Can't Concentrate Serum Sodium!

Gastrointestinal adverse effects

Overview of substances causing gastrointestinal adverse effects
Gastrointestinal adverse effects Substance Main clinical use
Acute cholestatic hepatitis with jaundice
  • Infections
Diarrhea
  • Lipid-lowering agent
  • Infections

Hepatic necrosis

  • Toxin
Hepatitis
  • Antimycobacterial therapy
  • Lipid-lowering agent
Pancreatitis
  • Alcohol
  • Recreational use

Pill-induced esophagitis

  • Oral iron supplementation (e.g., ferrous sulfate)
  • Potassium supplementation
  • Infections
Pseudomembranous colitis
  • Infections

Diuretics, Alcohol, Corticosteroids, Valproic acid, Azathioprine and Didanosine are Drugs that Abrupty Cause Violent Abdominal Distress.

Hematologic adverse effects

Overview of substances causing hematologic adverse effects
Hematologic adverse effects Substance Main clinical use
Agranulocytosis
  • Herpetic infections
  • Cancer treatment
Aplastic anemia
  • Infections

Autoimmune hemolytic anemia (positive direct Coombs test)

  • Infections

Drug reaction with eosinophilia and systemic symptoms (DRESS)

  • Infections
  • Chronic inflammatory diseases
  • Diuretics
  • Infections

Gray baby syndrome

  • Infections

Hemolysis in G6PD deficiency

  • Infections
  • Chronic inflammatory diseases
  • Diuretics
  • Infections (esp. lower UTI)
Megaloblastic anemia
  • Cancer treatment
  • Cancer treatment
  • Chronic inflammatory diseases
  • Infections
  • Chronic inflammatory diseases
  • Diuretics

Thrombocytopenia

  • Anticoagulation
  • Antiplatelet aggregation
  • Antiretroviral treatment (HIV)
  • Herpetic infections

Thrombotic complications (this side effect is mediated by increased estrogen level)

Clozapine, Propylthiouracile, Methimazole, Carbamazepine, Ticlopidine, Dapsone, Colchicine, Chemotherapeutics and Gangiclovir Causes Pretty Major Collapse To Defense Cells Called Granulocytes (agranulocytosis).

Carbamazepine, Methimazole, NSAIDs, Benzene, Chloramphenicol, Propylthiouracile Can't Make New Blood Cells Properly (aplastic anemia).

MetHyldopa, Penicilline, and Cephalosporins may induce HeMolytic anemia (Positive Coombs test).

YoU'RE Having a MEGA BLAST with Plays, Music, and Snacks! (HydroxyUREa, Phenytoin, Methotrexate and Sulfonamides may induce MEGAloBLASTic anemia)

Musculoskeletal/skin/connective tissue adverse effects

Overview of substances causing musculoskeletal/skin/connective tissue adverse effects
Musculoskeletal/skin/connective tissue adverse effects Substance Main clinical use

Drug–induced lupus

  • Infections
  • Infections
  • Chronic inflammatory diseases
  • Diuretics
  • Chronic inflammatory diseases

Fat redistribution

  • Acute inflammatory reactions
  • Chronic inflammatory diseases
  • Autoimmune diseases
  • Antiretroviral treatment (e.g., HIV)

Gingival hyperplasia

Hyperuricemia (gout)

  • Antimycobacterial treatment
  • Lipid-lowering agent

Myopathy

  • Lipid-lowering agent
  • Infections
  • Acute inflammatory reactions
  • Chronic inflammatory diseases
  • Autoimmune diseases
Osteoporosis
  • Acute inflammatory reactions
  • Chronic inflammatory diseases
  • Autoimmune diseases
  • Anticoagulation

Photosensitivity

  • Infections
  • Chronic inflammatory diseases
  • Diuretics
  • Infections
  • Cancer treatment

Stevens-Johnson syndrome (rash)

  • Infections
  • Chronic inflammatory diseases
  • Diuretics
  • Infections

Teeth discoloration

  • Infections

Tendon/cartilage damage

  • Infections

Methyldopa, Phenytoin, Hydralazine, Isoniazid, Procainamide, Sulfonamides, Minocycline and Etanercept may provoke Malar rash, Painful HIPS, & Myalgia (Systemic Lupus Erythematous).

Protease Inhibitors and Corticosteroids PICk your FAT somewhere else!

Cyclosporine, CA2+ channel blockers, and Phenytoin can Cause Chubby Puffy Gums!

Pyrazinamide, Furosemide, Niacin, Cyclosporine and Thiazides may induce Pain on your Feet, Needle-shaped Crystals, and Tophi (gout).

With 5-FLuorouracil, Amiodarone, Sulfonamides & Tetracyclines you may geT sunburn in a FLASh (photosensitivity)!

AntiEpiLEpTIC drugs, Penicillin, ALlopurinol and SULFonamides may provoke STEVE JOHNSON (syndrome), an EcLEcTIC PAL who loves SUrF!

TETracyclines may discolor your TEeTh!

Neurologic adverse effects

Overview of substances causing neurologic adverse effects
Neurologic adverse effects Substance Main clinical use

Cinchonism

Parkinson-like syndrome and/or tardive dyskinesia

  • Emesis
Peripheral neuropathy
  • Antimycobacterial therapy
  • Cancer treatment
Idiopathic intracranial hypertension
  • Supplement in case of deficiency
  • Infections
Seizures
  • Antimycobacterial therapy
  • Infections

Visual disturbance

  • Antimycobacterial therapy

Antipsychotics, Reserpine, and Metoclopramide may make your ARMs rigid as in Parkinson's disease.

Isoniazide, Bupropion, Imipenem/cilastatin, Tramadol and Enflurane lower seizures threshold (I BITE my tongue).

Topiramate, Digoxin, Isoniazid, Ethambutol, Vigabatrin and PDE-5 inhibitors: These Drugs Induce Problems to Vision and Eyes!

Multiorgan adverse effects

Overview of substances causing multiorgan adverse effects
Multiorgan adverse effects Substance Main clinical use
Antimuscarinic

Disulfiram-like reaction

  • Infections
  • Cancer treatment

Nephrotoxicity and/or ototoxicity

  • Cancer treatment
  • Infections

To remember that Sulfonylureas, Cephalosporines, Metronidazole, Griseofulvin and Procarbazine can cause disulfiram-like reaction: Sorry, Can't Mess with Gin and Port wine.

If you use Loop diuretics, Amphotericin B, cisPlatin, Vancomycin, or Aminoglycosides Listening And Peeing Vanish Away.

Respiratory adverse effects

Overview of substances causing respiratory adverse effects
Respiratory adverse effects Substance Main clinical use
Dry cough
Pulmonary fibrosis
  • Cancer treatment
  • Chronic inflammatory diseases
  • Infections (esp. lower UTI)
  • Cancer treatment

CArmustine, NiTrofurantoin, Busulfan, Amiodarone, Bleomycin, Methotrexate: I CAN'T Breathe Air Because of these Medications.

Renal and genitourinary adverse effects

Overview of substances causing renal and genitourinary adverse effects
Renal and genitourinary adverse effects Substance Main clinical use
Fanconi syndrome
  • Cancer treatment
  • Infections
Hemorrhagic cystitis
  • Cancer treatment
Interstitial nephritis
  • Infections
  • Antimycobacterial therapy
  • Infections
  • Chronic inflammatory diseases
  • Diuretics

Diuretics, Penicillins, Sulfonamides, PPIs, NSAIDs and Rifampin may cause blooDy Pee, Sterile Pyuria, 'N' Rash (interstitial nephritis).

References

  1. Yang X, Gandhi YA, Duignan DB, Marilyn E. Prediction of biliary excretion in rats and humans using molecular weight and quantitative structure–pharmacokinetic relationships. AAPS J. 2009; 11 (3): p.511. doi: 10.1208/s12248-009-9124-1 . | Open in Read by QxMD
  2. Yamazaki H, Inui Y, Wrighton SA, Guengerich FP, Shimada T. Procarcinogen activation by cytochrome P450 3A4 and 3A5 expressed in Escherichia coli and by human liver microsomes. Carcinogenesis. 1995; 16 (9): p.2167-70.
  3. Bui VN, Nguyen TT, Mai CT, et al. Procarcinogens - Determination and evaluation by yeast-based biosensor transformed with plasmids incorporating RAD54 reporter construct and cytochrome P450 genes. PLoS ONE. 2016; 11 (12): p.e0168721. doi: 10.1371/journal.pone.0168721 . | Open in Read by QxMD
  4. Smela ME, Currier SS, Bailey EA, Essigmann JM. The chemistry and biology of aflatoxin B(1): from mutational spectrometry to carcinogenesis. Carcinogenesis. 2001; 22 (4): p.535-45.
  5. Davydov DR. Microsomal monooxygenase as a multienzyme system: the role of P450-P450 interactions. Expert Opin Drug Metab Toxicol. 2011; 7 (5): p.543-58. doi: 10.1517/17425255.2011.562194 . | Open in Read by QxMD
  6. Mozayani A, Raymon L. Handbook of Drug Interactions. Springer Science & Business Media ; 2011
  7. Hukkanen J, Jacob P 3rd, Peng M, Dempsey D, Benowitz NL. Effect of nicotine on cytochrome P450 1A2 activity. Br J Clin Pharmacol. 2011; 72 (5): p.836-8. doi: 10.1111/j.1365-2125.2011.04023.x . | Open in Read by QxMD
  8. Phases of Clinical Trials. https://www.nccn.org/patients/resources/clinical_trials/phases.aspx. Updated: January 1, 2019. Accessed: January 20, 2019.
  9. ClinicalTrials.gov Protocol Registration Data Element Definitions for Interventional and Observational Studies. https://prsinfo.clinicaltrials.gov/definitions.html#StudyPhase. Updated: March 7, 2019. Accessed: July 15, 2020.