Tetracyclines are a class of broad-spectrumBroad-SpectrumFluoroquinolones antibiotics indicated for a wide variety of bacterial infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease. These medications bindBINDHyperbilirubinemia of the Newborn the 30S ribosomal subunit to inhibit protein synthesisSynthesisPolymerase Chain Reaction (PCR) of bacteriaBacteriaBacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology. Tetracyclines cover gram-positiveGram-PositivePenicillins and gram-negative organisms, as well as atypical bacteriaBacteriaBacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology such as chlamydiaChlamydiaChlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae.Chlamydia, mycoplasmaMycoplasmaMycoplasma is a species of pleomorphic bacteria that lack a cell wall, which makes them difficult to target with conventional antibiotics and causes them to not gram stain well. Mycoplasma bacteria commonly target the respiratory and urogenital epithelium. Mycoplasma pneumoniae (M. pneumoniae), the causative agent of atypical or "walking" pneumonia.Mycoplasma, spirochetesSpirochetesAn order of slender, flexuous, helically coiled bacteria, with one or more complete turns in the helix.Treponema, and even protozoaProtozoaNitroimidazoles. The oral absorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption of tetracyclines is decreased with the ingestion of some medications and supplements (e.g., milk of magnesia) or food (e.g., dairy products) that contain polyvalent cationsCationsPositively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.Electrolytes, such as calciumCalciumA basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Electrolytes and magnesiumMagnesiumA metallic element that has the atomic symbol mg, atomic number 12, and atomic weight 24. 31. It is important for the activity of many enzymes, especially those involved in oxidative phosphorylation.Electrolytes. Adverse effects include photosensitivity, GI upset, and skinSkinThe skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.Skin: Structure and Functions pigmentation in the case of minocycline. Tetracyclines suppress boneBoneBone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types growth and discolor teethTeethNormally, an adult has 32 teeth: 16 maxillary and 16 mandibular. These teeth are divided into 4 quadrants with 8 teeth each. Each quadrant consists of 2 incisors (dentes incisivi), 1 canine (dens caninus), 2 premolars (dentes premolares), and 3 molars (dentes molares). Teeth are composed of enamel, dentin, and dental cement.Teeth: Anatomy in children and are contraindicated in pregnancyPregnancyThe status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth.Pregnancy: Diagnosis, Physiology, and Care and breastfeedingBreastfeedingBreastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding. Of importance, 3 new tetracyclines were approved by the FDA in 2018, which may have a role in treating certain infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease due to drug-resistant organisms.
Contain a linear, fused 4-ring nucleusNucleusWithin a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus.The Cell: Organelles
Have a variety of attached functional groups
Chemical structure of tetracycline
Image: “Skeletal formula of tetracycline” by Vaccinationist. License: Public Domain
Block the attachment of aminoacyl-tRNA to the mRNAmRNARNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.RNA Types and Structure–ribosome complex
Demeclocycline is an antidiuretic hormoneAntidiuretic hormoneAntidiuretic hormones released by the neurohypophysis of all vertebrates (structure varies with species) to regulate water balance and osmolarity. In general, vasopressin is a nonapeptide consisting of a six-amino-acid ring with a cysteine 1 to cysteine 6 disulfide bridge or an octapeptide containing a cystine. All mammals have arginine vasopressin except the pig with a lysine at position 8. Vasopressin, a vasoconstrictor, acts on the kidney collecting ducts to increase water reabsorption, increase blood volume and blood pressure.Hypernatremia (ADH) antagonist at the renal tubule as well.
Tetracycline site of action on 30S ribosomal subunit
AbsorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption:
AbsorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption is decreased within 1–2 hours after consumption of dairy products, antacids, and any other products containing ironIronA metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen.Trace Elements, magnesiumMagnesiumA metallic element that has the atomic symbol mg, atomic number 12, and atomic weight 24. 31. It is important for the activity of many enzymes, especially those involved in oxidative phosphorylation.Electrolytes, calciumCalciumA basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Electrolytes, or aluminum (e.g., supplements, vitamins), as these elements can bindBINDHyperbilirubinemia of the Newborn with tetracyclines and reduce their ability to be absorbed.
Minocycline is most lipophilic → achieves therapeutic CSF levels
Minocycline distribution ↑ in salivaSalivaThe clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin.Salivary Glands: Anatomy and tears
Doxycycline distribution ↑ in prostatic fluids
Metabolism: The majority of 1st-generation tetracyclines are not metabolized.
Excretion:
Primarily renal excretion
Doxycycline excreted via bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: Anatomy/feces
Indications
Table: Tetracyclines and their indications
Drug
Indications
Pearls
TetracyclineTetracyclineA naphthacene antibiotic that inhibits amino Acyl tRNA binding during protein synthesis.Drug-Induced Liver Injury (oral tablet)
Gram-negative infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease:
KlebsiellaKlebsiellaKlebsiella are encapsulated gram-negative, lactose-fermenting bacilli. They form pink colonies on MacConkey agar due to lactose fermentation. The main virulence factor is a polysaccharide capsule. Klebsiella pneumoniae is the most important pathogenic species.Klebsiella
Escherichia coliEscherichia coliThe gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli
BacteroidesBacteroidesBacteroides is a genus of opportunistic, anaerobic, gram-negative bacilli. Bacteroides fragilis is the most common species involved in human disease and is part of the normal flora of the large intestine.Bacteroides
ShigellaShigellaShigella is a genus of gram-negative, non-lactose-fermenting facultative intracellular bacilli. Infection spreads most commonly via person-to-person contact or through contaminated food and water. Humans are the only known reservoir.Shigella
Acne: Cutibacterium (PropionibacteriumPropionibacteriumA genus of gram-positive, rod-shaped bacteria whose cells occur singly, in pairs or short chains, in V or y configurations, or in clumps resembling letters of the chinese alphabet. Its organisms are found in cheese and dairy products as well as on human skin and can occasionally cause soft tissue infections.Dog and Cat Bites) acnes
Respiratory infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease:
Haemophilus influenzaeHaemophilus InfluenzaeA species of Haemophilus found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through viii.Haemophilus
StreptococcusStreptococcusStreptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci.Streptococcus pneumoniae
S. pyogenes
KlebsiellaKlebsiellaKlebsiella are encapsulated gram-negative, lactose-fermenting bacilli. They form pink colonies on MacConkey agar due to lactose fermentation. The main virulence factor is a polysaccharide capsule. Klebsiella pneumoniae is the most important pathogenic species.Klebsiella
Mycoplasma pneumoniaeMycoplasma pneumoniaeShort filamentous organism of the genus mycoplasma, which binds firmly to the cells of the respiratory epithelium. It is one of the etiologic agents of non-viral primary atypical pneumonia in man.Mycoplasma
SkinSkinThe skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.Skin: Structure and Functions and soft tissueSoft TissueSoft Tissue AbscessinfectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease (SSTIs)
Staphylococcus aureusStaphylococcus aureusPotentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.Brain Abscess
S. pyogenes
Urinary tractUrinary tractThe urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra.Urinary Tract: AnatomyinfectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease (UTIs)
KlebsiellaKlebsiellaKlebsiella are encapsulated gram-negative, lactose-fermenting bacilli. They form pink colonies on MacConkey agar due to lactose fermentation. The main virulence factor is a polysaccharide capsule. Klebsiella pneumoniae is the most important pathogenic species.Klebsiella
E. coli
STDs
Chlamydia trachomatisChlamydia trachomatisType species of Chlamydia causing a variety of ocular and urogenital diseases.Chlamydia
Lymphogranuloma venereumLymphogranuloma venereumSubacute inflammation of the inguinal lymph glands caused by certain immunotypes of Chlamydia trachomatis. It is a sexually transmitted disease in the U.S. But is more widespread in developing countries. It is distinguished from granuloma venereum, which is caused by calymmatobacterium granulomatis.Chlamydial Infections
ChancroidChancroidChancroid is a highly transmissible STD caused by Haemophilus ducreyi. The disease presents with painful ulcer(s) on the genital tract (termed chancroid or “soft chancre”). Up to 50% of patients will develop painful inguinal lymphadenopathy. Chancroid (Haemophilus ducreyiHaemophilus ducreyiA species of Haemophilus that appears to be the pathogen or causative agent of the sexually transmitted disease, chancroid.Haemophilus)
SyphilisSyphilisSyphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis (Treponema pallidumTreponema pallidumThe causative agent of venereal and non-venereal syphilis as well as yaws.Treponema)—when penicillinPenicillinRheumatic Fever contraindicated
Ophthalmic infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease: Chlamydia trachomatisChlamydia trachomatisType species of Chlamydia causing a variety of ocular and urogenital diseases.Chlamydia (conjunctivitisConjunctivitisConjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis)
YawsYawsA systemic non-venereal infection of the tropics caused by treponema pallidum subspecies pertenue.Yaws, Bejel, and Pinta: TreponemaTreponemaTreponema is a gram-negative, microaerophilic spirochete. Owing to its very thin structure, it is not easily seen on Gram stain, but can be visualized using dark-field microscopy. This spirochete contains endoflagella, which allow for a characteristic corkscrew movement.Treponema pertenue
AmebiasisAmebiasisAmebiasis, or amoebic dysentery, is an infection caused by the parasite Entamoeba histolytica. Transmission is through the fecal-oral route or by consumption of contaminated food and water. Most patients infected with E. histolytica are asymptomatic, but about 10% may develop dysentery. Entamoeba spp./Amebiasis: Entamoeba histolyticaEntamoeba HistolyticaA species of parasitic protozoa causing entamoebiasis and amebic dysentery (dysentery, amebic). Characteristics include a single nucleus containing a small central karyosome and peripheral chromatin that is finely and regularly beaded.Amebicides
AnthraxAnthraxAnthrax is an infection caused by the bacterium Bacillus anthracis, which usually targets the skin, lungs, or intestines. Anthrax is a zoonotic disease and is usually transmitted to humans from animals or through animal products. Symptoms depend on which organ system is affected. Anthrax
Bacillus anthracisBacillus anthracisA species of bacteria that causes anthrax in humans and animals.Anthrax
Vincent infection (acute necrotizing ulcerative gingivitisGingivitisInflammation of gum tissue (gingiva) without loss of connective tissue.Chédiak-Higashi Syndrome)
FusobacteriumFusobacteriumA genus of gram-negative, anaerobic, rod-shaped bacteria found in cavities of humans and other animals. No endospores are formed. Some species are pathogenic and occur in various purulent or gangrenous infections.Dog and Cat Bites fusiforme
ListeriaListeriaListeria spp. are motile, flagellated, gram-positive, facultative intracellular bacilli. The major pathogenic species is Listeria monocytogenes. Listeria are part of the normal gastrointestinal flora of domestic mammals and poultry and are transmitted to humans through the ingestion of contaminated food, especially unpasteurized dairy products. Listeria Monocytogenes/Listeriosis monocytogenes
CholeraCholeraAn acute diarrheal disease endemic in india and southeast Asia whose causative agent is Vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated.Vibrio: Vibrio choleraeVibrio choleraeThe etiologic agent of cholera.Vibrio
Relapsing feverFeverFever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever: Borrelia recurrentisBorrelia recurrentisBorrelia
Rickettsial infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease
Typhus group
Rocky Mountain spotted feverFeverFever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
Coxiella burnetiiCoxiella burnetiiA species of gram-negative bacteria that grows preferentially in the vacuoles of the host cell. It is the etiological agent of q fever.Coxiella/Q Fever(Q feverFeverFever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever)
Zoonotic infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease:
BartonellaBartonellaBartonella is a genus of gram-negative bacteria in the family Bartonellaceae. As a facultative intracellular parasite, Bartonella can infect healthy people as well as act as an opportunistic pathogen. Bartonella species are transmitted by vectors such as ticks, fleas, sandflies, and mosquitoes. B. henselae is the most common of the 3 species known to cause human disease.Bartonella
BrucellosisBrucellosisBrucellosis (also known as undulant fever, Mediterranean fever, or Malta fever) is a zoonotic infection that spreads predominantly through ingestion of unpasteurized dairy products or direct contact with infected animal products. Clinical manifestations include fever, arthralgias, malaise, lymphadenopathy, and hepatosplenomegaly. Brucella/Brucellosis (Mediterranean/undulant feverUndulant feverBrucellosis (also known as undulant fever, mediterranean fever, or malta fever) is a zoonotic infection that spreads predominantly through ingestion of unpasteurized dairy products or direct contact with infected animal products. Clinical manifestations include fever, arthralgias, malaise, lymphadenopathy, and hepatosplenomegaly.Brucella/Brucellosis): in conjunction with aminoglycoside
PlaguePlagueThe plague is a bacterial infection caused by Yersinia pestis (Y. pestis), which primarily infects rodents. The disease is transmitted to humans via a flea bite. Inhalation of infectious droplets and handling infected animals or laboratory specimens are other means of transmission. The plague has 3 forms: bubonic (most common form), septicemic, and pneumonic. Yersinia pestis/Plague: Yersinia pestisYersinia pestisThe plague is a bacterial infection caused by Yersinia pestis (Y. pestis), which primarily infects rodents. The disease is transmitted to humans via a flea bite. Inhalation of infectious droplets and handling infected animals or laboratory specimens are other means of transmission. The plague has 3 forms: bubonic (most common form), septicemic, and pneumonic. Yersinia pestis/Plague
PsittacosisPsittacosisInfection with chlamydophila psittaci (formerly Chlamydia psittaci), transmitted to humans by inhalation of dust-borne contaminated nasal secretions or excreta of infected birds. This infection results in a febrile illness characterized by pneumonitis and systemic manifestations.Chlamydia (parrot feverFeverFever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever): Chlamydia psittaciChlamydia psittaciA genus of chlamydophila infecting primarily birds. It contains eight known serovars, some of which infect more than one type of host, including humans.Chlamydia
Off-label use: part of multidrug treatment for Helicobacter pyloriHelicobacter pyloriA spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen.Helicobacter (peptic ulcerPeptic ulcerPeptic ulcer disease (PUD) refers to the full-thickness ulcerations of duodenal or gastric mucosa. The ulcerations form when exposure to acid and digestive enzymes overcomes mucosal defense mechanisms. The most common etiologies include Helicobacter pylori (H. pylori) infection and prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs). Peptic Ulcer Disease disease)
Doxycycline
Oral tablet
Oral capsuleCapsuleAn envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides.Bacteroides
Oral syrup/suspension
Injection solution (IV)
TetracyclineTetracyclineA naphthacene antibiotic that inhibits amino Acyl tRNA binding during protein synthesis.Drug-Induced Liver Injury indications, plus:
Lyme diseaseLyme diseaseLyme disease is a tick-borne infection caused by the gram-negative spirochete Borrelia burgdorferi. Lyme disease is transmitted by the black-legged Ixodes tick (known as a deer tick), which is only found in specific geographic regions. Patient presentation can vary depending on the stage of the disease and may include a characteristic erythema migrans rash. Lyme Disease (BorreliaBorreliaBorrelia are gram-negative microaerophilic spirochetes. Owing to their small size, they are not easily seen on Gram stain but can be visualized using dark-field microscopy, Giemsa, or Wright stain. Spirochetes are motile and move in a characteristic spinning fashion due to axial filaments in the periplasmic space. Borrelia spp.)
RosaceaRosaceaRosacea is a chronic inflammatory disease of the skin that is associated with capillary hyperreactivity. This condition is predominantly seen in middle-aged women, and is more common in fair-skinned patients.Rosacea (inflammatory lesions only)
Staphylococcus aureusStaphylococcus aureusPotentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.Brain AbscessskinSkinThe skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.Skin: Structure and FunctionsinfectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease, including MRSAMRSAA strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins.Staphylococcus
ProphylaxisProphylaxisCephalosporins of PlasmodiumPlasmodiumA genus of protozoa that comprise the malaria parasites of mammals. Four species infect humans (although occasional infections with primate malarias may occur). These are plasmodium falciparum; plasmodium malariae; plasmodium ovale, and plasmodium vivax. Species causing infection in vertebrates other than man include: plasmodium berghei; plasmodium chabaudi; p. Vinckei, and plasmodium yoelii in rodents; p. Brasilianum, plasmodium cynomolgi; and plasmodium knowlesi in monkeys; and plasmodium gallinaceum in chickens.Antimalarial Drugs falciparum (malariaMalariaMalaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis.Plasmodium/Malaria)
1st-line treatment for Lyme diseaseLyme diseaseLyme disease is a tick-borne infection caused by the gram-negative spirochete Borrelia burgdorferi. Lyme disease is transmitted by the black-legged Ixodes tick (known as a deer tick), which is only found in specific geographic regions. Patient presentation can vary depending on the stage of the disease and may include a characteristic erythema migrans rash. Lyme Disease unless contraindicated
Doxycycline activity > tetracyclineTetracyclineA naphthacene antibiotic that inhibits amino Acyl tRNA binding during protein synthesis.Drug-Induced Liver Injury
No dose adjustment in renal dysfunction
Minocycline
Oral tablet
Oral capsuleCapsuleAn envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides.Bacteroides
Injection solution (IV)
TetracyclineTetracyclineA naphthacene antibiotic that inhibits amino Acyl tRNA binding during protein synthesis.Drug-Induced Liver Injury indications, plus:
MeningitisMeningitisMeningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis: Neisseria meningitidisNeisseria meningitidisA species of gram-negative, aerobic bacteria. It is a commensal and pathogen only of humans, and can be carried asymptomatically in the nasopharynx. When found in cerebrospinal fluid it is the causative agent of cerebrospinal meningitis. It is also found in venereal discharges and blood. There are at least 13 serogroups based on antigenic differences in the capsular polysaccharides; the ones causing most meningitis infections being a, b, c, y, and w-135. Each serogroup can be further classified by serotype, serosubtype, and immunotype.Neisseria
Atypical mycobacteriaMycobacteriaMycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections.Mycobacterium
Used in the treatment of chronic SIADHSIADHSyndrome of inappropriate antidiuretic hormone secretion (SIADH) is a disorder of impaired water excretion due to the inability to suppress the secretion of antidiuretic hormone (ADH). SIADH is characterized by impaired water excretion leading to dilutional hyponatremia, which is mainly asymptomatic but may cause neurologic symptoms. SSyndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
Induces nephrogenic diabetesDiabetesDiabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance.Diabetes Mellitus insipidus
SSTIs, including MRSAMRSAA strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins.Staphylococcus
Intraabdominal infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease, including MRSAMRSAA strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins.Staphylococcus
Derivative of tetracyclines, actually a glycylcycline
Use when no alternatives and/or tetracyclineTetracyclineA naphthacene antibiotic that inhibits amino Acyl tRNA binding during protein synthesis.Drug-Induced Liver InjuryresistanceResistancePhysiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow.Ventilation: Mechanics of Breathing present
IV use only
No dose adjustment in renal dysfunction
Not for use in bloodstream infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease
Not susceptible to tetracycline-resistance mechanisms
Adverse Effects and Contraindications
Adverse effects
GI upset:
NauseaNauseaAn unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.Antiemetics and vomitingVomitingThe forcible expulsion of the contents of the stomach through the mouth.Hypokalemia most common side effects
Advise patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship to consume medication with water and sit upright for 30 minutes after ingestion to prevent esophagitisEsophagitisEsophagitis is the inflammation or irritation of the esophagus. The major types of esophagitis are medication-induced, infectious, eosinophilic, corrosive, and acid reflux. Patients typically present with odynophagia, dysphagia, and retrosternal chest pain. Esophagitis.
Photosensitivity of the skinSkinThe skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.Skin: Structure and Functions:
Chemical interaction between drug/metabolite in the skinSkinThe skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.Skin: Structure and Functions and UV raysUV raysThat portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-uv or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-uv or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.Bullous Pemphigoid and Pemphigus Vulgaris may cause a severe sunburn-like reaction.
Advise patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship to avoid direct sunlight and artificial UV raysUV raysThat portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-uv or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-uv or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.Bullous Pemphigoid and Pemphigus Vulgaris (i.e., tanning beds) and wear protective clothing and sunscreenSunscreenChemical or physical agents that protect the skin from sunburn and erythema by absorbing or blocking ultraviolet radiation.Melanoma.
↓ BoneBoneBone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types growth: children < 8 years old
Tooth yellowing and enamelEnamelA hard thin translucent layer of calcified substance which envelops and protects the dentin of the crown of the tooth. It is the hardest substance in the body and is almost entirely composed of calcium salts. Under the microscope, it is composed of thin rods (enamel prisms) held together by cementing substance, and surrounded by an enamel sheath.Teeth: AnatomyhypoplasiaHypoplasiaHypoplastic Left Heart Syndrome (HLHS): typically in children < 8 years old
ContraindicationsContraindicationsA condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks).Noninvasive Ventilation
PregnancyPregnancyThe status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth.Pregnancy: Diagnosis, Physiology, and Care (category D):
The exception is doxycycline for treatment of RickettsiaRickettsiaRickettsiae are a diverse collection of obligate intracellular, gram-negative bacteria that have a tropism for vascular endothelial cells. The vectors for transmission vary by species but include ticks, fleas, mites, and lice. Rickettsia spp.
Children < 8 years old except for doxycycline for treatment of RickettsiaRickettsiaRickettsiae are a diverse collection of obligate intracellular, gram-negative bacteria that have a tropism for vascular endothelial cells. The vectors for transmission vary by species but include ticks, fleas, mites, and lice. Rickettsia spp.
Renal failureRenal failureConditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate.Crush Syndrome except with doxycycline because of its GI eliminationEliminationThe initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy
Precautions
BreastfeedingBreastfeedingBreastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding:
Present in breast milk in small amounts
Avoid prolonged or repeated courses.
Short-term use acceptable
Previous theoretical concern for staining of infants; teethTeethNormally, an adult has 32 teeth: 16 maxillary and 16 mandibular. These teeth are divided into 4 quadrants with 8 teeth each. Each quadrant consists of 2 incisors (dentes incisivi), 1 canine (dens caninus), 2 premolars (dentes premolares), and 3 molars (dentes molares). Teeth are composed of enamel, dentin, and dental cement.Teeth: Anatomy and possible bone depositionBone depositionBones: Remodeling and Healing inhibiting growth, but recent researchResearchCritical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws.Conflict of Interest suggests these are unlikely
Preexisting liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease/failure: High doses may lead to liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: AnatomytoxicityToxicityDosage Calculation.
Drug–drug interactions:
Anticonvulsants: decrease tetracyclineTetracyclineA naphthacene antibiotic that inhibits amino Acyl tRNA binding during protein synthesis.Drug-Induced Liver Injury effectiveness and alter anticonvulsantAnticonvulsantAnticonvulsant drugs are pharmacological agents used to achieve seizure control and/or prevent seizure episodes. Anticonvulsants encompass various drugs with different mechanisms of action including ion-channel (Na+ and Ca+2) blocking and GABA reuptake inhibition. First-Generation Anticonvulsant Drugs drug levels
WarfarinWarfarinAn anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.Anticoagulants: ↑ INR
Oral contraceptives: decreased effectiveness
Black box warning for tigecycline: associated with ↑ mortalityMortalityAll deaths reported in a given population.Measures of Health Status
Mechanisms of Resistance
Development of plasma-mediated efflux pumpsEfflux PumpsLincosamides for active ejection, limiting ability of the drug to accumulate in cells
Ribosomal protection proteinsProteinsLinear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein.Energy Homeostasis prevent binding.
Enzymatic destruction
Comparison of Medications
Table: Comparison of Tetracyclines
Medication
PharmacokineticsPharmacokineticsPharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body.Pharmacokinetics and Pharmacodynamics
Excreted via kidneysKidneysThe kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine.Kidneys: Anatomy and bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: Anatomy
Respiratory infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease
SSTIs
Acne
Clostridial infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease
STIsSTIsSexually transmitted infections (STIs) or sexually transmitted diseases (STDs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease.Sexually Transmitted Infections (STIs)
AnthraxAnthraxAnthrax is an infection caused by the bacterium Bacillus anthracis, which usually targets the skin, lungs, or intestines. Anthrax is a zoonotic disease and is usually transmitted to humans from animals or through animal products. Symptoms depend on which organ system is affected. Anthrax
Zoonotic infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease
GI upset
Tooth staining
EsophagitisEsophagitisEsophagitis is the inflammation or irritation of the esophagus. The major types of esophagitis are medication-induced, infectious, eosinophilic, corrosive, and acid reflux. Patients typically present with odynophagia, dysphagia, and retrosternal chest pain. Esophagitis
Doxycycline
Absorbed orally
Excreted via bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: Anatomy/feces
Like tetracyclineTetracyclineA naphthacene antibiotic that inhibits amino Acyl tRNA binding during protein synthesis.Drug-Induced Liver Injury, plus:
SpirocheteSpirocheteTreponema is a gram-negative, microaerophilic spirochete. Owing to its very thin structure, it is not easily seen on Gram stain, but can be visualized using dark-field microscopy. This spirochete contains endoflagella, which allow for a characteristic corkscrew movement.TreponemainfectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease
EsophagitisEsophagitisEsophagitis is the inflammation or irritation of the esophagus. The major types of esophagitis are medication-induced, infectious, eosinophilic, corrosive, and acid reflux. Patients typically present with odynophagia, dysphagia, and retrosternal chest pain. Esophagitis
Minocycline
Absorbed orally
Excreted via kidneysKidneysThe kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine.Kidneys: Anatomy and bileBileAn emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum.Gallbladder and Biliary Tract: Anatomy
Like tetracyclineTetracyclineA naphthacene antibiotic that inhibits amino Acyl tRNA binding during protein synthesis.Drug-Induced Liver Injury, plus:
Neisseria meningitidisNeisseria meningitidisA species of gram-negative, aerobic bacteria. It is a commensal and pathogen only of humans, and can be carried asymptomatically in the nasopharynx. When found in cerebrospinal fluid it is the causative agent of cerebrospinal meningitis. It is also found in venereal discharges and blood. There are at least 13 serogroups based on antigenic differences in the capsular polysaccharides; the ones causing most meningitis infections being a, b, c, y, and w-135. Each serogroup can be further classified by serotype, serosubtype, and immunotype.Neisseria
Atypical mycobacteriaMycobacteriaMycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections.Mycobacterium
GI upset
Least photosensitizing
Tooth staining
Slate-gray pigmentation of skinSkinThe skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.Skin: Structure and Functions
World Health Organization. (2019). World Health Organization Model List of Essential Medicines, 21st list 2019. Geneva: World Health Organization. http://apps.who.int/iris/handle/10665/325771
Moullan N, Mouchiroud L, Wang X, et al. (2015). Tetracyclines disturb mitochondrial function across eukaryotic models: a call for caution in biomedical research. Cell Reports 10:1681–1691. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4565776/
Chatzispyrou IA, Held NM, Mouchiroud L, Auwerx J, Houtkooper RH. (2015). Tetracycline antibiotics impair mitochondrial function and its experimental use confounds research. Cancer Research :4446–4449. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631686/
Sapadin AN, Fleischmajer R. (2006). Tetracyclines: nonantibiotic properties and their clinical implications. J Am Acad Dermatol 54:258–265. https://pubmed.ncbi.nlm.nih.gov/16443056/
Valentín S, Morales A, Sánchez JL, Rivera A. (2009). Safety and efficacy of doxycycline in the treatment of rosacea. Clin Cosmet Investig Dermatol; 2:129-40. https://pubmed.ncbi.nlm.nih.gov/21436975/
