<IP_ADDRESS>: Contemplations
Sometime now past in the Autumnal Tide,
When Phoebus wanted but one hour to bed,
The trees all richly clad, yet void of pride,
Were gilded o're by his rich golden head.
Their leaves and fruits seem'd painted but was true
Of green, of red, of yellow, mixed hew,
Rapt were my senses at this delectable view.
2I wist not what to wish, yet sure thought I,
If so much excellence abide below,
How excellent is he that dwells on high?
Whose power and beauty by his works we know.
Sure he is goodness, wisdom, glory, light,
That hath this under world so richly dight.
More Heaven than Earth was here, no winter and no night.
3Then on a stately Oak I cast mine Eye,
Whose ruffling top the Clouds seem'd to aspire;
How long since thou wast in thine Infancy?
Thy strength and stature, more thy years admire,
Hath hundred winters past since thou wast born?
Or thousand since thou brakest thy shell of horn,
If so, all these as nought, Eternity doth scorn.
4Then higher on the glistering Sun I gaz'd,
Whose beams was shaded by the leafy Tree.
The more I look'd, the more I grew amaz'd
And softly said, what glory's like to thee?
Soul of this world, this Universe's Eye,
No wonder some made thee a Deity:
Had I not better known (alas) the same had I.
5Thou as a Bridegroom from thy Chamber rushes
And as a strong man joys to run a race.
The morn doth usher thee with smiles and blushes.
The Earth reflects her glances in thy face.
Birds, insects, Animals with Vegative,
Thy heat from death and dullness doth revive:
And in the darksome womb of fruitful nature dive.
6Thy swift Annual and diurnal Course,
Thy daily straight and yearly oblique path,
Thy pleasing fervour, and thy scorching force,
All mortals here the feeling knowledge hath.

And is thy splendid Throne erect so high?
As, to approach it, can no earthly mould.
How full of glory then must thy Creator be?
Who gave this bright light luster unto thee:
Admir'd, ador'd for ever be that Majesty.
8Silent alone where none or saw, or heard,
In pathless paths I lead my wand'ring feet.
My humble Eyes to lofty Skies I rear'd
To sing some Song my mazed Muse thought meet.
My great Creator I would magnifie,
That nature had thus decked liberally:
But Ah and Ah again, my imbecility!
9I heard the merry grasshopper then sing,
The black clad Cricket bear a second part.
They kept one tune and played on the same string,
Seeming to glory in their little Art.
Shall creatures abject thus their voices raise?
And in their kind resound their maker's praise:
Whilst I, as mute, can warble forth no higher layes.
10When present times look back to Ages past
And men in being fancy those are dead,
It makes things gone perpetually to last
And calls back months and years that long since fled
It makes a man more aged in conceit,
Than was Methuselah or's grand-sire great:
While of their persons and their acts his mind doth treat.
11Sometimes in Eden fair he seems to be,
See glorious Adam there made Lord of all,
Fancies the Apple, dangle on the Tree,
That turn'd his Sovereign to a naked thrall,
Who like a miscreant's driven from that place
To get his bread with pain and sweat of face:
A penalty impos'd on his backsliding Race.
12Here sits our Grandame in retired place,
And in her lap her bloody Cain new born,
The weeping Imp oft looks her in the face,
Bewails his unknown hap and fate forlorn;
His Mother sighs to think of Paradise,
And how she lost her bliss, to be more wise,
Believing him that was, and is, Father of lyes.
13Here Cain and Abel come to sacrifice,
Fruits of the Earth and Fatlings each do bring,
On Abels gift the fire descends from Skies,
But no such sign on false Cain's offering;
With sullen hateful looks he goes his wayes.
Hath thousand thoughts to end his brothers dayes,
Upon whose blood his future good he hopes to raise.
14There Abel keeps his sheep, no ill he thinks,
His brother comes, then acts his fratricide.
The Virgin Earth of blood her first draught drinks,
But since that time she often hath been cloy'd;
The wretch with ghastly face and dreadful mind,
Thinks each he sees will serve him in his kind,
Though none on Earth but kindred near then could he find.
15Who fancies not his looks now at the Barr,
His face like death, his heart with horror fraught,
Nor Male-factor ever felt like warr,
When deep despair with wish of life hath fought,
Branded with guilt, and crusht with treble woes,
A Vagabond to Land of Nod he goes.
A City builds, that wals might him secure from foes.
16Who thinks not oft upon the Fathers ages.
Their long descent, how nephews sons they saw,
The starry observations of those Sages,
And how their precepts to their sons were law,
How Adam sigh'd to see his Progeny,
Cloath'd all in his black, sinful Livery,
Who neither guilt not yet the punishment could fly.
17Our Life compare we with their length of dayes
Who to the tenth of theirs doth now arrive?
And though thus short, we shorten many wayes,
Living so little while we are alive;
In eating, drinking, sleeping, vain delight
So unawares comes on perpetual night,
And puts all pleasures vain unto eternal flight.
18When I behold the heavens as in their prime,
And then the earth (though old) still clad in green,
The stones and trees, insensible of time,
Nor age nor wrinkle on their front are seen;
If winter come, and greenness then do fade,
A Spring returns, and they more youthfull made;
But Man grows old, lies down, remains where once he's laid.
19By birth more noble than those creatures all,
Yet seems by nature and by custom curs'd,
No sooner born, but grief and care makes fall
That state obliterate he had at first:
Nor youth, nor strength, nor wisdom spring again
Nor habitations long their names retain,
But in oblivion to the final day remain.
20Shall I then praise the heavens, the trees, the earth
Because their beauty and their strength last longer
Shall I wish there, or never to had birth,
Because they're bigger and their bodyes stronger?
Nay, they shall darken, perish, fade and dye,
And when unmade, so ever shall they lye,
But man was made for endless immortality.
21Under the cooling shadow of a stately Elm
Close sate I by a goodly Rivers side,
Where gliding streams the Rocks did overwhelm;
A lonely place, with pleasures dignifi'd.
I once that lov'd the shady woods so well,
Now thought the rivers did the trees excel,
And if the sun would ever shine, there would I dwell.
22While on the stealing stream I fixt mine eye,
Which to the long'd-for Ocean held its course,
I markt, nor crooks, nor rubs that there did lye
Could hinder ought but still augment its force:
O happy Flood, quoth I, that holds thy race
Till thou arrive at thy beloved place,
Nor is it rocks or shoals that can obstruct thy pace.
23Nor is't enough that thou alone may'st slide,
But hundred brooks in thy cleer waves do meet,
So hand in hand along with thee they glide
To Thetis house, where all imbrace and greet:
Thou Emblem true of what I count the best,
O could I lead my Rivolets to rest,
So may we press to that vast mansion, ever blest.
24Ye Fish which in this liquid Region 'bide
That for each season have your habitation,
Now salt, now fresh where you think best to glide
To unknown coasts to give a visitation,
In Lakes and ponds, you leave your numerous fry,
So Nature taught, and yet you know not why,
You watry folk that know not your felicity.
25Look how the wantons frisk to tast the air,
Then to the colder bottome streight they dive,
Eftsoon to Neptun's glassy Hall repair
To see what trade they, great ones, there do drive,
Who forrage o're the spacious sea-green field,
And take the trembling prey before it yield,
Whose armour is their scales, their spreading fins their shield.
26While musing thus with contemplation fed,
And thousand fancies buzzing in my brain,
The sweet-tongu'd Philomel percht ore my head,
And chanted forth a most melodious strain
Which rapt me so with wonder and delight,
I judg'd my hearing better than my sight,
And wisht me wings with her a while to take my flight.
27O merry Bird (said I) that fears no snares,
That neither toyles nor hoards up in thy barn,
Feels no sad thoughts, nor cruciating cares
To gain more good, or shun what might thee harm
Thy clothes ne're wear, thy meat is every where,
Thy bed a bough, thy drink the water cleer,
Reminds not what is past, nor whats to come dost fear.
28The dawning morn with songs thou dost prevent,
Sets hundred notes unto thy feathered crew,
So each one tunes his pretty instrument,
And warbling out the old, begin anew,
And thus they pass their youth in summer season,
Then follow thee into a better Region,
Where winter's never felt by that sweet airy legion.
29Man at the best a creature frail and vain,
In knowledge ignorant, in strength but weak,
Subject to sorrows, losses, sickness, pain,
Each storm his state, his mind, his body break,
From some of these he never finds cessation,
But day or night, within, without, vexation,
Troubles from foes, from friends, from dearest, near'st Relation.
30And yet this sinfull creature, frail and vain,
This lump of wretchedness, of sin and sorrow,
This weather-beaten vessel wrackt with pain,
Joys not in hope of an eternal morrow;
Nor all his losses, crosses and vexation,
In weight, in frequency and long duration
Can make him deeply groan for that divine Translation.
31The Mariner that on smooth waves doth glide,
Sings merrily and steers his Barque with ease,
As if he had command of wind and tide,
And now becomes great Master of the seas;
But suddenly a storm spoils all the sport,
And makes him long for a more quiet port,
Which 'gainst all adverse winds may serve for fort.
32So he that faileth in this world of pleasure,
Feeding on sweets, that never bit of th' sowre,
That's full of friends, of honour and of treasure,
Fond fool, he takes this earth ev'n for heav'ns bower,
But sad affliction comes and makes him see
Here's neither honour, wealth, nor safety;
Only above is found all with security.
33O Time the fatal wrack of mortal things,
That draws oblivions curtains over kings,
Their sumptuous monuments, men know them not,
Their names without a Record are forgot,
Their parts, their ports, their pomp's all laid in th' dust.
Nor wit, nor gold, nor buildings scape times rust;
But he whose name is grav'd in the white stone
Shall last and shine when all of these are gone.


14.4: Clinical Considerations
- Explain the differences between modes of action of drugs that target fungi, protozoa, helminths, and viruses
Because fungi, protozoa, and helminths are eukaryotic, their cells are very similar to human cells, making it more difficult to develop drugs with selective toxicity. Additionally, viruses replicate within human host cells, making it difficult to develop drugs that are selectively toxic to viruses or virus-infected cells. Despite these challenges, there are antimicrobial drugs that target fungi, protozoa, helminths, and viruses, and some even target more than one type of microbe. Table \(\PageIndex{1}\), Table \(\PageIndex{2}\), Table \(\PageIndex{3}\), and Table \(\PageIndex{4}\) provide examples for antimicrobial drugs in these various classes.
Antifungal Drugs
The most common mode of action for antifungal drugs is the disruption of the cell membrane. Antifungals take advantage of small differences between fungi and humans in the biochemical pathways that synthesize sterols. The sterols are important in maintaining proper membrane fluidity and, hence, proper function of the cell membrane. For most fungi, the predominant membrane sterol is ergosterol. Because human cell membranes use cholesterol, instead of ergosterol, antifungal drugs that target ergosterol synthesis are selectively toxic (Figure \(\PageIndex{1}\)).
The imidazoles are synthetic fungicides that disrupt ergosterol biosynthesis; they are commonly used in medical applications and also in agriculture to keep seeds and harvested crops from molding. Examples include miconazole, ketoconazole, and clotrimazole, which are used to treat fungal skin infections such as ringworm, specifically tinea pedis (athlete’s foot), tinea cruris (jock itch), and tinea corporis. These infections are commonly caused by dermatophytes of the genera Trichophyton , Epidermophyton , and Microsporum . Miconazole is also used predominantly for the treatment of vaginal yeast infections caused by the fungus Candida , and ketoconazole is used for the treatment of tinea versicolor and dandruff, which both can be caused by the fungus Malassezia .
The triazole drugs, including fluconazole, also inhibit ergosterol biosynthesis. However, they can be administered orally or intravenously for the treatment of several types of systemic yeast infections, including oral thrush and cryptococcal meningitis, both of which are prevalent in patients with AIDS. The triazoles also exhibit more selective toxicity, compared with the imidazoles, and are associated with fewer side effects.
The allylamines, a structurally different class of synthetic antifungal drugs, inhibit an earlier step in ergosterol biosynthesis. The most commonly used allylamine is terbinafine (marketed under the brand name Lamisil), which is used topically for the treatment of dermatophytic skin infections like athlete’s foot, ringworm, and jock itch. Oral treatment with terbinafine is also used for the treatment of fingernail and toenail fungus, but it can be associated with the rare side effect of hepatotoxicity.
The polyenes are a class of antifungal agents naturally produced by certain actinomycete soil bacteria and are structurally related to macrolides. These large, lipophilic molecules bind to ergosterol in fungal cytoplasmic membranes, thus creating pores. Common examples include nystatin and amphotericin B. Nystatin is typically used as a topical treatment for yeast infections of the skin, mouth, and vagina, but may also be used for intestinal fungal infections. The drug amphotericin B is used for systemic fungal infections like aspergillosis, cryptococcal meningitis, histoplasmosis, blastomycosis, and candidiasis. Amphotericin B was the only antifungal drug available for several decades, but its use is associated with some serious side effects, including nephrotoxicity (kidney toxicity).
Amphotericin B is often used in combination with flucytosine, a fluorinated pyrimidine analog that is converted by a fungal-specific enzyme into a toxic product that interferes with both DNA replication and protein synthesis in fungi. Flucytosine is also associated with hepatotoxicity (liver toxicity) and bone marrow depression.
Beyond targeting ergosterol in fungal cell membranes, there are a few antifungal drugs that target other fungal structures (Figure \(\PageIndex{2}\)). The echinocandins, including caspofungin, are a group of naturally produced antifungal compounds that block the synthesis of β(1→3) glucan found in fungal cell walls but not found in human cells. This drug class has the nickname “penicillin for fungi.” Caspofungin is used for the treatment of aspergillosis as well as systemic yeast infections.
Although chitin is only a minor constituent of fungal cell walls, it is also absent in human cells, making it a selective target. The polyoxins and nikkomycins are naturally produced antifungals that target chitin synthesis. Polyoxins are used to control fungi for agricultural purposes, and nikkomycin Z is currently under development for use in humans to treat yeast infections and Valley fever (coccidioidomycosis), a fungal disease prevalent in the southwestern US. 1
The naturally produced antifungal griseofulvin is thought to specifically disrupt fungal cell division by interfering with microtubules involved in spindle formation during mitosis. It was one of the first antifungals, but its use is associated with hepatotoxicity. It is typically administered orally to treat various types of dermatophytic skin infections when other topical antifungal treatments are ineffective.
There are a few drugs that act as antimetabolites against fungal processes. For example, atovaquone, a representative of the naphthoquinone drug class, is a semisynthetic antimetabolite for fungal and protozoal versions of a mitochondrial cytochrome important in electron transport. Structurally, it is an analog of coenzyme Q, with which it competes for electron binding. It is particularly useful for the treatment of Pneumocystis pneumonia caused by Pneumocystis jirovecii . The antibacterial sulfamethoxazole-trimethoprim combination also acts as an antimetabolite against P. jirovecii .
Table \(\PageIndex{1}\) shows the various therapeutic classes of antifungal drugs, categorized by mode of action, with examples of each.
| Mechanism of Action | Drug Class | Specific Drugs | Clinical Uses |
|---|---|---|---|
| Inhibit ergosterol synthesis | Imidazoles | Miconazole, ketoconazole, clotrimazole | Fungal skin infections and vaginal yeast infections |
| Triazoles | Fluconazole | Systemic yeast infections, oral thrush, and cryptococcal meningitis | |
| Allylamines | Terbinafine | Dermatophytic skin infections (athlete’s foot, ring worm, jock itch), and infections of fingernails and toenails | |
| Bind ergosterol in the cell membrane and create pores that disrupt the membrane | Polyenes | Nystatin | Used topically for yeast infections of skin, mouth, and vagina; also used for fungal infections of the intestine |
| Amphotericin B | Variety systemic fungal infections | ||
| Inhibit cell wall synthesis | Echinocandins | Caspofungin | Aspergillosis and systemic yeast infections |
| Not applicable | Nikkomycin Z | Coccidioidomycosis (Valley fever) and yeast infections | |
| Inhibit microtubules and cell division | Not applicable | Griseofulvin | Dermatophytic skin infections |
How is disruption of ergosterol biosynthesis an effective mode of action for antifungals?
Jack, a 48-year-old engineer, is HIV positive but generally healthy thanks to antiretroviral therapy (ART). However, after a particularly intense week at work, he developed a fever and a dry cough. He assumed that he just had a cold or mild flu due to overexertion and didn’t think much of it. However, after about a week, he began to experience fatigue, weight loss, and shortness of breath. He decided to visit his physician, who found that Jack had a low level of blood oxygenation. The physician ordered blood testing, a chest X-ray, and the collection of an induced sputum sample for analysis. His X-ray showed a fine cloudiness and several pneumatoceles (thin-walled pockets of air), which indicated Pneumocystis pneumonia (PCP), a type of pneumonia caused by the fungus Pneumocystis jirovecii . Jack’s physician admitted him to the hospital and prescribed Bactrim, a combination of sulfamethoxazole and trimethoprim, to be administered intravenously.
P. jirovecii is a yeast-like fungus with a life cycle similar to that of protozoans. As such, it was classified as a protozoan until the 1980s. It lives only in the lung tissue of infected persons and is transmitted from person to person, with many people exposed as children. Typically, P. jirovecii only causes pneumonia in immunocompromised individuals. Healthy people may carry the fungus in their lungs with no symptoms of disease. PCP is particularly problematic among HIV patients with compromised immune systems.
PCP is usually treated with oral or intravenous Bactrim, but atovaquone or pentamidine(another antiparasitic drug) are alternatives. If not treated, PCP can progress, leading to a collapsed lung and nearly 100% mortality. Even with antimicrobial drug therapy, PCP still is responsible for 10% of HIV-related deaths.
The cytological examination, using direct immunofluorescence assay (DFA), of a smear from Jack’s sputum sample confirmed the presence of P. jirovecii (Figure \(\PageIndex{3}\)). Additionally, the results of Jack’s blood tests revealed that his white blood cell count had dipped, making him more susceptible to the fungus. His physician reviewed his ART regimen and made adjustments. After a few days of hospitalization, Jack was released to continue his antimicrobial therapy at home. With the adjustments to his ART therapy, Jack’s CD4 counts began to increase and he was able to go back to work.
Antiprotozoan Drugs
There are a few mechanisms by which antiprotozoan drugs target infectious protozoans (Table \(\PageIndex{3}\)). Some are antimetabolites, such as atovaquone, proguanil, and artemisinins. Atovaquone, in addition to being antifungal, blocks electron transport in protozoans and is used for the treatment of protozoan infections including malaria, babesiosis, and toxoplasmosis. Proguanil is another synthetic antimetabolite that is processed in parasitic cells into its active form, which inhibits protozoan folic acid synthesis. It is often used in combination with atovaquone, and the combination is marketed as Malarone for both malaria treatment and prevention.
Artemisinin, a plant-derived antifungal first discovered by Chinese scientists in the 1970s, is quite effective against malaria. Semisynthetic derivatives of artemisinin are more water soluble than the natural version, which makes them more bioavailable. Although the exact mechanism of action is unclear, artemisinins appear to act as prodrugs that are metabolized by target cells to produce reactive oxygen species (ROS) that damage target cells. Due to the rise in resistance to antimalarial drugs, artemisinins are also commonly used in combination with other antimalarial compounds in artemisinin-based combination therapy (ACT).
Several antimetabolites are used for the treatment of toxoplasmosis caused by the parasite Toxoplasma gondii . The synthetic sulfa drug sulfadiazine competitively inhibits an enzyme in folic acid production in parasites and can be used to treat malaria and toxoplasmosis. Pyrimethamine is a synthetic drug that inhibits a different enzyme in the folic acid production pathway and is often used in combination with sulfadoxine (another sulfa drug) for the treatment of malariaor in combination with sulfadiazine for the treatment of toxoplasmosis. Side effects of pyrimethamine include decreased bone marrow activity that may cause increased bruising and low red blood cell counts. When toxicity is a concern, spiramycin, a macrolide protein synthesis inhibitor, is typically administered for the treatment of toxoplasmosis.
Two classes of antiprotozoan drugs interfere with nucleic acid synthesis: nitroimidazoles and quinolines. Nitroimidazoles, including semisynthetic metronidazole, which was discussed previously as an antibacterial drug, and synthetic tinidazole, are useful in combating a wide variety of protozoan pathogens, such as Giardia lamblia , Entamoeba histolytica , and Trichomonas vaginalis . Upon introduction into these cells in low-oxygen environments, nitroimidazoles become activated and introduce DNA strand breakage, interfering with DNA replication in target cells. Unfortunately, metronidazole is associated with carcinogenesis (the development of cancer) in humans.
Another type of synthetic antiprotozoan drug that has long been thought to specifically interfere with DNA replication in certain pathogens is pentamidine. It has historically been used for the treatment of African sleeping sickness (caused by the protozoan Trypanosoma brucei ) and leishmaniasis (caused by protozoa of the genus Leishmania ), but it is also an alternative treatment for the fungus Pneumocystis . Some studies indicate that it specifically binds to the DNA found within kinetoplasts (kDNA; long mitochondrion-like structures unique to trypanosomes), leading to the cleavage of kDNA. However, nuclear DNA of both the parasite and host remain unaffected. It also appears to bind to tRNA, inhibiting the addition of amino acids to tRNA, thus preventing protein synthesis. Possible side effects of pentamidine use include pancreatic dysfunction and liver damage.
The quinolines are a class of synthetic compounds related to quinine, which has a long history of use against malaria. Quinolines are thought to interfere with heme detoxification, which is necessary for the parasite’s effective breakdown of hemoglobin into amino acids inside red blood cells. The synthetic derivatives chloroquine, quinacrine (also called mepacrine), and mefloquine are commonly used as antimalarials, and chloroquine is also used to treat amebiasis typically caused by Entamoeba histolytica . Long-term prophylactic use of chloroquine or mefloquine may result in serious side effects, including hallucinations or cardiac issues. Patients with glucose-6-phosphate dehydrogenase deficiency experience severe anemia when treated with chloroquine.
| Mechanism of Action | Drug Class | Specific Drugs | Clinical Uses |
|---|---|---|---|
| Inhibit electron transport in mitochondria | Naphthoquinone | Atovaquone | Malaria, babesiosis, and toxoplasmosis |
| Inhibit folic acid synthesis | Not applicable | Proquanil | Combination therapy with atovaquone for malaria treatment and prevention |
| Sulfonamide | Sulfadiazine | Malaria and toxoplasmosis | |
| Not applicable | Pyrimethamine | Combination therapy with sulfadoxine (sulfa drug) for malaria | |
| Produces damaging reactive oxygen species | Not applicable | Artemisinin | Combination therapy to treat malaria |
| Inhibit DNA synthesis | Nitroimidazoles | Metronidazole, tinidazole | Infections caused by Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis |
| Not applicable | Pentamidine | African sleeping sickness and leishmaniasis | |
| Inhibit heme detoxification | Quinolines | Chloroquine | Malaria and infections with E. histolytica |
| Mepacrine, mefloquine | Malaria |
List two modes of action for antiprotozoan drugs.
Antihelminthic Drugs
Because helminths are multicellular eukaryotes like humans, developing drugs with selective toxicity against them is extremely challenging. Despite this, several effective classes have been developed (Table \(\PageIndex{3}\)). Synthetic benzimidazoles, like mebendazole and albendazole, bind to helminthic β-tubulin, preventing microtubule formation. Microtubules in the intestinal cells of the worms seem to be particularly affected, leading to a reduction in glucose uptake. Besides their activity against a broad range of helminths, benzimidazoles are also active against many protozoans, fungi, and viruses, and their use for inhibiting mitosis and cell cycle progression in cancer cells is under study. 2 Possible side effects of their use include liver damage and bone marrow suppression.
The avermectins are members of the macrolide family that were first discovered from a Japanese soil isolate, Streptomyces avermectinius . A more potent semisynthetic derivative of avermectin is ivermectin, which binds to glutamate-gated chloride channels specific to invertebrates including helminths, blocking neuronal transmission and causing starvation, paralysis, and death of the worms. Ivermectin is used to treat roundworm diseases, including onchocerciasis (also called river blindness, caused by the worm Onchocerca volvulus ) and strongyloidiasis (caused by the worm Strongyloides stercoralis or S. fuelleborni ). Ivermectin also can also treat parasitic insects like mites, lice, and bed bugs, and is nontoxic to humans.
Niclosamide is a synthetic drug that has been used for over 50 years to treat tapeworm infections. Although its mode of action is not entirely clear, niclosamide appears to inhibit ATP formation under anaerobic conditions and inhibit oxidative phosphorylation in the mitochondria of its target pathogens. Niclosamide is not absorbed from the gastrointestinal tract, thus it can achieve high localized intestinal concentrations in patients. Recently, it has been shown to also have antibacterial, antiviral, and antitumor activities. 3 4 5
Another synthetic antihelminthic drug is praziquantel, which used for the treatment of parasitic tapeworms and liver flukes, and is particularly useful for the treatment of schistosomiasis (caused by blood flukes from three genera of Schistosoma ). Its mode of action remains unclear, but it appears to cause the influx of calcium into the worm, resulting in intense spasm and paralysis of the worm. It is often used as a preferred alternative to niclosamide in the treatment of tapeworms when gastrointestinal discomfort limits niclosamide use.
The thioxanthenones, another class of synthetic drugs structurally related to quinine, exhibit antischistosomal activity by inhibiting RNA synthesis. The thioxanthenone lucanthone and its metabolite hycanthone were the first used clinically, but serious neurological, gastrointestinal, cardiovascular, and hepatic side effects led to their discontinuation. Oxamniquine, a less toxic derivative of hycanthone, is only effective against S. mansoni , one of the three species known to cause schistosomiasis in humans. Praziquantel was developed to target the other two schistosome species, but concerns about increasing resistance have renewed interest in developing additional derivatives of oxamniquine to target all three clinically important schistosome species.
| Mechanism of Action | Drug Class | Specific Drugs | Clinical Uses |
|---|---|---|---|
| Inhibit microtubule formation, reducing glucose uptake | Benzimidazoles | Mebendazole, albendazole | Variety of helminth infections |
| Block neuronal transmission, causing paralysis and starvation | Avermectins | Ivermectin | Roundworm diseases, including river blindness and strongyloidiasis, and treatment of parasitic insects |
| Inhibit ATP production | Not applicable | Niclosamide | Intestinal tapeworm infections |
| Induce calcium influx | Not applicable | Praziquantel | Schistosomiasis (blood flukes) |
| Inhibit RNA synthesis | Thioxanthenones | Lucanthone, hycanthone, oxamniquine | Schistosomiasis (blood flukes) |
Why are antihelminthic drugs difficult to develop?
Antiviral Drugs
Unlike the complex structure of fungi, protozoa, and helminths, viral structure is simple, consisting of nucleic acid, a protein coat, viral enzymes, and, sometimes, a lipid envelope. Furthermore, viruses are obligate intracellular pathogens that use the host’s cellular machinery to replicate. These characteristics make it difficult to develop drugs with selective toxicity against viruses.
Many antiviral drugs are nucleoside analogs and function by inhibiting nucleic acid biosynthesis. For example, acyclovir(marketed as Zovirax) is a synthetic analog of the nucleoside guanosine (Figure \(\PageIndex{4}\)). It is activated by the herpes simplex viral enzyme thymidine kinase and, when added to a growing DNA strand during replication, causes chain termination. Its specificity for virus-infected cells comes from both the need for a viral enzyme to activate it and the increased affinity of the activated form for viral DNA polymerase compared to host cell DNA polymerase. Acyclovir and its derivatives are frequently used for the treatment of herpes virus infections, including genital herpes, chickenpox, shingles, Epstein-Barr virus infections, and cytomegalovirus infections. Acyclovir can be administered either topically or systemically, depending on the infection. One possible side effect of its use includes nephrotoxicity. The drug adenine-arabinoside, marketed as vidarabine, is a synthetic analog to deoxyadenosine that has a mechanism of action similar to that of acyclovir. It is also effective for the treatment of various human herpes viruses. However, because of possible side effects involving low white blood cell counts and neurotoxicity, treatment with acyclovir is now preferred.
Ribavirin, another synthetic guanosine analog, works by a mechanism of action that is not entirely clear. It appears to interfere with both DNA and RNA synthesis, perhaps by reducing intracellular pools of guanosine triphosphate (GTP). Ribavarin also appears to inhibit the RNA polymerase of hepatitis C virus. It is primarily used for the treatment of the RNA viruses like hepatitis C (in combination therapy with interferon) and respiratory syncytial virus. Possible side effects of ribavirin use include anemia and developmental effects on unborn children in pregnant patients. In recent years, another nucleotide analog, sofosbuvir (Solvaldi), has also been developed for the treatment of hepatitis C. Sofosbuvir is a uridine analog that interferes with viral polymerase activity. It is commonly coadministered with ribavirin, with and without interferon.
Inhibition of nucleic acid synthesis is not the only target of synthetic antivirals. Although the mode of action of amantadine and its relative rimantadine are not entirely clear, these drugs appear to bind to a transmembrane protein that is involved in the escape of the influenza virus from endosomes. Blocking escape of the virus also prevents viral RNA release into host cells and subsequent viral replication. Increasing resistance has limited the use of amantadine and rimantadine in the treatment of influenza A. Use of amantadine can result in neurological side effects, but the side effects of rimantadine seem less severe. Interestingly, because of their effects on brain chemicals such as dopamine and NMDA (N-methyl D-aspartate), amantadine and rimantadine are also used for the treatment of Parkinson’s disease.
Neuraminidase inhibitors, including olsetamivir (Tamiflu), zanamivir (Relenza), and peramivir (Rapivab), specifically target influenza viruses by blocking the activity of influenza virus neuraminidase, preventing the release of the virus from infected cells. These three antivirals can decrease flu symptoms and shorten the duration of illness, but they differ in their modes of administration: olsetamivir is administered orally, zanamivir is inhaled, and peramivir is administered intravenously. Resistance to these neuraminidase inhibitors still seems to be minimal.
Pleconaril is a synthetic antiviral under development that showed promise for the treatment of picornaviruses. Use of pleconaril for the treatment of the common cold caused by rhinoviruses was not approved by the FDA in 2002 because of lack of proven effectiveness, lack of stability, and association with irregular menstruation. Its further development for this purpose was halted in 2007. However, pleconaril is still being investigated for use in the treatment of life-threatening complications of enteroviruses, such as meningitis and sepsis. It is also being investigated for use in the global eradication of a specific enterovirus, polio. 6 Pleconaril seems to work by binding to the viral capsid and preventing the uncoating of viral particles inside host cells during viral infection.
Viruses with complex life cycles, such as HIV, can be more difficult to treat. First, HIV targets CD4-positive white blood cells, which are necessary for a normal immune response to infection. Second, HIV is a retrovirus, meaning that it converts its RNA genome into a DNA copy that integrates into the host cell’s genome, thus hiding within host cell DNA. Third, the HIV reverse transcriptase lacks proofreading activity and introduces mutations that allow for rapid development of antiviral drug resistance. To help prevent the emergence of resistance, a combination of specific synthetic antiviral drugs is typically used in ART for HIV (Figure \(\PageIndex{5}\)).
The reverse transcriptase inhibitors block the early step of converting viral RNA genome into DNA, and can include competitive nucleoside analog inhibitors (e.g., azidothymidine/zidovudine, or AZT) and non-nucleoside noncompetitive inhibitors (e.g., etravirine) that bind reverse transcriptase and cause an inactivating conformational change. Drugs called protease inhibitors (e.g., ritonavir) block the processing of viral proteins and prevent viral maturation. Protease inhibitors are also being developed for the treatment of other viral types. 7 For example, simeprevir (Olysio) has been approved for the treatment of hepatitis C and is administered with ribavirin and interferon in combination therapy. The integrase inhibitors (e.g., raltegravir), block the activity of the HIV integrase responsible for the recombination of a DNA copy of the viral genome into the host cell chromosome. Additional drug classes for HIV treatment include the CCR5 antagonists and the fusion inhibitors (e.g., enfuviritide), which prevent the binding of HIV to the host cell coreceptor (chemokine receptor type 5 [CCR5]) and the merging of the viral envelope with the host cell membrane, respectively. Table \(\PageIndex{4}\) shows the various therapeutic classes of antiviral drugs, categorized by mode of action, with examples of each.
| Mechanism of Action | Drug | Clinical Uses |
|---|---|---|
| Nucleoside analog inhibition of nucleic acid synthesis | Acyclovir | Herpes virus infections |
| Azidothymidine/zidovudine (AZT) | HIV infections | |
| Ribavirin | Hepatitis C virus and respiratory syncytial virus infections | |
| Vidarabine | Herpes virus infections | |
| Sofosbuvir | Hepatitis C virus infections | |
| Non-nucleoside noncompetitive inhibition | Etravirine | HIV infections |
| Inhibit escape of virus from endosomes | Amantadine, rimantadine | Infections with influenza virus |
| Inhibit neuraminadase | Olsetamivir, zanamivir, peramivir | Infections with influenza virus |
| Inhibit viral uncoating | Pleconaril | Serious enterovirus infections |
| Inhibition of protease | Ritonavir | HIV infections |
| Simeprevir | Hepatitis C virus infections | |
| Inhibition of integrase | Raltegravir | HIV infections |
| Inhibition of membrane fusion | Enfuviritide | HIV infections |
Why is HIV difficult to treat with antivirals?
To learn more about the various classes of antiretroviral drugs used in the ART of HIV infection, explore each of the drugs in the HIV drug classes provided by US Department of Health and Human Services at this website.
Key Concepts and Summary
- Because fungi, protozoans, and helminths are eukaryotic organisms like human cells, it is more challenging to develop antimicrobial drugs that specifically target them.
- Antifungal drugs interfere with ergosterol synthesis, bind to ergosterol to disrupt fungal cell membrane integrity, or target cell wall-specific components or other cellular proteins.
- Antiprotozoan drugs increase cellular levels of reactive oxygen species, interfere with protozoal DNA replication (nuclear versus kDNA, respectively), and disrupt heme detoxification.
- Antihelminthic drugs disrupt helminthic and protozoan microtubule formation; block neuronal transmissions; inhibit anaerobic ATP formation and/or oxidative phosphorylation; induce a calcium influx in tapeworms, leading to spasms and paralysis; and interfere with RNA synthesis in schistosomes.
- Antiviral drugs inhibit viral entry, inhibit viral uncoating, inhibit nucleic acid biosynthesis, prevent viral escape from endosomes in host cells, and prevent viral release from infected cells.
- Because it can easily mutate to become drug resistant, HIV is typically treated with a combination of several antiretroviral drugs , which may include reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors , and drugs that interfere with viral binding and fusion to initiate infection.
Footnotes
- 1 Centers for Disease Control and Prevention. “Valley Fever: Awareness Is Key.” www.cdc.gov/features/valleyfever/. Accessed June 1, 2016.
- 2 B. Chu et al. “A Benzimidazole Derivative Exhibiting Antitumor Activity Blocks EGFR and HER2 Activity and Upregulates DR5 in Breast Cancer Cells.” Cell Death and Disease 6 (2015):e1686
- 3 J.-X. Pan et al. “Niclosamide, An Old Antihelminthic Agent, Demonstrates Antitumor Activity by Blocking Multiple Signaling Pathways of Cancer Stem Cells.” Chinese Journal of Cancer 31 no. 4 (2012):178–184.
- 4 F. Imperi et al. “New Life for an Old Drug: The Anthelmintic Drug Niclosamide Inhibits Pseudomonas aeruginosa Quorum Sensing.” Antimicrobial Agents and Chemotherapy 57 no. 2 (2013):996-1005.
- 5 A. Jurgeit et al. “Niclosamide Is a Proton Carrier and Targets Acidic Endosomes with Broad Antiviral Effects.” PLoS Pathogens 8 no. 10 (2012):e1002976.
- 6 M.J. Abzug. “The Enteroviruses: Problems in Need of Treatments.” Journal of Infection 68 no. S1 (2014):108–14.
- 7 B.L. Pearlman. “Protease Inhibitors for the Treatment of Chronic Hepatitis C Genotype-1 Infection: The New Standard of Care.” Lancet Infectious Diseases 12 no. 9 (2012):717–728.


11.11: 20th Century Architecture
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Architecture is generally described as any creatively designed and constructed building or structure enhancing the city, town, or landscape. It is also the science of designing the building so the structure is safe, inhabitable, and will still be standing in the event of damage from fire, flood, earthquake, or other natural disasters — the architects below designed buildings in styles unique to their ideas, designs, and creations.
|
Architect |
Style |
Specialty Designs |
Specialty Materials |
|
Antoni Guadí |
Catalan Modernism |
Helicoid and hyperboloid forms |
Brick, mortar, concrete, ceramic pieces |
|
Frank Lloyd Wright |
Organic architecture Prairie School |
Sloping roofs, open plans, low profile, long/low windows, cantilevered balconies |
Concrete |
|
Oscar Niemeyer |
Abstract forms and curves |
Free-flowing curves |
Metal, concrete, glass |
|
Julia Morgan |
Arts and Crafts |
Craftsman Style |
Re-enforced concrete, tiles |
|
Eero Saarinen |
Neo-futuristic |
Sweeping, arching, structural curves |
Steel, glass |
|
Unknown |
Systemic and functional |
Style based on use |
Mud, water, thatch |
The Sagrada Familia in Barcelona, Spain (13.1), was designed and partially built by Antoni Gaudí Cornet (1852-1926), a Spanish artist following Catalan modernism with a distinctive style reflecting his individualization. Gaudí was inspired by the art from Persia, India, and Japan and incorporated these ideas along with the neo-Gothic movement, a growing art movement at the time. He also integrated his design with an organic style from nature.
The Basilica Temple Expiatori de la Sagrada Familia is a Roman Catholic Basilica started by Gaudí in 1883 who used the Gothic and Art Nouveau styles with curvilinear forms and columns as his design inspiration. When Gaudí died in 1926, the building was only twenty-five percent complete. Construction carried on, only interrupted by the Spanish Civil War, with a planned completion date of 2026, the one-hundredth anniversary of Gaudi's death.
The interior of the church is a standard cross with five aisles and a central nave vault stretching forty-five meters, the side naves reaching thirty meters (13.2). The columns are uniquely Gaudi designed with tree-like structures and spreading branches to support the load, a three-dimensional intersection of helicoidal columns. In the center of the nave, the designs intersect with the multi-colored columns. There is extensive glasswork in windows on each end of the church. The outside façade is heavily decorated with iconic religious carvings (13.3). Eighteen spires were designed for the completed cathedral; however, only eight spires (13.4) have been built to date.
Antoni Gaudí transcended conventional modernism with his unique, organic style of design. He never drew plans on paper, opting for building three-dimensional models to view all the details.
Casa Batllo (13.5), built between 1904 and 1906, is in the center of Barcelona. The façade of the building was designed on imagination and whimsy, built from stone and colored glass. The wavy shape of the building was plastered with lime mortar and covered in glass and tile mosaic. The roof (13.6) of the building is built in the shape of an ornate animal exhibiting oversized iridescent scales and tiled spine. Casa Batllo is a modern marvel of shape, light, color, and design.
VIDEO*: www.khanacademy.org/humaniti...r-construction
Frank Lloyd Wright (1867-1959), one of America's premier architects, designed more than 1,000 buildings in his lifetime. Wright's philosophy on design extended to the environment where the building was to be placed. The structure needed to be in harmony with humanity living in the house or using the building and the surrounding land. He was a leader of the Prairie School movement—a 20 th -century style based on the Midwestern United States—loosely following the Arts and Crafts Movement.
Constructed in 1936, Fallingwater (13.7) is one of the most famous Wright homes. The 5330 square foot house appears to float over a waterfall, jutting out above the river on a 4,100-hectare nature preserve. The waterfall cannot be observed from anywhere in the house, and you must leave the home and walk down a short trail to even see the waterfall, a contentious point with the homeowner since they wanted to see the waterfall. Wright disagreed with the owners and believed in exercising the sense of hearing to appreciate the waterfall from the house, the sound creating a magical atmosphere. Wright designed the furnishings for the living room (13.8), with a strong reflection of Japanese design and architecture. The fireplace has the same brick inside and outside, only separated by a glass window giving the appearance of sitting in nature. The living room was built on top of a large boulder that Wright incorporated directly into the design. Fallingwater is now owned and maintained by the Western Pennsylvania Conservancy.
Wright also designed the Solomon R. Guggenheim Museum (13.9) in New York City in a cylindrical formation. The grand interior contains a ramp gallery (13.10) from the first floor to the massive skylight on the top floor. Opening in 1959, the museum received criticism from architects, artists, and critics, however, the public widely praised the design as new and innovative.
The Guggenheim Museum, with its spiral design, influenced Oscar Niemeyer (1907-2012), a Brazilian architect who was a leader in modern architecture. In 1960, Niemeyer was known for his planned city of Brasilia, the newly designated capital of Brazil and the United Nations Headquarters in New York City. He embraced modernism with its curved lines and organic shapes, offering a contrast to the geometric severity of the current architectural designs.
Niemeyer was an advanced engineer who experimented with his favorite medium, concrete, and developed techniques using reinforced concrete to improve the plasticity of the material, challenging traditional architecture, breaking from the past, and making a giant leap into the future. Dedicated in 1970, the Cathedral of Brasilia (13.11) was constructed as a hyperboloid structure with sixteen concrete columns weighing 90 tons each. As the official building for the executive branch of government, The Palacio do Planalto (13.12) was one of the essential Niemeyer buildings. The four-story structure designed with tapering lines formed the columns standing against the broad expanse of glass walls.
From California, Julia Morgan (1872-1957) was one of the greatest American architects. Known for her large buildings founded on Craftsman-style structures, she designed more than 700 buildings. Hearst Castle in San Simeon, California, is her best-known work along with Asilomar in Monterey, California. Graduating from the University of California, Berkeley, Morgan was the first woman to be admitted at I Ecole Nationale Superieure des Beaux-Arts in Paris for the architecture program. Morgan returned home to her Northern California home and was the first woman in California to be granted an architectural license. After she started her own company, one of her first significant designs were many of the buildings at Mills College.
She met William Randolph Hearst, who hired her to design the Los Angles Examiner Building in 1914, and in 1919, Hearst hired Morgan to design his most significant and most complex project, Hearst Castle (13.13) in San Simeon. Morgan designed the buildings, landscaping, pools, and animal shelters, spending 28 years to supervise every aspect of the Hearst Castle project. Inspiration for the buildings came from the grandeur of Europe, a Mediterranean style main house with two ornate twin towers. The iconic Greek Neptune pool (13.14) boasts marble columns and statues, while several guest cottages are scattered around the gardens. The elaborately decorated interior rooms (13.15) have marble fireplaces with an extensive collection of art and tapestries hanging on the walls.
Located on 107 acres on the beach in Monterey, Asilomar (13.16), Morgan designed most of the buildings between 1913 and 1928 in the Arts & Crafts architectural style. The movement-based its designs on the harmony between nature and the craftsman, creating expertly crafted buildings from local resources to blend in with the surrounding landscape. Asilomar was initially constructed for the YWCA with 16 buildings, 11 are still standing. Today the property is owned by California State Parks (13.17) and is a popular place as a conference center. Julia Morgan paved the way for all women architects who followed her.
Large sweeping arching curves are associated with the designs of Eero Saarinen (1910-1961), a Finnish American architect and industrial designer known for his neo-futuristic styles. Saarinen was the designer of the iconic Saint Louis Arch (13.18) TWA terminal at JFK Airport, New York, and the Milwaukee Art Museum. Saarinen designed the St. Louis Arch to rise from a small forest on the edge of the Mississippi River, signifying the gateway to the West. The TWA Flight Center (13.19) opened in 1962 using Saarinen's design, employing modernism and human movement originally called the grand center of flight. The design from overhead resembles a bird, TWA’s logo. The 31,700 square meter Milwaukee Art Museum (13.20) was open to the public in 1957, a dynamic structure resembling winged flight.
The Dogon are a group of people living on the central plateau in Mali, just south of the Niger River. The Dogon settled the area in the 13 th century and still follow the religious traditions of their ancestors reflected in their dance masks, elaborate wooden sculptures, and beautiful architecture. The Dogon villages (13.21) are groups of unique mud buildings designed for different purposes. Their granaries have a distinctive pointed roof covered with woven thatch and containing the owner’s possessions. There are separate granary buildings for women and men; the male granary is designed to house pearl millet and other grains while the female granary is a storage hut for personal belongings and goods for sale like woven cotton or pottery.
Although all the villages are laid out slightly differently, the architecture of the village is based on the body of a human lying stretched out on the ground, the head oriented to the north where the togu na is located. The togu na (13.22) is a building for men and used to rest during the heat of the day and as a place to discuss affairs of the village. The roof is quite low to the ground, the low height designed to prevent fighting amongst the men during their conversations. For menstruating women, there is a house on the outside of the village the women occupy for five days and then return to their family. On the highest position in the area, stands the house of the Hogon, the village elder. Multiple structures may have carved human figures, each one with a different meaning. The support pillars or columns are tree trunks carved with human forms.


7.7: Geologic Structures
INTRODUCTION
Geologic structures such as faults and folds are the architecture of the earth’s crust. Geologic structures influence the shape of the landscape, determine the degree of landslide hazard, bring old rocks to the surface, bury young rocks, trap petroleum and natural gas, shift during earthquakes, and channel fluids that create economic deposits of metals such as gold and silver.
Folds, faults, and other geologic structures accommodate large forces such as the stress of tectonic plates jostling against each other, and smaller forces such as the stress of gravity pulling on a steep mountainside. An understanding of the structures that shape the earth’s crust can help you see when and where the crust was subjected to pushing or pulling, terrane accretion or crustal rifting.
PHYSICAL BEHAVIOR OF ROCKS: STRESS AND GEOLOGIC STRUCTURES
Before exploring geologic structures, we need to look at how rocks respond to the forces that create the structures. Stress refers to the physical forces that cause rocks to deform. There are three basic types of stress that deform rocks:
- compression (pushing together)
- tension (pulling apart)
- shear (twisting or rotating)
In response to stress, rocks will undergo some form of bending or breaking, or both. The bending or breaking of rock is called deformation or strain.
If rocks tend to break, they are said to be brittle. If a rock breaks, it is said to undergo brittle behavior. If rocks tend to bend without breaking, they are said to be ductile. If a rock bends but is able to return to its original position when the stress is released, it is said to undergo elastic behavior. If a rock bends and stays bent after stress is released, it is said to undergo plastic behavior.
A combination of elastic and brittle behavior causes earthquakes. Rocks get bent in an elastic fashion until they reach their limit, then they break in brittle fashion. The rocks on either side of a break act like rubber bands and snap back into their original shape. The snap is an earthquake. The break along which the rocks slide back to their original shape is a fault.
Earthquakes and faults occur in the shallow crust, where rocks are relatively cold and therefore brittle. In the deep crust and in the earth’s mantle, rocks are very hot and subject to high pressure caused by the weight of the overlying rock. The heat and pressure cause deep crustal and mantle rocks to be ductile. In fact, rocks deep in the continental crust and upper mantle can be so hot and soft that they behave almost like a slow-moving liquid, even though they are actually solid. They “flow,” or bend in a plastic manner, at a geological pace.
Now let us look at the specific types of geologic structures, the breaks and bends that deform rock in response to stress.
FOLDS
Ductile rocks behave plastically and become folded in response to stress. Even in the shallow crust where rocks are cool and relatively brittle, folding can occur if the stress is slow and steady and gives the rock enough time to gradually bend. If the stress is applied too quickly, rocks in the shallow crust will behave as brittle solids and break. Deeper in the crust, where the rocks are more ductile, folding happens more readily, even when the stress and strain occurs rapidly.
Anticlines and Synclines
The most basic types of folds are anticlines and synclines. Imagine a rug, the sides of which have been pushed toward each other forming ridges and valleys – the ridges are “up” folds and the valleys are “down” folds. In terms of geologic structures, the up folds are called anticlines and the down folds are called synclines.
In block diagrams like those shown below, the top of the block is the horizontal surface of the earth, the map view. The other two visible sides of the box are cross-sections, vertical slices through the crust. The colored layers represent stratified geologic formations that were originally horizontal, such as sedimentary beds or lava flows. Use the block diagrams to visualize the three-dimensional shapes of the geologic structures. Keep in mind that erosion has stripped away the upper parts of these structures so that map view reveals the interior of these structures.
In map view, an anticline appears as parallel beds of the same rock type that dip away from the center of the fold. In an anticline, the oldest beds, the ones that were originally underneath the other beds, are at the center, along the axis of the fold. The axis is an imaginary line that marks the center of the fold on the map.
In map view, a syncline appears as a set of parallel beds that dip toward the center. In a syncline the youngest beds, the ones that were originally on top of the rest of the beds, are at the center, along the axis of the fold.
Anticlines and synclines form in sections of the crust that are undergoing compression, places where the crust is being pushed together.
Plunging Anticlines and Synclines
A plunging anticline or a plunging syncline is one that has its axis tilted from the horizontal so that the fold is plunging into the earth along its length. Plunge direction is the direction in which the axis of the fold tilts down into the earth.
In map view, a plunging anticline makes a U-shaped or V-shaped pattern that points, or closes, in the direction of plunge. A cross-section at a right angle to the axis of a plunging anticline looks the same as an anticline.
In map view, a plunging syncline makes a U-shaped or V-shaped pattern that opens in the direction of plunge.
Basins and Domes
A basin is a bowl-like depression in the strata (layers of rock). A basin is similar to a syncline, but instead of an axis it has a single point at the center. The strata all dip toward the center point and the youngest rock is at the center. In map view, the strata form concentric circles – a bull’s eye pattern – around the center point.
A dome is an bulge in strata. A dome is similar to an anticline, but instead of an axis it has a single point at the center. The strata all dip away from the center point and the oldest rock is at the center. In map view, the strata form concentric circles – a bull’s eye pattern – around the center point.
FAULTS
A fault is a planar surface within the earth, along which rocks have broken and slid. Faults are caused by elastic strain that culminates in brittle failure. The rocks on either side of a fault have shifted in opposite directions, called the offset directions. If a fault is not vertical, there are rocks above the fault and rocks beneath the fault.
The rocks above a fault are called the hanging wall.
The rocks beneath a fault are called the footwall.
Normal and Detachment Faults
In a normal fault, the hanging wall has moved down relative to the footwall.
A detachment fault is a particular kind of normal fault that generally dips at a low angle. It separates rocks that were deep in the crust and ductile (granite and gneiss) from rocks of the upper crust (sedimentary or volcanic) that were brittle. Detachment faults occur along the boundaries of metamorphic core complexes (see below).
Normal and detachment faults form in sections of the crust that are undergoing tension, places where the crust is being stretched apart. A divergent plate boundary is a zone of large normal faults. Normal faults also occur in other zones of crustal tension, such as in the Basin and Range landscape region of the western United States.
Reverse and Thrust Faults
In a reverse or thrust fault, the hanging wall has moved up relative to the footwall. The difference between a reverse fault and a thrust fault is that a reverse fault has a steeper dip, more than 30°.
Reverse and thrust faults form in sections of the crust that are undergoing compression. A convergent plate boundary is a zone of major reverse and thrust faults. In fact, subduction zones are sometimes referred to as mega-thrust faults. Reverse and thrust faults also occur in other settings where the crust is being compressed, such as the Transverse Mountain Ranges, just north of Los Angeles.
Strike-Slip Faults
Strike-slip faults are steep or vertical faults along which the rocks on either side have moved horizontally in opposite directions. A transform plate boundary is a zone of large strike-slip faults. The San Andreas fault is an example of a major strike-slip fault at a transform boundary. Strike-slip faults also occur in other settings.
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Contributors and Attributions
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Original content from Kimberly Schulte (Columbia Basin College) and supplemented by Lumen Learning . The content on this page is copyrighted under a Creative Commons Attribution 4.0 International license.


1.5: CHAPTER 4 AQUINAS’S NATURAL LAW THEORY
Aquinas’s Natural Law Theory
Grace does not destroy nature but perfects it. 1
They show that the requirements of the law are written on their hearts, their consciences also bearing witness, and their thoughts sometimes accusing them and at other times even defending them. 2
1. Introduction to Aquinas
Thomas Aquinas
(1225–1274) was an intellectual and religious revolutionary, living at a time of great philosophical, theological and scientific development. He was a member of the Dominican Friars, which at that time was considered to be a cult, and was taught by one of the greatest intellects of the age,
Albert the Great
(1208–1280). In a nutshell Aquinas wanted to move away from Plato’s thinking, which was hugely influential at the time, and instead introduce Aristotelian ideas to science, nature and theology.
Aquinas wrote an
incredible
amount — in fact one of the miracles accredited to him was the amount he wrote! His most famous work is
Summa Theologica
and this runs to some three and half thousand pages and contains many fascinating and profound insights, such as proofs for God’s existence. The book remained a fundamental basis for Catholic thinking right up to the 1960s! But do not worry we will only be focusing on a few key ideas! Specifically
books I–II, questions 93–95.
2. Motivating Natural Law Theory: The Euthyphro Dilemma and Divine Command Theory
The likely answer from a religious person as to
why
we should not steal, or commit adultery is: “because God
forbids
us”; or if we ask
why
we should love our neighbour or give money to charity then the answer is likely to be “because God
commands
it”. Drawing this link between what is right and wrong and what God commands and forbids is what is called the
Divine Command Theory
(DCT).
There is a powerful and influential challenge to such an account called the
Euthyphro dilemma
after the challenge was first raised in Plato’s
Euthyphro
. The dilemma runs as follows:
Either
God commands something is right because it is, or it is right because God commands it. If God commands something because it is right, then God’s commands do not make it right, His commands only tell us what is right. This means God simply drops out of the picture in terms of
explaining why
something is right.
If on the other hand something is right
because
God commands it then
anything
at all could be right; killing children or setting fire to churches could be morally acceptable. But if a moral theory says this then that looks as if the theory is wrong.
Most theists reject the first option and opt for this second option — that God’s commands
make
something right. But they then have to face the problem that it make morality haphazard. This “
arbitrariness problem
” as it is sometimes called, is the reason that many, including Aquinas, give up on the Divine Command Theory.
So for Aquinas what role, if any at all, does God have when it comes to morality? For him, God’s commands are there to help us to
come to see
what, as a matter of fact, is right and wrong rather than determine what is right and wrong. That is, Aquinas opts for the first option in the Euthyphro dilemma as stated above. But then this raises the obvious question: if it is not God’s commands that make something right and wrong, then what does? Does not God just fall out of the picture? This is where his Natural Law Theory comes in.
3. Natural Law Theory
Aquinas’s Natural Law Theory contains four different types of law:
Eternal Law, Natural Law, Human Law and Divine Law
. The way to understand these four laws and how they relate to one another is via the Eternal Law, so we’d better start there…
By “Eternal Law’” Aquinas means God’s rational purpose and plan for
all
things. And because the Eternal Law is part of God’s mind then it has always, and will always, exist. The Eternal Law is not simply something that God decided at some point to write.
Aquinas thinks that
everything
has a purpose and follows a plan. He, like Aristotle, is a teleologist (the Greek term “
telos
” refers to what we might call a purpose, goal, end/or the true final function of an object) (see Chapter 3; not to be confused with a telelogical ethical
theory
such as Utilitarianism) and believes that
every
object has a
telos
; the acorn has the
telos
of growing into an oak; the eye a
telos
of seeing; a rat of eating and reproducing etc. (notice this links to his view on sex, see Chapter 10). If something fulfills its purpose/plan then it is following the Eternal Law.
Aquinas thinks that something is
good
in as far as it fulfils its purpose/plan. This fits with common sense. A “
good
” eye is one which sees well, an acorn is a good if it grows into a strong oak tree.
But what about humans? Just as a good eye is to see, and a good acorn is to grow then a good human is to…? Is to what? How are we going to finish this sentence? What do you think?
Aquinas thinks that the answer is
reason
and that it is this that makes us distinct from rats and rocks. What is right for me and you as humans is to act according to reason. If we act according to reason then we are partaking in the
Natural Law
.
If we all act according to reason, then we will all agree to some overarching general rules (what Aquinas calls
primary precepts
). These are absolute and binding on all rational agents and because of this Aquinas rejects
relativism
.
The first primary precept is that
good is to be pursued and done and evil avoided
. He thinks that this is the guiding principle for all our decision making.
Before unpacking this, it is worth clarifying something about what “law” means. Imagine that we are playing Cluedo and we are trying to work out the identity of the murderer. There are certain rules about how to move around the board, how to deal out cards, how to reveal the murderer etc. These rules are all written down and can be consulted.
However, in playing the game there are other rules that operate which are so obvious that they are neither written down nor spoken. One such rule is that a claim made in the game cannot both be true and false; if it
is
Professor Plum who is the murderer then it cannot be true that it
is not
Professor Plum who is the murderer. These are
internal rules
which
any
rational person can come to recognize by simply thinking and are not external like the other rules — such as you can only have one guess as to the identity of the murderer. When Aquinas talks of Natural Laws, he means internal rules and not external ones.
Natural Law does not generate an external set of rules that are written down for us to consult but rather it generates general rules that any rational agent can come to recognize simply in virtue of being rational. For example, for Aquinas it is not as if we need to check whether we should pursue good and avoid evil, as it is just part of how we already think about things. Aquinas gives some more examples of primary precepts:
1.
Protect and preserve human life.
2.
Reproduce and educate one’s offspring.
3.
Know and worship God.
4.
Live in a society.
These precepts are
primary
because they are true for all people in
all instances
and are consistent with Natural Law.
Aquinas also introduces what he calls the
Human Law
which gives rise to what he calls “
Secondary Precepts
”. These might include such things as do not drive above 70mph on a motorway, do not kidnap people, always wear a helmet when riding a bike, do not hack into someone’s bank account. Secondary precepts are
not generated by our reason
but rather they are imposed by governments, groups, clubs, societies etc.
It is
not
always morally acceptable to follow secondary precepts. It is only morally acceptable if they are consistent with the Natural Law. If they are, then we ought to follow them, if they are not, then we ought not. To see why think through an example.
 Aquinas would argue that this secondary precept is practically
irrational
because it treats people differently based on an arbitrary difference (gender). He would reason that if the men in power in Saudi actually really thought hard then they too would recognize that this law is morally wrong. This in turn means that Aquinas would think that
this
human law
does not
fit with the Natural Law. Hence, it is morally wrong to follow a law that says that men can, and women cannot, drive. So although it is presented as a secondary precept, because it
is not
in accordance with Natural Law, it is what Aquinas calls an
apparent good
. This is in contrast with those secondary precepts which are in accordance with the Natural Law and which he calls the real goods.
Unlike primary precepts, Aquinas is
not
committed to there being only one set of secondary precepts for all people in all situations. It is consistent with Aquinas’s thinking to have a law to drive on the right in the US and on the left in the UK as there is no practical reason to think that there is one correct side of the road on which to drive.
It is clear that on our own we are not very good at discovering primary precepts and consequently Aquinas thinks that what we ought to do is talk and interact with people. To discover our real goods — our secondary precepts which accord with Natural Law — we need to be part of a society. For example, we might think that “treat Christians as secondary citizens” is a good secondary precept until we talk and live with Christians. The more we can think and talk with others in society the better and it is for this reason that “live in society” is itself a primary precept.
But looking at what we have said already about Natural Laws and primary and secondary precepts, we might think that there is no need for God. If we can learn these primary precepts by rational reflection then God simply drops out of the story (recall the Euthyphro dilemma above).
Just to recap as there a lots of moving parts to the story. We now have Eternal Law (God’s plans/purpose for all things), Natural Laws (our partaking in the Eternal Law which leads to primary precepts), Human Laws (humans making specific laws to capture the truths of the Natural Laws which lead to secondary precepts) and now finally Aquinas introduces the
Divine Law
.
The Divine Law, which is discovered through
revelation
, should be thought of as the Divine equivalent of the Human Law (those discovered through rational reflection and created by people). Divine laws are those that God has, in His grace, seen fit to give us and are those “mysteries”, those rules given by God which we find in scripture; for example, the ten commandments. But why introduce the Divine Law at all? It certainly feels we have enough Laws. Here is a story to illustrate Aquinas’s answer.
A number of years ago I was talking to a minister of a church. He told me about an instance where a married man came to ask his advice about whether to finish an affair he was having. The man’s reasoning went as follows — “I am having an affair which just feels so right, we are both very much in love and surely God would want what is best for me! How could it be wrong if we are so happy?”
In response, the minister opened the Bible to the Ten Commandments and pointed out the commandment that it says that it is wrong to commit adultery. Case closed. The point of this story is simple. We can be confused and mistaken about what we think we have most reason to do and because of this we need someone who actually knows the mind of God to guide us, and who better to know this than God Himself. This then is precisely what is revealed in the Divine Law.
Or consider another example. We recognize that we find it hard to forgive our friends and nearly always impossible to forgive our enemies. We tell ourselves we have the right to be angry, to bear grudges, etc. Isn’t this just human? However, these human reasons are
distortions
of the Eternal Law. We need some guidance when it comes to forgiveness and it is where the Divine Law which tells us that we should forgive others — including our enemies. Following the Human Laws
and
the Divine Laws will help us to fulfil our purposes and plans and be truly happy.
4. Summary of Aquinas’s Natural Law Theory
For Aquinas everything has a function (a
telos
) and the good thing(s) to do are those acts that fulfil that function. Some things such as acorns, and eyes, just do that naturally. However, humans are free and hence need guidance to find the right path. That right path is found through
reasoning
and generates the “internal” Natural Law. By following the Natural Law we participate in God’s purpose for us in the Eternal Law.
However, the primary precepts that derive from the Natural Law are quite general, such as,
pursue good and shun evil
. So we need to create secondary precepts which can actually guide our day-to-day behaviour. But we are fallible so sometimes we get these secondary precepts wrong, sometimes we get them right. When they are wrong they only reflect our apparent goods. When they are right they reflect our real goods.
Finally, however good we are because we are finite and sinful, we can only get so far with rational reflection. We need some
revealed guidance
and this comes in the form of Divine Law. So to return to the Euthyphro dilemma. God’s commands through the Divine Law are ways of
illuminating
what is in fact morally acceptable and
not what determines
what is morally acceptable. Aquinas rejects the Divine Command Theory.
5. Putting this into Practice: The Doctrine of Double Effect (DDE)
Let’s consider some examples to show that what we have said so far might actually work. Imagine someone considering suicide. Is this morally acceptable or not? Recall, it is part of the Natural Law to preserve and protect human life. Clearly suicide is not preserving and protecting human life. It is therefore irrational to kill oneself and cannot be part of God’s plan for our life; hence it is morally unacceptable.
Imagine that someone is considering having an abortion after becoming pregnant due to rape. The same reasoning is going to apply. We ought to preserve and protect human life and hence an abortion in this case is morally wrong.
However, as we will see, Aquinas thinks that there are
some
instances where it
is
morally acceptable to kill an innocent person and therefore there may be occasions when it is morally acceptable to kill a foetus. But how can this be correct? Will this not violate the primary precept about preserving life? The answer is to understand that for Aquinas,
an action is not just about what we do externally but is also about what we do internally
(i.e. our motivations). With this distinction he can show that, for example, killing an innocent
can be
morally acceptable.
To make this clear, Aquinas introduces one of his most famous ideas: the “
Doctrine of Double Effect
”. Let’s see how this works.
| Imagine a child brought up in a physically, sexually and emotionally abusive family. He is frequently scared for his life and is locked in the house for days at a time.  His father bleeds out and dies in a matter of minutes. Do you think the son did anything wrong? |
Many people would say that he did nothing morally wrong and in fact, some might even go as far as to say that he should get a pat on the back for his actions. What about Aquinas? What would he say?
We might think that given the Natural Law to “preserve and protect life” he would say that this action is morally wrong. But, in fact, he would say the son’s action was not morally wrong (Aquinas discusses self-defence in the
Summa Theologica
(II–II, Qu. 64)).
So why is the son killing the father not in direct contradiction with the primary precept? Aquinas asks us to consider the difference between the external act — the fact that the father was killed, and the internal act — the motive.
In our example, the action is one of
self-defence
because of the son’s internal action and because of this, Aquinas would think the killing is morally acceptable. This distinction and conclusion is possible because of Aquinas’s Doctrine of Double Effect which states that if an act fulfils four conditions then it is morally acceptable. If not, then it is not.
1. The first principle is that the act must be a
good
one.
2. The second principle is that the act must come about before the consequences.
3. The third is that the intention must be good.
4. The fourth, it must be for serious reasons.
This is abstract so let’s go back to our example. The act of the son was performed to
save his own life
so that is good — we can tick (1). Moreover, the act to save his life came about first — we can tick (2).  That would be doing evil to bring about good and that is never morally acceptable. The intention of the son was to preserve and protect his life, so the intention was good — tick (3). Finally, the reasons were serious as it was his life or his father’s life — tick (4).
So given that the act meets all four principles, it is in line with the DDE and hence the action is
morally acceptable
, even though it caused someone to die and hence seems contrary to the primary precept of preserving life.
We can draw a contrasting case. Imagine that instead of slashing his father in self-defence, the son
plans
the killing. He works out the best time, the best day and then sets up a trip wire causing his father to fall from his flat window to his death. Does this action meet the four criteria of the DDE? Well, no, because the son’s
intention is to kill the father rather than save his own life
— we must put a cross at (3).
We have already seen that suicide is morally impermissible for Aquinas, so does that mean that
any
action you take that leads knowingly to your own death is morally wrong? No. Because even though the external act of your own death is the same, the internal act — the intention — might be different.
An action is judged via the Natural Law both externally and internally.
Imagine a case where a soldier sees a grenade thrown into her barracks. Knowing that she does not have time to defuse it or throw it away, she throws herself on the grenade. It blows up, killing her but saving other soldiers in her barracks. Is this wrong or right? Aquinas says this is morally acceptable given DDE. If we judge this act
both
internally and externally we’ll see why.
The intention — the internal act — was
not
to kill herself even though she could
foresee
that this was certainly what was going to happen. The act itself is good, to save her fellow soldiers (1). The order is right, she is not doing evil so good will happen (2). The intention is good, it is to save her fellow soldiers (3). The reason is serious, it concerns people’s lives (4).
 The intention is not good and hence the DDE does not permit this suicidal action.
Finally, imagine that a woman is pregnant and also has inoperable uterine cancer. The doctors have two choices; to take out the uterus and save the mother, but the foetus will die; or leave the foetus to develop and be born healthy, but the woman will die. What would Aquinas say in this instance? Well using the DDE he would say that it is morally
acceptable
to remove the cancer.
The action is to remove the cancer; it has the foreseeable consequences of the foetus dying but that is not what is intended. The action — to remove the cancer — is good (1). The act of removing the cancer comes before the death of the foetus (2). The intention to save the woman’s life is also good (3). Finally, the reasons are serious as they are about the life and death of the woman and the foetus (4).
So even though this is a case where the doctor’s actions bring about the death of the foetus it would be acceptable for Aquinas through his Natural Law Theory, as is shown via the DDE.
6. Some Thoughts about Natural Law Theory
There are many things we might consider when thinking through Aquinas’s Natural Law Theory. There are some obvious problems we could raise, such as the problem about whether or not God exists. If God does not exist then the Eternal Law does not exist and therefore the whole theory comes tumbling down. However, as good philosophers we ought always to operate with a
principle of charity
and grant our opponent is rational and give the strongest possible interpretation of their argument. So, let’s assume
for the sake of argument
that God exists. How plausible is Aquinas’s theory? There are a number of things that we can pick up on.
Aquinas’s theory works on the idea that if something is “natural”, that is, if it fulfils its function, then it is morally acceptable, but there are a number of unanswered questions relating to
natural
.
We might ask, why does “natural” matter? We can think of things that are not “natural” but which are perfectly acceptable, and things which
are
natural which are not. For example, wearing clothes, taking medication and body piercing certainly are not natural, but we would not want to say such things are morally wrong.
On the other hand we might consider that violence is a natural response to an unfaithful partner, but also think that such violence is morally unacceptable. So it is not true that we can discover what is morally acceptable or not simply by discovering what is natural and what is not.
Put this worry aside. Recall, Aquinas thinks that reproduction is natural and hence reproduction is morally acceptable. This means that sex that
does not
lead to reproduction is morally unacceptable. Notice that Aquinas is not saying that if sex does not lead to pregnancy it is wrong. After all, sometimes the timing is not right. His claim is rather that if there is
no potential
for sex to lead to pregnancy then it is wrong. However, even with this qualification this would mean a whole host of things such as homosexuality and contraception are morally wrong. We might take this as a reason to rethink Aquinas’s moral framework (we discuss these apparent problems in more detail in Chapter 10).
There is, though, a more fundamental worry at the heart of this approach (and Aristotle’s) to ethics. Namely, they think that
everything
has a goal (telos). Now, with some things this might be plausible. Things such as the eye or an acorn have a clear function — to grow, to see — but what about humans? This seems a bit less obvious! Do humans (rather than our individual parts) really have a
telos
? There are certainly some philosophers — such as the existentialists, for example
Simone de Beauvoir
(1908–1986) — who think that there is no such thing as human nature and no such thing as a human function or goal. But if we are unconvinced that humans have a goal, then this whole approach to ethics seems flawed.
Next we might raise questions about DDE. Go back to our example about abortion. For Aquinas it
is
morally acceptable to remove the uterus even if we know that in doing so the foetus will die. What is not morally acceptable is to intend to kill the foetus by removing the uterus. On first reading this seems to makes sense; we have an intuitive feel for what DDE is getting at. However, when we consider it in more detail it is far from clear.
Imagine two doctors who (apparently) do exactly the same thing, they both remove the uterus and the foetus dies. The one intends to take out the uterus — in full knowledge that the foetus will die — the other intends to kill the foetus. For the DDE to work in the way that Aquinas understands it, this difference in intention makes the moral difference between the two doctors. However, is there really a moral difference? To put pressure on the answer that there is, ask yourself what you think it means to intend to do something. If the first doctor says “I did not intend to kill the foetus” can we make sense of this? After all, if you asked her “did you know that in taking out the uterus the foetus would die?” she would say “yes, of course”. But if she did this and the foetus died, did not she intend (in some sense) to kill the foetus? So this issue raises some complex question about the nature of the mind, and how we might understand intentions.
Finally, we might wonder how easy it is to work out what actually to do using the Natural Law. We would hope our moral theory gives us direction in living our lives. That, we might think, is precisely the role of a moral theory. But how might it work in this case?
For Aquinas, if we rationally reflect then we arrive at the right way of proceeding. If this is in line with the Natural Law and the Divine Law then it is morally acceptable. If it is out of line, then it is not. The assumption is that the more we think, the more rational we become, the more convergence there will be. We’ll all start to have similar views on what is right and wrong. But is this too optimistic? Very often, even after extensive reflection and cool deliberation with friends and colleagues, it is not obvious to us what we as rational agents should do. We all know people we take to be rational, but we disagree with them on moral issues. And even in obviously rational areas such as mathematics, the best mathematicians are not able to agree. We might then be sceptical that as rational agents we will come to be in line with the Natural and Divine Laws.
SUMMARY
|
Aquinas is an intellectual giant. He wrote an incredible amount covering a vast array of topics. His influence has been immense. His central idea is that humans are created by God to reason — that is our function. Humans do the morally right thing if we act in accordance with reason, and the morally wrong thing if we don’t.
Aquinas is an incredibly subtle and complex thinker. For example, his Doctrine of Double Effect makes us to reflect on what we actually mean by “actions”, “intentions” and “consequences”. His work remains much discussed and researched and typically still plays a central role in a Christian Ethics that rejects Divine Command Theory. |
COMMON STUDENT MISTAKES
• Thinking that Aquinas is a Divine Command Theorist.
• Thinking that Eternal Law is something that God decided to write.
• Thinking that Natural Laws are laws of science — e.g. law of thermodynamics.
• Thinking that all the “laws” are absolute.
• Thinking that it is always morally required of us to follow secondary precepts.
• Thinking that Aquinas is committed to there being only one set of secondary precepts for all people in all situations.
ISSUES TO CONSIDER
1. If God exists then what — if anything — do you think that has to do with what is right and wrong?
2. We might answer the “arbitrariness” dilemma by citing God’s nature. Why might this answer be problematic?
3. What is the Eternal Law?
4. What are Natural Laws and primary precepts?
5. What are Human Laws and secondary precepts?
6. What are Divine Laws?
7. Just as a good eye is to see, and a good acorn is to grow then a good human is to…? Is to what? How are we going to finish this sentence?
8. People often talk about what is “natural”? What do you think they mean by this? How useful is the notion of “natural” in a moral theory?
9. Think of a descriptive claim. Think of a prescriptive claim. Why might it be problematic moving from one to the other?
10. If people thought long enough, do you think there would be convergence on what is morally right and wrong?
11. What is the Doctrine of Double Effect?
12. What is the difference — if anything — between intending to bring about some end and acting where you know your action will bring about that end?
KEY TERMINOLOGY
Apparent goods
A priori
A posteriori
Eternal Law
External acts
Natural Law
Primary precepts
Real goods
Secondary precepts
Internal acts
Doctrine of Double Effect
References
Aquinas, Thomas, Summa Theologica , freely available at http://www.summatheologica.info/summa/parts/?p=1
―, Romans (Commentary on the Letter of Saint Paul to the Romans)
Plato, Euthyphro , translated by Benjamin Jowett, freely available at http://classics.mit.edu/Plato/euthyfro.html
|
1 T. Aquinas, Summa Theologica , I, I:8, http://www.summatheologica.info/summa/parts/?p=1 2 T. Aquinas, Romans , 2:15. |


7.5: Safety
Falls Among Older Adults: An Overview
Each year, one in every three adults age 65 and older falls. Falls can cause moderate to severe injuries, such as hip fractures and head traumas, and can increase the risk of early death. Fortunately, falls are a public health problem that is largely preventable.
How big is the problem?
- One out of three adults age 65 and older falls each year, but less than half talk to their healthcare providers about it.
- Among older adults (those 65 or older), falls are the leading cause of injury death. They are also the most common cause of nonfatal injuries and hospital admissions for trauma.
- In 2008, over 19,700 older adults died from unintentional fall injuries.
- In 2009, 2.2 million nonfatal fall injuries among older adults were treated in emergency departments and more than 581,000 of these patients were hospitalized.
- In 2000, direct medical costs of falls totaled a little over $19 billion—$179 million for fatal falls and $19 billion for nonfatal fall injuries. This equals $28.2 billion in 2010 dollars.
What outcomes are linked to falls?
- Twenty to thirty percent of people who fall suffer moderate to severe injuries such as lacerations, hip fractures, or head traumas. These injuries can make it hard to get around or live independently, and increase the risk of early death.
- Falls are the most common cause of traumatic brain injuries (TBI). In 2000, TBI accounted for 46% of fatal falls among older adults.
- Most fractures among older adults are caused by falls. The most common are fractures of the spine, hip, forearm, leg, ankle, pelvis, upper arm, and hand.
- Many people who fall, even if they are not injured, develop a fear of falling. This fear may cause them to limit their activities leading to reduced mobility and loss of physical fitness, which in turn increases their actual risk of falling.
Who is at risk?
Fall-related Deaths
- In 2008, 82% of fall deaths were among people 65 and older.
- Men are more likely to die from a fall. After taking age into account, the fall death rate in 2007 was 46% higher for men than for women.

- Rates also differ by ethnicity. Older non-Hispanics have higher fatal fall rates than Hispanics.
Fall Injuries
- The chances of falling and of being seriously injured in a fall increase with age. In 2009, the rate of fall injuries for adults 85 and older was almost four times that for adults 65 to 74.
- People age 75 and older who fall are four to five times more likely than those age 65 to 74 to be admitted to a long-term care facility for a year or longer.
- Women are more likely than men to be injured in a fall. In 2009, women were 58% more likely than men to suffer a nonfatal fall injury.
- Rates of fall-related fractures among older women are more than twice those for men.
- Over 90% of hip fractures are caused by falls. In 2007, there were 264,000 hip fractures and the rate for women was almost three times the rate for men.
- White women have significantly higher hip fracture rates than black women.
How can older adults reduce risk?
To lower their hip fracture risk, older adults can:
- Get adequate calcium and vitamin D—from food and/or from supplements.
- Do weight bearing exercise.
- Get screened and treated for osteoporosis.
Falls in the Bathroom
Activities that take place in the bathroom, such as showering and bathing, are a simple part of most peoples’ daily routine. Yet, slips in the tub and falls in the shower or from the toilet may cause serious injuries.
According to a CDC study published in the Morbidity and Mortality Weekly Report , an estimated 234,000 people ages 15 and older were treated in U.S. emergency departments (ED) in 2008 for injuries that occurred in bathrooms. Four out of 5 of these injuries were caused by falls—which can have especially serious consequences for older adults.
Almost one-third (30 percent) of adults aged 65 and above who were injured in bathrooms were diagnosed with fractures. Among adults aged 85 and older, 38 percent were hospitalized as a result of their injuries.
Read the new CDC study on bathroom injuries and the related press release.
Steps for Safety in the Bathroom
Certain home safety measures may reduce the risk for all household members of being injured in the bathroom. Some prevention strategies include:
- Adding non-slip surfaces and grab bars inside and outside the tub or shower to reduce slips and falls.
- Installing grab bars next to the toilet for added support, if needed.
Preventing Falls among Older Adults
Four out of five injuries that took place in bathrooms in 2008 were the result of falls. Falls can be especially dangerous for adults ages 65 and older.
Older adults can take steps to make falls less likely. If you are 65 or older, take the following steps to reduce your risk of falling:
- Get some exercise : Lack of exercise can lead to weak legs, which increases the chance of falling. Exercise programs like Tai Chi can increase strength as well as improve balance, making falls less likely for aging adults.
- Be mindful of medications: Some medicines—or combinations of medicines—can have side effects like dizziness or drowsiness. This can make falls more likely. Having a doctor or pharmacist review all your medications can help reduce the chance of risky side effects and drug interactions.
- Keep your vision sharp: Poor vision can make it harder to get around safely. To help make sure you’re seeing clearly, have your eyes checked every year and wear glasses or contact lenses with the right prescription strength.
- Eliminate hazards at home. About half of all falls happen at home. A home safety check can help identify fall hazards, like clutter and poor lighting that should be removed or changed.
Make your own home safe for older adults.
- What would you need to do to make your home safer for older adults?
- How much would it cost and how much time would it take for you to make these changes?
Violence Elder Abuse
Elder maltreatment includes several types of violence that occur among those ages 60 and older. The violence usually occurs at the hands of a caregiver or a person the elder trusts. There are six types of elder maltreatment:
- Physical—This occurs when an elder is injured as a result of hitting, kicking, pushing, slapping, burning, or other show of force.
- Sexual—This involves forcing an elder to take part in a sexual act when the elder does not or cannot consent.
- Emotional—This refers to behaviors that harm an elder’s self-worth or emotional well being. Examples include name calling, scaring, embarrassing, destroying property, or not letting the elder see friends and family.
- This is the failure to meet an elder’s basic needs. These needs include food, housing, clothing, and medical care.
- This happens when a caregiver leaves an elder alone and no longer provides care for him or her.
- Financial—This is illegally misusing an elder’s money, property, or assets.
Elder maltreatment can have several physical and emotional effects on an elder.
Many victims suffer physical injuries. Some are minor like cuts, scratches, bruises, and welts. Others are more serious and can cause lasting disabilities. These include head injuries, broken bones, constant physical pain, and soreness. Physical injuries can also lead to premature death and make existing health problems worse.
Elder maltreatment can have emotional effects as well. Victims are often fearful and anxious. They may have problems with trust and be wary around others.
Many cases are not reported because elders are afraid to tell police, friends, or family about the violence. Victims have to decide: tell someone they are being hurt or continue being abused by someone they depend upon or care for deeply.
Risk Factors
A combination of individual, relational, community, and societal factors contribute to the risk of becoming a perpetrator of elder maltreatment. They are contributing factors and may or may not be direct causes.
Understanding these factors can help identify various opportunities for prevention.
Risk Factors for Perpetration
-
Individual Level
- Current diagnosis of mental illness
- Current abuse of alcohol
- High levels of hostility
- Poor or inadequate preparation or training for care giving responsibilities
- Assumption of caregiving responsibilities at an early age
- Inadequate coping skills
- Exposure to maltreatment as a child
-
Relationship Level
- High financial and emotional dependence upon a vulnerable elder
- Past experience of disruptive behavior
- Lack of social support
-
Community Level
- Formal services, such as respite care for those providing care to elders, are limited, inaccessible, or unavailable
-
Societal Level
- A culture where there is high tolerance and acceptance of aggressive behavior.
- A culture where health care personnel, guardians, and other agents are given greater freedom in routine care provision and decision making.
- A culture where family members are expected to care for elders without seeking help from others.
- A culture where persons are encouraged to endure suffering or remain silent regarding their pains.
- A culture where there are negative beliefs about aging and elders.
In addition to the above factors, there are also specific characteristics of institutional settings that may increase the risk for perpetration of vulnerable elders in these settings, including: unsympathetic or negative attitudes toward residents, chronic staffing problems, lack of administrative oversight, staff burnout, and stressful working conditions.
Protective Factors for Elder Maltreatment
Protective factors reduce risk for perpetrating abuse and neglect. Protective factors have not been studied as extensively or rigorously as risk factors. However, identifying and understanding protective factors are equally as important as researching risk factors.
Several potential protective factors are identified below. Research is needed to determine whether these factors do indeed buffer elders from maltreatment.
The goal is to stop elder maltreatment before it starts. While not much research has been done, there are several things we can do to prevent it:
- Listen to elders and their caregivers
- Report abuse or suspected abuse to Adult Protective Services
- Educate oneself and others about how to recognize and report elder abuse
- Learn how the signs of elder abuse differ from the normal aging process
- If you take care of an elder here are some things you can do to prevent violence:
- Get help from friends, family, or local relief care groups
- Take a break—if only for a couple of hours
- Involve more people than just family in financial matters
- Find an adult day care program
- Seek counseling or other support if you are feeling depressed
- If you are having problems with drug or alcohol abuse, get help
Sources
Falls Among Older Adults: An Overview: www.cdc.gov/HomeandRecreationalSafety/Falls/adultfalls.html
Falls in the Bathroom: http://www.cdc.gov/features/fallrisks/
Violence Elder Abuse: Centers for Disease Control, http://www.cdc.gov/violenceprevention/pdf/EM-FactSheet-a.pdf