Sunday, June 24, 2012

Drugs by Design


     Designer shoes, clothes, luggage - today, the name tag of companies such as Gucci or Prada add 'value' or, at least are often deemed more valuable by the purchaser than similar or even the same item without the cachet of the designer logo. These designer products cater to the consumer who wishes to be noticed and often feels the need to declare to the world that he or she has the wealth (and the sophistication) to own this special product.
Prada Men's Shoe

     Designer drugs have often been called 'research chemicals', 'bath salts', or 'plant food'. A discussion about 'designer drugs' is not about what you can afford or how the world sees you. A discussion about 'designer drugs' is, effectively, a discussion about chemistry.
     'Designer' substances are not (usually) created or consumed for reasons of vanity or glamour but rather have a more 'practical' purpose. Designer drugs are chemicals that have been created to avoid the restrictions of drug laws, altering the drug in question just enough to place it in a different class than the 'prohibited' substance but not altered enough that its effects are less significant.
'Designer' Drugs

     'Designing' of the new drug usually involves starting with the drug in question and modifying its chemical structure or occasionally by finding drugs with entirely different chemical structures that produce similar effects to (usually illegal) recreational drugs. These new substances can then be sold on the 'gray market' where little or no regulation is applied.
     The use of the term 'designer drug' was first used by in the 1980s but the first appearance of what would now be termed designer drugs occurred as early as the 1920s.
     Perhaps the best known of the early 'designer drugs' was a chemical alteration of morphine (a diacetyl ester), created in 1874 by an English chemist and then marketed as a cough suppressant in 1899 by Bayer Pharmaceuticals. The new drug was ten times more effective than codeine to treat coughs, was a better pain-killer than morphine, was safe and non-habit forming. They named it heroin (see post: AHistory of Heroin).

     The second International Opium Convention (Geneva, 1925) specifically banned morphine (other than by prescription) which led to heroin (as well as a number of alternative esters of morphine) to be manufactured and sold on the 'gray', but effectively still legal market. When heroin was declared illegal, the drug trade simply adapted.
     By 1925 in Egypt, narcotic addiction had become such a problem that a law was passed making trafficking as well as possession, criminal offences.  The price of narcotics increased significantly and the dangers of imprisonment for narcotics use sent users into hiding but chemistry came to their rescue.
     A chemist by the name of Dr. Hefti of Altstatten, a suburb of Zurich, began to produce a drug he called 'Dionyl' (see post: Dawn of the Drug Dealers), indistinguishable from heroin but different enough chemically that it could be sold without infringing Swiss narcotics laws.
Zurich

     Dionyl (acetylpropionylmorphine) is an opiate analogue, a derivative of morphine, developed in the early 1900s after first being synthesised in Great Britain in 1875 but shelved along with heroin and various other esters of morphine.
     Dionyl was never used medically but was sold as one of the first ' designer drugs' for around five years. The effects of this designer drug was virtually identical to heroin and consequently dionyl was  banned internationally in 1930 by the Health Committee of the League of Nations.
Morphine

     There were many other narcotic alterations, created to skirt the laws. Benzylmorphine  was a semi-synthetic narcotic, created in 1896. It was similar to codeine, except with a benzyl group attached to the basic morphine molecule just as the methyl group creates codeine. It is about 90 per cent as strong as codeine by weight.
     Diethyl ether (ethyl ether, ether, ethoxyethane), is a compound with the formula (C2H5)2O. It is a colorless and highly flammable liquid. It is used as a solvent, as fuel and was once used as a general anesthetic. Because of these anesthetic effects, it has also been used as a recreational drug.
     Ether was likely created by Jabir ibn Hayyan, a scientist 'of all trades', said to have been the first practical alchemist. He was an astronomer, an astrologer, an engineer, a geographer, philosopher, physicist, pharmacist and physician born in Persia in 721 AD.
Jabir ibn Hayyan

     Hayyan's creation was first synthesized in 1540 by Valerius Cordus (a sixteenth century German physician) who named it 'sweet oil of vitriol', synthesized by the distillation of ethanol with sulfuric acid (oil of vitriol).
     In the late 19th century, it was not considered proper for women to drink alcohol, and so a 'designer drug' was created. Instead, the women took extremely potent 'medicines' when the men did their drinking. One product was called 'Hoffmannstrophen' or 'Hoffmann's Drops', made up of 3 parts alcohol to 1 part ether.
     There was also 'compound spirit of ether', ('Hoffmann's anodyne', 'aetheris spiritus compositus'), a solution of ether and ethereal oil in alcohol, used as a painkiller or sedative. Its use as an anesthetic drug was introduced by Friedrich Hoffman, an 18th century German physician and chemist.
Valerius Cordus

     Ether will burn the mouth when taken straight but when mixed with alcohol it is possible to ingest orally. In the 19th century and early 20th century ether drinking became popular among Polish peasants. It is a traditional and still relatively popular recreational drug among Lemkos, a small ethnic group living in the Carpathian Mountains. The ether is consumed in a small quantity poured over milk or water with sugar or orange juice in a shot glass.
     In more recent times (1980s to present), the use of the term designer drug initially referred to various synthetic opioid drugs, based mostly on the fentanyl molecule (see post: A Basket Full of Narcotics).
     One, narcotic derivative called MPPP (desmethylprodine) was found to contain MPTP, an nerve toxin impurity which caused brain damage that could result in a syndrome identical to full-blown Parkinson's Disease, from just one dose. Other problems were highly potent fentanyl analogues, which were sold as China White (α-methylfentanyl) which caused several accidental overdoses.
Sweet Oil of Vitriol (Ether)

     One of the main problems for law makers faced with the onslaught of hundreds of new, often poorly-defined drugs which began to appear on the illicit market was how to develop legislation to ban or regulate their use. Frequently, novel drugs have appeared directly in response to legislative action, drugs similar to the compound that had recently been banned (just like Dionyl had been similar but not identical to heroin).
     Many of the chemicals fall under the various drug analogue legislations in certain countries, but Most countries do not have general analogue legislation, where, if a new drug is similar enough to the banned drug, it too is also banned. In these cases, novel compounds can fall outside of the law after only minor structural modifications.

Ethnic Lemkos
     The United States tried to address this problem with the Controlled Substances Act and the Controlled Substance Analogue Substance Analogue Enforcement of 1986, which attempted banned designer drugs pre-emptively by making it illegal to manufacture, sell, or possess chemicals that were substantially similar in chemistry and pharmacology to Schedule I or Schedule II drugs.
     In Germany, Canada, the United Kingdom, and Sweden, new drugs are banned when they become recognized as a danger. In Sweden, the police and customs are able to seize drugs that are not on the list of drugs covered by the anti-drug laws if the police suspect that the purpose of the holding is related to drug abuse.
     Australia has enacted legislation, banning drugs based on chemical structure alone, making chemicals illegal even before they are created. Even this type of law however, would still not cover drugs that have no structural similarity to any controlled drug, even if they produced similar effects.
     In the late 1990s and early 2000s, there was an explosion in designer drugs being sold over the internet. The term of 'research chemicals' was coined by some marketers of designer drugs in an attempt to by-pass the 'intent' clause of the U.S. 'analogue drug laws'. Despite this, by July, 2004, the 'Drug Enforcement Administration' (DEA) in 'Operation Web Tryp', raided multiple suppliers (JLF Primary Materials) and vendors ('RAC Research').
     These internet companies were knowingly carrying on business in a 'gray' area. The majority of these chemical suppliers sold 'research chemicals' in bulk form as powder, not as pills, as selling in pill form would invalidate the claims that they were being sold for non-consumptive research.
Amanita Muscaria

     JLF Primary Materials (also known as JLF Poisonous Non-Consumables) was a mail order company based in Elizabethtown, Indiana, specializing in plants and chemicals, especially those reputed to have psychoactive properties such as the mushroom, amanita muscaria (see post: The High Priest) and Trichocereus pachanoi, also known as the San Pedro cactus (see post: Drugs Used in Religion-The New World).
     The company made no claim as the quality of any of their products. and the JLF catalogue proudly bore 'The Longest Warning Label You've Ever Seen'. JLF stated in their advertisements that:
     'Our products are poisonous and are not intended for human or animal consumption. Do not take internally. JLF assumes no liability for damages resulting from prohibited use (abuse) of these products. Customer automatically accepts all responsibilities for any consequences incurred from said misuse or abuse. Check local and state laws before ordering.'
San Pedro Cactus

     But, 'designer drug' became best known with the increased use of MDMA (Ecstasy) during the mid 1980s. MDMA (3,4-methylenedioxy methamphetamine) is a synthetic, psychoactive drug that is chemically similar to the stimulant methamphetamine and the hallucinogen mescaline.
     The compound was first synthesized by Merck in 1912 but not put into use until the 1940s when it was tested as a 'truth drug' by the CIA.In the 1960s, an American biochemist, Alexander Shulgin, researching psychedelic drugs, tested MDMA on himself. Shulgin promoted the drug for 'therapeutic' possibilities and others began to use MDMA in marriage therapy and psychotherapy.
Dr. Alexander Shulgin

     


     The early alternative name for MDMA was 'Adam', a reference to the innocent 'inner child' from Eden. Once the euphoric effects of the drug became known, it became fashionable as early as 1984 in the Dallas 'Starck Club', known under the slang name of 'X' or 'X-T-C' (hence Ecstasy).
     By mid-1984, sale of MDMA was declared illegal and possession was illegal within the next 12 months. Ecstasy has become the 'drug of choice' at modern 'raves', gatherings with loud music and flashing lights, flooding the senses. There have been 3 phases associated with the ecstasy high. Within the first hour, your senses 'light up', you start 'rushing'. The next is the plateau stage, lasting about 4 hours followed by the last stage, a long, gentle 'comedown' and 'afterglow' which may last into the next day.
The Starck Club, Dallas

     MDMA produces feelings of increased energy, euphoria, emotional warmth, and distortions in time, perception, and tactile experiences, exerting its primary effects in the brain on neurons which use the neurotransmitter serotonin (see post: The Genetics of Drug Addiction).
     MDMA binds to the serotonin transporter and increases and prolongs the serotonin signal. Through several mechanisms, MDMA accentuates the effects of serotonin and also has similar effects on the neurotransmitter, norepinephrine, causing increased heart rate and blood pressure. MDMA also releases dopamine, but to a much lesser extent.
MDMA (Ecstasy)

     MDMA can produce confusion, depression, sleep problems, drug craving, and severe anxiety. These problems can occur soon after taking the drug or, sometimes, even days or weeks after taking MDMA. Chronic users perform more poorly than nonusers on certain types of cognitive or memory tasks. One study in nonhuman primates showed that exposure to MDMA for only 4 days caused damage to serotonin nerve terminals that was still evident 6 to 7 years later. 
     Phencyclidine (1-(1-phenylcyclohexyl)piperidine), commonly also known as PCP with street names such as angel dust, Cadillac, DOA (dead on arrival), peace pill, rocket fuel, synthetic marijuana, zombie and many others is a recreational dissociative drug (a type of hallucinogen which reduce or block signals to the conscious mind from other parts of the brain).
Phencyclidine (PCP)

     PCP was synthesized in 1926 and tested as a human anesthetic by US pharmaceutical company Parke Davis. Despite the production of halluciantions, manic episodes, disorientation and delirium, the drug was marketed for human use in 1959.
     Use in humans was abandoned because many patients became agitated, delusional and irrational while recovering from their operations. PCP use was eventually limited to anesthetizing and tranquilizing large animals but is now illegal, still sold on the street, made illegally in labs.
Parke Davis

     In its pure form, PCP is a white crystalline powder with a bitter taste. It can be mixed with dyes and can be sold in tablets, capsules and coloured powder. PCP is easily synthesized and is often passed off to street buyers as another drug such as methamphetamine, mescaline, LSD even THC.
     For smoking, it can be applied to parsley, oregano, even marijuana (called 'superweed', 'killerweed', 'supergrass' or 'peaceweed'). It is usually snorted or ingested but also, at times, injected.
     When smoked or snorted, PCP rapidly enters the bloodstream and then the brain. PCP acts by altering the distribution of the neurotransmitter glutamate in the brain, this neurotransmitter involved in a person's perception of pain, responses to the environment, and memory. PCP also alters dopamine levels in the brain.
     The effects of PCP on a person are unpredictable. The way a person feels after taking PCP depends on many factors such as age, body weight, and sex, the amount of PCP consumed, whether the person has eaten recently as well as the use of other drugs, including non-prescription, prescription, and street drugs. Short-term effects of PCP vary greatly and it is often impossible to predict the behaviour of someone who has taken the drug. PCP can produce feelings of well-being and relaxation in users but, in others, can induce severe traumatic effects such as feelings of anxiety, fear, panic, agitation and paranoia.
     Overdoses are life-threatening. Intoxication with PCP can cause convulsions, coma, hyperthermia and death (usually because breathing stops). There are no antidotes for PCP intoxication and comas resulting from PCP may last 7-10 days.
     Use of PCP over an extended period of time can lead to memory loss, difficulties speaking and thinking. These symptoms can last for a year or more after last use. Severe anxiety and depression are common and may continue indefinitely.
Ketamine

     Ketamine (initially known as CI-581)was synthesized in 1962 as a derivative of PCP by Parke Davis. Ketamine's shorter duration of action and made it favorable over PCP as a 'dissociative anesthetic'.  The FDA approved the drug for medical use in 1970 and ketamine anesthesia was first given to American soldiers during the Vietnam War. It is a rapid acting anesthetic drug used mainly by veterinarians and sometimes in human surgery.
     Commercial ketamine is a liquid while the street drug is usually sold as a powder. The powder may be dissolved in a liquid, snorted, or smoked in a cigarette. Ketamine dissolves in liquid and it is odourless and tasteless, allowing it to be slipped into drinks. Its sedative effects have been used to prevent victims from resisting sexual assault and for this reason, it can be referred to as a 'date rape' drug.
Ketamine Powder

     Ketamine is a NMDA receptor antagonists ( inhibits the action of, the N-Methyl d-aspartate receptor). Toxic changes in brain cells (Olney lesions) have been shown to be induced in the brain (of rats) by these dissociative anesthetics (ketamine and PCP).
     Known in the club scene as vitamine Kspecial K, breakfast cereal, kit-kat, and many other names, ketamine became popular in the early 1970s in dance clubs a s fashionable hallucinogenic. In the brain, the drug acts by redistributing the neurotransmitter glutamate which is involved in memory, learning, the perception of pain and responses to the environment.
Brain Scan Showing Evidence of Olney Lesions

     The speed at which ketamine reaches the brain varies greatly. After snorting the effects are usually felt within 1 to 10 minutes and can last for about one hour. When taken by mouth the effects are felt more slowly but may last up to four hours.
     Ketamine produces a drunken, dizzy feeling. Some people describe 'near-death' or 'out-of-body' experiences and sensations of weightlessness. This experience is often described as being in or 'going through the k-hole'.
     Ketamine produces vivid dreams or hallucinations which may be intense and terrifying can cause rapid loss of consciousness if injected. The drug can also produce the sensation that the mind is separated from the body (dissociation).

     Ketamine can cause vomiting. When taken in large amounts, ketamine may depress the central nervous system, leading to slower breathing, seizures, severe high blood pressure, coma and possibly death.  In large doses, like amphetamines, it can cause schizophrenia-like psychosis.
Through the 'K' Hole?

     Methaqualone (Known as Quaalude in North America, Mandrax (in combination with an anti-histamine) in Europe) is a sedative-hypnotic similar in effect to barbiturates. Methaqualone was first synthesized in India in 1951 and patented in the US in 1962 as a treatment for insomnia and as a muscle relaxant.

     David Bowie sang about 'Quaaludes and Red Wine' and the American novelist, Edmund White described the effects as 'twilight drowsiness, lowering of the pain threshold and a stripping away of the defences and inhibitions, leading some to take the drug for heavy 'S and M' sessions.'
David Bowie-'Quaaludes and Red Wine'

     Recreationally, the drug was called 'mandies', 'mandrake', 'mandrix' or 'disco biscuits') and 'luding out' was a popular college pastime. Smoking methaqualone, either alone or with additives was popular in the US during the mid-1970s.
     The drug was banned in 1984 but is still continued to be produced in illegal labs. Today, methaqualone is one of the most commonly used hard drugs in South Africa, due to its relatively low cost. It is known as M-pills, buttons, 'geluk-tablette' (happy tablets) or smarties and is crushed and mixed in a pipe with marijuana.

     Amyl nitrite, a compound with the formula  C5H11ONO was first used in the mid-1800s but became popular as an inhalant in gay dance clubs during the 1960s. This drug, along with its similar cousins, butyl nitrite, isobutyl nitrite and octyl nitrite were known as 'poppers' and often sold as incense or room deodorisers.  
     Trade names included Rush, Locker Room, Thrust and Lightening Bolt.
     Amyl nitrite is a vasodilator (it expands blood vessels and lowers blood pressure) and is used medically to treat heart disease such as angina and also to treat cyanide poisoning. Physical effects include decrease in blood pressure, headache, flushing of the face, increased heart rate, dizziness, and relaxation of involuntary muscles, especially the walls of blood vessel and the anal sphincter.

     The effects are rapid, typically within a few seconds and disappear soon after (within minutes). As an inhalant, the drug that induces a brief euphoric state, and when combined with other intoxicant stimulant drugs such as cocaine or ecstasy, the euphoric state intensifies and can be prolonged.
     All of these drugs - from morphine derivatives to sedatives to the euphorics of vasodilators - have been created or used for their 'psychoactive' properties, to attain pleasure, euphoria, shed anxiety or feel powerful. And there are literally hundreds more, some with mechanisms of action similar to the drugs discussed, others which mimic marijuana or other chemicals.
Rush 'Poppers'

     In the late 1990s and early 2000s, a new type of 'designer drug' came onto the scene, one which did not aim to bring pleasure to the user but rather enhance the user's performance, to make him/her faster, stronger, more agile. These new 'designer drugs' were the anabolic steroids created for competitive athletes.
     Steroids had been banned by the International Olympic Committee in 1976, but the huge number of different anabolic agents available for human and veterinary use overwhelmed the ability of laboratories to test for all available drugs had always lagged behind the ability of athletes (and their chemists/doctors) to find new compounds to enhance their performance.
   
Effects of Anabolic Steroids
     Many of the new compounds are undetectable with standard tests and, when a new test is devised, the chemist will often have already created the 'next generation' of anabolic drug which can slip under the radar of detection.

     'Bath salts' may resemble the sweet-smelling epsom salts some people put in their bath but, on the street, the term refers to the latest in 'designer drugs'. Known as 'Ivory Wave', 'Purple Wave', 'Vanilla Sky' and 'Bliss', these 'bath salts' have been the reason for thousands of calls to poison centers across the U.S. in 2011-2012.
     Methylenedioxypyrovalerone (MDPV) is a stimulant which acts on certain neurotransmitters in the brain (norepinephrine-dopamine reuptake inhibitor). MDPV was developed in 1969 but started to be used as a designer drug in 2004. Bath salts containing MDPV  are sold as recreational drugs in gas stations and convenience stores labelled as 'bath salts'.

     Another chemical commonly found in 'bath salts' is mephedrone (4-methylmethcathinone) another synthetic stimulant (also known as meph, drone, and MCAT) in the same class as the amphetamines. The drug is manufactured in China and is chemically similar to the cathinone compounds found in the khat plant commonly chewed in eastern Africa and Yemen. It comes in the form of tablets or a powder, which users can swallow, snort or inject.
     Agitation, paranoia, hallucinations, high blood pressure, chest pain and the tendency to suicide (even days after the stimulating effects of the drug have worn off) are all commonly seen in cases of 'bath salt' consumption.
Methylenedioxypyrovalerone (MDPV)

     In May 2012, police in Florida shot a man who was eating the face of his unconscious victim, 'the face-eater' having apparently consumed 'bath salts'.
     Designer drugs are perhaps a pharmacological 'arms race'. Laws backed by better detection lead to the development of a different or 'stealthier' compound, triggering new detection techniques and new laws which, of course, create the 'incentive' (because the market and the money are always there) to create another 'better research chemical', a 'better' designer drug.

   
Mephedrone

     *Designer drugs: subject of research for the novel The Judas Kiss- Amazon Kindle.

Tuesday, June 12, 2012

A Basket-Full of Narcotics



'To numb' or 'to deaden', was the original meaning of 'narcotic', a term first used by the ancient Roman-Greek physician Galen.
Galen

     Originally, narcotic referred to any substance that relieved pain, dulled the senses, or induced sleep but today, the term is used in a number of ways. Strictly speaking, in medical terms, a narcotic is a substance that binds at opioid receptors (see post: The Genetics of Drug Addiction), cellular membrane proteins activated by substances such as heroin or morphine. Non-medical usage of the term 'narcotic' often refers to any illicit substance.
     From a legal perspective, 'narcotic' refers to opium, opium derivatives, and their semi-synthetic substitutes, but not always. In the United States of America, from a legal perspective, cocaine which is not a true narcotic is referred to as such because of its 'numbing' effects.
Papaver Somniferum
-The Opium Poppy

     So this term, 'narcotic' remains confusing. Historically, it has been used to refer to substances such as alcohol and tobacco (Edward Hitchcock, 1830), mandrake root, containing hallucinogenic alkyloids (Galen), cocaine and even cannabis. Today, legislation in many countries classifies cocaine and cannabis as 'narcotics'.

     The use of narcotics (substances that bind to opioid receptors) pre-dates history. The opium poppy (papaver somniferum) was (and still is) a prime source of the raw drug (opium).


Mandrake Roots

     Opium, which itself contains up to 12% morphine, was used by the Minoans, ancient Greeks, Egyptians and Sumerians. Many famous writers and artists have used opium in one form or another. Wars have been (and still are) fought over control of this drug.
   
     But the most common usage of narcotics today is in medicine and nowhere are narcotics more important than for surgery and in the operating theater.
     The historical importance of the opium poppy and the importance of narcotics in general in anaesthesia is noted by the Royal College of Anaesthetists (U.K.) which prominently displays the fruit and flower of the opium poppy on its coat of arms.


Opium 'Sap' on Poppy Bud




     These drugs, (opioid-receptor) narcotics, are obviously an important medical tool. Narcotics can relieve pain and promote sleep. But they can be as dangerous as they can be useful.
     Narcotics can induce euphoria, slow down and even stop a patient's breathing and can easily become addictive, forcing the user to seek out more of the drug in ever increasing doses as his/her metabolism becomes accustomed to the drug and demands more in order to achieve the same state of euphoria, the same 'high'.


     Most of us have heard of opium. Most of us are familiar with morphine but these two types of narcotics are only the earliest forms of the drug, the basic template(s) from which more sophisticated types of narcotic have been created.
The Royal College of Anaesthetists (UK)

     But how many kinds of narcotics are there? Close to one hundred if synthetic and semi-synthetic, antagonists and inverse-antagonists, metabolites and other derivatives are included. All are based on the structure of the morphine molecule (they all attach to similar opioid receptors).

     In medicine, there are different narcotics for different purposes - some act quickly, others more slowly; the effects of some last hours, others only minutes. Some are highly addictive.
     Historically, heroin was one of the best pain relievers ever created and was used for obstetrical cases even into the 1980s. Because of its highly addictive qualities, however, heroin is no longer used in the medical field.


Chemical Structure of Morphine


   
     Potency of the specific narcotic stands out as one of the most important (and dangerous) aspect of these newer narcotics. Fentanyl, for instance, can be given intravenously (IV) or even via a skin patch. Given by vein, it is more than 100 times as powerful as morphine, its effects are immediate but last less than one hour in the body (morphine may last up to 5 hours). The shorter lasting effects of fentanyl would suggest that this particular morphine derivative would be less appealing for drug abusers/street addicts but this is not always the case.


Chemical Structure of Heroin
     Known as 'street heroin', fentanyl has become a serious addiction among addicts in Estonia, where it first appeared during a heroin shortage. The light brown, sugary powder can be dissolved in water then injected but a dose as small as 2 milligrams can be lethal. Sufentanil is another morphine derivative, even more potent than fentanyl (up to 1000 times more potent than morphine).


     Below, is a summary of some narcotic medications and how they differ:

Drug(intravenous)    Relative Strength    Onset of Action    Duration of Action

morphine                          1.0                  20 minutes            1-2 hours


meperidine(pethidine)         0.1                  1 minute                2-4 hours


hydromorphone                10                    15 minutes             >5 hours


fentanyl                           75-125               immediate             0.5-1 hour


sufentanil                         500-1000           1.4-4 minutes            ?

     These operating room narcotics are very different one from the other. Some are long-acting but take a relatively long time for the effects to 'kick in' (morphine). Others have a quick onset, are short acting but are extremely powerful (fentanyl, sufentanil). How does the doctor administering these drugs (to the patient or to himself) make sure he is giving the correct narcotic? They are all the color of water...Mistakes are easy to make.


     *Physicians and drug addiction: subject of research for the novel Whip the Dogs - Amazon Kindle