Psychopharmacology

Subject:
Psychopharmacology

Submitted by:
Rida

Roll No.

MS Clinical Psychology Semester II

Barbiturate:

Introduction:
Barbiturates are derivatives of barbituric acid and are synthesized by condensation of
malonic acid derivatives with urea derivatives. Barbiturates, which first appeared in 1903,
continue to be used today. Barbiturates act by depressing the central nervous system and slowing
down many areas of the brain, assisting the induction of sleep. Perhaps the greatest danger with
barbiturates is that, as with many drugs, they are addictive.

Drugs Acting Upon the Central Nervous System:

The central nervous system directs the functions of all tissues of the body. The peripheral
nervous system receives thousands of sensory inputs and transmits them to the brain via the
spinal cord. The brain processes this incoming information and discards 99% as unimportant.
After sensory information has been evaluated, selected areas of the central nervous system
initiate nerve impulses to organs or tissue to make an appropriate response.

Chemical influences are capable of producing a myriad of effects on the activity and
function of the central nervous system. Since our knowledge of different regions of brain
function and the neurotransmitters in the brain is limited, the explanations for the mechanisms of
drug action may be vague. The known neurotransmitters are: acetylcholine which is involved
with memory and learning; norepinephrine which is involved with mania-depression and
emotions; and serotonin which is involved with biological rhythms, sleep, emotion, and pain.

Central Nervous System Stimulants:

Stimulants are drugs that exert their action through excitation of the central nervous
system. Psychic stimulants include caffeine, cocaine, and various amphetamines. These drugs are
used to enhance mental alertness and reduce drowsiness and fatigue. However, increasing the
dosage of caffeine above 200 mg (about 2 cups of coffee) does not increase mental performance
but may increase nervousness, irritability, tremors, and headache. Heavy coffee drinkers become
psychically dependent upon caffeine. If caffeine is withheld, a person may experience mild
withdrawal symptoms characterized by irritability, nervousness, and headache.

Amphetamines:

The stimulation caused by amphetamines is caused by excessive release of

norepinephrine from storage sites in the peripheral nervous system. It is not known whether the
same action occurs in the central nervous system. Two other theories for their action are that they
are degraded slower than norepinephrine or that they could act on serotonin receptor sites.
Therapeutic doses of amphetamine elevate mood, reduce feelings of fatigue and hunger, facilitate
powers of concentration, and increase the desire and capacity to carry out work. They induce
exhilarating feelings of power, strength, energy, self-assertion, focus and enhanced motivation.
The need to sleep or eat is diminished.

Levoamphetamine (Benzedrine), dextroamphetamine (Dexedrine), and

methamphetamine (Methedrine) are collectively referred to as amphetamines. Benzedrine is a
mixture of both the dextro and levoamphetamine isomers. The dextro isomer is several times
more potent than the levo isomer. The misuse and abuse of amphetamines is a significant
problem which may include the house wife taking diet pills, athletes desiring an improved
performance, the truck driver driving non-stop coast to-coast, or a student cramming all night for
an exam.

Barbiturates commercial names

Widespread concern about the safety of barbiturates eventually led to the development of
alternative medicines and, since the 1970s, barbiturates have been widely replaced by reputedly
“safer” benzodiazepine drugs.

1. Phenobarbital
2. Pentobarbital
3. Amobarbital
4. Secobarbital
5. sodium thiopental

are the more commonly used barbiturates for insomnia.

Barbiturates are the drugs that are derived from barbituric acid (Wesson and

Smith, 1977). However, barbituric acid does not have any therapeutic activity, but, its derivatives
enhance the action of GABA. Barbiturates were first used in medicine in the early 1900s and
became popular in the 1960s and 1970s in treatment for anxiety, insomnia, or seizure disorders.
They evolved into recreational drugs that some people used to reduce inhibitions, decrease
anxiety, and to treat unwanted side-effects of illicit drugs. This fact precludes barbiturates from
being used in surgery or in the presence of other analgesics. With regular use, tolerance to the
effects of barbiturates develops. There are several side-effects in older adults, pregnant women,
and babies. 

 Surface Activity in Drug Action:

Barbiturates are known to be surface active and hence should be capable of generating

liquid membranes at the interface in accordance with Kesting's liquid membrane hypothesis.
There are several instances where the role of surface activity in the biological actions of
barbiturates has been indicated. In these studies the formation of liquid membranes in series with
a supporting membrane, either by barbiturates alone or by barbiturates in association with
membrane lipids (lecithin and cholesterol), has been demonstrated. For this, data on the
hydraulic permeability in the presence of lecithin-cholesterol-barbiturate mixtures have been
utilized.

 Soporific Agents (Hypnotics and Sedative Drugs):

Barbiturates  action on the CNS is expressed in very diverse ways, ranging from small
changes in patient behavior to the onset of more obvious effects such as sedation, sleep, or
general anesthesia, depending, as a rule, on the administered dosage. The pharmacological basis
of such CNS depression is extremely complex in its own right. Drugs act on various parts of the
CNS by interfering with transmission of impulses in synapses, and generally speaking, stopping
transmission of impulses to the spinal cord.

Clinically beneficial barbiturates are conventionally subdivided into four groups:

1. Long-acting barbiturates (6–8 h): mephobarbital, metharbital, and phenobarbital.

2. Intermediate-lasting barbiturates (4–6 h): amobarbital, butabital, and talbutal.
3. Short-acting barbiturates (2–4 h): pentobarbital, secobarbital.
4. Ultrashort-acting barbiturates (10–30 min): methohexital, thiopental.

Despite the fact that the present classifications are extremely convenient for practical medical
personnel, it should be kept in mind that the duration of drug action especially of the first three
groups of compounds depends on various factors besides the structure of the compounds, such as
drug form, method of administration, pathology for which the drug is being used, general
treatment time, etc.

 Long-acting barbiturates:
 Phenobarbital

Phenobarbital, 5-ethyl-5-phenylbarbituric acid or 5-ethyl-5-phenylhexa-hydropyrimindin-

2,4,6-trione , has been synthesized in several different ways. There is no major difference
between them. The first method consists of ethanolysis of benzyl cyanide in the presence of acid,
giving phenylacetic acid ethyl ether, the methylene group of which undergoes acylation using the
diethyloxalate, giving diethyl ester of phenyloxobutandioic acid , which upon heating easily
loses carbon oxide and turns into phenylmalonic ester.

Another method of phenobarbital synthesis starts with condensation of benzyl cyanide

with diethylcarbonate in the presence of sodium ethoxide to give α-phenylcyanoacetic ester.
Alkylation of the ester using ethylbromide gives α-phenyl-α-ethylcyanoacetic ester , which is
further converted into the 4-iminoderivative. Acidic hydrolysis of the resulting product gives
Phenobarbital.

Intermediate-acting barbiturates
Amobarbital

Amobarbital, 5-ethyl-5-isoamylbarbituric acid, like all barbiturates, is synthesized by

reacting malonic acid derivatives with urea derivatives. In particular, in order to make
amobarbital, α-ethyl-α-isoamylmalonic ester is reacted with urea (in the presence of sodium
ethoxide), giving amobarbital.

Short-action barbiturates

Pentobarbital

Pentobarbital, 5-ethyl-5-(2-amil)barbituric acid , is synthesized by methods analogous to

that of amobarbital, the only difference being that the alkylation of α-ethylmalonic ester is
carried out with 2-bromopentane (not 1-bromo-3-methylbutane) to give pentobarbital.

Pentobarbital is basically considered an isomer of amobarbital. They are similar in terms

of action, and the difference lies in the fact that pentobarbital is shorter lasting and easier to
tolerate. It is used as a relaxant as well as a soporific for short-term insomnia. The most
frequently used synonym of this drug is nembutal.

 Central Nervous System Depressants (Barbiturates and Hypnotic Agents)

Two barbiturates primarily used in surgical practice are thiopental and methohexital.

Barbiturates are hypnotics, and at therapeutic doses have a very weak analgesic and muscle
relaxant effect. Intravenous injection of a therapeutic dose of propofol produces hypnosis
rapidly with minimal excitation, usually within 40 seconds from the start of an
injection. Etomidate classified as a sedative hypnotic drug because of the quick loss of
consciousness upon intravenous administration.

 Uses:

Barbiturates (mainly phenobarbital) are occasionally used by doctors to treat the following

conditions:

 seizure disorder (epilepsy)

 increased pressure in the skull
 severe trauma to the skull
 some types of convulsions

Barbiturates can also be used as a form of anesthetic.

 Off-label uses include treatment for:

 migraines
  alcohol and benzodiazepine poisoning and withdrawal
 jaundice
 trauma

However, they are not a popular drug because of the risk of poor outcomes and adverse
effects. Today, it is rare to use them for sleep disorders. Phenobarbital is most likely to be used
for treating seizures. The World Health Organization (WHO) list it as a first-line treatment for
epilepsy for adults and children in the developing world, because of its low cost and
proven effectiveness. Barbiturates are available in pill, liquid, rectal, and injectable forms.

Using intervention techniques like medically assisted detoxification programs to help lift

the cloud of confusion off a person struggling with barbiturate abuse. This can help them benefit
from the services offered during treatment. A medical detox can also alleviate any discomfort
associated with barbiturate withdrawal. People are not advised to stop taking barbiturates cold
turkey. After the detox process is complete, treatment can begin, followed by aftercare.
Struggling with barbiturate abuse or addiction does not have to be a life sentence. Contact us
today if you or someone you care about is suffering with barbiturate addiction.

Specific drugs: Any medical

Drug class: Mechanism: Major effects: Side effects:
Subgroup: Examples: use:
Sedatives Diazepam (Valium),
clonazepam
(Klonopin), Drowsiness,
Agonist at Anxiety,
lorazepam (Ativan), falls, impaired
benzodiazepine insomnia,
temazepam Calm, relaxed coordination,
Benzodiazepines site on the epilepsy,
(Restoril), muscles, sleepy impaired
GABA-A many other
flunitrazepam memory,
receptor diseases
(Rohypnol), dizziness
triazolam (Halcion),
alprazolam (Xanax)
Mainly just
Zolpidem (Ambien), sleepy,
Benzodiazepine eszopiclone sometimes Same as
Same as above Insomnia
agonists (Lunesta), zopiclone, hallucinations benzodiazepines
zaleplon (Sonata) and sleep-like
states
Same as
Epilepsy,
Phenobarbital, benzodiazepines
Agonist at other
pentobarbital, , plus breathing
barbiturate site Calm, euphoric, diseases in
Barbiturates thiopental (sodium suppressed,
on the GABA-A sleepy the past and
pentothal, sodium terrible
receptor more rarely
amytal), secobarbital withdrawal,
today
death
Alcohol Opens BK Calm, euphoric, Same as Alcohol
potassium loss of benzodiazepines withdrawal
channels inhibitions , plus nausea,
(hyperpolarizing (facilitates vomiting,
neurons), closes socializing, breathing
SK potassium talking, singing, suppressed,
channels in sex), relaxed terrible
 withdrawal
reward center of
(including
brain (causing
psychosis and
DA release),
seizures), brain
probably other
damage, various
effects
diseases, death
Same as
Agonist at GHB
Euphoric, benzodiazepines
receptor (may Narcolepsy
energetic, , plus nausea,
desensitize it or (improves
Gammahydroxybutyrate (GHB), sleepy, calm vomiting,
inhibit GABA), cataplexy,
GBL, 1,4-butanediol (mix of breathing
agonist at not simply a
stimulant and suppressed,
GABA-B sleep aid)
sedative effects) psychosis,
receptor
seizures, death
Stimulants Amphetamine
(Adderall),
methamphetamine
(Desoxyn),
methylphenidate
(Ritalin),
phentermine, 4-
methylaminorex, Anxiety,
Euphoric,
phenmetrazine paranoia,
Increase release energetic, able ADHD,
(Preludin), psychosis, high
and inhibit to work, narcolepsy,
methcathinone, blood pressure,
reuptake of 5- concentrate, obesity,
fenfluramine heart attack,
HT, DA, and stay awake. rarely
(Pondimin, Fen- stroke, brain
NE. Reduces depression
Phen), damage when
appetite.
dexfenfluramine used excessively
(Redux),
pseudoephedrine
(Sudafed), ephedrine,
phenylpropanolamin
Amphetamines
e (old Triaminic),
phenylephrine
(Sudafed PE)
Euphoric,
energetic, deep
Same as
and unusual
amphetamine,
thoughts,
plus brain
perceived
damage,
inspiration and
confusion,
novelty,
Like above, but agitation,
MDMA (ecstasy), enhances sex,
releases a lot frequently death None
MDA, MDEA dancing, music,
more 5-HT due to
art, touch and
hyperthermia,
senses.
heart attack,
Contentment.
water
Connection to
intoxication, and
other people,
other problems.
strong
emotions.
Cocaine Inhibits 5-HT, Same as Same as Local
NE, and DA amphetamine amphetamine, anesthesia
reuptake, blocks (above) plus a worse risk and bleeding
 control,
voltage-gated
of heart attack diagnostic
sodium channels
tests
Morphine, heroin
(diacetylmorphine),
hydrocodone
(Vicodin),
Nausea,
oxycodone Activate all Euphoric, pain
constipation, Pain relief,
(Percocet, opioid receptors relief, calm,
Full opioid vomiting, rarely
Oxycontin), fentanyl, completely. relaxed, sleepy,
agonists drowsiness, depression
Demerol, codeine, Reduce NE appetite
breathing and diarrhea
opium, release. suppression
suppressed
hydromorphone
Narcotics (Dilaudid),
oxymorphone
(Opana), methadone
Only activate
certain subtypes
Buprenorphine Pain relief, not Pain relief,
Partial, of opioid Nausea,
(Suboxone), quite as rarely
selective, or receptors, and/or constipation,
pentazocine, euphoric or depression,
mixed opioid do not activate vomiting,
nalbuphine, tramadol relaxing as full opioid
agonists them fully, drowsiness
(Ultram), tifluadom agonists (above) addiction
and/or block
certain subtypes.
Might relieve
Unusual
Memory, nausea,
thoughts and
thinking, vomiting,
feelings,
Active ingredient is mostly reflexes, and and
Agonist at sometimes
tetrahydrocannabinol, some other coordination are neuropathic
Cannabis cannabinoid calm, happy,
active ingredients like cannabidiol in impaired. May pain. Pills
receptors hungry,
smaller quantities contribute to already legal,
enhanced
psychosis in the other forms
appreciation of
long term. under
art
investigation.
Psychedelic Mescaline (peyote Anxiety,
s cactus), 2C-series Feeling of insomnia,
drugs (2C-B, 2C-I, novelty, paranoia,
Phenethylamine 2C-C, 2C-T-7), 3C- Partial agonist at inspiration, temporary
None
s E, 4-MTA, PMA, 5-HT2 receptors reverence. Fast, psychosis. May
DO-series drugs (2A and possibly disordered contribute to
(DOC, DOB, DOI, 2C). This thoughts, psychosis in the
DOM) receptor is trances. long term, or
Psilocybin and mostly Perceptual cause
psilocin (both in excitatory, but it anomalies: "flashbacks" Psilocybin
mushrooms), is inhibitory in patterns move, (HPPD). Some and LSD
bufotenin (in toads), certain parts of colors brighter, cause nausea, have been
Tryptamines DMT (in plants), 5- the brain dealing seeing sounds, increased body tested for the
MeO-DMT (in with perception. smelling colors. temperature, treatment of
plants), 5-MeO- Crazy ideas and tremors. cluster
DiPT, DET, AMT, beliefs. headaches
4-HO-DiPT
Ergolines Lysergic acid Same as above, Same as above, Other
diethylamine (LSD), plus agonism at plus other ergolines are
LSA (ergine, in other 5-HT, DA, effects, depends used for
plants) and NE of frequency of many
 diseases but
receptors. use and dose. are not
psychedelic.
Anesthesia.
Feeling of Nausea, A related
distance from vomiting, coma, drug,
reality and violence, memantine,
NMDA
body, numbing extreme is used in
Dissociative Phencyclidine (PCP), (glutamate
of sensations confusion, Alzheimer's
anesthetics dextromethorphan, ketamine receptor)
and pain. temporary disease, and
antagonists
Convincing and psychosis. PCP these could
absorbing causes brain be used in
hallucinations. damage. stroke
sufferers.
Extreme
confusion,
Loss of
temporary
Scopolamine and atropine (in plants), Muscarinic memory, Many
psychosis, hot,
Deliriants diphenhydramine (Benadryl), (ACh receptor) convincing and legitimate
dry skin, dry
dimenhydrinate (Dramamine) antagonists absorbing uses
mouth, huge
hallucinations.
pupils, fast
heartbeat, death
Calm, relaxed,
euphoric, pain Many diseases,
relief, death, nausea,
Unknown, hallucinations, vomiting,
Diethyl ether (starter fluid), toluene,
probably strange accidental General
gasoline, glue, paint, xenon, freon,
multiple sensations asphyxiation, anesthesia
halothane, sevoflurane
mechanisms (different falls, varies
inhalants cause depending on
different effects particular drug
Inhalants from this list)
Calm, euphoric,
Unknown, but pain relief, General or
Nitrous oxide opioid pathways memory loss, Similar to above partial
are necessary unconsciousnes anesthesia
s
Stimulate NO "Head rush",
Dangerously
Isoamyl nitrite, system (NO is a muscle low blood Heart
Nitrites
isobutyl nitrite neurotransmitter relaxation, pressure, conditions
) dizziness fainting
Other Dysphoria,
Convincing,
panic, headache, Theoretically
Selective agonist absorbing
inability to talk, similar to
Salvinorin A (salvia divinorum) of the kappa hallucinations,
falls, sweating, pain relievers
opioid receptor visionary states,
persisting (pentazocine)
pain relief
anxiety
GABA-A Vaguely like a Nausea, other Useful in
Muscimol (amanita muscaria)
agonist hallucinogen side effects research
Nicotinic
Nicotine (tobacco) acetylcholine See Wikipedia, PubMed, Google
receptor agonist
Caffeine (coffee, tea, other plants) Adenosine Alertness, Insomnia, Headaches
receptor wakefullness, anxiety,
antagonist, energy, appetite headaches on
 inhibits some
PDE enzymes
suppression, withdrawal,
causing
headache relief diuresis
increased cAMP
signaling
Anxiety,
Depending on
Methaqualone (Quaalude, Sopor), Falls, poor depression,
the drug: Calm,
thalidomide, meprobamate Various coordination and insomnia,
sleepy,
(Miltown), carisoprodol (Soma), mechanisms, memory, coma, pain,
euphoric,
glutethimide, chloral hydrate mostly related to other side anesthesia,
relaxed
(knockout drops, Micky), GABA, similar effects vary epilepsy,
muscles, pain
ethchlorvynol (Placidyl), to barbiturates from drug to muscle
relief, nausea
methyprylon, primidone drug relaxation,
relief
nausea
Disclaimer: Do not use drugs for fun. Take drugs exactly as prescribed by a trustworthy doctor. This chart provides a
rough overview, it is an oversimplification, it has omissions, and it may have blatant inaccuracies due to ongoing
scientific debate or the writer's idiocy.

 Balance in the CNS function:

 Classification of CNS drugs:

Neurological:

 Sedative-hypnotics
 Antiepileptic and anticonvulsive drugs
 Drugs for Parkinson’s disease
 Analgesics and anesthetics
 Central stimulants

Psychological:

 Antipsychotic drugs
 Antidepressant and antimanic drugs
 Drugs for dementia

Sedative-Hypnotic Drugs

Insomnia:

 1-5%, more in old women;

 trouble in falling asleep or too easily to be waken up;
 can be primary or secondary; - harmful to daily life: excessive daytime sleepiness and a
lack of energy, feel anxious, depressed, or irritable.

Anxiety:
 It is characterized by excessive, exaggerated anxiety and worry about everyday life
events with no obvious reasons for worry; It can be extremely debilitating, having a serious
impact on daily life.

 ORGANIZATION OF THE CNS:

The CNS comprises the brain and spinal cord and is responsible for integrating sensory
information and generating motor output and other behaviors needed to successfully interact with
the environment and enhance species survival. The human brain contains about 100 billion
interconnected neurons surrounded by various supporting glial cells. Throughout the CNS,
neurons are either clustered into groups called nuclei or are present in layered structures such as
the cerebellum or hippocampus.