Tutorial 4.

4
Drug administration and absorption
Drugs are usually administrated in 4 ways, mentioned here below.

Ingestion
Ingestion is one of the most preferred routes. Once a drug its swallowed, it is carried to the
intestine where is absorbed into the bloodstream.
However, some drugs pass through the stomach wall because they do not have to reach the
intestine and have an effect soon (e.g., alcohol).
One advantage of the oral route it that is relatively safe and ease. A disadvantage is the
unpredictability: the absorption into the bloodstream can be influenced by factors such as
the type of food in the stomach.

Injection
Drug injection is common in medical practice because the drug’s effects are strong, fast, and
predictable. The injection can be made subcutaneously (SC) into the tissue just below the
skin; intramuscularly (IM), into the large muscles, or intravenously (IV) into veins that run
just below the skin. Many addicts prefer the intravenous because the drugs go directly to
the brain.
After an intravenous injection, there is a possibility to encounter the effects of an overdose,
an impurity, or an allergic reaction. Moreover, many addicts develop scar tissue, infections
and collapsed visible veins.

Inhalation
Some drugs can be absorbed into the bloodstream through the capillaries network in the
lungs, like tobacco or marijuana. The main side effects are the difficulty in regulate the dose
inhaled and the lungs damage if the substances are inhaled habitually.

Absorption through mucous membranes

Some membranes can be administered through the mucous membrane of nose, mouth, and
rectum. Cocaine for example is commonly administered though the nasal membranes,
snorted, but now without damage.

Drug penetration, action, and elimination

1. A drug enters the bloodstream, and it is carried first in the blood to the blood vessels of
the central nervous system. A protective filter here, the blood-brain barrier makes
difficult to many dangerous blood-born chemicals to pass from the blood vessels of the
CNS to its neurons.

2. Psychoactive drugs influence the nervous system, some act on neural membrane though
the CNS as alcohol. Others can bind to a particular synaptic receptor; or influence the
synthesis, transport, and release of a particular neurotransmitters.

3. The actions of most drugs are terminated by enzymes synthesized by the liver. These
liver enzymes stimulate the conversion of active drugs to non-active form, a process
called drug metabolism. This method eliminates a drug’s ability to pass though lipid
membranes of cell so that it can no longer penetrate in the blood-barrier.
 Drug tolerance
Drug tolerance is a state of decreased sensitivity to a drug that develop as a result of
exposure to it. It can be showed when a given dose does not produce the same effect as
before, and when it takes more of the drug to produce the same effect.
This causes a shift in the dose-response curve, a graph that show the magnitude of the effect
of different doses of drug.

There are 3 important effects about the specificity of drug tolerance:

 Cross tolerance happens when exposure to one drug can produce tolerance to other
drugs that act by the same mechanism.
 Drug sensitization it is the increase in the sensitivity to a drug. Often happen that drug
tolerance develop some effects of a drug but not others.
 Drug tolerance is not a specific phenomenon, there is no single mechanism that
underlies all examples of it.

Two categories of changes underlie drug tolerance:

1. Metabolic tolerance occurs when the body metabolizes drugs at an accelerated rate.
The drug still affects the brain the same way, but the body metabolizes the drug
more quickly. Thus, the same drug has a diminished effect.
2. Functional tolerance refers to the way the body can build a tolerance foreign
substance. This happen because a person constantly needs more to achieve the
same effect that they felt the first time they used it. (e.g., psychoactive drugs)

Drug withdrawal
A drug withdrawal is an unpleasant sensation during abstention of it in the body after a
period of time, usually opposite to the original effect of the drug.
Individuals who suffer withdrawal reactions when they stop taking a drug are said to be
physically dependent on that.

Addicts are people who consume drug despite of its adverse effect.
They sometimes take drug to prevent or alleviate withdrawal symptoms, and if it was the
only factor, would be easily cured by hospitalizing them until the symptoms would go away.
However, most addicts restart their drug taking even after month of enforced abstinence.

It was believed that the major cause of addiction was the physical dependence, and the
term psychological dependence was coined to refer to the exception of this general rule.
Psychological dependence was said to be the cause of any compulsive drug taking that
occurred in the absence of physical dependence; now we know this is not the major
motivating factor in addiction.

Focus on drug withdrawal

Contingent drug tolerance
It refers to demonstrations that tolerance develops only to drug effect that are actually
experienced, therefore what patient do while they are under drug’s influence.
Most studies employ the before-and-after design.
Usually, two groups of subjects receive the same drug injections and the same repeated
test, but one group receives the drug before the test and the other group after that. In the
end, both groups receive the same dose of the drug followed by a test.

Conditioned drug tolerance

It focusses on the situation in which drugs are taken. Therefore, tolerance effects are
expressed only when a drug is administered in the same situation in which it has previously
been administered.
Conditioned compensatory responses theory argues that when a drug is repeatedly
administered in the same environment, that environment begins to elicit responses that
counteract the drug effects and lead to the development of tolerance.
(Drug conditioned stimulus, effect unconditioned stimulus, Pavlov theory)

Conditioned withdrawal effect

The prediction of the conditioned compensatory responses theory is that in absence of
drug, the drug environment should elicit effects opposite to the original effect of the drug.
Withdrawal effect by the drug environment are conditioned withdrawal effects.

Synapses and addictions

Drugs facilitate or inhibit transmission at a synapse.
A drug that blocks a neurotransmitter and decrease an activity at a synapse is an antagonist.
A drug that increases activity at a synapse is an agonist.

Drugs act in many ways, varying in affinity, the tendency to bind to a receptor that can vary
from strong to weak.
The tendency to activate the receptor it referred as drug’s efficacy.
Therefore, a drug that binds to a receptor but fails to stimulate it, has a high affinity but low
efficacy (it is antagonist).

Despite many differences among abused drugs, they share certain effects on dopamine and
norepinephrine synapses. Researchers found many brain areas that directly or indirectly
would increase the release of dopamine or norepinephrine in the nucleus accumbens.
This area it is activate when imagine something pleasant, as sugar or sexual excitement.
People with major depression in fact show less than normal response in the nucleus
accumbens.

Five commonly abused drugs

Nicotine, a compound present in tobacco, stimulates acetylcholine receptors known as
nicotinic receptors. Nicotine increases dopamine release that has mostly a stimulant effect.
Twin studies shows that nicotine addiction has a major genetic component, the estimate
heritability is about 65%.
Smokers’ syndrome is characterized by chest pain, coughing, labored breathing and greater
susceptibility to infections of the respiratory tract.

Alcohol is classified as depressant because at moderate doses it depresses neural firing;

however, at low doses it can stimulate neural fairing and facilitate social interactions.
Heritability estimates are about 55%. It reduces the flow of calcium into neurons by acting
on ion channel or interferes with the function of secondary messenger inside neurons.
Alcohol produces both tolerance and physical dependence, and the withdrawal syndrome
comprises three phases. The first is characterized by agitation, headache, nausea, vomiting;
and the second after cessation of drinking, by convulsive activity.
The third is called delirium tremens and is characterized by hallucinations, agitation,
confusion, hyperthermia, and tachycardia.

Marijuana leaves contain the chemical tetrahydrocannabinol (THC) and other cannabinoids.
It has been used medically to relieve pain, nausea or increase the appetite. It also alters
sensory experiences. Purified THC has been approved for medical use in some countries but
is not everywhere legal.
However, it affects short-term memory, intensify emotions, sensory distortions, and motor
impairment.

Cocaine and amphetamine are stimulant drugs, whose primary effect is to produce general
increases in neural and behavioral activity.
Cocaine it prepared from the leaves of the coca bush. It is usually common to treat the coca
paste and extract cocaine hydrochloride, consumed by snorting or by injection.
Cocaine is frequently consumed in binges; cocaine sprees are binges in which extremely high
level of intake are maintained for a period of a day or two.
The symptoms of psychotic behavior observed during cocaine sprees is called cocaine
psychosis, when there is the risk of loss of consciousness, seizures, respiratory arrest, heart
attack or stroke.
Both cocaine and amphetamine (speed)stimulate dopamine and synapses in the nucleus
accumbens and everywhere else, increasing in the presynaptic terminal the dopamine
presence.
Usually, the presynaptic terminal reabsorbs released dopamine through a protein called the
dopamine transporter.
Amphetamine and cocaine inhibit the transporter and extend the effect of released
dopamine.

Opiates drugs are derived from opium poppy. Opiates family include morphine, heroin, and
methadone. Opiates relax people and decrease their attention to real-world problem.
Heroin enters fast in the brain than morphine and produces a bigger rush of effect and is
more strongly addictive.

Researcher found that brain produces certain neuropeptides known as endorphins that
relieve pain by acting on receptors in the brain. Endorphin indirectly activate dopamine
release.
Opiates stimulate endorphin synapses, which inhibit neurons that inhibit release of
dopamine. By inhibiting an inhibitor, opiates increase the release of dopamine.