Pharmacodynamics Notes – Kent
Andrei P. Paelma
Agonist
• Activates receptors to produce the
desired response.
Conventional Agonist
• increase the proportion of activated
receptors.
Inverse agonists
• stabilize the receptor in its inactive
conformation and act similarly to
competitive antagonists.
Drugs that acts as Agonist
• Many hormones, neurotransmitters (eg,
acetylcholine, histamine,
norepinephrine),
• drugs morphine, phenylephrine,
isoproterenol, benzodiazepines,
barbiturates
Antagonist
prevents receptor activation
Effects on preventing activation:
• Antagonists increase cellular function if
they block the action of a substance that
normally decreases cellular function.
• Antagonists decrease cellular function if
they block the action of a substance that
normally increases cellular function.
Receptor antagonists
Can be classified as reversible or irreversible
Reversible antagonists
readily dissociate from their receptor
Irreversible antagonists
form a stable, permanent or nearly
permanent chemical bond with their
receptor by alkylation.
3 Antagonism
Competitive Antagonism
The binding of the antagonist to the
receptor prevents binding of the agonist to
the receptor
Non-competitive Antagonism
agonist and antagonist can be bound
simultaneously, but antagonist binding
reduces or prevents the action of the
agonist.
Reversible-Competitive Antagonism
Agonist and antagonist form short-lasting
bonds with the receptor, and a steady state
among agonist, antagonist, and receptor is
reached.
Such antagonism can be overcome by
increasing the concentration of the agonist.
For example, naloxone (an opioid receptor
antagonist that is structurally similar to
morphine), when given shortly before or after
morphine, blocks morphine’s effects.
However, competitive antagonism by
naloxone can be overcome by giving more
morphine.
5 CATEGORIES OF DRUG
ACTION
1. STIMULATION
• the rate of cell activity of the secretion
from a gland increases.
• It refers to selective enhancement of the
level of activity of specialized cells.
Stimulant Drug type, Effect &
Addiction Signs
• group of drugs that result in increased
• the popular “crack” form comes as
activity in the body.
• Sometimes referred to as “uppers”
• the most common method for crack cocaine
• frequently abused due to their
performance-enhancing and euphoric
effects.
• those who abuse stimulants experience
heightened energy levels and enhanced
focus.
• speed up mental and physical processes,
which can produce desirable effects in
the short-term by increasing levels of
dopamine in the brain.
Legal and Illicit stimulants
Commonly abused stimulants include:
Cocaine, methamphetamine
Other Stimulant Examples:
• Ecstasy (party drug)
• Speed
• Methamphetamine
• Cocaine
• Cigarettes
• Caffeine
Cocaine
• Cocaine is the most well-known
stimulants in the world. highly addictive
drug, it is made from and named for the
South American coca plant.
• Cocaine usually comes in the form of a
fine white powder
• Cocaine and crack cocaine can be used
via a multitude of methods
• most common form of ingestion for
powdered cocaine is snorting the drug
Crack
crystallized rocks.
is to smoke it.
Signs of cocaine use
✓ Excitability
✓ Dilated pupils
✓ Runny nose
✓ Weight loss
✓ Nosebleeds
Methamphetamine
• is a highly addictive stimulant, more
commonly known simply as “meth.”
• usually found in either powder or crystal
form
• it can be used in a multitude of fashions,
from smoking the drug to injecting it
intravenously.
• Its popularity as a recreational drug is
due to the initial rush of euphoria that
accompanies it.
• once that initial rush has passed,
emotions generally get more negative,
with feelings of anger and fear being
common during the “crash.”
Signs of use on Methamphetamine
✓ Extremely high body temperatures that
can result in fainting
✓ Severe itching
✓ Broken teeth and dry mouth, commonly
referred to as “meth mouth” due to poor
 dental hygiene and nutrition associated
with use of the drug
✓ Cognitive issues
✓ Users of methamphetamine can easily
overdose, which can lead to extreme
physical problems and death.
Prescription stimulant
• They are often prescribed to treat
attention deficit hyperactivity disorder
(ADHD), a condition that affects an
individual’s ability to focus and control
impulses.
• Includes Ritalin, Adderall, Concerta.
• They are often referred to as “study
drugs”
• Long-term effects from continued abuse
of these prescription stimulants include
depression, cardiovascular
complications, nausea, insomnia, stunted
growth in children and teens, anxiety,
hypertension, aggressiveness, and manic
state
Adderall
Adderall is a combination of amphetamine
and dextroamphetamine that can also be
used to treat narcolepsy.
Ritalin
Ritalin contains methylphenidate and is also
used to treat mild depression and
narcolepsy.
Concerta
Contains methylphenidate
Other Stimulant examples:
• Adrenaline stimulates heart
• Pilocarpine stimulate salivary glands
• Picrotoxin stimulates CNS
2. DEPRESSION
• cell activity and function of a specific
organ are reduced.
• Sometimes called “downers,” these
drugs come in multicolored tablets and
capsules or in liquid form.
• Zyprexa, Seroquel and Haldol, are
known as “major tranquilizers” or
“antipsychotics,” as they are supposed to
reduce the symptoms of mental illness.
• Xanax, Klonopin, Halcion and Librium
are often referred to as “benzos” or
benzodiazepines
• Amytal, Numbutal and Seconal, are
classed as barbiturates these are drugs
that are used as sedatives (calm or
soothe) and sleeping pills.
DEPRESSANTS: SHORT TERM EFFECTS
✓ Slow brain function
✓ Slowed pulse and breathing
✓ Lowered blood pressure
✓ Poor concentration
✓ Confusion
✓ Fatigue
✓ Dizziness
✓ Slurred speech
✓ Fever
✓ Sluggishness
✓ Visual disturbances
✓ Dilated pupils
✓ Disorientation, lack of coordination
✓ Depression
✓ Difficulty or inability to urinate
✓ Addiction
Higher doses of depressant can cause
impairment of memory, judgment and
coordination, irritability, paranoia and 3. REPLACEMENT
suicidal thoughts. Some people experience
Replacement drugs such as insulin replace
the opposite of the intended effect, such as
essential body compounds.
agitation or aggression.
Example:
Tranquilizer
➢ Levodopa in Parkinsonism
refers to a drug which is designed for the
➢ Insulin in Diabetes Mellitus
treatment of anxiety, fear, tension, agitation,
➢ Iron in anemia
and disturbances of the mind, specifically to
reduce states of anxiety and tension.

DEPRESSANTS: LONG TERM EFFECTS 4. Inhabitation or Killing of

organisms (CYTOTOXIC ACTION)
✓ can produce depression, chronic
• Drugs that inhibit or kill organisms
fatigue, breathing difficulties, sexual
interfere with bacterial cell growth.
problems and sleep problems.
✓ As a dependency on the drug Example:
increases, cravings, anxiety or panic
➢ Penicillin exerts its bactericidal effects by
are common if the user is unable to
blocking the synthesis of the bacterial
get more.
cell wall.
✓ Withdrawal symptoms include
➢ Zidovudine, also known as
insomnia, weakness and nausea. Can
azidothymidine, is an antiretroviral
be life threatening
medication used to prevent and treat
✓ For continual and high dose users,
HIV/AIDS.
agitation, high body temperature,
delirium, hallucinations and
convulsions can occur.
5. IRRITATION
• Drugs also can act by the mechanism of
Depressants irritation
• Laxatives irritate the inner wall of the
colon, thus increasing peristalsis and
defecation.

Study well Ms. Clara Aton <3

DRUG TOLERANCE
• Tolerance refers to a decreased
responsiveness over the course of therapy.
• A person may develop tolerance to a drug
when the drug is used repeatedly.
• Tolerance is common. It can develop when
your body is regularly exposed to a
medication.
• Tolerance can happen if you’ve been using a
medication or other drug for a while. If you
think your body has developed drug
tolerance, talk to your doctor. Don’t
suddenly stop taking the drug. There are
steps your doctor can take to manage drug
tolerance and help you feel better.
• With certain medications, developing
tolerance means your doctor will need to
reevaluate your treatment This can be
challenging sometimes, because increasing
the dose might mean more side effects. It
might be harder to find other medications
that work. For other, unregulated drugs,
there are more risks of overdose and other
complications.
Drug tolerance can be a challenge in the
treatment of certain conditions, including:
✓ chronic pain
✓ immune-related conditions
✓ seizure disorders
✓ some mental health conditions. When
tolerance develops, doctors have to find
new ways to effectively manage
symptoms.
IMPORTANT FACTS ABOUT TOLERANCE
✓ It can happen with any drug, including
prescription and unregulated drugs, like
cocaine.
✓ Your condition might worsen because the
medication isn’t working as well.
✓ Cross-tolerance could occur. This is
tolerance to other drugs in the same class.
✓ With certain classes of drugs, like opioids,
tolerance can increase the risk of
dependence, addiction, and overdose.
✓ When your body develops tolerance, using
higher doses increases the risk of overdose.
✓ A benefit of tolerance might be fewer side
effects as your body gets used to the
medication.
Tachyphylaxis
• Refers to a rapid decrease in response to
the drug (acute tolerance).
• Drug categories that can cause
tachyphylaxis include narcotics,
barbiturates, laxatives, and psychotropic
agents.
Difference between drug tolerance and
drug dependence
The difference between tolerance and
dependence has to do with how the body reacts
to the presence or absence of a specific drug.
Tolerance
certain cell receptors in the body that activate
when the drug is present stop responding like
they once did.
If your body has developed a tolerance to a
medication, it means the medication at your
current dose has stopped working as effectively
as it once did. It might mean your body becomes
used to the medication, and you don’t get the
same benefits or effects as before. Your doctor
may need to increase the dose, change the
regimen, or in some cases, prescribe a different
medication.
Dependence
if the drug isn’t present or the dose is suddenly
reduced, you might experience withdrawal. This
means the body can only function normally
when the drug is present.
If your body is dependent on a drug, it’s
important to not abruptly stop taking it. Your
doctor will put you on a schedule to gradually
ease off the drug to avoid withdrawal
symptoms. They can also recommend resources
to support you.
Withdrawal symptoms
depend on which drug you’ve been using. They
can be mild, like nausea or vomiting, or more
serious, like psychosis or seizures.
How is addiction different?
Drug Addiction
➢ Addiction is more than drug dependence.
➢ Addiction can occur without being
dependent on drugs
➢ Addiction may involve using drugs despite
the consequences, being unable to stop
using drugs, neglecting social and work
obligation because of drug use
➢ It’s a health condition like any other chronic
condition.
➢ It involves changes in brain activity
➢ Neurotransmitters like dopamine are
repeatedly triggered and increase drug
cravings.
➢ Addiction is also referred to as substance
use disorder.
➢ Addiction is a driving need to use a drug
despite the potential for harm, like
compromising work, social, and family
needs.
➢ A person with a substance use disorder will
experience a cycle of stress and anxiety
around getting the drug.
People develops addiction which depends on
genetic factors including family history of
addiction as well as social and environmental
factors. It’s not an intentional choice.
RISK OF DRUG TOLERANCE
Relapse or Flare up of condition
➢ The medication may become not as
effective, like with antipsychotics and anti-
seizure drugs.
Need for higher doses.
➢ More of the drug is needed to achieve
symptom relief, which may increase
negative side effects of the drug.
Addiction.
➢ For example, higher doses of opioids can
increase the risk of developing a substance
use disorder in some people.
Unintentional medication errors.
➢ This may occur from changes to dosing or
regimen.
Cross-tolerance.
➢ For instance, in certain cases, alcohol can
cause cross-tolerance to other drugs, like
diazepam or valium.
Opioids
➢ Also known as narcotics
➢ The opioids analgesics relieve pain by
binding to opioids receptors in the central
nervous system.
➢ Act as agonist to produce the effect of
analgesia
➢ Gives relief for moderate to severe pain
➢ Used when pain is too severe to be
controlled by NSAID analgesics
➢ All narcotic analgesics are prescription
medications
➢ Important to the abuse potential of opioids
is their ability to activate the brain reward
system, reinforcing an addictive effect.
➢ As drugs of abuse, opioids are taken orally,
sniffed, smoked, or injected subcutaneously
(skin-popping) or intravenously (mainlining).
➢ IV use will produce effects in seconds. IV
use casually causes a “rush” of feelings in
the lower abdomen, along with warm skin
flushing and a strong sense of euphoria.
➢ Smoking or sniffing produces a longer onset
and effect.
EXAMPLES OF OPIOIDS
✓ Opium
✓ Heroin
✓ Morphine
✓ Oxycodone
✓ Methadone
✓ Hydrocodone
✓ Codeine
The primary effects of opioids
• analgesia, drowsiness, slurred speech, and
detachment from the environment
Signs of overdose of opioids include pinpoint
pupils, clammy skin, depressed respiration,
coma, and death, if not treated.
Withdrawal symptoms occur with decreased
amounts or cessation of the drug after
prolonged moderate to heavy use.
➢ Symptoms may include craving, abdominal
cramps, diarrhea, nausea, and vomiting.
➢ Symptoms appear about 8 to 10 hours after
the last dose, peak within 36 to 48 hours,
and usually subside in 96 hours.
Treatment
A narcotic antagonist such as naloxone should
be given as soon as life support is instituted.
✓ Methadone (Dolophine) in decreasing
doses over 10 to 14 days is most often used
to decrease symptoms during opioid
detoxification.
✓ Buprenorphine (Buprenex) is an agonist-
antagonist opioid that may be used for
detoxification and maintenance therapy.
✓ Naltrexone (oral ReVia, injectable Vivitrol)
is an opioid antagonist that blocks euphoria
and all other opioid effects.
How is drug tolerance addressed if you
need medication?
➢ Anti-depressants -Depression symptoms
can worsen in some people.
➢ Antibiotics - They can have weaker effects.
This is different from drug-resistance
➢ Anxiolytics - Your body may develop
tolerance and dependence. Anticonvulsant
and other effects of benzodiazepines, a type
of anxiolytic, aren't well understood.
GABAA receptors may play a role.
➢ Cancer - Multi-drug tolerance can develop
after initial success in the treatment of
different cancers. A "drug holiday" can
sometimes reset effectiveness.
DRUG DEPENDENCE
• Drug dependence occurs when you need
one or more drugs to function.
• People viewed dependence as a more
severe problem than abuse.
• Dependence can be bodily response to a
substance.
• This often occurs if you rely on medications
to control a chronic medical condition e.g:
High blood pressure, diabetes, glaucoma.
Dependence may involve:
✓ some or all the symptoms of addiction
✓ development of a high tolerance for the
substance as your body adapts to the drug,
leading to a desire for larger or more
frequent doses
✓ physical symptoms of withdrawal when you
attempt to stop using the drug
You can often determine if an addiction has
turned into dependence by looking at behavior.
When a person addicted to drugs hasn't had
them for a period of time, this can cause a
physical reaction. Physical symptoms of
withdrawal occur when the body becomes
stressed without the drug. These symptoms
include:
✓ anxiety
✓ depression
✓ muscle weakness
✓ nightmares
✓ body aches
✓ sweating
✓ nausea
✓ vomiting
Abuse
considered the mild or early phase of
inappropriate drug use that led to dependence.
Placebo Effect
➢ A placebo effect is a psychological benefit
from a compound that may not have the
chemical structure of a drug effect.
➢ The placebo is effective in approximately
one third of persons who take a placebo
compound.
➢ The placebo effect is more than positive
thinking believing a treatment or procedure
will work. It's about creating a stronger
connection between the brain and body
and how they work together.
➢ Placebos work on symptoms modulated by
the brain, like the perception of pain.
➢ Placebos may make you feel better, but
they will not cure you.
➢ They have been shown to be most effective
for conditions like pain management,
stress-related insomnia, and cancer
treatment side effects like fatigue and
nausea.
Does the placebo effect mean failure or
success?
• placebo effect was considered a sign of
failure
• A placebo is used in clinical trials to test the
effectiveness of treatments and is most
often used in drug studies.
However, experts have concluded that reacting
to a placebo is not proof that a certain
treatment doesn't work, but rather that
another, non-pharmacological mechanism may
be present.
How placebos work is still not quite understood,
but it involves a complex neurobiological
reaction that includes everything from increases
in feel-good neurotransmitters, like endorphins
and dopamine, to greater activity in certain
brain regions linked to moods, emotional
reactions, and self- awareness. All of it can have
therapeutic benefit. "The placebo effect is a way
for your brain to tell the body what it needs to
feel better.
GOODLUCK MS. ATON <3