PHARMA:

DRUGS AFFECTING THE CENTRAL NERVOUS

SYSTEM (CNS)
➢ Central nervous system is composed of
the brain and spinal cord.
➢ Parasympathetic Nerves:
○ Constrict pupils
○ Stimulate saliva
○ Constrict airways
○ Slow heartbeat
○ Stimulate activity of stomach NEUROTRANSMISSION
○ Inhibit release of glucose ➢ The process whereby neurons
○ Stimulate gallbladder communicate with each other.
○ Stimulate activity of intestines ➢ Action potential
○ Contract bladder ➢ Neurotransmitter: chemical signal
○ Promote erections of genitals
➢ Sympathetic Nerves:
○ Dilate pupils
○ Inhibit salivation
○ Relax airways
○ Increase heartbeat
○ Inhibit activity of stomach
○ Stimulate release of glucose
○ Inhibit gallbladder ★ If a stimulus comes into contact with a
○ Inhibit activity of intestines dendrites of the neuron, a complicated
○ Secrete epinephrine and process of action potential must happen
norepinephrine before it senses the signal to the receiving
○ Relax bladder neuron.
○ Promote ejacualtion and vaginal
contraction

➢ Neurotransmitters are the target

➢ Neuron Anatomy
○ Neuron is the functional unit of the
brain.
○ Drug action happens in the synapse.
○ 13 billion neurons inside our brain
substance of study of drug developers.
➢ Dopamine and serotonin are
neurotransmitters that activates the CNS
(excitatory)
➢ GABA is a neurotransmitter that depresses
the CNS (inhibitory)
➢ Adrenaline
○ Fight or flight neurotransmitter
➢ Noradrenaline
○ Concentration neurotransmitter
➢ Dopamine
○ Pleasure neurotransmitter
➢ Serotonin DRUG ACTION
○ Mood neurotransmitter 1) Binding with receptor sites (mimics)
➢ GABA ○ They activate/mimic binding of
○ Calming neurotransmitter receptor sites (activation)
➢ Acetylcholine 2) Blocking receptor site (inhibits)
○ Learning neurotransmitter ○ Certain substances or processes
➢ Glutamate would not happen, depending on
○ Memory neurotransmitter drugs.
➢ Endorphins 3) Blocking neurotransmitters’ reuptake
○ Euphoria neurotransmitter ○ Bind to receptors, there is another
receptor in the presynaptic that will
ACCORDING TO MOLECULAR STRUCTURES reuptake or recycle the substance or
1) Peptides agent for it to be abundant for
○ Endorphins another action potential.
2) Monoamines
○ Serotonin, histamine, norepinephrine,
epinephrine, catecholamines
3) Amino acids
○ Glutamate (excitatory in action)
○ GABA (inhibitory in
action/depressant) but both amino
acids because of molecular
structures.

★ From dendrite there is a receptor that

reuptakes some substances back at the
post synaptic cleft ready for another
process of action potential for another
release of drug or neurotransmitters. And
★ Depression activity of the nervous system
the process of neurotransmission
works with the continuum. Brain reaction
happens.
is within the continuum meaning either,
★ Reuptake involves the neurotransmitter
from no activity at all to hyperactivity/too
being pumped back into the neuron that
much activity.
released it, in order to clear the synapse..
★ There is a homeostasis in between, a
degree of activity with lesser action.
- Coma – no action (sleep, relaxing –
below the continuum) while when
you go beyond homeostasis you
become so excited you get anxious
and for some seizures
- Seizures – too much activity (you
become excited, anxious)

ACCORDING TO ACTION
1) Stimulants – speed up DRUGS AFFECTING THE CENTRAL NERVOUS
2) Depressants – slow down SYSTEM (CNS)
3) Hallucinogen – alter thoughts, feelings, 1) Anesthetics
perceptions 2) Psychoactive/Psychotropic
3) Anticonvulsants
4) Antiparkinsonism
5) Analgesics
6) Others
PSYCHOTROPIC/PSYCHOACTIVE DRUGS
➢ Alters brain function, resulting in
temporary changes in perception, mood,
consciousness and behavior.
➢ (Can cross BBB and does not have an
addicting effect).
➢ Acts upon CNS by way of altering mental
processes or recognition.
➢ Neurotransmitters that are involved are
the Dopamine, Serotonin, GABA.
PSYCHOTROPIC DRUGS MAY
BE GROUPED INTO:
1) Antipsychotics
○ Also known as neuroleptics
○ Function: lowers dopamine levels to
reduce hallucinations, delusions,
dementia.
○ Most common disorder is:
⤷ Schizophrenia → disorganized
thoughts and speech (mental
disorder that makes the brain too
active that causes disorganized
thoughts and speech. To calm
the brain down)
⤷ Psychosis → affects brain
processes information.
(experience reality in a different
way. Example: hear voices,
believe that someone will harm
them)
○ Antipsychotic drugs are used to calm
the brain down.
○ Mechanism of action:
⤷ Dopamine and serotonin (5HT
-Hydroxy tryptamine) receptors
block D2 receptor or the D
receptor subtype)
- Other types of receptors are
not bound so the normal
function will continue but
for antipsychotic drugs,
they inhibit or block specific
D2 receptors so it will
reduce, stop or lower the
certainty of dopamine
reaction.
- Dopamine is excitatory.
ANTIPSYCHOTICS
➢ 1st Generation - D2 blockers (classified as
D2 blockers)
1) Haloperidol
2) Phenothiazines
○ Adverse effects: tardive dyskinesia
(stiff movement/jerky movement of
the body that can not control)
➢ 2nd Generation - D and D2 blockers
1) Clozapine
○ Also use as an antiemetic drug (treats
nausea and vomiting)
○ Same function to decrease the
activity of the dopaminergic
(dopamine) but also, serotonin
2) Antidepressants
○ Function: used to treat depression
where the CNS generally needs to be
excited and stimulated.
○ Used for minor as well as major
depressive illness, phobic states,
obsessive compulsive behaviour, and
certain anxiety disorders.
○ Mechanism of Action:
⤷ Increase the presence of
monoamines like dopamine,
norepinephrine, epinephrine,
histamine and serotonin.
- These are the ones
responsible for excitatory
action.
a) SSRIs (selective serotonin reuptake
inhibitors)
○ Mechanism of action
- They block the reuptake of
serotonin
 - Examples: fluoxetine, citalopram,
trazodone

★ Processes where after binding and action

is passed on to the postsynaptic neuron,
these neurotransmitters are now re-up
taken to be processed again.

b) SNRIs (serotonin and norepinephrine ★ Monoamines, drugs bind to enzymes so

inhibitors) or TCA (tricyclic that it will stay active for a longer period
antidepressants) of time in the synaptic cleft.
○ Mechanism of action
- They block the reuptake of both 3) Anxiolytic/Sedatives
serotonin and norepinephrine ○ Sedative (anxiolytic) are the agents
- Examples: Amitriptyline and which reduce anxiety and exert a
imipramine calming effect with little or no effect
○ Depends on the condition or needs of on motor or mental functions.
the patient whether that is need (sedates a person)
serotonin or serotonin and ○ Hypnotics are the drugs which
norepinephrine (A and B) produce drowsiness and encourage
the onset and maintenance of sleep.
c) MAOI (monoamines oxidase inhibitors)
○ Mechanism of Action:
- Inhibit monoamines (enzymes that
degrade and essentially cleans
the neurotransmitters in the brain)
- Examples: phenelzine,
tranylcypromine, and lithium
○ Lithium is a drug of choice used for
manic depression (bipolar disorder)

★ The most common anxiolytic/sedatives

are benzodiazepine and barbiturate. They
actually have its action on a ligand-gated
cheap protein ion specifically acting upon
the GABA receptor subtype A and they
increase binding which inters activates
receptors and promotes influx of chloride
 ions into the cells, inhibiting or slows
down the CNS (relaxes).
★ Safer, less addicting, has a larger
therapeutic window so it has fewer side
effects/adverse effects.
UNDER ANXIOLYTIC/SEDATIVES
1) Benzodiazepines (BZD)
○ Mechanism of Action:
- Binds to sites on the GABA A
(gaba aminobutyric acid, sub unit
A) receptors.
○ Ideal for oral sedation
○ Examples:
- Diazepam (valium)
- Triazolam (halcion)
- Chlordiazepoxide
○ Propylene glycol - IV form
2) Barbiturates
○ Mechanism of Action:
- Same with BZD (but more
indesirable effect)
- Contraindicated in patients with
intermittent porphyria (blood
clotting disease)
- Porphyria → most common
adverse effect of barbiturates; has
a synthesis of porphyrin; it affects
the clotting time of a persons
○ Examples:
- Thiopental - quick onset, short
duration of action (not usually
favored or given because of its
undesirable effect; it has a quick
onset but short duration of action)
- Midazolam: new short acting drug
also used as anesthetic agent; are
not analgesics.
★ Benzodiazepines and Barbiturates are
sedatives but they are not analgesics,
they do not provide pain relief. These
drugs just calm the person down but do
not address pain relief.
★ Psychoactive or psychotropic are two
terms that are used to refer to the same
drug. Although in some articles they
differentiate these two drugs as
psychoactive or psychotropic.
Psychotropic drugs can cross the blood
brain barrier and do not have addicting
effects.
○ Marijuana is said to be psychotropic.
ANTICONVULSANT
➢ Objectives:
1) To understand what seizure is by
understanding what happens in the
neuronal synaptic cleft.
2) To be familiarized with the
Mechanism of action of
anticonvulsant drugs.
3) To learn about the major classification
of antiepileptic/anticonvulsant drugs
and its side effects.
4) To know that there must be balance
in everything we do.
ANTICONVULSANTS
➢ Also known as anti-epileptic drug.
➢ Are diverse groups of pharmacological
agents used in the treatment of epileptic
seizures.
SEIZURE
➢ It is a sudden burst of uncontrolled
electrical/burst of electrical activity in the
brain that occurs when neurons become
excessively active.
★ It happens when there is an imbalance
between excitatory and inhibitory
processes in the brain that produces too
little inhibition or too much excitation.

➢ Goldilocks principle: where she can’t eat
too much but just the right amount of
food.
2 MAJOR CLASSIFICATION OF SEIZURES
1) Focal (affects only one side of the brain)
2) Generalized (affects both sides of the
brain)
★ If there is a message that needs to be sent
to a target site among neurons, electrical
waves between these neurons happen.
★ Action potential → complex and fast
process inside the cell.
MECHANISM OF ACTION:
ANTICONVULSANTS
➢ Block voltage-gated sodium and calcium
channels.
➢ Enhance neuronal inhibition of firing action
potential.
➢ inhibit glutamate release
★ Neurotransmitter glutamate → amino acid
but in action is excitatory/stimuli, one of
the most important terms to remember.
What happens in the synaptic cleft when
seizure occurs:
★ Sending neuron (excitatory neuron) and
postsynaptic neuron = granting of action
potential happens. Glutamate, envelope
with vesicles to be release in AMPA
(α-amino-3-hydroxy-5-methyl-4-
isoxazolepropionic acid) binds to sodium
ions and NMDA (N-methyl-d-aspartate)
bind to calcium ions, Kainate receptors. If
too much epilepsy happens, GABA
balances and calms the system down.
CLASSIFICATION OF ANTIEPILEPTIC DRUGS
➢ Blocks voltage-gated sodium ion
channels
○ Zonisamide
○ Lamotrigine
○ Valproic acid
○ Topiramate
➢ Blocks sodium and calcium channels
(special acts on both sodium and calcium
channels)
○ Carbamazepine
○ Oxcarbazepine
○ Phenytoin
★ Acts within one either sodium or calcium.
○ Gabapentin
 ○ Pregabalin
★ Alpha 2-delta 2 subunits of calcium
channel (works on GABA transmitters)
➢ Blocks voltage-gated calcium ion
channels
○ Levetiracetam (bind to walls of the
vesicle of glutamate – SV2A protein)
- This binding to the walls of
glutamate vesicles will impair the
synaptic release of glutamate and
thus decreases the neuronal
excitability
○ Felbamate (blocks NMDA receptors) –
where calcium and sodium ions bind.
○ Benzodiazepine
○ Barbiturates - acts on GABA
(Phenobarbital/Primidone – more
familiar in benzodiazepine and
diazepam)
★ GABA is inhibitory, inhibits neuronal
activity. Binds with longer stay in the
synaptic cleft to create equilibrium that
the system needs)
○ Tiagabine – inhibits reuptake of GABA
★ Process of neurotransmitters, reuptake
into the neuron back in the neuron via
GABA reuptake transporters
SIDE EFFECTS
➢ Most anticonvulsant
○ Sedation and dizziness for all drugs
a) Carbamazepine and oxcarbazepine causes
hyponatremia (low concentration of
sodium in the blood)
b) Vigabatrin causes loss of visual field (loss
of eyesight or vision is being affected)
c) Lamotrigine causes double vision.
d) Phenytoin causes gingival hyperplasia and
hirsutism (is a condition in women that
results in excessive growth of dark or
coarse hair in male-like pattern.) One
common brand is dilantin.
★ It is related to dentistry, an antiepileptic
drug which causes gingivitis. If a patient
has gingival hyperplasia, you better
check on the drug that the patient is
taking to be cautious in the treatment.
e) Valproic acid, gabapentin and pregabalin
can cause weight gain and peripheral
edema
f) Topiramate causes weight loss
g) Topiramate and zonisamide can cause
cognitive problems.
h) Felbamate and valproic acid causes liver
toxicity
i) Vigabatrin – inhibits GABA-T
★ One responsible for degradation of GABA
neurotransmitters. GABA transaminase
(ase means enzyme which catalyzes the
GABA neurotransmitters.) --- Vigabatrin
inhibits action of GABA-T/Transaminase
enzymes
★ If the transporter is blocked then the
reuptake permits the availability of GABA
neurotransmitter. There should be
inhibition and blockage, for some drugs
are classified by their pharmacologic
action like blockage.
★ Matter of balancing the inhibitory and
excitatory substance in the neuronal
pathway of the brain.
ANTI-PARKINSONIAN DRUG
➢ Treat Parkinson's disease.
➢ PARKINSON’S DISEASE
○ Is a neurological disorder that results
in a progressive loss of coordination
and movement (degenerative
disease, it is an irreversible
deterioration of nigro-striatal
pathway)
- An irreversible
deterioration
○ Cardinal Signs:
- Bradykinesia
- Rigidity
- Tremors
★ You need to have these 3 signs before you
can be diagnosed with Parkinson because
there are some tremors or rigidity which
are not Parkinson. So, it doesn’t mean that
if you’re having tremors this might be
 Parkinson. It should be the complete 3
cardinal signs that should be present.
★ It is present among older people because
of the degeneration of a structure in the
brain but according to studies, it was
noted that the younger generation that is
affected with this disease and youngest
was 16 years old.
★ Brain of an individual with Parkinson’s
disease. Have the nigro-striatal pathway
that is degenerating, and it did not
maintain enough level of dopamine.
★ Neurotransmitter dopamine is not only
responsible for the behavior like “feel
good” but also in some reactions
➢ Striatum: responsible for movement
➢ Substantia Nigra: sends dopamine to
help coordinate brain inputs (if there is
a degeneration of this pathway then
the Parkinson occurs)
➢ Neocortex: relays sensory information
and plans for future action.
★ What happens on the macromolecular
level or on the neurosynaptic cleft of
the CNS?
○ First, inside the dopaminergic
neuron, dopamine is synthesized
in two processes (two enzymes
such as TH and AADC)
1) TH (tyrosine hydroxylase): Synthesize
tyrosine
○ Which is an amino acid (precursor of
L-dopa and L-dopa is a precursor of
dopamine. Means no dopamine if
there is no L-dopa.)
○ Tyrosine is a precursor of L-dopa
○ L-dopa is a precursor of dopamine
○ Dopamine is combined with D2
receptors
2) AADC/ DDC (L- Amino Acid
Decarboxylase): Enzyme to synthesize
L-dopa for it to be able to produce
dopamine for it to be loaded into the
vesicles when there is an action potential
in the synaptic cleft.
○ After the release of dopamine, you
will have your receptors in the post
synaptic cleft or receiving neuron.
Different subtypes of dopamine
neuron. D1 – D5. Dopamine is specific
to D2 receptors
3) MAO (Monoamine oxidase)
○ Type A: oxidizes serotonin,
norepinephrine and all the other
neurotransmitters.
○ Type B: specific to dopamine.
4) COMT (catechol-O-methyltransferase):
○ Other enzymes that are situated in
the glial cells for the metabolism of
excess dopamine, either degraded or
cleansed.
★ Glial cells – are a type of neuron, but they
are not involved in the main neuronal
activity, just supporting function to the
main neurons to extend whatever support
the neurons need.
MECHANISM OF ACTION:
ANTI-PARKINSONIAN DRUG
1) To enhance dopamine activity
2) To depress cholinergic overactivity
(acetylcholine)
○ Acetylcholine – chief
neurotransmitter of the
 parasympathetic nervous system available on the synaptic cleft to bind
(slows down heart rate, contracts to D2 receptors.
smooth muscles and it is more of the 4) Selegiline
rest function of the nervous system) ○ Selective inhibits MAO-B
(monoamineOxidase-B)
CLASSIFICATION OF ANTIPARKINSONISM 5) Rasagiline
DRUGS ○ Selective inhibits MAO-B
1) Levodopa (monoamineOxidase-B)
○ Dopamine cannot cross blood-brain - They inhibit the enzyme so that
barrier (BBB) more dopamine is readily
○ Levodopa is a prodrug which is available in the synaptic cleft
converted to dopamine in the body 6) Tolcapone
○ Half-life: t1/2 = 1-2 hours ○ Selectively inhibit COMT
- It is the precursor of dopamine (catechol-O-Methyltransferase)
inside the body. Half-life is 1 – 2 7) Bromocriptine
hours in the body. ○ Mimic dopamine
○ Blood-Brain Barrier (BBB) 8) Ropinirole
- Created to protect the brain ○ Mimic dopamine
- Not all substances can pass this 9) Pramipexole
barrier ○ Mimic dopamine
- L-dopa can pass 10) Rotigotine
- Highly selective semipermeable ○ Mimic dopamine
border of endothelial cells 11) Apomorphine
○ Mimic dopamine action (these are
dopamine agonist)
○ Is a parenteral form used for
temporary relief for signs of rigidity or
tremors.
12) Benztropine
○ Blocks cholinergic activities
13) Procyclidine
○ Blocks cholinergic activities
★ BBB – tight endothelial cells, where it is
14) Trihexyphenidyl
created to protect the brain. Not all forms
○ Blocks cholinergic activities
of drug can cross the BB barrier.
15) Biperiden
★ Outside the barrier, there is the synthesis
○ Blocks cholinergic activities (increase
of tyrosine to become Levodopa so that it
in acetylcholine release) to restore
can cross to BBB for it to become
the balance
dopamine which is needed in
homeostasis.
★ Amantadine
○ Is an antiviral drug
2) Carbidopa
○ It enhances the release of dopamine
○ Inhibits DDC (dopa-decarboxylase)
in the brain and diminishes the
3) Entacapone
reuptake of dopamine. The response
○ Inhibits peripheral COMT
starts early and its adverse effects are
(Catechol-O-methyltransferase)
minor
synthesize another kind of dopamine,
○ Theory is believed to enhance the
susceptible to breakdown.
release of dopamine in the brain and
○ Drugs, addresses the synthesize of
acts on the reuptake of the
levodopa.
neurotransmitter’s dopamine.
○ There are glial cells that need to be
inhibited to have more dopamine
SIDE EFFECTS
➢ Levodopa and Carbidopa
○ Nausea and vomiting
○ Loss of appetite
○ Discoloration of sweat and saliva (very
distinct side effects)
➢ Rasagiline and Selegine
○ Dyskinesia and visual hallucinations
(inhibit the Type B monoamine
oxidase)
➢ Entacapone and Tolcapone
○ Severe diarrhea (inhibit the COMT)
➢ Dopamine Agonists
○ Daytime sleepiness (makes person
sleepy during daytime)
○ Pulmonary and cardiac fibrosis =
Bromocriptine
★ Michael J. Fox - very popular actor during
their time, main actor of family ties – a
sitcom during 80’s.
THE GOLDILOCKS RULE
➢ To give what is just right, not too much
and not too little.
GENERAL ANESTHESIA
➢ Anesthesia:
○ Reversible reduction or complete loss
of sensation to pain or
consciousness.
○ Reversible meaning it is a transitory
condition, transient, or temporary.
Sometimes in modern anesthetics,
the condition from unconsciousness
to consciousness is very smooth.
○ Anesthesia is classified as general
and local.
CLASSIFICATION
➢ Is based on what part of the body is numb
or has loss of sensation.
1) General – whole body is numb
2) Local – region, a part of the body is numb
GENERAL ANESTHETICS
➢ Are drugs which produce reversible loss
of all sensation and consciousness.
○ Sometimes drugs used to anesthetize
patients are termed as anesthesia but
more appropriate to be called as
anesthetics/anesthetic solutions.
Anesthesia refers to a condition of a
body (an adj or noun) describing a
condition of the body.
➢ Cardinal features:
○ Loss of all sensation
○ Sleep (unconsciousness) and amnesia
(or not having a memory of the
present situation)
○ Immobility and muscle relaxation
(important in surgery, the purpose of
anesthesia actually done when
surgical procedures are made)
○ Removal of somatic and autonomic
reflexes
★ You can not get anesthetic drugs without
having a surgery or by just having a
headache because it is not addressed by
taking anesthetics. It is employed to better
achieve surgeries.
★ Dental practice, general anesthesia is also
employed occasionally when or
especially the oral surgeons will remove
tumors or cysts that are cancerous. It is
not done by the oral surgeons; it is carried
out by the anesthesiologist.
STAGES OF ANESTHESIA
➢ According to Guedel, these stages in 1920
are no longer seen as a clear cut stage by
stage happening because we have a
more recent kind of drug.
1) Stage of analgesia/Induction
○ Loss of pain, from the beginning of
anesthetic inhalation to loss of
consciousness.
- (The pain is progressively being
abolished or removed; surgery
cannot be immediately carried
out because there is no total loss
of sensation).
○ Loss of consciousness
- (After inhalation to loss of
consciousness) --- surgery
cannot be carried out.
2) Stage of delirium
○ Excitement, jerky breathing
- (Progressive sensation of regular
breathing and becomes in a state
of delirium) --- surgery cannot be
also carried out. Almost not seen
in modern anesthesia but seen in
old or earlier times, the
anesthetic drugs use this stage.
3) Surgical anesthesia
○ Cessation of spontaneous breathing
- Most surgical and dental
procedures in the
hospitals/clinics are carried out at
this stage)
4) Medullary paralysis
○ Cessation of breathing to failure of
circulation
- Sometimes the cessation of
breathing and failure of
circulation can lead to death if not
addressed or given attention at
the right time.)
★ Nowadays, they use not only one type of
anesthesia but 2 or more like a
combination of both, one to address
analgesia and one to address immobility
and unconsciousness, one to address loss
of sensation.
★ Modern drugs are safer because of the
inventions and technology that are being
used to produce anesthetic drugs.
CLASSIFICATION
1) Inhalational
a. Gas
- Nitrous oxide
b. Volatile gas
- Ether
- Halothane
- Isoflurane
- Desflurane
- Sevoflurane
2) Intravenous
a. Fast acting drugs
- Thiopentone sodium
- Propofol
b. Slower acting drugs
- Benzodiazepines (Diazepam)
- Opioids (Fentanyl)
INHALATION ANESTHETICS
➢ Nitrous Oxide (N2O)
○ Is a colorless, odorless, heavier than
air, non-inflammable gas supplied
under pressure in steel cylinders.
(Like that is used for oxygen)
- In dental clinics in first world
countries, N2O is used to sedate
patients that are unconscious,
especially children, but it has side
effects.
○ Good analgesic but weak muscle
relaxant
○ Onset of action is quick and smooth;
recovery is rapid
- Nitrous Oxide used as a sedation
agent in dentistry. In some dental
schools, they are trained to use
nitrous oxide as a sedation agent.
But in the Philippines, there are
no cases of using this unless
given by an anesthesiologist.
○ Also described as “laughing gas”
- If it is administered along with air,
it produces the stage of
excitement and euphoria. They
like to be high, feel good, laugh
and on some occasions they are
sad, which sometimes leads to
amnesia.
➢ Ether (Diethyl Ether)
 ○ With a pungent odor and produces
irritating vapors which are
inflammable and explosive.
○ One of the first substances to be
employed for general anesthesia.
- Inflammable and explosive so it is
not safe to use but ether is the
first substance to be employed
for general anesthesia.
○ Derived from plants, the opium plant
“poppy” native to Turkey. Presence of
white liquid when we cut it.
➢ There are endogenous opioids in the body
namely: Enkephalins, dynorphins and
endorphins. (painkiller neurotransmitter)
○ We can tolerate certain levels of pain
because of endogenous opioids.

CLASSIFICATION
1) Group 1
a. Etomidate
b. Propofol
c. Barbiturates
➢ Unconsciousness but not immobility
2) Group 2 ★ The Origin of Pain – where pain starts
a. Ketamine ★ A complex process which starts in the
b. Nitrous Oxide nociceptive or nerve endings (like
c. Xenon fingertips, skin and other nerve endings of
d. Cyclopropane an organ). After the primary, nociceptive
➢ Analgesia but not unconsciousness information will detect the pain signal and
and immobility. it will send it to the second neuron. Then it
★ That is why they are given in combination. will bring the information to the spinal
Xenon, unlike the rest of group 2, does not cord (the dorsal horn of the spinal cord).
produce side effects at all, so it is Which now goes or brings the signal into
commonly used. the hypothalamus or the brain (where
pain is perceived).
3) Group 3
a. Halothane
b. Enflorane
c. Sevoflurane
d. Isoflurane
e. Desflurane
➢ Unconsciousness but not immobility.

ANALGESICS

➢ A drug which relieves pain without loss of

consciousness.
➢ Analgesia → “a” means absent, “gesia”
means pain ★ Pain starts at the nociceptor that are
numerous at the nerve ending (e.g. skin)
DIVIDED INTO TWO MAIN GROUPS: ★ Nociceptive information is transmitted
a) Opioid/Narcotic/Morphine-like from the periphery to the spinal dorsal
analgesics horn by primary sensory neurons. At the
b) Non-opioid/Non-narcotic/Aspirin-like spinal level, these neurons transmit
nociceptive information to second order
OPIOID ANALGESIC neurons (“Ascending pathways”) through
➢ Morphine of the most important alkaloid the release of neurotransmitters like the
of opium excitatory amino acids (EAA) glutamate
 and aspartate, calcitonin gene-related
peptide (CGRP), substance P (SP) galanin
(Gal) and neuropeptide Y (NPY). In the
brain, the nociceptive information is then
perceived as a pain sensation. The
transmission of nociceptive information at
the spinal level is modulated by
interneurons (mainly inhibitory) through
the release of opioid peptides and GABA
and also by supraspinal descending
neurons (“Descending pathways”) through
the release of serotonin (5-HT) and
noradrenaline (NA). Descending pathways
may inhibit or enhance nociceptive
transmission from the spinal cord.
★ Opioid Receptors are G protein-coupled
receptors (GPCRs)
★ The pain signal takes a series of action
potentials (to elicit an impulse or
message). To enhance the movement in
the pre-synaptic cleft, the
neurotransmitters are released for pain,
specific neurotransmitters are Glutamate
(excitatory), Substance P, and CGRP
(Calcitonin-Gene Related Peptide).
★ 2nd order on the dorsal root of spinal
cord, AMPA allows the Calcium and
Sodium ions to pass in the postsynaptic, it
will also be hyperpolarized to create
hypersensitivity or hyperactivity of
neurons.
MECHANISM OF ACTION: ANALGESIC
➢ Endogenous opioids exert their effects by
binding to opioid receptors, which are
abundantly present in CNS
➢ mu, delta or kappa
➢ Closing of calcium channels
➢ Opening of potassium channels
★ Opioid receptors are made of or looks like,
GPCR or G-protein type of receptor.
★ Delta and kappa are abundant in neurons
but for pain receptors it specifically binds
in the mu receptors and closes the
calcium ion channel to inhibit the influx of
calcium ions for it not to activate the 3
neurotransmitters. Activation of these
receptors will also open the potassium ion
channels so there will be moving up or
influx of potassium ions.
OPIOIDS
➢ The majority of available opioid analgesics
acts primarily at the mu-opioid receptors
mimicking the effects of endogenous
opioid peptides
➢ Examples:
○ Synthetic Opioids Agonists - Fentanyl
(not a natural one)
○ Hydrocodone
○ Hydromorphone
○ Meperidine
○ Oxycodone
○ Oxymorphone
○ Methadone (potent agonist and
antagonist of the NMDA receptor)
○ Buprenorphine (mixed
agonist-antagonist)
○ Naloxone (antagonist - used to block
or reverse the effects of opioids)
★ Opioids agonist that mimics the
endogenous receptors.
★ Naloxone gives an opposite reaction since
it is classified as antagonist.
★ Either acting as a potent agonist or
antagonist.
ADVERSE SIDE EFFECTS OF OPIOIDS:
1) Nausea: due to direct stimulation of the
chemoreceptor trigger zone in the
medulla
2) Respiratory Depression in Overdose: due
to reduced brain respiratory center
responsiveness to carbon dioxide
3) Suppression of the Immune System:
because opioid receptors are involved
with regulation of immunity
○ If there are overused or abuse of
these opioids or narcotic receptors, it
will give withdrawal symptoms
 where it gives the opposite effect of
having a relief in pain.
4) Histamine Release (causes hypotension):
morphine and meperidine (in injection
form also causes of flushing in the skin of
the face, neck and upper thorax due to
dilation of blood vessels)
○ Very potent foreign substance or
alkaloid.
5) Some (Meperidine): causes tachycardia
due to structural similarity to Atropine
6) Some opioids produce a dose-dependent
bradycardia by increasing the centrally
mediated vagal stimulation
○ If the vagus nerve is stimulated, then
there will be a sense of euphoria. The
bradycardia at a certain dose will now
make your heart rate slower.
NSAIDs (Non-Steroidal Anti Inflammatory
Drugs)
➢ They relieve pain without interacting with
opioid receptors.
➢ Mode of action:
○ They act primarily on peripheral pain
mechanisms and also in CNS to raise
pain threshold.
○ The arachidonic acid is liberated,
converted to prostaglandins (PGs) →
cyclooxygenase pathway (COX1 and
COX2) and 5-Lipoxygenase (LOX)
○ Cyclooxygenase 1 & 2
CLASSIFICATION OF NSAIDs
Selective Non Selective
COX1 selective COX2
Inhibitors COX Inhibitors
Inhibitors
Ketorolac Naproxen, Meloxicam,
Flurbiprofen Ibuprofen, Diclofenac,
Ketoprofen Piroxicam, Celexocib
Indomethacin Diflunisal and
Aspirin Etodolac
★ Selective COX1 Inhibitors – inhibits a
specific receptor that is responsible for
hyperactivity of the nervous system.
★ Non-selective COX Inhibitors
★ Selective COX2 Inhibitors
★ In dentistry analgesics are prescribed
according to severity of pain or purpose,
like anti-inflammatory drugs.
SIDE EFFECTS
1) Gastrointestinal (GI) bleeding and peptic
ulcers
2) Increased bleeding
3) Kidney injury in susceptible patients like
old age and with heart problems
4) Cardiovascular problems
DENTAL PHARMACOLOGY
NSAID (Non-Steroidal Anti-Inflammatory
Drugs)
➢ Analgesic
➢ Antipyretic
➢ Anti-inflammatory
➢ MOA:
○ Inhibit COX1 and COX2 enzymes
(cyclooxygenase)
★ Cyclooxygenase which are responsible in
the synthesis or the precursor of
prostaglandin that are responsible for
inflammatory process
INJURY DUE TO INFECTION
➢ 5-LOX-Lipoxygenase
➢ COX-Cyclooxygenase
★ Thromboxane is responsible for
vasoconstriction and platelet adhesion
(enhance clotting)
★ COX1 is responsible for synthesis of
thromboxane and prostaglandins which is
useful in normal processes.
★ Prostaglandins mediate inflammation
COX1 ○ Meloxicam
➢ Prostaglandins responsible for: ○ Diclofenac
○ Gastric mucosa ➢ Nonselective (inhibits both COX1 and
○ Renal perfusion COX2); prostaglandins in the stomach can
○ Platelet formation be reduced because it inhibits COX1
- Responsible or needed for which has physiologic action that protects
clotting the gastric mucosa which has a possibility
★ Activated by the body as they are needed of bleeding. COX2 was developed to avoid
for body processes these problems.
○ Aspirin
COX2 ○ Diclofenac
➢ Prostaglandins responsible for: ○ Indomethacin
○ Inflammation ○ Nabumetone
○ Pain ○ Sulindac
○ Fever ○ Tolmetin
○ Platelet inhibition ○ Ketorolac
- Bleeding is formed by COX2, ○ Ibuprofen
usually responsible for uterine ○ Naproxen
contraction during menstruation ○ Mefenamic acid
★ Induced by tissue damaged ○ Peroxicam
★ Bleeding is common in COX2 ➢ Chemicals
○ Salicylates
○ Acetic acid
○ Derivatives
○ Propionic acids
○ Anthranilic/Fenamates
○ Oxicam/Enolic acid

ANALGESICS USED IN DENTISTRY

➢ Dental pain or odontalgia is one of the
reasons why patients come to the clinic.
And pain relievers the analgesics are
★ Inflammatory response which causes pain usually mainstay of the dental pain are the
inhibits COX2 or COX1. NSAIDs
★ All NSAIDs inhibit COX2, but the clinical
relevance is it spares COX1. thromboxane GUIDELINES
A2 continues because the function of 1) Mild-to-moderate pain with little
thromboxane is platelet inhibition inflammation-paracetamol or low-dose
ibuprofen
CLASSIFICATION OF NSAIDs 2) Postextraction or similar acute but shot
➢ COX2 lasting pain
○ Celecoxibs - Ketorolac, a propionic acid derivative,
○ Meloxicam diclofenac
- Decrease PGs synthesis 3) Gastric intolerance to conventional
- Spare COX1, therefore NSAIDs or predisposed patients
thromboxane synthesis - Etoricoxib or paracetamol
➢ Selective COX1 4) Patients with history of asthma or
○ Aspirin anaphylactoid reaction to aspirin/other
○ Naproxen NSAIDs
➢ Selective COX2 - COx2 inhibitor
○ Celecoxibs 5) Pediatric patients
 - Paracetamol, aspirin, ibuprofen and
naproxen
- **Due to risk of Reye’s syndrome,
aspirin should be avoided unless viral
infection can be rules out
6) Pregnancy
- Paracetamol is the safest;
- Low dose aspirin is probably the
second best
7) Hypertensive, diabetic, ischemic heart
disease, epileptic and other patients
receiving long-term regular medication
- Possibility of drug interaction with
NSAIDs should be considered and the
physician consulted.
8) Patients with risk factors for
cardiovascular diseases, stroke
- Avoid etoricoxib/celecoxib
- Ibuprofen or low-dose aspirin may be
used

★ Ibuprofen 200 mg or naproxen 200-225

mg
○ Common analgesics or NSAIDs for
the treatment of mild odontogenic
pain
★ Paracetamol 500-1000mg

★ NSAIDs + Mefenamic acids NSAIDs +

paracetamol
○ Mild to moderate
★ Ibuprofen 400 mg/Naproxen

If NSAIDs are not enough in patients increased

in severity, you can give mild opioids
★ Oxycodone 5 mg
★ Hydrocodo 10 mg
★ Codein 60 mg
★ Tramadol 50-75 mg

DRUG INTERACTIONS
➢ NSAID + another NSAIDs cannot be
combined = exacerbate their toxic effects
➢ NSAID + Paracetamol
○ Better to combine this two which is
also known as Acetaminophen
○ Paracetamol = Acetaminophen