DRUGS AFFECTING CNS  Barbiturates

II. SEDATIVE - HYPNOTICS  Benzos

 Non-benzos (Nonbenzodiazepine)
 Sedative – calms subject without inducing sleep
Examples (ze & zo)
 Hypnotics – with sleep
 Clonazepam
 anxiety
 Diazepam (1960s)
 insomnia
 Brand Name: Valium
NT involved is GABA - affects the
- hyper
limbic system that regulates emotions
 Lorazepam (1977)
and behaviors, specifically the
 Brand Name: Ativan
amygdala, the part of the brain that
- banned because risk of dependence
registers trauma. An imbalance in
increases with higher doses and longer-
GABA—either depletion or excess—can
term use
lead to anxiety or insomnia.
 Alprazolam (1981) – latest
PTSD occurs because the limbic
 Brand Name: Xanax or Xanor
system, specifically the thalamus and
Mechanism of Action
hypothalamus, registers traumatic
 enhance GABAA receptor
experiences. These areas are
interconnected through the mesolimbic  GABA is inhibitor so if inenhance, mas nag-
pathway. iinhibit
Receptor involved is GABAA  imagine depress ka na because you have
- GABA receptor (ligand gated ion depleted GABA, kung magbibind pa ioopen yung
channel) is pentagonal = it has 5 channel then mas magnenegative, so benzos
subtypes (2 alpha, 2 beta, 1 gamma or ibblock lang yung GABAA para no opening of
delta) channel di makakapasok ang chloride ion, para
- pumapasok na ion is chloride which is di mas lalong madepress ang tao
negatively charged  if nagbind sa There is generation of drugs to reduce adverse effects.
alpha receptor, it will open (chloride Adverse Effects
channel)  Cl- goes inside (normally  Drowsiness
positive outside, negative inside =  Diziness
hyperpolarization)  magkakaron ng  Decrease Concentration
slowing down
B. BARBITURATES
 same na nagbbind sa GABAA subunit
(mechanism of action)
 difference is that ang benzodiazepines
(frequency of closing and opening of the ion
channel) while barbiturates (duration = mas
tinatagalan niyang nakabukas)
 ―barb‖
Examples (barb)
 Sedation – there is decreased responsiveness  Phenobarbital
 Pentobarbital
CLASSIFICATION  very low therapeutic index, therefore mataas ang
toxicity
 counterpart of party drugs
Adverse Effects
A. BENZODIAZEPINES  Respiratory Depression - major side effect
 ―dia‖ & ―pam‖ – anti-anxiety drugs - konting overdose can lead to coma or death
 mostly ends in ―pam‖  Intermittent Porphyria (genetic) - disorder that is
 have narrow therapeutic index: contraindicated sa barbiturates
- can’t produce porphyrins (sobrang sakit ng
tyan
C. NON-BZD HYPNOTICS  When a person is stressed, the body
 z drugs may struggle to synthesize these
 don’t treat anxiety but only insomnia neurotransmitters effectively, making it
Examples difficult for the limbic system and
 Zolpidem nervous system to manage the stress.
 Zaleplon  With prolonged use of certain
 Zopiclone medications, the body may become
 these 3 are all agonists (they mimic or accustomed to them, leading to receptor
enhance the inhibitory function of upregulation, which can reduce the
GABA) medication's effectiveness. However,
 Flumazenil – GABA antagonist homeostasis is generally restored over
- not totally antagonist but competitive = time.
nakikipagcompete with other drugs  Amygdala – regulation of fear
- has very little intrinsic activity Depression
- the reaction is kabaliktaran *at least 5 of these symptoms that manifest for at least
or a minimum of 2 weeks
III. ANTIDEPRESSANTS *this is not a usual fluctuation of hormones or feeling of
sadness that any person feels any time, but these are
*In a spectrum of CNS excitability, a patient is either
symptoms that last longer than usual times of sadness,
below the homeostasis or below the stable point, or
melancholic state, or unmotivated state
sometimes above.
 depressed mood
*Too much or too little neurotransmitter affects a
 diminished interest or pleasure
patient’s wellbeing.
 insomnia
 elevate mood in depressive illness
 agitation
 To treat:
 fatigue
a. depression
 diminished cognitive abilities
 whether unipolar (depression
alone) or bipolar (manifesting
both manic depressive situation
or disorder)
 manic – feelings of sadness
Neuroses – less severe
 ex. anxiety, depression, OCD, ADHD
 there is something wrong sa pathway ng
brain (limbic system)
Psychoses together with schizophrenia – more
severe, unaware na siya sa nangyayari sakanya
―es‖ plural, ―is‖ singular *left is healthy person – abundant level of monoamines
Monoamine Hypothesis *right is depressed person – low level of monoamines
*there are debates going around to what causes *Norepinephrine (excitatory) – responsible for arousal,
depression but this is the best wherein depression alertness, attention, focus
occurs due to the decreased or insufficient *If more adrenaline is deficient, that person becomes
monoaminergic activity in the brain depressed
 NT involved: Dopamine (5HT), Serotonin, *Serotonin – responsible for mood and sleep  that’s
Norepinephrine (decreased) why this is also deficient in patients with insomnia
 these 3 are monoamines *Dopamine – used to be accountable for the cum,
 drugs that increase their activity are feelings of the person, but now it is more on associated
called typical anti-depressants with reward and motivation
because there are other drugs that act *So if dopamine is deficient, the person becomes
with different mechanisms demotivated or lacks drive or sometimes doesn’t enjoy
 1 Hypothesis: may deficiency either sa tatlong
st
pleasurable things they used to enjoy
neurotransmitter = depression
 2 Hypothesis: there is upregulation of the
nd

monoamines  dumadami receptors

  Desipramine
 Amitriptyline
 Doxepin
 Imipramine
 Nortriptyline
―DAD Is Necessary‖
= T(atay) CA
Adverse Effects
*In normal process of neurotransmission, if there is  dry mouth
action potential, there is release of serotonin and  blurred vision
norepinephrine in the synaptic cleft  weight gain – one hallmark adverse effect of
*However, in person with depression, after binding to the TCAs and other anti-depressant drugs
receptor, the excess are being reuptaken by the the  drowsiness
transporters (Norepinephrine: NET, Serotonin: SERT)   dizziness
if reuptaken, it is supposed to be a good news because
they will be metabolized or synthesized again to be in
B. SSRIs (Selective Serotonin
the vesicle for another potential to be released, but the
problem in a person with depression there is also
Reuptake Inhibitors)
increase of MonoAmine Oxidase subtype A (MAO-A)  Mechanism of Action
because of the presence of MAO-A in the peripheral wall *Inhibition of reuptake of serotonin by blocking SERT
of presynaptic neuron, the NT that are reuptaken are *These drugs block SERT but NET is not blocked which
st
being degraded or undergoes metabolism by this is why although this is the first line in treatment for 1
enzyme converting NT into inactive metabolites  generation anti-depressants (most commonly used)
therefore affecting the number of NT that are being there are known side effects because of the open
synthesized Norepinephrine transporter
*although SSRIs are the safest in overdose, unlike TCAs
which have low therapeutic index, SSRIs slow to being
CLASSIFICATION
overdose, it has a half-life of 18-24 hours so because of
*These 3 (TCAs, SSRIs, SNRIs) are all inhibitor of a
that length of time of the drug is reduced to 50%, a once
receptor
a day dosage is life
*MAOI (MonoAmine Oxidase subtype A inhibitors) are
 Sertraline (Zoloft)
the enzyme itself that degrades the NT
 Paroxetine (Paxil)
 Citalopram
A. TCAs (Tricyclic Antidepressants)  Escitalopram
Mechanism of Action O
st
*belongs to 1 generation of anti-depressants, they  Fluoxetine (Prozac)
actually inhibit SERT and NET (blocked)  so there will  Fluvoxamine
be slow clearance in the synapse  therefore, if NT stay ―When you are S(ad)RRIs, you want some SPaCE or
longer they will bind longer to the post-synaptic neuron some time oFF
to produce the effect that is intended and there is a
better serotonin and norepinephrine neurotransmission
*for SSRIs and SNRIs they are also inhibitors of the
C. SNRIs (Serotonin-Norepinephrine
transporters but for TCAs they do not only block the 2 Reuptake Inhibitors)
transporters but also the Muscarinic and Histaminic Mechanism of Action
receptors in the post-synaptic neurons *blocks not only NET but also SERT  therefore inhibits
*these drugs act by also blocking the histamine reuptake of both NT or MonoAmine  therefore it
receptors that is a receptor for acetylcholine  if enhances the longer lodging of NT on the synapse 
histamine receptor (which acts as antagonist), histamine results to better quality of signal transmission with the
NT will not bind to it  gives sedative effect post-synaptic neuron and achieving a more calm and
*Muscarinic receptor – binding site for Ach  so if ACh motivated behavior
is not bound, the cholinergic activities will not take effect  Venlafaxine
*This is why TCAs are more favored over other anti-  Milnacipran
depressants because it exerts lesser adverse effects  Duloxetine
due to this blockade of 4 receptors
―Very Millennial Drug‖ = new discovery (replacement for
SSRI which has more adverse effect like the serotonin
syndrome)

D. MAOIs (MonoAmine Oxidase

Inhibitors)
Mechanism of Action
*blocks the MonoAmine Oxidase  in depression, it is
specific to subtype A, because there 2 subtypes (A and
B)
*In Parkinson’s disease MAO-B involved in metabolizing
dopamine while MAO-A is involved in metabolizing
noradrenaline, serotonin, and dopamine and they are
present in the peripheral nerve ending and also in the
intestine while MAO-B is mostly present in brain
*Selegiline (Anti-parkinson drug) – inhibits only MAO-B
but in depression they can also be used as transdermal
patch
 Moclebemide
 Isocarboxasid
 Phenelzine
―Mom Is Phenomenal‖ – MAOIs
Adverse Effects
 dry mouth
 blurred vision
 weight gain
 drowsiness
 dizziness
*cholinergic effects but specifically for MAOIs there are
also:
a. Food-drug interaction
(tyramine)
*if a person taking MAOI drug and its food with tyramine
(cured foods) it will have severe interaction
ex. cheese, sausages
 except Moclebemide
 Phentolamine – antagonist
*blocks MAO-B if there is accidental interaction
with cheese or food taken with tyramine (beer
and red wine has tyramine)
b. Drug interaction
 Ephedrine – a cough syrup

―You’ll never find a rainbow if you’re looking down.‖

There are studies that believe stress leads to cell death

in the hippocampal formation so although the
physiological changes of these are unknown, experts
may speculate that they are accompanied with the
alteration of NT or MonoAmines and alter gene
transcription.