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JRB2014

Central Nervous System















Neurons
Interact with each other
Brain is in balance
o Excitation
o Inhibition

Neurotransmitters:

1. Glutamate
Most excitatory
Derived from glucose
Receptor of glutamate:
NMDA
Most pharmacologic use
Ionotropic Na channel
AMPA
Kainate less studied Metaboprotic
(mGlut)
Example:
Ketamine (Dissociative anesthesia)
NMDA blocker

2. GABA Gamma aminobutyric Acid Glycine
(Inhibitor)
Found mainly in brain
Glycine found mainly in spinal cord
o Inhibitor for Glycine Strychnine
Most inhibitory neurotransmitter
3 types of receptors:
GABA
A
Ionotropic Cl Channel
GABA
B

GABA
C

Examples of GABA
Zolam, zepam, barbital, benzo,
olanzapine
MOA:
Opens Cl channel
Cl enters
Hyperpolarization

MIXED-TYPE Neurotransmitters (INH + EXC)

3. Histamine
Derived from Histidine
Receptors:
H1
Found mainly in brain
Wakefulness
Found in vomiting center
Chemoreceptor
trigger zone (area
postrema)
IgE
Mast cell
Histamine
Cause vessel-
dilation
Brochodilation
Pruritus
Can cross BBB
Indications:
Allergy
Insomnia
Antiemetic
ADR: Drowsiness,
Somnolence
Examples:
1
st
Gen:
Diphenhydramine
Meclizine
Cyclizine
Chlorpheniramine
Brompheniramine
Hydroxyzine
2
nd
Gen:
Loratadine
Desloratadine
Cetirizine
Levocetirizine
H2
tidine
Nervous System
CNS -
oligodendrites
Brain Spinal cord
PNS - Schwann
cells
Somatic
(Skeletal
muscle)
Autonomic
(Visceral)
Dendrites
Myelin Sheath (Covers)
Axon
Nodes of Ranvier
Metaboprotic
JRB2014
Gastric secretion
Found in parietal cells
HCl produced
from parietal cells
Pepsinogen ->
pepsin
G-gastrin
Examples:
Cimea tidine
(Enzyme inh)
Ranitidine
Famotidine
Nizatidine
4. Acetylcholine
5. Monoamines
a. Norepinephrine (Catecholamine)
b. Dopamine (Catecholamine)
Tyrosine DOPA Dopamine
Receptors
o D1 D5
Metaboprotic (Mixed
Inhibitory and Excitatory)
c. Serotonin (5HT)
Precursor: TRYPTOPHAN
Tryptophan5-OH-tryptophan
5-OH-tryptamine 5HT
1

(Receptor)
6. Opioid Peptide






























































































JRB2014
CNS DISEASES

ALL CNS DRUGS ARE LIPID SOLUBLE
CNS: (Psychosis and Neurotics)
Psychosis
o Impaired reality
Hallucination
May nakikita, naririnig,
naamoy na hindi nakikita
ng ibang tao
Delusion
False belief
o Most common: Schizophrenia
Exact cause: Unknown
Most related cause:
DOPAMINE
Increase DOPAMINE
secretion in mesolimbic
and mesocortical
Psychosis
Pathways
*Mesocortical
o Midbrain cortex
of frontal lobe
*Mesolimbic
o Midbrain Limbic
system (emotion
arise)
o Amygdala
o Hippocampus
o Frontal lobe
o LOVE <3
Nigrostriatal
o Substantia nigra
Striatum (Black
substance or gray
matter)
o Fine motor control
Tuberoinfundibular
o Endocrine control
o Pituitary gland
Connected to
hypothalamus
o Dopamine
Inhibit prolactin

Neurotic
o Not impaired reality
o Intact reality
o Bulimia
o Depression
o Depression

Positive Symptoms
Hallucination
Delusion
Negative Symptoms
Alogia absence of thought
Avolition absence of voluntariness
Anhedonia lack of interest
Attention deficit
Affect blunting expression of mood

D2 Antagonist (Dopamine Receptor Antagonist)
Typical (First one to be discovered)
o *Aliphatic (Least potent)
Chlorpromazine
Promethazine
o *Piperidine Derivative
Thioridazine
Mesoridazine
o *Piperazine Derivative
Perphenazine
Fluphenazine
o Thioxanthine
Thiothixene
o Butyrophenone
Haloperidol
Droperidol
o ADR for TYPICAL:
Inhibitory for:
alpha1 orthostatic
hypotension
m- dry mouth, blurring,
constipation
H1 sedation, drowsiness,
somnolence
Neuroleptic Malignant Syndrom
Hyperthermia 40 41 C
Muscle rigidity (fatal)
Most common in
Chlorpromazine and
Haloperidol
Weight Gain
Sexual dysfunction
Atypical (Less EPS)
o More effective for negative symptoms
o Inverse agonist for serotonin
o Clozapine
Long term using may develop
severe infection
Agranulocytosis (Absence of
granulocytes)
Basophils, Eosinophil,
Neutrolphil BEN
Attack neutrophils
o Quetiapine
o Olanzapine
o Loxapine
o Rispridone
o Paliperidone
o Aripiprazole

ADR of all antipsychotics
o Extrapyramidal symptoms (EPS)
Tremors
Rigidity
Bradykinesia
o Tardive dyskinesia irreversible EPS
Oculogyric
Circumoral twitching
*Addiction
Pathway
Thought formation,
behavior, emotion

*Phenothiazine
ADR:
Gynecomastia,
galactorrhea

JRB2014
PARKINSONISM

Parkinsons Disease
Degenerative
Attacks nigrostriatal
Tremors (pill-rolling)
Bradykinesia
Rigidity
Unstable gait

Primary Treatment:
LEVODOPA
o Levo isomer
o Prodrug of Dopamine which can cross BBB
o Dopamine is incapable of crossing BBB
Dopamine causes inotropy
o Substrate for dopamine
o Given orally
o Subjected for peripheral
dopadecarboxylase (DDC) decrease
CNS bioavailability
o ADR: On and Off phenomenon
o Can be given with:
Carbidopa
DDC inhibitor
Tolcapone and Entacapone
Catechol-o-
methyltransferease
(COMT)
o Cannot cross BBB
COMT INHIBITOR

1. Levodopa
Carbidopa
Tolcapone
Entacapone

ADRs:
GI
o Anorexia
o Nausea and Vomiting
Heart
o Arrhythmia
CNS
o Psychosis

CONTRAINDICATED WITH ANTIPSYCHOTICS


2. Dopamine Receptor Agonist
Bromocriptine
Pergolide
Rotigotine
Ronipirole


Rescue drug: APOMORPHINE
Severe NV
D2 agonist

Defect in Parkinsonism Increase ACh
3. Cholinergic Antagonist
Benztropine
Biperiden
Orphenadrine
o Muscle relaxant

4. Amantadine
Antiviral Influenza A
Crosses BBB
ADR:
o Insomnia
o Liveroreticularis
o Headache
o Reticularis

5. MAO Inhibitors
Types:
o A - degrades DA, NE, 5HT
o B Selective to DA
Selegiline
Rasagiline
Do not accompany with cheese, wine, chicker
liver (tyramine-rich foods)
CI: Levodopa, Dopamine receptor agonist




































ADRs:
Arrhythmia
NV
Anorexia
ADRs:
Blind as a bat..
CI:Pt with glaucoma,
urinary retention
JRB2014
MOOD

Depression Mania
Unipolar
Bipolar

Common:
Sleep disturbance
Anhedonia

DSM-IV Diagnosis of Mental Disorder

Bipolar
Linked to psychosis
Drug of Choice: Lithium (PO)
o Carbonate
o Citrate
Lithium LOW TI
o Weight gaine
o Acne
o Thirsty (polydipsia)
o Insomnia
o Cardiotoxic, hemotoxic, nephrotoxic,
hepatotoxic
o Hyponatrimia dehydration
Increase lithium toxicity

Monoamine Hypothesis
Decrease NE, 5HT Depression
Increase NE, 5HT Mania

1. SSRIs Selective 5HT Reuptake Inhibitor
Inhibit SERT (Serotonin Transporter)
Setraline
Paroxetine
Fluoxetine
Fluvoxamine
Citalopram
Escitalopram

2. SNRIs Selective NE Reuptake Inhibitor
Inhibit SERT and NERI
ADR: Hypertension
Duloxetine
Venlafaxine
Desvenlafaxine
Milnacipran

3. TCAs
Tryptiline or Pramine
Inhibit SER/NET
ADR:
o Cardiotoxic
o Myocarditis
o Inhibit:
Alpha1 - hypotension
H1 - Somnolence
M atropine-like
Imipramine
Desipramine
Clomipramine
Amitryptiline
Nortryptiline
Protryptiline

4. Unicyclic
Bupropion

5. Tetracyclic
Amoxapine
Mirtazapine

6. 5HT
2A
Antagonists
Trazodone
Nefazodone
ADR: Hepatoxicity

7. MAOIs
*Phenelzine
*Isocarboxazid relative to isoniazid
*Tranylcypromine
Moclobemide MAO A
Selegiline MAO B
Rasagiline MAO B
CI: SSRI/SNRI
ADR:
o Serotonin Syndrome
Seizures
Coma
Death
o Hyper excitability
o Priapism Erection (Uncontrolled)

ADR of Antidepressants:
Weight gaine
Sexual dysfunction (MAOi)
Impotence
Orthostatic hypotension (except SNRIs)





















JRB2014
SEDATIVES-HYPNOTICS

Anxiolytic/Tranquilizer
Induce calmness and sleep

Indications:
Anxiety disorders
insomnia

Barbituates
anticonvulsants
Barbita inducer
Number of DDI
Steeper curve (Dose-response)
Examples:
Phenobarbital
Primidone
Secobarbital
Amobarbital
Pentobarbital

Benzodiazepines
Zepam, Zolam
Safer
Examples:
Diazepam
Diazepam Desmethyldiazepam
Oxazepam Inactive
Chlordiazepoxide
Clorazepate
Clonazepam
Alprazolam
*Oxazepam
*Lorazepam
*Midazolam
*Triazolam

Stages:
1. Sedation
2. Somnolence
3. Analgesia
4. Anesthesia
5. Medullary Depression

Pre-Operation:
1. Anxiolytics
2. Muscle Relazation
3. Antegrade Amnesia











ANTICONVULSANTS

Convulsion/Seizure:
Drug-induced
Metabolic
Tumor

Epilepsy Chronic Disease

Two Types:
1. Generalized:
Tonic-clonic (GTC) or Grand Mal
Petit Mal/Absence
2. Partial not entire cortex (Part only)
Simple Partial
Conscious
Complex Partial
Unconscious

Drugs:

1. Na Channel Blockers
Phenytoin
Carbamazepine
Oxcarbazepine
Lamotrigine
Topiramate
Zonisamide
*Valproic acid

2. Increase GABA
Phenobarbital
Primidone
Diazepam
Clonazepam
Alprazolam
Tiagabine
Vigabatrine
Gabapentine
Pregabaline

3. Glutamate
Felbamate
Leveriracetam
*Ethosuximide Ca Channel blocker (T-type)

ADR of all except *
Confusion
Ataxia
Nystagmus uncontrolled eye movement
Diplopia









*Short-acting (without
active metabolite)
(LTOM-Little TOM)
ADRs:
Hirsutism
Gingival hyperplasia
Teratogenic
o Fetal Hydrantol
Syndrome
Neural tube defect
ADRs:
Drowsiness
Somnolence
ADRs:
Increase GABA (prevent
GABA degradation)
JRB2014
ANESTHESIA

Sensory:
General (Systemic) entire CNS (Unconscious)
Local (Topical) Infiltration

Parameter: Minimum Alveolar Concentration

General:
1. Inhalation
Nitrous oxide
Halothane - Hepatoxicity
Enflurane
Desflurane
Isoflurane
Sevoflurane
Methoxyflurane
MOA:
Unknown
Meyer-overtson
o Generalized-nonspecific CH CCIII
membrane permeability
ADR:
Malignant Hyperthermia
Muscle rigidity
Genetic mutation
Antidote: Dantrolene

2. Intravenous
Midazolam
Thiopenthal -
Propofol act as barbital
Ketamine
o Dissociative anesthesia
o Analgesia and amnesia
o NMDA
ADR:
CNS Depression
Cardiovascular depression

Stages of Anesthesia

I. Stage of analgesia
a. No pain
II. Stage of Excitation
a. Stage of delirium
b. Combative
c. Irregulat Vital Signs
III. Surgical Anesthesia
a. Go Signal
b. Regular vital signs
IV. Respiratory/Medulla depression








Local:
1. Esterv- Plasma with degradation; esterase
Cocaine
Procaine
Tetracaine
Benzocaine
Propoxycaine

2. Amide- Hepatic degradation; amidases
Lidocaine
Prilocaine
Etidocaine
Bupivacaine
Mepivacaine

Classification is based on the kind of bond in the
structure
All local anesthetics are synthetic except COCAINE
All local anethetics are ampiphilic
o Water and lipid soluble
All local anesthetics are weak bases and Na Channel
Blocker
Small fibers get block first.
o Types:
Type A
Alpha motor control,
proprioception
Beta light touch and
pressure
Delta smallest; pain and
temp
Type B
Type C


Myelinated fiber are block first
o Conduction salutatory conduction
o 2-3 nodes of ranvier
ADRs
o Cardiovascular depressant
o Cocaine
Tachycardia
Vasoconstriction
Hypertension
Euphoria, bliss
Stimulates reward path
Insomnia
Inhibition of NET












Sympathetic
Smaller
Pain
JRB2014
OPIOID ANALGESICS

Central analgesic
Addicting

1. Full Agonist
Morphine
Heroin
Methadone
Oxymorphone
Hydromorphone
Fentanyl
Alfentanil
Remifentanil
Sulfentanil

2. Partial Agonist
Codeine cough suppressant
Oxycodone
Hydrocodone
Propoxyphene
Diphenoxylate - antidiarrheal
*Dextromethorpan
*Loperamide
Tramadol

3. Mixed Agents (Analgesics)
Nalbuphine
Pentazocine
Buprenorphine

Opioid Receptors
Mu well associated with analgesic factor;
proprioception
Kappa
Delta

Pain is always ASCENDING

CNS effects:
Analgesia
Decrease cough reflux
Cause euphoria
CNS Depressant
Respiratory depressant
o Suicide-Sufentanil
Opioid Agonist Overdosage
o Extreme miosis
o Pinpoint
o Smooth muscle relaxant
ALL OPIOID ANALGESIC ARE CARDIAC DEPRESSANT

Antagonist IV
Naloxone
Naltrexone
Nalmifene

USED FOR WITHDRAWAL METHADONE




*Cannot cross BBB

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