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
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
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
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
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
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
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
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
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