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PHAR 270 (Module 1 (Module 1.4. (Drug advertising (Catch the audience'…

- - - - regulatory protesin
      - transporters
      - enzymes
      - structural proteins
      - interactions
        
        agonist
        
        partial agonist
        
        allosteric activator
        
        competative antagonist
        
        non competative antagonist
      - signalling mechanisms
        
        ligand gated ion channels
        
        g protein coupled receptors
        
        intracellular receptors
        
        regulated transmembrane enzymes
        
        carrier proteins
  - - - absorption
        
        aqueuous pores
        
        diffusion through lipid
        
        active or carrier mediated transport
      - distribution
        
        free drug
        
        drug bound to protein
      - excretion
        
        kidneys
        
        glomerular, tubular, passive tubular
        
        gi
        
        body fluids
        
        lungs
      - biotransformation
        
        phase 1
        
        oxidative reactions via cytochrome P450
        
        other oxidative reactions
        
        hydrolysis of esters/amides
        
        phase 2
        
        UGT, SULT, GST, NAT
        
        first pass effect
        
        genetic, age, disease
    - - Eternal
        
        sublingual and buccal
        
        rectal
        
        Oral
      - Topical Routes
        
        On skin
        
        through skin
        
        intravaginal, intraocular, intraotic, intranasal
        
        inhalation
      - Parenteral
        
        intravenous
        
        intramuscular
        
        subcutaneuous
  - - - VD
      - clearance
      - halflife
      - plateau principle
      - dosages
        
        adults
        
        kids
      - compliance
  - - - acute
      - sub-chronic
      - chronic
      - other (cancer)
    - - Phase 1
      - Phase 2
      - Phase 3
        
        Target population
        
        Inclusion/Exclusion
        
        Ethical considerations/consent
        
        Comparator
        
        Randomization
        
        Blinding
        
        what is measured
        
        compliance
        
        QOL
        
        analysis of results
      - Phase 4
    - - Innovator drugs
      - Generic Drugs
    - - Chemical
      - Generic
      - Brand
    - - Catch the audience's attention
      - Use of celebrities or authorities to endorse
      - Fear
      - Offer easy solution to problem
      - before and after
      - Discredit drugs made by other manufacturers
  - - - TI
      - difficult to predict?
        
        Adverse event may be rare
        
        Toxic reaction appears after prolonged use
        
        Not all toxic effects detected in animals
        
        Adverse effect is unique to particular period or circumstance
    - - Extension of therapeutic effect
      - Effects in non-target tissues or organs
      - unrelated to main drug action
      - Drug idiosyncrasy
      - Allergic reaction
      - Adverse biotransformation reaction
      - Drug dependence and addiction
      - Teratogenesis
      - Risk?
        
        Age
        
        Multiple diseases
        
        Genetics
    - - Synergistic
      - Potentiation
      - Additive
      - Antagonism
      - Altered physiology
      - Pharmacokinetic
        
        Absorption
        
        Distribution
        
        Biotransformation
        
        Elimination
      - risk?
        
        Age
        
        Polypharmacy
        
        Genetic factors
        
        Drug Properties
        
        Narrow TI
        
        Saturated metabolism
        
        Extensive blood protein
        
        small volume of distribution
        
        active transport to reach site of action
        
        elimated by one of biotransformation or renal excretion
        
        organ with high blood flow
    - - grapefruit juice
      - tyramine
- - - - GABA mediated inhibition
      - Inhibits glutamate
      - Short term
        
        CNS, CVS, GI, Liver
        
        Blackouts, Psychiatric, drinking and driving, respiratory depression, coma and death
      - Chronic
        
        CNS, CVS, Liver, Vitamin B1, PNS, Cancer, Ebryo
      - Drugs to treat alcholism
        
        dissulfiram, naltrexone, acomprosate,
  - - - Generalized
        
        Tonic clonic, myoclonic, atonic, absence, status epilepticus
      - Partial
        
        Simple partial, complex partial, secondarily generalized
      - Treatment (Anticonvulsants)
        
        Increase inhib input
        
        Block electrical activity
        
        Decrease glutamate
        
        Adverse effects: CNS, GI, Hepatic, Hematologic, Metabolic, Immune
        
        Drug interactions
        
        Toxicity/overdose
        
        safety in pregnancy
        
        dependence
    - - Barbiturates
        
        lethality
        
        patterns of use
        
        potential for abuse
        
        dependence
      - Benzodiazepines
        
        Flumazenil
        
        Increase synpatic inhibition
        
        ativate benzodiazepine receptor
        
        effects of short term use
        
        CNS, lung, GI, motor coordination
        
        effects of long term use
        
        impaired thinking, memory, disorientation, slurred speech, weak muscles
        
        letahlity
        
        patterns of use
        
        potential for abuse
        
        dependence
        
        pregnancy and breast feeding
  - - - Reactive depression
      - major depression
      - depression associated with bipolar disorder
      - Theories for cause
        
        amine
        
        neurotrophic
        
        neuroendocrine
      - Antidepressants
        
        Block neurotransmitter reuptake systems
        
        SSRI
        
        SNRI
        
        TCAS
        
        Second generation antidepressants
        
        Block neurotransmitter metabolism
        
        MAOIS
        
        Increase the amount of NT released
        
        Presynpatic autoreceptor blockade
        
        Electroconvulsive therapy
    - - Treatment
        
        reduce mood to normal with antipsychotic
        
        Antipsychotic
        
        Phenothiazine antipsychotic
        
        Block dopamine
        
        Block cholingergic (muscarinic)
        
        Block histamine
        
        block a-adrenoceptors
        
        Haloperidol
        
        Second-generation antipsyhcotics (atypical)
        
        Stabilize mood
        
        Lithium
        
        valproic acid
        
        carbamazepine
        
        clonazepam
  - - - Non steroidal anti-inflammatory drugs
        
        Non-selective COX inhibitors
        
        Ibuprofen
        
        Naproxen
        
        Diclofenac
        
        COX-2 selective inhibitors
        
        Celecoxib
        
        meoxicam
    - - Receptors
        
        MOP
        
        KOP
        
        DOP
      - Classifications
        
        Agonists
        
        Mixed agnoists/antagonists
        
        Antagonists
      - endogenous (endorphins)
      - Opiate narcotics
      - semisynthetic opioids
      - synthetic opioids
      - pharmacological effects
        
        analgesia
        
        euphoria
        
        sedation
        
        hypnosis/sleep
        
        supresion of cough centre
        
        respiratory depression
        
        decreased GI motility
        
        endocrine effects
        
        miosis
        
        nausea/vomiting
      - therapeutic uses
        
        relief of severe pain
        
        treatment of diarrhea
        
        supression of cough
        
        opioid depndence
      - Opioid abuse
        
        prescription opioid abuse
        
        effects of opioid abuse
        
        opioid dependence
        
        treatment
        
        cessation of drug use
        
        methadone maintenance
        
        neonatal drug dependence
        
        opioid overdose
- - - - CNS
      - PNS
        
        Motor neuron
        
        somatic
        
        Ganglion = ACH
        
        Receptor = N
        
        Neuromuscular blocking drugs
        
        Non-depolarizing neuromuscular blockers
        
        Depolarizing neuromuscular blockers
        
        Depolarizing phase
        
        Desensitizing phase
        
        Adverse
        
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        Clinical indications
        
        Surgical relaxation
        
        endotracheal intubation
        
        control of ventilation
        
        autonomic
        
        PNS
        
        Preganglion =ACH
        
        Receptor = N
        
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        Agonists
        
        Glaucoma
        
        Poor muscle tone in bladder
        
        Asthma (diagnosis)
        
        Dry Mouth
        
        Antagonists
        
        respiratory disorders
        
        GI disorders
        
        Urinary disorders
        
        SNS
        
        Preganglion = ACH
        
        Receptor = N
        
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        Agonist
        
        Direct (EP)
        
        Indirect (NEP)
        
        Combination
        
        Anaphylaxis
        
        Cardiac application
        
        Nasal congestion
        
        Local vasoconstriction
        
        Opthalmic
        
        Pulmonary
        
        Genitourinary
        
        Side effects
        
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        Antagonists
        
        Pheochromocytoma
        
        Benign prostatic hyperplasia
        
        Angina and congestive heart failure
        
        glaucoma
        
        Neurological disease
        
        sensory neuron
  - - - hypnosis, amnesia, analgesia, areflexia, relaxation
      - facilitation of Gaba-mediated inhibitation at GABA cl- channel
      - antagonism of glutamic acid excitation of NMDA channel receptors
      - Inhaled anesthetics
        
        N2O
        
        Volatile anesthetics
      - Intravenous anesthetics
        
        Propofol
        
        Ketamine
    - - topical anesthesia
      - local infiltration anesthesia
      - spinal
      - epidural
      - toxicity
        
        allergy (rare)
        
        systemic toxicity
  - - - Genetic factors
      - co-existing disorders
      - personality traits
      - environmental risk factors
      - developmental aspect
    - - increase dopamine
      - produce novelty
      - reduce anxiety
    - - Abuse potential of drug
        
        Dependance liability
        
        Route of administration
        
        amount of frequency of use
        
        Nature of drug
      - availability
      - inherent harmfulness
    - - Tolerance
        
        metabolic
        
        cellular
      - withdrawal
      - Addiction