CNS Pharmacology Notes

Central Nervous System Pharmacology

Central Nervous System (CNS)

  • The CNS comprises the brain and spinal cord.
  • The peripheral nervous system includes peripheral nerves.

Mechanism of Action

  • Brain disorders affect sensory, integrative, and motor functions.
  • Neurotransmitters facilitate neuron connections.
  • Drugs can alter abnormal and normal CNS activity, influencing mood, sleep, movement, and pain.

Theories of Neurotransmission

  • Chemical neurotransmitters act as messengers for communication between neurons.
  • Two models of neurotransmission:
    • "Hard-wired" model
    • "Chemical-soup" model

Fast vs. Slow Neurotransmitters

  • Fast neurotransmitters:
    • Act within 10 ms.
    • Examples: gamma-aminobutyric acid (GABA), glutamate.
  • Slow neurotransmitters:
    • Act within 10 to 20 ms.
    • Examples: neuromodulators, norepinephrine, serotonin.

Sequence of Neuronal Events

  • Presynaptic neuron depolarizes, releasing neurotransmitters (NT) into the synapse.
  • NT binds to the postsynaptic neuron, opening ion channels.
  • Open ion channels change the membrane potential.

Ionotropic vs. Metabotropic Receptors

  • Ionotropic receptors:
    • Have a neurotransmitter binding site.
    • Directly open ion channels for chloride, sodium, potassium, or calcium.
    • Can result in inhibitory or excitatory responses.
  • Metabotropic receptors:
    • Neurotransmitter binding activates a G protein.
    • The G protein then indirectly opens an ion channel.
    • Can result in inhibitory or excitatory responses.

Major Neurotransmitters

  • Acetylcholine
  • Amino acids: GABA, Glutamate, Aspartate, Glycine, Taurine
  • Dopamine
  • Norepinephrine
  • Serotonin
  • Histamine
  • Opioid peptides
  • Tachykinins

Acetylcholine

  • Can be excitatory OR inhibitory.
  • Acts on Cholinergic receptors:
    • Muscarinic
    • Nicotinic
  • Drugs can change acetylcholine levels or activity by:
    • Activating or blocking cholinergic receptors.
    • Inhibiting cholinesterase.

Amino Acids

GABA
  • Inhibitory.
  • Acts on GABA receptors: A and B receptors.
  • Drugs can either activate or inhibit GABA receptors.
  • Regulates CNS excitability.
  • Drugs targeting GABA are used for anxiety, seizures, and tremors.
Glutamate/Aspartate
  • Excitatory.
  • Acts on ionotropic or metabotropic receptors.
  • Plays a role in memory, neuronal toxicity, and apoptosis.
  • Drugs targeting glutamate are used for seizures.
Glycine
  • Inhibitory
  • Acts on strychnine-insensitive receptors.
  • Causes membrane hyperpolarization.
Taurine
  • Inhibitory

Dopamine

  • Inhibitory.
  • Acts on Dopamine receptors: 5 subtypes.
  • Found in several neuronal tracts.
  • Effects include hormone release, mood regulation, motor coordination, and olfaction.

Norepinephrine

  • Excitatory or Inhibitory.
  • Acts on α-adrenergic and β-adrenergic receptors.
  • Found in several neuronal tracts.
  • Involved in:
    • Regulation of anxiety
    • Cerebellar function
    • Learning
    • Memory
    • Mood
    • Sensory processing

Serotonin

  • Excitatory or Inhibitory.
  • Acts on 5-HT receptors.
  • Effects on emotional processing, appetite, mood, sleep, and hallucinations.
  • Drug actions include:
    • Stimulating or blocking serotonin receptors.
    • Blocking its reuptake.

Histamine

  • Excitatory.
  • Acts on Histamine receptors.
  • Effects on sedation, sleep, temperature regulation, and vasomotor function.
  • Antihistamines counteract these effects, causing drowsiness.

Peptides

Opioid peptides
  • Enkephalins.
  • Inhibit pain neurotransmission.
Tachykinins
  • Neurokinin A and B.
  • Modulate cardiovascular and behavioral responses to stress.
  • Substance P - Involved in pain processing.

Mechanisms of CNS Drug Action

  • Most drugs:
    • Alter the synthesis, storage, or release of a neurotransmitter.
    • Block reuptake of a neurotransmitter.
    • Inhibit degradation of a neurotransmitter.
    • Activate/block neurotransmitter receptors.

Neuronal Systems in CNS

Cognitive Processing
  • Prefrontal cortical structures interpret sensory information, stimulating the motor system.
  • Utilizes memory and is influenced by emotions.
  • Drugs include: antipsychotics, CNS stimulants, hallucinogens, and sedative-hypnotics.
Memory
  • Procedural memory
  • Declarative memory
  • Dementia: memory disorder.
  • Drugs include: cholinesterase inhibitors, CNS depressants.
Emotional Processing
  • Generation of emotions: anger, anxiety, fear, happiness, love, and sadness.
  • Disorders: anxiety states, mood disorders, schizophrenia.
  • Drugs include: antianxiety, antidepressants, antipsychotics, CNS stimulants, and opioids.
Sensory Processing
  • Involves perceiving external stimuli and transmitting information to the brain.
  • Disorders: sleep disorders, chronic pain, sensory processing defects.
  • Drugs: antidepressants, hallucinogens, anesthetics, opioid analgesics, and sedative-hypnotics.
Motor Processing
  • Enables body movement.
  • Disorders: Parkinson’s disease and Huntington’s disease.
  • Drugs: anti-parkinsonian, antispasmodics, CNS stimulants, muscle relaxants, and sedative-hypnotics.

Overview of Sedative-hypnotic and Anxiolytic Drugs

  • Sedative: reduces excitement
  • Hypnotic: induces sleep
  • Anxiolytic = antianxiety: reduces anxiety
  • Anxiety disorders:
    • Acute anxiety
    • Panic disorder
    • Phobic disorder
    • Obsessive-compulsive disorder
    • Generalized Anxiety Disorder (GAD)

Physical effects of Anxiety Disorders

  • Dizziness, decreased sex drive, irritability
  • Sweating, chest pain
  • Increased muscle tension
  • Rapid breathing & breathlessness
  • Heart palpitations
  • Increased blood pressure
  • Nausea or diarrhoea

Sedative-Hypnotic and Anxiolytic Drugs

  • Benzodiazepines: Alprazolam, Clonazepam, Diazepam, Lorazepam, Midazolam, Chlordiazepoxide, Estazolam, Fluroazepam, Oxazepam, Temazepam, Triazolam
  • Antihistamines: Diphenhydramine, Hydroxyzine
  • Barbiturates: Amobarbital, Pentobarbital, Phenobarbital, Thiopental
  • Other sedative-hypnotic drugs: Chloral hydrate, Melatonin, Zolpidem, Zaleplon
  • Non sedating anxiolytics: Buspirone, Propanolol

How do sedative-hypnotics affect neurotransmitters

  • Block acetylcholine - antihistamine
  • Activate GABA - Barbituates and BZDS

Benzodiazepines

  • Pharmacokinetics:
    • Clinical uses include anxiety, alcohol detoxification, insomnia, seizure disorders, anesthesia induction
  • Mechanisms:
    • Benzos bind to receptors on the GABA-chloride ionophore.
    • The benzodiazepine receptors are called omega receptors (1 and 2).
  • Pharmacologic Effects:
    • The benzodiazepines produce a dose-dependent but limited depression of the CNS
  • Adverse Effects:
    • Motor incoordination, dizziness, drowsiness, impair cognitive processing and planning, may interfere with driving and other psychomotor skills

Barbiturates

  • Pharmacokinetics:
    • The onset and duration of action of barbiturates are determined by their lipid solubility and rate of metabolic inactivation
  • Mechanism of Action:
    • Barbiturates bind to a site on the GABA-chloride ionophore that is distinct from the site to which Benzo’s bind
  • Effects:
    • Considerable sedation
    • May cause hangover and daytime sedation when used for insomnia
    • May also cause tolerance and physical dependence during continuous use
  • Indications:
    • Used for the treatment of anxiety disorders and insomnia
    • Seldom used today since the development of BDZs

Barbiturates vs BZDs

Barbiturates
  • Acts on GABA
  • Increases time of open chloride channels- even chloride outside GABA
  • Greater toxicity and lower safety margin
  • Considerable sedation
  • Physical dependence
  • Indications- anxiety, insomnia, not for muscle relaxation, anesthesia
  • Induce metabolism of other drugs
Benzodiazepines
  • Acts on GABA-diff from barbs location
  • Increases frequency of open chloride channels
  • BZDs receptors-omega 1 and 2 receptor
  • Dose-dependent CNS depression
  • Not as much respiratory depression and death
  • Indications-anxiety, seizures, muscle spasms, insomnia, spasticity
  • Less physical dependence
  • Anterograde amnesia - surgery

Antihistamines

  • Treats mild insomnia and anxiety disorders
  • Tolerance
  • No significant physical dependence or abuse
  • Crosses the blood-brain barrier

Other Sedative-Hypnotic Drugs

  • Chloral hydrate:
    • Older hypnotic
    • Occasionally used for preanesthetic sedation in pediatric patients
    • “Mickey Finn” = chloral hydrate + alcohol
  • Zolpidem:
    • Selectively activates the omega 1 benzodiazepine receptor on the GABA-chloride ionophore
    • Less tolerance and dependence
    • Short duration of action
  • Zaleplon:
    • Shortest duration of action
  • Melatonin:
    • A neuroendocrine hormone that interacts with specific receptors in the CNS
    • Sets biological clock
    • Released prior to the onset of sleep and produces drowsiness
    • Available OTC
    • Effective treatment for jet lag, insomnia in shift-change workers and elderly patients
    • May cause fatigue and lethargy

Nonsedating Anxiolytic Drugs

  • Buspirone:
    • Serotonin partial agonist- chronic anxiety
    • Produces an anxiolytic effect without causing marked sedation, amnesia, tolerance, dependence, or muscle relaxation
  • Propranolol:
    • A beta-adrenergic receptor antagonist
    • Used to prevent stage fright or acute situational or performance anxiety
    • Symptom relief – decreases heart rate

Epilepsy

  • Seizures - abnormal electrical activity in the brain that cause involuntary movements, sensations, or thoughts
  • Causes:
    • Head trauma, stroke, brain tumors, hypoxia, hypoglycemia, fever, alcohol withdrawal, and other condition that alter neuronal function
  • Epilepsy -recurrent seizures with no other cause
  • 1-2% of population
  • 2nd most common neurological disorder
  • Seizures-last about 10 seconds to 5 minutes
  • Preceded by aura
  • Tonic – increased muscle tone
  • Clonic – muscle spasms and relaxations

Antiepileptic Drugs

Classification of Seizures
  • Two main categories of seizures:
    • Partial (focal) seizures- 60% of seizures
      • one cerebral hemisphere
      • Patients is conscious
    • Generalized seizures
      • both cerebral hemispheres
      • patient loses consciousness
  • Mechanisms of Antiepileptic Agents:
    • suppress the formation or spread of abnormal electrical discharges in the brain
    • Three Main Mechanisms:
      • (1) inhibition of the sodium or calcium influx responsible for neuronal depolarization
      • (2) augmentation of inhibitory GABA neurotransmission
      • (3) inhibition of excitatory glutamate neurotransmission
Drugs for partial and generalized seizures
  • Carbamazepine
    • blocks Na channels inhibiting repetitive firing
  • Phenobarbital
    • Enhances GABA action
    • Active metabolite of primidone
  • Phenytoin
    • Inhibits Na and Ca influx
    • Adverse side effect- gingivial hyperplasia, block folate, osteoporosis
  • Valproate
    • Enhances GABA action
    • Inhibits Na and Ca
Adjunct drugs for seizures
  • Clorazepate
  • Felbamate
  • Gabapentin
    • Mechanism unknown
  • Lamotrigine
    • Inhibits glutamate, blocks Na channels preventing repetitive firing
    • Adverse side effect stevens johnson syndrome
  • Topiramate, Tiagabine, Vigabutrin, Zonisamide, Levetiracetam
Status epilepticus
  • Continuous seizing
  • Leads to brain damage
  • Provide pulmonary support
  • Bad prognosis if seizure >60 minutes
  • Drugs for status epilepticus
    • Diazepam
    • Lorazepam-most frequently used
    • Phenobarbital
    • Phenytoin

Drugs for Neurodegenerative Diseases

  • Neurodegenerative diseases- loss of neuronal function
    • Parkinson’s Disease
    • Huntington’s Disease
    • Alzheimer’s Disease
    • Multiple Sclerosis
    • Amyotrophic lateral sclerosis

Symptoms of Parkinson's

  • Resting tremor
  • Rigidity
  • Bradykinesia
  • Head and trunk bent forward, arms half flexed and knees slightly bent.

Causes of Parkinson’s Disease

  • Dopaminergic neurons in substantia nigra and basal ganglia degenerate
    • Decreased levels of dopamine
  • Cholinergic neurons- excessive activity
  • Goal of Parkinsons Treatment
    • Levadopa
      • Precursor of dopamine
      • Metabolized and converted to dopamine
    • Carbidopa
      • Inhibits conversion of levadopa to dopamine in peripheral tissue
      • Does not cross BBB
    • Tolcapone
      • Inhibits COMT
      • Increases effectiveness of levadopa
      • 2x increase in levadopa t ½
    • Amantadine
      • Increasing release of dopamine
      • Inhibit reuptake of dopamine
  • Mechanism of Parkinson’s treatment
    * Inihibits Dopamine Breakdown
    * Selegiline
    * Inhibits MAO-B
    · Anticholinergic meds
    * Benzotropine
    * Trihexyphenidyl
    Inhibit dopamine reuptake
    * Prolongs dopamine action
    * Reduce tremor
    Dopamine receptor agonists- directly activate remaining functional receptors
    * Bromocriptine
    * Pergolide
    * Pramipexole-selective D3
    * Ropinirole-selective D2
    Delays need for dopa
    * Apomorphine
    Treats acute “freezing”
    * Injection – 5 to 10 mins

Huntington’s Disease

  • Hereditary disorder
  • Abnormal movement- dance-like movement
  • Involves limbs, tongue, face, personality
  • Psychosis develops
  • Begin in 30’s and progresses for 10-15 years
  • Death – respiratory depression
  • Degeneration of GABA neurons
    • Excessive dopaminergic activity in the basal ganglia
    • May result from glutamate-induced toxicity
  • Treatment
    • Drugs that block dopamine receptors
      • Haloperidol
    • Drugs that potentiate GABA
      • diazepam

Alzheimer’s Disease

  • Progressive dementia
  • Destruction of cholinergic neurons
  • Cholinergic neurons- critical role in memory
  • Major changes in brain- cortical breakdown, plaques
  • Treatment of Alzheimer’s
    • Improvement of cholinergic function
      • Centrally acting cholinesterase inhibitors May slow deterioration of cognitive function- increases acetylcholine by decreasing its breakdown
        • Donepezil
        • Tacrine
        • Rivastigmine
        • Galantamine
          Blocking glutamate actions on NMDA(N-methyl-D- aspartate) receptors
        • Reduces decline in function by preventing over- stimulation of NMDA receptors
      • Memantine

Multiple Sclerosis

  • Symptoms- pain, spasticity, weakness, ataxia, fatigue, speech problems, gait problems, loss of bladder control
  • Autoimmune or viral origin
  • Treatment goals
    • Reduce organ and CNS dysfunction
    • Decrease severity of acute exacerbations
    • Reduce or prevent relapses and progression
  • Demyelination of neurons in CNS
    • Disruption of nerve transmission
    • Inflammatory response
    • Plaques form
    • Oligodendrocytes decreased
  • Multiple Sclerosis Treatment
    • Antispastic drugs
      • Baclofen
      • Tizanidine
        Adrenal corticosteroids
      • Prednisone
      • Interferon beta-1b
        Slows the progression of MS
      • Natalizumab
        Blocks cell adhesion and lymphocytes to CNS
      • Mitoxantrone antineoplastic
        Suppresses immune cells that attack myelin
      • Glatiramer
        Mimics myelin basic protein

Amyotrophic Lateral Sclerosis

  • AKA Lou Gehrig disease
    • Disease of motor neurons
      Muscle wasting, weakness and respiratory failure
  • The excitotoxicity hypothesis- postulates that excessive levels of the excitatory neurotransmitter glutamate→ neuronal death
  • Treatment-mostly symptomatic
    Baclofen (anti-spastic)
    Gabapentin (anti-epileptic)
    * Riluzole
    protects motor neurons
    Prolongs life by ~ 3 months

Psychotherapeutic Drugs

  • Psychoses
    Gross disturbance in comprehension of reality
    Schizophrenia
    Most common form of psychosis
    Positive symptoms- delusions, hallucinations, disorganized thinking
    Negative symptoms-apathy, withdrawal, lack of pleasure
    Neg symptoms- challenging to treat
  • What causes Schizophrenia
    * Dopamine hypothesis- abnormal neurotransmission in several parts of brain
    * Hypofrontality hypothesis- abnormal neurotransmission in prefrontal cortex
    * Drug therapy goal-Block dopamine 2 receptors and serotonin receptors
    * Brain structure changes- abnormal prefrontal lobe cortex, lateral ventricular enlargement

Typical Antipsychotics

  • Typical Antipsychotics
    * Phenothiazines
    Chlorpromazine
    Fluphenazine
    Thioridazine
    Trifluoperazine
    Thioxanthenes
    Thiothixene
    Butyrophenones
    Haloperidol
    Block dopamine-2 receptors in mesolimbic pathways
    Adverse Effects
    * Extrapyramidal SE(EPS)
    Dystonia
    Akathisia
    Pseudoparkinsonism
    Tardive dyskinesia
    Neuroleptic malignant syndrome

Atypical Antipsychotics

  • Atypical Antipsychotics
    * Clozapine
    * Olanzapine
    * Risperidone
    * Quetiapine
    * Ziprasidone
    * Aripiprazole
    Block serotonin and dopamine receptors
    Most common SE: sedation and weight gain
    Fewer EPS than typical
    6 weeks to see maximal response from anti- psychotic therapy
    Possible Indications for Antipsychotics

  • Schizophrenia

  • Drug induced psychosis

  • Manic stage of bipolar

  • Psychosis

  • Agitation in dementia

Another look at Typical vs. Atypical Antipsychotics

Typical antipsychotics
  • Older agents
  • Many side effects
    Extrapyramidal symptoms(EPS)
    Excessive sedation
    Alleviates positive symptoms
    Blocks dopamine receptors
Atypical antipsychotics
  • New agents
  • Less EPS
    Side effects
    * Weight gain
    * Sedation
    Endocrine changes- hyperglycemia
    Less EPS
    Alleviates positive and negative symptoms
    Blocks dopamine receptors and 5-HT 2 receptors

Mood Disorders

  • Mood disorders
    * Depression
    Depressed mood, loss of interest in life, sleep disturbances, feelings of worthlessness
    Suicidal tendencies
    anxiety
    Abnormalities in serotonin, NE and/or dopamine

Antidepressant Drugs

Tricyclic (TCA’s)

Amitriptyline
Clomipramine
Desipramine
Imipramine
Nortriptyline
Block neuronal uptake of NE and serotonin
Treat depression, sleep and anxiety disorders
Overdose- cardiac arrhythmia, seizures

Selective serotonin reuptake inhibitors

Fluvoxetine
Fluvoxamine
Paroxetine
Sertraline
Citalopram
Escitalopram
Block neuronal reuptake of serotonin
Few side effects compared with TCAs- less sedation

Other Antidepressants

Bupropion
Depression and smoking cessation
Inhibits reuptake of dopamine, norepinephrine, serotonin
St. John’s Wort - hypericin
Mirtazapine
Increases norepinephrine and serotonin
Depression and anxiety
Venlafaxine
Antidepressant- blocks reuptake of norepi and serotonin
Trazodone – inhibits reuptake of serotonin
Monoamine Oxidase Inhibitors
Not DOC – due to SE
Phenelzine, tranylcypromine, selegiline
SE – hypertensive crisis
Avoid tyramine containing foods – cheese, beer, wine, fish, chocolate
SSRI and MOAI = trouble= sertotonin syndrome

Bipolar disorder

➢Bipolar disorder
Recurrent changes in mood, energy and behavior; mood cycling
Mood extremes- depressive and manic stages
Bipolar Medications
* Lithium
Mood stabilizer- greater activity against mania
MOA unknown-?
SE: neurotoxicity/cardiotoxicity
Monitor serum levels
Carbamazepine/Valproate/Lamotrigine
Antiepileptic
Benzodiazepines
Antipsychotics- risperidone, olanzapine

Opioid Analgesics and Antagonists

  • Pain: an unpleasant sensory and emotional experience that usually alerts an individual to tissue damage
  • Protective function- high morbidity
  • 3 types pain relievers:
    • Analgesics
    • General anesthetics
    • Local anesthetics
Analgesics
  • Opioid analgesics
    * Act in spinal cord and brain to inhibit the neurotransmission of pain
  • Nonopioid analgesics
    * Inhibit pain impulse formation by stimuli
    * Peripheral tissues
Different Types of Pain
  • Somatic pain- dermal, SQ tissue pain
  • Visceral pain- abdominal pain
  • Neuropathic pain- nerve damage or compression
Opioid Receptors

μ (mu)receptors
most analgesic relief- supraspinal
Respiratory depression, decreased GI motility, euphoria
μ receptor agonists- morphine, heroin, fentanyl, codeine
κ (kappa)receptors
less analgesia- spinal, sedation
Pentazocine- κ agonist and partial μ antagonist
σ (sigma) receptors
hallucinations and dysphoria
Strong Opioids
* Morphine
High affinity for μ receptors, varying affinity for κ receptors
CNS effects: works in CNS to produce analgesia, sedation, euphoria, miosis, n/v, and respiratory depression
CV effects: vasodilation due to histamine release
GI effects: decreases motility of smooth muscle
Indications: trauma, MI, cancer

Fentanyl
  • Most potent opioid agonists- 80 x morphine potency
  • Available as TD patch
Meperidine
  • Moderate to severe acute pain
  • Adverse effects- large doses cause tremors and seizures
Methadone
  • Pain or opioid addiction- milder withdrawal symptoms
  • Less euphoria and longer duration of action than morphine

Oxycodone
Used in combination with acetaminophen
Moderate to severe pain
Moderate Opioid Agonists
Codeine
Mild to moderate pain
Antitussive
Propoxyphene
Mild to moderate pain
For greater analgesia- combined with aspirin or acetaminophen
Tramadol
Moderate and chronic pain
Affinity for μ receptors
Also blocks reuptake of norepi & serotonin
Mixed opioid agonist-antagonists
Buprenorphine
Partial agonist at μ receptor
Can antagonize morphine
Butorphanol
Nalbuphine
Pentazocine
Preoperative and postoperative analgesia
Analgesia during labor and delivery
Less euphoria
Opioid Antagonists
Naloxone
Opioid overdose- reverses coma and respiratory depression
Replaces all receptor bound opioid molecules
Quick acting- 30 seconds
Competitive antagonist of μ and κ receptors
Naltrexone
Competitive opioid receptor antagonist
Treats overdose
Longer duration of action than naloxone- 48hours
Drugs of Abuse
Drug dependence due to:
Psychologic dependence
Due to the positive reinforcement of drug use that results from the activation of neurons
Physical dependence
Neuronal adaptation to the drug’s presence
Reinforcement to prevent an unpleasant withdrawal syndrome (negative withdrawal symptoms)
CNS Depressants
CNS depressants
Ethanol-#1 drug abuse problem in US
Potentiates GABA
Inhibits ACH release- sedation, delirium
Combination with Barbs or BZDs→ deadly
Vasodilation- decreases body heat
CNS Depressants Continued
Barbiturates-GABA
Benzodiazepines-GABA, “roofies”
Opioids
Heroin
Highly lipid soluble- BBB
Produces intense euphoric sensation
High physical dependence and drug tolerance
CNS Stimulants Stimulants-increase energy and feelings of well being; activate sympathetic NS
Amphetamines-releases NE and dopamine
Ectasy- amphetamine derivative, increases dopamine & serotonin levels
Nicotine
Caffeine
➤Cocaine-blocks the
reuptake of NE & dopamine
Alters tactile sensation
Hallucinogens
Marijuana-
Active ingredient- tetrahydrocannabinol(THC)
Inhibits voltage gated calcium channels
Modulates ACH, dopamine, serotonin levels
Dronabinol- cannabis derivative, treats chemotherapy induced nausea and stimulates appetite in AIDS patients
Lyseric acid diethylamide(LSD)
Produce hallucinations - false perceptions resulting from abnormal sensory processing
Effects may last 12 hours
Activates serotonin receptors
Sympathetic activation- increased heart rate and blood pressure
Hallucinogens Continued
Phencyclidine(PCP)
“angel dust”
Inhibits reuptake of dopamine, serotonin, and nor-epi
Also, blocks N-methyl-D-aspartate (NMDA) receptors
Produces euphoria, hallucinations, and sometimes hostile behavior
Management of Drug Abuse
Naloxone or flumazenil
May be administered to counteract the acute CNS depression caused by toxic doses of an opioid or a benzodiazepine
Lorazepam
Used to control agitation
Haloperidol
May be administered for psychosis
Management of Drug Abuse
Lorazepam or chlordiazepoxide
Can be administered to suppress the acute manifestations of withdrawal from alcohol, including delusions, hallucinations, a coarse tremor, and agitation
Methadone
Used to suppress withdrawal reactions in opioid users
Management of Drug Abuse
Nicotine
Available in chewing gum and patches
Reduces nicotine withdrawal symptoms
Bupropion
Nicotine withdrawal- anxiety, restlessness, headaches, irritability, difficulty concentrating
Reduces nicotine withdrawal symptoms
Clonidine
Effective in reducing the sympathetic nervous system symptoms of alcohol, opioid, or nicotine withdrawal
Management of Drug Abuse
Bromocriptine
Can lesson the symptoms of cocaine withdrawal
Disulfiram
Occasionally employed to sustain abstinence in alcoholics, causes accumulation of acetaldehyde →profuse vomiting, nausea
Naltrexone
Prevents the euphoric and other effects obtained with opioid administration
Also used to treat opioid dependence
Local and General Anesthetics
Anesthesia→ condition w/o perception of pain
Local anesthetics→block conduction of pain impulses to the spinal cord
General anesthetics→interfere with sensory processing and prevent the perception of pain
Essential to surgical practice- analgesia, amnesia, unconsciousness, and muscle relaxation
Local Anesthetics
Indications
Numb a particular part of body
Topical anesthesia- example anesthetic ointment for hemorrhoids
Infiltration anesthesia-injecting directly into sc tissue, ex dental procedures
Iontophoresis-small electric current to force molecules of the anesthetic into body
Nerve Block-regional anesthesia, injected into nerve plexus
Spinal anesthesia-blocks somatic sensory and motor fibers, injected into subarachnoid space
Epidural Anesthesia-injected into lumbar space
Local Anesthetics

  • Ester-type
    * Benxocaine
    * Chloroprocaine
    * Cocaine
    * Procaine
    Reversible inhibition of axonal nerve conduction by binding to the Na channel and decreasing the nerve membrane permeability to Na
    Local Anesthetics
  • Amide-type
    * Lidocaine-most common
    Comes in sprays, lotions, gels, parenteral formulations
    * Etidocaine
    * Bupivacaine
    * Mepivacaine
    * Ropivacaine
    * Prilocaine- only topical and infiltration
    Adverse Effects of Local Anesthetics
    Due to absorption into systemic circulation
    CNS stimulation-tremors, restlessness, euphoria
    Headache, nausea, seizures
    Vasodilators- hypotension, cardiac depression
    General anesthetics
    Prevents pain during major surgeries
    Usually produces unconsciousness and amnesia
    Suppress respiratory fxn and decrease blood pressure
    Potency of anesthetics is expressed as the minimum alveolar concentration required to produce anesthesia
  • Inhalational Anesthetics
    * Non-halogenated
    Nitrous Oxide
    More rapid action
    * Halogenated
    Halothane
    Desflurane
    Enflurane
    Isoflurane
    Parenteral Anesthetics
    Fentanyl
    IV or epidural in combo. with other drugs for surgical/ob analgesia/anesthesia
    Ketamine
    Used in pediatrics with BDZs for anesthesia during minor surgery
    Midazalom
    Short acting BZD
    Preop sedation, endoscopy
    Propofol/Thiopental
    Used following administration of inhaled anesthetic to prolong anesthesia