Nervous System Drugs
CNS Drugs
CNS Drugs
• Anesthetics
• Anxiolytics & Sedative-Hypnotics
• Antiepileptics
• Antipsychotics
• Antidepressants
• CNS Stimulants
Anesthetics
Anesthetics
• are depressant drugs that
produce a partial or total loss of
the sense of pain
General Anesthetics
• total loss of the sense of pain
with loss of consciousness
Stages of General Anesthesia
Stage I:
– cortical stage (twilight sleep)
Stage II:
– delirium
Stage III:
– surgical anesthesia
Stage IV:
– medullary depression (overdose)
Volatile / Inhalational
Ether & Chloroform
• “anesthetics from hell”
• characteristics:
– flammable and explosive
– irritating
– hepatotoxic and nephrotoxic
– can cause cardiac arrhythmias
– produce nausea and vomiting
during recovery
Nitrous Oxide (N2O)
• aka: laughing gas
• least toxic
• least potent
• poor muscle relaxant
Halogenated Hydrocarbons
• addition of a halogen
– reduce flammability
– increase potency
• ethyl chloride, trichloroethylene
Halogenated Hydrocarbons
• with bromine only
– toxic
• with chlorine only
– toxic
– cause arrhythmias
Fluorinated Hydrocarbons
• addition of fluorine decreases:
– flammability
– volatility
– arrhythmias
Fluorinated Hydrocarbons
• Halothane
– standard inhalational anesthetic
agent
• Methoxyflurane
– used during labor
Fluorinated Hydrocarbons
• Enflurane
– NOT for patients with epilepsy
– for patients with asthma
• Isoflurane
– best general anesthetic so far
Fluorinated Hydrocarbons
• Sevoflurane
• Desflurane
Non-volatile / Intravenous
Ultra Short-Acting Barbiturates
• Thiopental
– most potent and widely used
• Thiamylal
• Methohexital
Benzodiazepines
• Diazepam (Valium®)
• Lorazepam (Ativan®)
• Midazolam (Dormicum®)
Opiates & Opioids
• used for analgesic properties
• Morphine
• Fentanyl
Neuroleptic Anesthetic
• anesthesia with:
– adrenergic blocking activity
– sedation
– anti-emesis
– anti-convulsion
• INNOVAR = droperidol* + fentanyl
*anti-emetic drug
Dissociative Anesthetic
• anesthesia with:
– sedation
– immobility
– amnesia
• Ketamine
• Propofol
Local Anesthetics
Local Anesthetics
• loss of sensation or motor
function in a circumscribed
area
Prototype
• Cocaine
– alkaloid from Erythroxylon coca
Linkages
• Ester
– short-acting
Ester-type local anesthetics
• Benzocaine
• Butacaine
• Hexylcaine
• Meprylcaine
• Propoxycaine
• Tetracaine
Linkages
• Amide
– long-acting
Amide-type local anesthetics
• Bupivacaine
• Etidocaine
• Mepivacaine
• Prilocaine
Anxiolytics &
Sedative-Hypnotics
Anxiety
• unpleasant state of tension,
apprehension or uneasiness
• fear that seems to arise from an
unknown source
• symptoms:
– tachycardia
– sweating
– trembling
– palpitation
Benzodiazepines
• MOA: enhances the binding of
GABA to its receptor, thus
increasing the frequency of
opening of chloride channels
on the membrane
Benzodiazepines
Benzodiazepines
• Diazepam (Valium®)
• Lorazepam (Ativan®)
• Midazolam (Dormicum®)
• Oxazepam
• Alprazolam
• Halazepam
• Temazepam
• Flurazepam
• Triazolam
Barbiturates
• MOA: enhances the binding of
GABA to its receptor, thus
prolonging the duration of
opening of chloride channels
on the membrane
Barbiturates
Barbiturates
• Long-acting (6 hr or more)
– phenobarbital
– mephobarbital
– metharbital
Barbiturates
• Intermediate-acting (3-6 hr)
– amobarbital
– butabarbital
Barbiturates
• Short-acting (less than 3 hr)
– pentobarbital
– secobarbital
Barbiturates
• Ultra short-acting
– methohexital
– thiamylal
– thiopental
Antiepileptic Drugs
1st Generation
• phenobarbital (barbiturate)
• phenytoin (hydantoin)
• ethosuximide (succinimide)
• carbamazepine (iminostilbene)
• valproic acid (dialkylacetate)
2nd Generation
• felbamate
• gabapentin
• lamotrigine
• topiramate
• tiagabine
• levetiracem
• oxcarbazepine
• zonisamide
• pregabalin
Antipsychotics
Psychosis
• schizophrenia
• mental disorder
– characterized by delusions,
hallucinations, thinking or speech
disturbances
Antipsychotics
• Antischizophrenics
• Neuroleptics
• Major tranquilizers
Antipsychotics
Antipsychotics
• Phenothiazines
– chlorpromazine
– fluphenazine
– promethazine
– thioridazine
Antipsychotics
• Benzisoxazoles
– risperidone
• Dibenzodiazepines
– clozapine
Antipsychotics
• Butyrophenones
– haloperidol
– droperidol
• Thioxanthines
– thiothixene
Antidepressants
Depression
• pervasive mood altering
disorder affecting energy,
sleep, appetite, libido and
ability to function
Biogenic Amine Theory
• proposes that depression is due
to the deficiency of
monoamines such as
norepinephrine, serotonin and
dopamine at certain key sites in
the brain
Antidepressants
• Thymoleptics
• Minor tranquilizers
Antidepressants
Antidepressants
• Tricyclic Antidepressants (TCAs)
– imipramine
– desipramine
– amytriptyline
– nortriptyline
Antidepressants
• Selective Serotonin Reuptake
Inhibitors (SSRIs)
– fluoxetine
– paroxetine
– trazodone
– sertraline
Antidepressants
• Monoamine Oxidase Inhibitors
(MAOIs)
– phenelzine
– isocarboxazid
– tranylcypromine
CNS Stimulants
Psychomotor stimulants
• Methylxanthines
• Nicotine
• Cocaine
• Amphetamine
Methylxanthines
• Caffeine
– 1,3,7 – trimethylxanthine
• Theophylline
– 1,3 – dimethylxanthine
• Theobromine
– 3,7 – dimethylxanthine
Psychomimetics
• Hallucinogens, Psychedelics
Psychomimetics
• Lysergic acid diethylamide
– LSD
– ergot derivative
Psychomimetics
• Tetrahydrocannabinol
– THC
– cannabis
– marijuana
Psychomimetics
• Phencyclidine
– angel dust
• Mescaline
– from cactus
– Lophophora williamsii
ANS Drugs
Autonomic Nervous System
ANS Drugs
• Adrenergic Drugs
– sympathetic system
• Cholinergic Drugs
– parasympathetic system
Adrenergic Drugs
Adrenergic Drugs
• Adrenergic Agonists
– sympathomimetics
• Adrenergic Antagonists
– sympatholytics
– anti-adrenergics
Adrenergic Agonists
Direct-acting
• Catecholamines
– dopamine
– dobutamine
– epinephrine / adrenalin
– norepinephrine / noradrenalin
– isoproterenol
Dopamine
Epinephrine
Norepinephrine
Direct-acting
• Non-catecholamines
– phenylephrine
– tetrahydrozoline
– methoxamine
– clonidine
– metaproterenol
– terbutaline
– albuterol
– ritodrine
Indirect-acting
• Amphetamine
• Tyramine
Mixed-acting
• Ephedrine
• Metaraminol
• Phenylpropanolamine (PPA)
Adrenergic Antagonists
Alpha-blockers
• Prazosin
• Terazosin
• Doxazosin
• Phenoxybenzamine
• Phentolamine
Beta-blockers
• Non-selective
– propranolol
– pindolol
– timolol
– nadolol
Beta-blockers
• Selective
B – Betaxolol
B – Bisoprolol
E – Esmolol
A – Acebutolol
A – Atenolol
M – Metoprolol
Mixed Alpha & Beta-blockers
• Labetalol
• Carvedilol
Cholinergic Drugs
Cholinergic Drugs
• Cholinergic Agonists
– parasympathomimetics
• Cholinergic Antagonists
– parasympatholytics
– anti-cholinergics
Cholinergic Drugs
• A substance (or ligandA substance
(or ligand) is cholinergic if it is
capable of producing, altering, or
releasing acetylcholineA substance
(or ligand) is cholinergic if it is
capable of producing, altering, or
releasing acetylcholine
("indirect-acting") or mimicking its
behaviour at one or more of the
body's acetylcholine receptor types
("direct-acting").
• A receptor is cholinergic if it uses
acetylcholine as its neurotransmitter.
Cholinergic Agonists
Direct-acting
• Acetylcholine
• Bethanechol
• Carbachol
• Pilocarpine
Indirect-acting
• Anti-cholinesterases
• 2 types
Reversible
• Carbamates
• short-acting
– physostigmine
– neostigmine
– pyridostigmine
– edrophonium
Irreversible
• Organophosphates
• long-acting
– parathion
– malathion
– isoflurophate
Cholinergic Antagonists
Anti-muscarinic
• Atropine
• Scopolamine
• Ipratropium
Ganglionic blockers
• Nicotine
• Trimethaphan
• Mecamylamine
Neuromuscular blockers
• Non-depolarizing
– tubocurarine
– pancuronium
– atracurium
• Depolarizing
– succinylcholine
End of Lecture 2
