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