DRUGS OF THE CENTRAL NERVOUS SYSTEM

 Anti-psychotics
 Drugs for Parkinson’s disease
 Antidepressants, Mood stabilizers
 Anxiolytic, Sedative Hypnotics
 Anti-convulsants
 Anesthetics
 Opioid analgesics and opioid antagonists
 CNS Stimulants

UNDERSTANDING CNS PHARMACOLOGY

THE CONCEPT OF NEUROTRANSMISSION
MAJOR NEUROTRANSMITTER FUNCTION
GLUTAMATE The major EXCITATORY neurotransmitter
Memory. Learning and stress response
Gamma-aminobutyric acid The major INHIBITORY Neurotransmitter
(GABA)
SEROTONIN/ Thought process
5-HT Mood, wakefulness, sleep
(5-hydroxytryptamine) Feeding behavior
Control of sensory transmission
DOPAMINE MOTOR CONTROL (nigrostriatal pathway)
BEHAVIORAL EFFECT (mesolimbic and mesocortical)
ENDOCRINE CONTROL (tuberohypophyseal pathway)
NOREPINEPHRINE Arousal and mood
Blood pressure regulation
ACETYLCHOLINE Memory
Motor control
HISTAMINE Wakefulness (central receptors)

CNS/PSYCHIATRYC DISEASES AND NEUROTRANSMITTERS

Anxiety ↑ Catecholamines
Mania ↑ NE & serotonin
Depression ↓ NE & serotonin
(Biogenic Amine Theory)
Schizophrenia ↑ Dopamine (Dopamine Hypothesis)
Parkinson’s Disease ↓ Dopamine, ↑ ACh,
damage to the basal ganglia
 ANTI-PSYCHOTICS
PSYCHOSIS is defined as grossly impaired reality testing manifested by delusions, hallucinations, confusion and impaired memory.

SCHIZOPHRENIA is one of the psychiatric illnesses manifesting with psychosis.

DOPAMINE THEORY
DOPAMINE HYPERACTIVITY is responsible psychotic symptoms.
* Other neurotransmitters associated with schizophrenia
include: 5HT, NE and glutamate

SYMPTOMS OF SCHIZOPHRENIA
Delusions
POSITIVE Hallucinations
SYMPTOMS Combativeness
Insomnia
Affective flattening
NEGATIVE (poor eye contact, lack of expression)
SYMPTOMS Alogia
(poor vocabulary, poor content of
Speech)
Avolition-apathy
(detachment, indifference)
Anhedonia – asociality
(lack of interest)
Attention (inattentiveness)

ANTIPSYCHOTICS are grouped into:

1) TYPICAL
2) ATYPICAL

TYPICAL PHENOTHIAZINES
Aliphatic
Chlorpromazine
Promethazine
Triflupromazine
Piperidine
Thioridazine
Piperacetazine
Mesoridazine
Piperazine
Acetophenazine
Perphenazine
Carphenazine
 Fluphenazine
Prochlorperazine
Trifluoperazine

THIOXANTHENES
Thiothixene
Chlorprothixene
BUTYROPHENONES
Haloperidol
Droperidol
ATYPICAL Clozapine
Loxapine
Olanzapine
Quetiapine
Risperidone
Sertindole
Remoxipride
Pimozide
Molindone

 In terms of potency, the different phenothiazines can be listed in decreasing potency as follows: Piperazines, Piperidines,
Aliphatics.

 Haloperidol & the Piperazine phenothiazines like Fluphenazine are classified as high potency antipsychotics.

 Anticholinergic effects are more commonly seen w/ Chlorpromazine, Thioridazine & Clozapine.

 Dystonic reactions such as an oculogyric crisis & pseudoparkinsonism such as tremors are side effects most likely to be
seen w/ the high potency antipsychotics like Trifluphenazine.

 Neuroleptic malignant syndrome w/c resembles malignant hyperthermia is more commonly seen w/ the high potency
antipsychotics.

 Droperidol is a component of neurolepanesthesia.

 Promethazine anti-histaminic and antiemetic property.

 Thioridazine can cause retinal deposits to form. This may lead to blindness.
COMPARISON OF THE TYPICAL AND ATYPICAL ANTIPSYCHOTICS
TYPICAL ATYPICAL

Receptor blockade dopamine dopamine & serotonin

Positive symptoms effective effective

Negative symptoms effective more effective

EPS (Extrapyramidal more less

symptoms)

Tardive dyskinesia high low

DRUGS FOR PARKINSONISM

Parkinsonism is a neurodegenerative disorder characterized by motor abnormalities such as tremor, rigidity, bradykinesia and
postural instability.

The pathophysiology of Parkinsonism involves

LOSS OF DOPAMINERGIC CELLS

IN THE BASAL GANGLIA,
DEPIGMENTATION OF
SUBSTANTIA NIGRA

IMBALANCE between
DOPAMINE and
ACETYLCHOLINE

IMPAIRED
NEUROTRANSMISSION
in the EXTRAPYRAMIDAL TRACT

LOSS OF FINE MOTOR CONTROL

Tremors, limb rigidity, dyskinesia
SIGNS and SYMPTOMS
TREMORS
 Resting tremor (minimal shaking evident at rest)
 Pill rolling tremor (thumb and forefinger)
 Action tremor (minimal shaking evident during activity)
LIMB RIGIDITY
 Cogwheeling movement
AKINESIA
 Difficulty initiating movements
BRADYKINESIA
 Slowness in performing common voluntary movement
MASKED FACE
 Fixed facial expression with minimal evidence of expression
GAIT AND POSTURAL DIFFICULTY
 Patients walk with stooped, flexed posture; short struffling stride; diminished arm swing

TREATMENT OF PARKINSONISM involve:

 Non-pharmacologic
o Physical therapy
o Nutrition
 Pharmacologic
o Neuroprotective drugs
o Drugs that correct the balance of Dopamine and Acetylcholine

DRUGS THAT CORRECT THE BALANCE OF DA and ACh

LEVODOPA Levodopa is the immediate precursor of dopamine

AMANTADINE Stimulate the release of dopamine from intact striatal

dopaminergic terminals

APOMORPHINE DIRECT DOPAMINERGIC RECEPTOR AGONISTS. They mimic

the activity of dopamine
BROMOCRIPTINE
PERGOLIDE
PRAMIPEXOLE
ROPINIROLE

SELEGILINE Inhibitor of MAO-B isoenzyme. This blocks the degradation

of dopamine  increased dopamine availability

BENZTROPINE CHOLINERGIC ANTAGONISTS

ORPHENADRINE They reduce the functional imbalance between dopamine
and acetylcholine in the striatum.
TRIHEXYPHENIDYL

CARBIDOPA Increase the transport and bioavailability of levodopa

(USED AS ADJUNCTS)
TOLCAPONE

 Levodopa is currently the most effective treatment for Parkinsonism.

 Amantadine may be used in the treatment of EPS induced by anti-psychotic drugs.

  Carbidopa is used mainly to reduce the peripheral conversion of Levodopa to Dopamine due to its ability to inhibit the
peripheral dopamine decarboxylase enzyme. It can therefore increase the CNS bioavailability of Levodopa.

 Bromocriptine stimulates the D2 receptors, the same receptors of Dopamine in the brain. Dopamine is aka prolactin
inhibiting hormone. Bromocriptine can therefore counteract the effects of an excess prolactin secretion such as what
usually happens in patients w/ hypersecretory pituitary adenoma (tumor).

 Tolcapone is an inhibitor of Catechol-O-Methyl Transferase (COMT) w/c can convert Levodopa to 3-O-Methyldopa, a
metabolite w/c can interfere w/ the transport of Levodopa across the blood brain barrier.

COMMON ADVERSE EFFECTS

 Nausea, vomiting
 Dizziness, headache, insomnia
 Confusion, hallucinations, nightmares
 Abnormal involuntary movements (dyskinesia, choreiform or dystonic movements)

 Levodopa is associated with CARDIOVASCULAR SYMPTOMS such as orthostatic hypotension, tachycardia and
dysrhythmia

 Amantadine has been associated with urinary retention and ankle edema.

 LIVEDO RETICULARIS (mottling of the skin) has been noted on patients taking Amantadine and Bromocriptine

 Anti-cholinergic drugs should be used with caution in patients with GI and GU obstruction, narrow-angle glaucoma,
severe cardiac disease.

ANTI-DEPRESSANTS/ MOOD STABILIZERS

Depression
 is the most common of the affective disorders
 it may range from a very mild condition, bordering on normality, to severe (psychotic) depression accompanied by
hallucinations and delusions.
 Worldwide, depression is a major cause of disability and premature death.

The symptoms of depression include emotional and biological components.

 Emotional symptoms:
o Misery, apathy and pessimism
o Low self-esteem: feelings of guilt, inadequacy and ugliness
o Indecisiveness, loss of motivation.
 Biological symptoms:
o Retardation of thought and action
o Loss of libido
o sleep disturbance and loss of appetite

There are two distinct types of depressive syndrome:

Unipolar disorder, in which the mood swings are always in the same direction (DEPRESSION)

Bipolar affective disorder, in which depression alternates with mania.

** Mania is in most respects exactly the opposite of depression, with excessive exuberance, enthusiasm and self-confidence,
accompanied by impulsive actions, these signs often being combined with irritability, impatience and aggression, and sometimes
with grandiose delusions of the Napoleonic kind.

TREATMENT OPTIONS FOR DEPRESSION

 Pharmacotherapy
 Psychotherapy
 Electroconvulsive therapy
ANTI-DEPRESSANT DRUGS
MONOAMINE OXIDASE INHIBITORS (MAOI) Phenelzine
Isocarboxazid
Tranylcypromine
Selegiline
Moclobemide
Deprenyl

TRICYCLIC ANTIDEPRESSANTS (TCA) Imipramine

Desipramine
Clomipramine
Trimipramine
Amitriptyline
Nortriptyline
Protriptyline
Doxepin

SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRI) Fluoxetine

Fluvoxamine
Sertraline
Paroxetine

2nd GENERATION ANTIDEPRESSANTS Trazodone

Bupropion
Amoxapine
Maprotiline

3rd GENERATION ANTIDEPRESSANTS Venlafaxine

Mirtazapine
Nefazodone

Antidepressants have similar efficacy but they differ in structure, mechanisms of action, adverse effects and drug interactions.

STRUCTURE/ MECHANISM OF ACTION

MONOAMINE OXIDASE Ring-closed amphetamine derivatives
INHIBITORS (MAOI)
MOA: blockade of the oxidative deamination (by monoamine oxidase)
of DA, NE and 5HT  increased levels of the biogenic amine in the
synaptic cleft

TRICYCLIC ANTIDEPRESSANTS Have a three fused-ring system

(TCA)
MOA: reduction of the CNS neuronal uptake of 5HT and NE 
 prolonged synaptic availability of the biogenic amines

SELECTIVE SEROTONIN Selectively inhibit 5HT uptake.

REUPTAKE INHIBITORS (SSRI)
2nd GENERATION SNRI (Serotonin-Norepinephrine Reuptake Inhibitor)
ANTIDEPRESSANTS

Moclobemide is a MAO-A inhibitor (selective for serotonin, NE & tyramine) while Selegiline & Deprenyl are MAO-B inhibitors
(selective for dopamine).

Clomipramine & fluvoxamine are also used in obsessive-compulsive disorder.

ADVERSE EFFECTS
Common side effects are nausea, anorexia, insomnia, loss of libido and failure of orgasm.
NOTES:

TCAs
 Most are long-acting, and they are often converted to active metabolites.
 Important side effects: sedation (H1 block); postural hypotension (α-adrenoceptor block); dry mouth, blurred vision,
constipation (muscarinic block); occasionally mania and convulsions. Risk of ventricular dysrhythmias due to HERG
channel block.
 Dangerous in acute overdose: confusion and mania,
 Liable to interact with other drugs (e.g. alcohol, anaesthetics, hypotensive drugs and non-steroidal anti-inflammatory
drugs; should not be given with monoamine oxidase inhibitors).
 Tricyclic antidepressants cause severe cardiotoxicity (dysrhythmia) in overdose
MAOIs
 Hypotension is a common side effect
 Excessive central stimulation may cause tremors, excitement, insomnia and, in overdose, convulsions
 Atropine-like side effects (dry mouth, blurred vision, urinary retention, etc.) are common with MAOIs, although they are
less of a problem than with TCAs.
SSRIs
 In combination with MAOIs, SSRIs can cause a 'serotonin syndrome' characterised by tremor, hyperthermia and
cardiovascular collapse, from which deaths have occurred.

DRUG-DRUG INTERACTIONS
MAOIs + Tyramine  hypertensive crisis, cerebral stroke
+ TCA serotonin syndrome
+ SSRI  serotonin syndrome
TCAs + MAOI  serotonin syndrome
SSRIs + MAOI  serotonin syndrome

DRUGS FOR BIPOLAR DISORDER

Lithium
 First-line agent
 Available as Lithium carbonate and Lithium citrate
 Mechanism of action still unknown
 Has narrow therapeutic index
 Lithium toxicity:
o EARLY ONSET
 GI upset
 Polydipsia
 Nocturia
 Polyuria
 Dry mouth
  Hand tremor
 Leukocytosis
o LONG TERM USE
 Weight gain
 Altered taste
 Decreased libido
 Hypothyroidism
 Rash
 Acne
 Psoriasis
 Alopecia
o TOXICITY (abrupt onset)
 Severe drowsiness
 Course hand tremor
 Muscle twitching
 Seizures
 Choreoathetosis
 Vomiting
 Confusion
 Vertigo

Valproic acid
 More commonly employed as an anticonvulsant (especially in epilepsy in children)
 Its mechanism of action as a mood stabilizer is not yet fully understood.
 Has multiple drug interactions. It is an INHIBITOR of CYP450 enzyme system

Carbamazepine
 Also an anticonvulsant
 Considered as second-line
 Its mechanism of action as a mood stabilizer is not yet fully understood.
 Is an INDUCER of the CYP450 enzyme system.

ANXIOLYTICS/ SEDATIVE-HYPNOTICS
DRUGS FOR THE TREATMENT OF ANXIETY

BENZODIAZEPINES Alprazolam
Chlordiazepoxide
Clonazepam
Clorazepate
Diazepam
Lorazepam

Midazolam
Estazolam
Flurazepam
Temazepam
Triazolam
 Clonazepam
Midazolam
Oxazepam
Triazolam

BARBITURATES Phenobarbital
Amobarbital
Butabarbital
Pentobarbital
Secobarbital

AZASPIRODECANEDIONES Buspirone
Gepirone
Isapirone
Tiospirone

IMIDAZOPYRIDINE Zolpidem

BENZODIAZEPINES
 The presence of 3-hydroxyl group determines metabolism
o Agents WITH 3-hydroxyl group are easily metabolized
o Agents WITHOUT the 3-hydroxyl group are long acting.
 Most long acting agents form the intermediate metabolite DESMETHYLDIAZEPAM
 MOA: binding to an allosteric site in the GABA receptor  increase in CHLORIDE channel opening  neuronal membrane
HYPERPOLARIZATION  depression of the limbic system and the reticular formation
 Aside from their anxiolytic property, the benzodiazepines have other significant actions:
o HYPNOTIC
o ANTICONVULSANT
o MUSCLE RELAXANT
 Benzodiapines have been noted to produce ANTEROGRADE AMNESIA. This property makes benzodiazepines desirable
agents for pre-operative medication.
 Flumazenil, a GABA receptor antagonist, is the antidote for benzodiazepine toxicity.

BARBITURATES
 Currently, the barbiturates have been used less as anxiolytics due to the numerous adverse effects, drug interactions and
high degree of tolerance noted on these drugs.
 Barbiturates are 5,5-disubstituted derivatives of barbituric acid; The two side chains at 5 position is responsible for the
sedative hypnotic effect.
 The barbiturates are WEAK ACIDS. (In the event of toxicity, ALKALINIZATION of the urine leads to increased excretion.)
 Phenobarbital is used more commonly as an anti-convulsant
 MOA: binding to an allosteric site in the GABA receptor  increase in CHLORIDE channel opening  neuronal membrane
HYPERPOLARIZATION  depression of the limbic system and the reticular formation
 BENZODIAPINES and BARBITURATES, though they act on the same receptor, they have different binding sites.

AZASPIRODECANEDIONES
 Buspirone binds to central DOPAMINE and 5HT receptors. It has no anticonvulsant or hypnotic properties. It does not
enhance the depressant effect of alcohol and other CNS depressant agents

IMIDAZOPYRIDINE
 Zolpidem has strong sedative effects with minimal anxiolytic actions.
 physical dependence with zolpidem is rare.
ADVERSE DRUG REACTIONS (ADRs)

BENZODIAZEPINES CNS depression, drowsiness, ataxia, confusion, dysarthria

Nausea, vomiting, diarrhea
POTENTIAL FOR ABUSE AND DEPENDENCE

BARBITURATES RESPIRATORY DEPRESSION

BRADYCARDIA
ORTHOSTATIC HYPOTENSION
STEVEN-JOHNSON SYNDROME
EXFOLIATIVE DERMATITIS
CNS effects
Headache, fever, hepatotoxicity
MEGALOBLASTIC ANEMIA (Phenobarbital)
**Among the many ADRs

AZASPIRODECANEDIO Restlessness, dizziness, headache, diarrhea, paresthesia

NES

ANTI-EPILEPTIC DRUGS
Seizure is characterized by EXCESSIVE, HYPERSYNCHRONOUS DISCHARGE OF CORTICAL NEURON ACTIVITY
Epilepsy is a chronic seizure disorder, wherein the seizures occur and recur unpredictably.
Convulsions are violent, involuntary contractions of the voluntary muscles. A patient may have a epilepsy without convulsion (as
in the case of petit mal)

Antiepileptics PREVENT or REDUCE THE SPREAD OF EXCITATION FROM THE CNS SEIZURE FOCI.
This is achieved by the action of these drugs to
 inhibit SODIUM CHANNELS in the CNS
 promotion of GABA activity
 modulation of CALCIUM CHANNEL activity

DIFFERENT TYPES OF SEIZURES

PARTIAL Simple partial seizure

SEIZURE no alteration/loss of consciousness
The excessive
neuronal discharge Complex partial seizure
occurs locally
WITH alteration/loss of
consciousness
 GENERALIZED Absence (petit mal)
SEIZURES
alterations of consciousness
The discharge (absences)
occurs within both -- patient just stares blankly; This
hemispheres alteration lasts for 10-30
seconds.

Myoclonic
involuntary jerking of the facial,
limb or trunk muscles

Tonic-clonic (grand mal)

sustained tonic muscle extension
(stiffening) & muscle contractions
alternating w/ relaxation

DRUG OF CHOICE FOR SEIZURE DISORDERS

SEIZURE TYPE DRUG OF CHOICE ALTERNATIVE DRUGS
Simple Partial Carbamazepine Phenytoin
Phenobarbital
Primidone
Lamotrigine
Oxcarbazepine
Complex Partial Carbamazepine Phenytoin
Lamotrigine Primidone
Absence Lamotrigine Clonazepam
Ethosuximide Valproic acid
Myoclonic Valproic acid Clonazepam
Status Epilepticus Diazepam Phenytoin
Phenobarbital
Tonic-Clonic Lamotrigine Phenobarbital
Carbamazepine Primidone
Phenytoin Valproic acid

COMMONLY USED ANTI-EPILEPTICS

Carbamazepine Sodium-channel blocker
Also used for the treatment of
trigeminal neuralgia
teratogenic (cleft palate)
Phenobarbital Promotes GABA mediated chloride
influx
anxiolytic & hypnotic agent
CYP450 enzyme inducer
ADR: megaloblastic anemia
(prolonged therapy)
Phenytoin Sodium-channel blocker
antiarrhythmic agent (Class IB: Na
channel blocker)
CYP450 enzyme inducer
 teratogenic (fetal hydantoin
syndrome, cleft palate)
ADR: gingival hyperplasia,
Arrhythmias
Valproic acid Increases level of GABA; also affects
Potassium channels
teratogenic (neural tube defects)
ADR: hepatotoxicity
Primidone phenobarbital derivative
ADR: megaloblastic anemia
(prolonged therapy)

GENERAL ANESTHETICS
General anaesthesia involves three main neurophysiological changes:
 unconsciousness
 loss of response to painful stimulation
 loss of reflexes

TWO TYPES OF GEN. ANESTHETICS

Intravenous anesthetics are used for:
 induction of anesthesia
 maintenance of anesthesia throughout surgery
Inhalational anesthetics (gases or volatile liquids) are used for maintenance of anesthesia.

Both the inhaled and the intravenous anesthetics can depress spontaneous and evoked activity of neurons in many regions of the
brain.

In the past decade, considerable evidence has accumulated that a primary molecular target of general anesthetics is the GABAA
receptor-chloride channel, a major mediator of inhibitory synaptic transmission.

In addition to their action on GABAA chloride channels, certain general anesthetics have been reported to cause membrane
hyperpolarization (ie, an inhibitory action) via their activation of potassium channels.

INHALATIONAL ANESTHETIC
Minimum Alveolar Concentration (MAC) is the concentration of anesthetic gas needed to eliminate movement among 50% of
patients challenged by a standardized skin incision. MAC is the standard of comparison for potency of general anesthetic agent.
MAC is inversely proportional to potency of the anesthetic.

STAGES OF ANESTHESIA
Stage I Initially, there is analgesia w/o amnesia
(Analgesia) Later, analgesia & amnesia are both present
Stage II Excitation
(Delirium) Patient may vocalize, but is amnesic
Loss of consciousness
irregular respiration & involuntary
activity
Stage III recurrence of regular respiration
(Surgical Anesthesia) Then, there would be complete cessation of spontaneous
respiration signs of increasing depth of anesthesia
Stage IV severe depression of the vasomotor
(Medullary Depression) center in the medulla as well as the respiratory center
INHALED ANESTHETICS
Halothane prototype among inhalational
anesthetics
low MAC, high potency
weak analgesia, good bronchial smooth
muscle relaxation
ADR: arrhythmia, hepatotoxic,
malignant hyperthermia
Nitrous oxide N2O or laughing gas
high MAC, low potency
good analgesia, poor skeletal muscle
relaxation
ADR: diffusion hypoxia
hysterical laughing
Sevoflurane ADR: nephrotoxic (due to
formation of fluoride ion)
contraindicated in patients w/
kidney failure
Enflurane DOC: patients w/ asthma
ADR: nephrotoxic (due to
formation of fluoride ion)
contraindicated in patients w/
kidney failure
Methoxyflurane most potent member of the general
anesthetics but is no longer used
clinically
ADR: nephrotoxic (formation of
fluoride ion)

Halothane is not hepatotoxic in pediatric patients & that, combined with its pleasant odor, make it the agent of choice in
children.

Malignant hyperthermia w/c may develop in susceptible individuals exposed to inhalational anesthetics. It is appropriately
treated w/ Dantrolene w/c can inhibit further release of Ca from the sarcoplasmic reticulum.
All inhalational anesthetics can trigger malignant hyperthermia in susceptible individuals.

N2O + Droperidol + Fentanyl = neuroleptanesthesia

INTRAVENOUS ANESTHETICS
Thiopental ULTRA-SHORT ACTING BARBITURATE
induces anesthesia but not to maintain anesthesia
ADR: respiratory depression
Propofol ADR: severe hypotension
Ketamine dissociative anesthetic
ADR: hallucinations, unpleasant dreams
Droperidol + Fentanyl neuroleptanalgesia
neuroleptanesthesia (if combined w/ a more potent anesthetic)
Midazolam preanesthetic medication
Diazepam ADR: respiratory depression
Lorazepam

Dissociative anesthesia produces rapid analgesia & amnesia while maintaining laryngeal reflexes.
LOCAL ANESTHETICS
The first local anesthetic to be discovered was COCAINE. It is the only naturally occurring local anesthetic. The rest of the agents of
this group are SYNTHETIC.

All local anesthetics have the hydrophilic amino group linked to a lipophilic aromatic moiety by ESTER or AMIDE BOND.
The bond is the basis for the grouping of the local anesthetics.

GROUPS OF LOCAL ANESTHETICS

ESTERS AMIDES
Metabolism metabolized by blood/ tissue metabolized by hepatic amidases
esterases
Half-life shorter longer
Examples Benzocaine Bupivacaine
Cocaine Etidocaine
Procaine Lidocaine
Tetracaine Mepivacaine
Chloroprocaine Prilocaine
Ropivacaine

Tip:
* All amide local anesthetics have two i’s.
The concept of local anesthesia is to produce a blockade of the sensation of pain, tactile and other sensory stimuli within the area
into which the agent was introduced.

This blockade is achieved by inhibition of the voltage-gated Na channel  REVERSIBLY BLOCKADE OF NERVE IMPULSE
CONDUCTION  loss of sensation

SMALL, MYELINATED nerve fibers that conduct pain and temperature are blocked first.

All the local anesthetics have local vasodilating property EXCEPT for Cocaine and Mepivacaine.
Cocaine produces significant vasoconstriction. This effect is responsible for the necrosis & perforation of the nasal septum seen in
association w/ chronic inhalation of cocaine powder.
The other local anesthetics produce vasodilation. This is the reason why local vasoconstrictors are incorporated to preparations of
the local anesthetics.
Other cardiovascular ADRs include: hypotension, bradycardia and myocardial depression

Cocaine, unlike the other local anesthetics, produce EUPHORIA. The others produce CNS stimulatory symptoms (confusion 
tremors  restlessness  seizure  coma  respiratory depression  death) if significantlt large amount pass the blood brain
barrier.

Prilocaine can predispose to the development of methemoglobinemia when given in

large doses during regional anesthesia
Tetracaine commonly used spinal anesthetic that is 10x more potent than procaine
Cocaine causes vasoconstriction and euphoria
Lidocaine - antiarrythmic agent (Class IB)

OPIOID ANALGESICS
Opioid analgesics mimic the actions of endogenous opioid peptides at CNS opioid receptors, raising the pain threshold & increasing
pain tolerance.

There are three opioid receptors: mu, delta and kappa

OPIOID ANALGESICS & THEIR RECEPTOR ACTIONS
Mu (μ) Delta (δ) Kappa (κ)
Codeine Weak agonist Weak agonist
Fentanyl Agonist
Meperidine Agonist
Methadone Agonist
Morphine Agonist Weak agonist Weak agonist
Butorphanol Partial agonist Agonist
Buprenorphine Partial agonist
Pentazocine Antagonist Agonist
or partial agonist
Nalbuphine Antagonist Partial agonist
Naloxone Antagonist Antagonist Antagonist
Nalorphine Antagonist Antagonist Antagonist
Naltrexone Antagonist Antagonist Antagonist

OPIOID ANALGESICS
Morphine prototype agonist
DOC: moderate to severe pain, pain in acute MI
poisoning triad: coma, pinpoint pupils & respiratory depression
Apomorphine Emetic
Codeine Also known as methylmorphine
Antitussive
Dextromethorphan Antitussive
Heroin diacetylmorphine or diamorphine
Fentanyl given w/ Droperidol (neurolept analgesia); available only as an IV
preparation
Meperidine Also known as Pethidine
pain associated with labor (less likely to induce neonatal respiratory
depression)
Diphenoxylate structural analog of Meperidine
given w/ Atropine (minimizes addiction potential of Diphenoxylate)
I: diarrhea
Loperamide I: diarrhea
Tramadol mu-selective
inhibits reuptake of NE & serotonin
Tramadol is a weak mu-receptor agonist that does not require an S2 license
for dispensing. It is a synthetic analogue of Codeine.

Remember HECk of a DREAM to recall all actions of Morphine.

H- istamine release
E- mesis
C- ardiovascular

D- epression of cough reflex (antitussive), decrease GI motility (for diarrhea), depression of CNS (sedation)
R- espiratory depression
E- uphoria
A- nalgesia
M- iosis

Fentanyl 80x that of morphine

Hydromorphone 7x that of morphine
Methadone Equivalent to morphine
Oxycodone 2/3 that of morphine
Propoxyphene 1/6 that of morphine
Codeine 1/8 that of morphine
Meperidine 1/10 that of morphine
Pentazocine 1/15 that of morphine