Lectures as PPT

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PHL- 322
General Anesthesia
Goals of surgical anesthesis
1. Loss of pain sensation
2. Loss of consciousness
3. SKM relaxation
4. Autonomic stabilization
Traditional monoanesthesia
Traditional monoanesthesia vs. modern balanced anesthesia
Stages of anesthesia (not with modern drugs);
1. Stage of analgesia,
2. Stage of excitement (stimulation of CNS; ↑ Resp, ↑ BP, ↑ HR),
3. Stage of surgical anesthesia (normal vital functions),
4. Stage of medullary paralysis (↓ Resp. CVS → coma → death).
Balanced anesthesia
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2.
3.
4.
Regimen for balanced anesthesia
Pre-anesthetic medication (anxiolytics, analgesics, anti-mascarinics),
Induction (Thiopental, BDZ, NMB),
Maintenance (halothane or nitrous oxide),
Recovery (AChE inh, analgesics).
Combinations
 Neurolept-analgesia can be considered a special form of
combination anesthesia, in which the short-acting opioid analgesics
fentanyl, alfentanil, remifentanil is combined with the strongly
sedating and affect-blunting neuroleptic droperidol. This procedure is
used for minor procedures in high-risk patients (e.g., advanced age,
liver damage) and in diagnosis purpose.
 Neurolept-anesthesia refers to the combined use of a short-acting
analgesic, an injectable anesthetic, a short-acting muscle relaxant, and
a low dose of a neuroleptic.
 In regional anesthesia (spinal anesthesia) with a local anesthetic,
nociception is eliminated, while consciousness is preserved. This
procedure, therefore, does not fall under the definition of general
anesthesia.
General anesthetics
Classification of general anesthetics
1. Inhalational anesthetics. They serve to maintain anesthesia. Examples are
halothane, enflurane, isoflurane, desflurane, sevoflurane nitrous oxide.
2. Injectable anesthetics are frequently employed for induction. Examples are
thiopental, etomidate, propofol, ketamine.
The mechanism of action of anesthetics
1. Meyer-Overton study; uptake into the hydrophobic interior of the plasmalemma of
neurons results in inhibition of electrical excitability and impulse propagation in the
brain. This concept would explain the correlation between anesthetic and of
anesthetic drugs (↑ lipophilicity →↑ potency).
2. Franks & Lieb study; interaction of anesthetic drugs with lipophilic domains of
membrane proteins.
Anesthetic potency can be expressed in terms of the minimal alveolar concentration
(MAC) at which 50% of patients remains immobile following a defined painful
stimulus (surgical skin incision). Whereas the poorly lipophilic N2O must be inhaled
in high concentrations (>70% of inspired air has to be replaced), much smaller
concentrations (<5%) are required in the case of the more lipophilic halothane.
The rates of onset and cessation of action vary widely between different inhalational
anesthetics and also depend on the degree of lipophilicity.
Inhalational Anesthetics
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1. Halothane
Halothane causes unconsciousness; however, does not provide adequate analgesia (N2O).
Halothane is associated with reversible reduction in glomerular filtration rates.
Advantages:
Halothane is relatively potent and is nonflammable.
The drug's low blood:gas p.c. explains both relatively rapid anesthesia induction and recovery.
Halothane can be used to provide controlled hypotension to reduce/manage bleeding.
Of choice in pediatric anesthesia.
Disadvantages:
Hepatitis
(trifluoroacetic acid)
↑ salivation and
tracheobronchial secretions (↑ mucous)
Malignant hyperthermia (↑ Ca2+ from SR),
(Mutation in ryanodine R gene), Dantrolene.
Hypotention (VD), Bradycardia,
Dysrhythmias (NE)
Relaxation
(blood loss)
Inhalational Anesthetics
2. Enflurane
 Enflurane is similar to halothane in its potency and moderate speed of induction.
 Enflurane provides unconsciousness with slight stimulation of salivation and
tracheobronchial secretions.
 Enflurane is associated with reversible reduction in glomerular filtration rates.
 Fluoride (metabolite) usually does not reach levels required for kidney toxicity.
Advantages:
 Rapid, smooth adjustment of depth of anesthesia with limited effects on pulse or
respiration.
 Compared to halothane: less arrhyhmias, nausea, post-operative shivering and vomiting.
 Relaxation of skeletal muscles may be adequate for surgery.
 Mainly used for adult anesthesia.
Disadvantages:
Seizures
Relaxation
(blood loss)
Malignant hyperthermia
Inhalational Anesthetics
3. Isoflurane
 Isoflurane may provides adequate muscle relaxation greater than seen with halothane, which
may be adequate for abdominal procedures.
 Initially, until deeper levels of anesthesia are reached, isoflurane stimulates airway reflexes
with attendant increases in secretions, coughing and laryngospasm (greater with isofluorane
than enflurane and halothane).
 As with enfluirane, isoflurane relaxation of uterine muscle is not desirable if uterine
contraction is required to limit blood loss.
 Isoflurane is associated with reversible reduction in glomerular filtration rates.
 Unlike enflurane, convulsive activity has not been seen with isoflurane.
Advantages:
 Rapid, smooth adjustment of depth of anesthesia with limited effects on pulse or
respiration.
 Depth of anesthesia is easily controlled.
 No hepatic or renal toxicity.
 Cerebral blood flow and intracranial pressure are readily controlled.
 Isoflurane may be the most widely used inhalational agent.
 Relaxation of skeletal muscles may be adequate for surgery.
 Arrhythmias are uncommon.
Disadvantages:
Malignant hyperthermia.
Inhalational Anesthetics
4. Desflurane
 Very limited solubility (similar to nitrous oxide) allows rapid onset and recovery and precise
controlled anesthesia.
 Since laryngospasm and coughing are associated with desflurane administration, this agent
is typically administered following induction by an i.v. drugs.
 Recovery twice as rapid as for isoflurane.
 Circulatory effects are similar to isoflurane: cardiac output is preserved.
 Reversible reduction of glomerular filtration rate.
 Seizure-like activity is not observed.
 Malignant hyperthermia has not been seen with desflurane.
 No renal toxicity.
 Some muscle relaxation is present, allowing intubation, and lessening dosage requirements
for muscle relaxants.
5. Sevoflurane
 Low blood solubility; high potency allow excellent anesthesia control.
 Pharmacological properties resemble desflurane.
 Very commonly used.
 Increase fluoride levels rarely associated with kidney or renal damage.
 Compared to desflurane, sevoflurane is more extensively metabolized, releasing more
fluoride.
Inhalational Anesthetics
6. Nitrous Oxide (N2O)
 With a MAC value of l05%, N2O, by itself is not suitable or safe as a sole anesthetic agent.
 N2O is an effective strong analgesic.
 N2O is effective when combined with: Thiopental, MR., Hyperventilation to reduce CO2.
 Despite the relative insolubility of N2O, large quantities of gas are rapidly absorbed due to
its high-inhaled concentration. This concentration effect speeds induction as fresh gas is
literally drawn into the lung from the breathing circuit.
 Since N2O is often administered with a second gas, the second gas effect also enhances the
rate of induction.
 If administration of N2O is abruptly discontinued, rapid transfer of the gas from blood
and tissues to the alveoli ↓arterial tension of O2. This process is called diffusional hypoxia.
 N2O has minimal effects on the circulation compared to the other inhalational agents with
which it is co-administered.
 N2O by itself has minimal effects on respiratory drive.
 It has minimal skeletal muscle relaxation.
 No significant effects on the liver, kidney, or GI tract.
Advantages:
Excellent analgesia, Nonflammable, Very rapid onset and recovery, Little or no toxicity, Use as
an adjunct to other inhalational agents allows reduction in their dosage.
Disadvantages:
No skeletal muscle relaxation, Weak anesthetic potency, Post-anesthesia hypoxia (diffusion
hypoxia), Not suitable as a sole anesthetic agent.
Intravenous anesthetics
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1. Thiopentone (Thiopental)
It is an ultra short barbiturate with very high lipid solubility.
Rapid action due to rapid transfer across blood-brain barrier.
Short duration (about 5 min) due to redistribution, mainly to muscle.
Slowly metabolized, and liable to accumulate in body fat; therefore may cause prolonged effect
if given repeatedly (toxic).
No analgesic effect.
It is used for induction of general anesthesia followed by a drug for maintenance.
It is also used alone for short time anesthesia.
Disadvantage
Severe vasospasm
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Cardiovascular depression
2. Etormidate
Similar to thiopentone, but more quickly metabolized.
Less risk of cardiovascular depression.
May cause involuntary movement during induction.
Possible risk of adrenocortical suppression (Addison's disease).
Hypersensitivity reactions
Intravenous anesthetics
3. Propofol (Michael Jackson's Killer)
 It can induce prolonged sedation.
 Similar to thiopentone, but more rapidly metabolized (rapid induction and recovery) so it
is suitable for one day surgery.
 Lacks tendency to induce involuntary movement and adrenocortical suppression.
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4. Ketamine
Phencyclidine analog with similar properties.
Action differs from other agents; probably related to an effect on NMDA-type receptors.
Onset of action is relatively slow (2-5 min).
Produces "dissociative anesthesia", in which patient may remain conscious, though
amnesic and insensitive to pain.
Disadvantage:
Cerebral hemorrhage
Dysphoria and hallucinations
Pre-anesthetic medication
Primary Goals:
 Anxiety relief without excessive sedation.
 Amnesia during preoperative period while retaining cooperation.
 Relief of preoperative pain.
Secondary Goals:
 Reduction in the requirement for inhalational agents.
 Reduction in side effects associated with some inhalational agents such as salivation,
bradycardia, post-anesthetic vomiting.
 Reduction in acidity and volume of gastric contents.
 Reduction of stress in preoperative period.
Pre-anesthetic medication
Sedative and hypnotics:
 Benzodiazepines are frequently used as preanesthetics because of the following properties:
 Anxiolytic.
 Sedation.
 Relatively little respiratory and cardiac depression.
 Amnesia.
 Barbiturates (pentobarbital and secobarbital) also produce sedation and reduce presurgical
nervousness.
 Midazolam is a good amnestic (a form of memory loss), rapid onset, short duration; popular in
same-day surgery setting due to rapid return of normal mental status; when administrated in
combination with opioids, there is a decrease in catecholamine release in surgery.
Opioid analgesics:
 Opioids such as morphine, meperidine and fentanyl are frequently used as preanesthetics
because of the following properties:
 Presurgical pain relief.
 Anxiolyic.
 Sedation.
 Reduction in the amount of general anesthesia required (about l0% - 20 % reduction).
Pre-anesthetic medication
Anticholinergics:
 To decrease vagal effects that occur during surgery, and to reduce secretions that are produced
during operation or by succinylcholine.
 For reducing secretion (glycopyrrolate > scopolamine > atropine)
 For preventing reflex bradycardia (atropine > scopolamine > glycopyrrolate)
 For sedation (scopolamine > glycopyrrolate > atropine )
Antiemetics:
 Hydroxyzine and droperidol.
 Ondansetron, tropisetron and granisetron (5-HT3 blockers).
Gastrokinetic agents:
 Gastrokinetic drugs ↑ upper gastrointestinal motility, ↑ gastroesophageal sphincter tone, relax
the pylorus and duodenum as well as they ↑ GER.
 To ↓ the risk of aspiration pneumonitis especially in high-risk patients:
1. Acute pain; "full stomach" emergency surgery.
2. Patient with hiatus hernia
or esophageal reflux
Attention deficit hyperactivity disorder (ADHD)
 ADHD is a developmental disorder characterized by "the co-existence of intentional problems
and hyperactivity.
 Each behavior occurring infrequently alone" and symptoms starting before seven years of age.
 ADHD affecting about 3 to 5 % of children globally.
 It is a chronic disorder with 30 to 50 % of those individuals diagnosed in childhood
continuing to have symptoms into adulthood. Adolescents and adults with ADHD tend to
develop coping mechanisms to compensate for some or all of their impairments.
 The specific causes of ADHD are not known. There are, however, a number of factors that
may contribute to, or exacerbate ADHD. They include
1. genetics,
2. diet (artificial food colors, the preservative sodium benzoate) and
3. the social and physical environments (alcohol and tobacco smoke exposure during pregnancy
and environmental exposure to lead or insecticides in very early life).
Attention deficit hyperactivity disorder (ADHD)
The three key symptoms are:
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Inattention
Inattention to details, or makes careless mistakes in schoolwork, work, or other activities
has difficulty sustaining attention in tasks or play activities.
does not seem to listen when spoken to directly.
does not follow through on instructions and fails to finish schoolwork, chores (not due to
oppositional behavior or failure to understand instructions).
has difficulty to organizing tasks and activities. The child often avoids, dislikes, or is reluctant to
engage in tasks that require sustained mental effort.
often loses things necessary for tasks or activities (toys, school assignments, pencils, books, or
tools).
often easily distracted by extraneous stimuli.
Hyperactivity
often fidgets with hands or feet or squirms in their seat .
often leaves the seat in the classroom or in other situations in which remaining seated is
expected .
often runs about or climbs excessively in situations in which it is inappropriate.
often talks excessively.
Impulsivity
often blurts out answers before the questions have been completed.
often experiences difficulty awaiting his or her turn .
often interrupts or intrudes on others (butts into conversations or games).
Things That Look Like ADHD
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Depression
Anxiety
Hearing problems
Visual problems
Seizure disorder
Oppositional defiant disorder
Autism
Learning disabilities
Parenting problems
Substance use
Medication side-effects
Lead poisoning
Attention deficit hyperactivity disorder (ADHD)
 While no one really knows what causes ADHD, it is generally agreed by the medical and
scientific community that ADHD is biological in nature.
 Many researchers have suspected that ADHD may result from a problem associated
with the communication between neurons.
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ADHD Medications
Class
Stimulants
Amphetamine
Drug Name
Adderall (D, L)
Dexedrine (D)
Dextrostat (D)
Dexedrine
Spansule
Adderall XR
Vyvanse (D)
Stimulants
Focalin (D)
Methylphenidate
Methylin
Ritalin
Metadate ER
Methylin ER
Ritalin SR
Metadate CD
Ritalin LA
Concerta
Focalin XR
Daytrana patch
Form
Duration
Common Side Effects
Short-acting
Short-acting
Short-acting
Long-acting
4-6 hours
4-6 hours
4-6 hours
6-8 hours
Some loss of appetite, weight loss,
sleep problems, irritability, tics
(stereotyped motor movement).
Long-acting
8-12 hours
Long-acting
10-12 hours
Short-acting
4-6 hours
Short-acting
3-4 hours
Short-acting
3-4 hours
Intermediate-acting 6-8 hours
Intermediate-acting 6-8 hours
Intermediate-acting 4-8 hours
Intermediate-acting 8-10 hours
Intermediate-acting 8-10 hours
Long-acting
10-12 hours
Long-acting
6-10 hours
Long-acting
10-12 hour
Some loss of appetite, weight loss,
sleep problems, irritability, tics.
ADHD Medications
Class
Drug Name
Form
Duration
Common Side Effects
Non-stimulants
Strattera
(Atomoxetine)
(selective NE reuptake
inhibitor)
Sustained release
(long-acting)
24 hours
Guanfacine
(alpha-2-adrenergic
agonists)
Sustained release
(long-acting)
24 hours
Bupropion
Bupropion SR
4-5 hours
12 hours
Imipramine
Nortriptyline
Short-acting
Sustained release
(long-acting)
Extended release
(long-acting)
NA
NA
Sleep problems, anxiety, fatigue, upset
stomach, dizziness, dry mouth. Rarely,
liver damage. There are some
concerns about a link between
atomoxetine and suicidal thoughts.
Sleepiness, headache, fatigue,
abdominal pain. Rarely, guanfacine
can cause low blood pressure and
heart rhythm changes.
Sleep problems, headaches. Although
rare, bupropion may increase the risk
of seizures.
Desipramine
NA
Antidepressants
Bupropion XL
24 hours
8-24 hours Sleep problems, anxiety, fatigue, upset
stomach, dizziness, dry mouth,
8-24 hours
elevated heart rate, risk of heart
arrhythmias.
8-24 hours
Not recommended for children.
Associated with cases of fatal heart
problems.
Eating disorder
 It is a serious psychological condition.
 It is present when a person undergos severe disturbances in
eating behavior, such as extreme reduction of food intake or
extreme overeating, or feelings of extreme worry or interest
about body weight or shape.
 The sufferer is obsessed with food, diet and often body image
to the point where their quality of life suffers, and their health
is at extreme risk from their long-term poor or inadequate diet.
 Most victims of an eating disorder do not recognize that they
have a problem and they will refuse treatment and attempt to
hide their abnormal behavior from others.
Height Healthy
Without Weights
Shoes
(Min/Max)
148 cm
44-55 kg
150 cm
45-56 kg
152 cm
46-58 kg
154 cm
47-59 kg
156 cm
49-61 kg
158 cm
50-62 kg
160 cm
51-64 kg
162 cm
52-66 kg
164 cm
54-67 kg
166 cm
55-69 kg
168 cm
56-71 kg
170 cm
58-72 kg
172 cm
59-74 kg
174 cm
61-76 kg
176 cm
62-77 kg
178 cm
63-79 kg
180 cm
65-81 kg
182 cm
66-83 kg
184 cm
68-85 kg
186 cm
69-86 kg
188 cm
71-88 kg
190 cm
72-90 kg
192 cm
74-92 kg
194 cm
75-94 kg
196 cm
77-96 kg
198 cm
78-98 kg
200 cm
80-100 kg
202 cm
82-102 kg
204 cm
83-104 kg
Classification of Eating disorder
Anorexia Nervosa is characterized by self-starvation and excessive weight loss. Symptoms are:
 Refusal to maintain body weight at or above a minimally normal weight for height, body type,
age, and activity level
 Intense fear of weight gain or being “fat“
 Feeling “fat" or overweight despite dramatic weight loss
 Loss of menstrual periods
 Extreme concern with body weight and shape
 Often leads to bone loss, loss of skin integrity, etc.
 It greatly stresses the heart, increasing the risk of heart attacks and related heart problems.
 The risk of death is greatly increased in individuals with this disease
Bulimia Nervosa is characterized by a secretive cycle of binge-eating followed by purging.
Bulimia includes eating large amounts of food, more than most people would eat in one meal, in
short periods of time, then getting rid of the food and calories through vomiting, laxative abuse,
or over-exercising. Symptoms include:
Repeated episodes of bingeing and purging
 Frequent dieting
 Extreme concern with body weight and shape
 Feeling out of control during a binge and eating beyond the point of comfortable fullness
 Purging after a binge, (typically by self-induced vomiting, abuse of laxatives, diet pills and/or
diuretics, excessive exercise, or fasting)
Classification of Eating disorder
Binge Eating Disorder (compulsive overeating) is
characterized primarily by periods of uncontrolled, impulsive, or
continuous eating beyond the point of feeling comfortably full.
While there is no purging, there may be sporadic fasts or
repetitive diets and often feelings of shame or self-hatred after a
binge. People who overeat compulsively may struggle with
anxiety, depression, and loneliness, which can contribute to their
unhealthy episodes of binge eating. Body weight may vary from
normal to mild, moderate, or severe obesity.
Night eating syndrome, characterized by morning anorexia,
evening polyphagia (abnormally increased appetite for
consumption of food, frequently associated with insomnia).
Other eating disorders can include some combination of the
signs and symptoms of anorexia, bulimia, and/or binge eating
disorder. While these behaviors may not be clinically considered a
full syndrome eating disorder, they can still be physically
dangerous and emotionally draining.
Common causes of eating disorder
 Major life transitions. Many patients with eating disorders have
difficulty with change. Anorexics, in particular, typically prefer that
things are predictable, orderly and familiar. Consequently, transitions
such as the onset of puberty, entering high school or college, or major
illness or death of someone close to them can overwhelm these
individuals and cause them to feel a loss of control.
 Family patterns and problems. Children of parents who diet
frequently are more likely to worry about their weight, judge their
appearance negatively, and begin dieting themselves.
 Social problems. Many patients describe going through a painful
experience such as being teased about their appearance, being
shunned, or going through a difficult break-up of a romantic
relationship. They begin to believe that these things happened because
they were fat, and that if they become thin, it would protect them
from similar experiences.
 Failure at school, work or competitive events.
Treatment of eating disorder
Eating disorder conditions that often require hospitalization include:
excessive and rapid weight loss
serious metabolic disturbances
clinical depression or risk of suicide
severe binge eating and purging
psychosis
Ideally, the treatment team includes:
an internist -- usually acts as the manager of the team
a dietitian or nutritionist
an individual psychotherapist
a psycho-pharmacologist
both intensive group therapy, cognitive-behavioral therapy and
antidepressant medications, combined or alone, benefited patients.
Treatment of eating disorder
Antidepressants
Tricyclics such as Amitriptyline, Clomipramine, Desipramine, Imipramine.
SSRIs as Citalopram, Escitalopram, Fluoxetine (Prozac), Fluvoxamine, Paroxetine,
Sertraline.
MAOIs such as Brofaromine, Isocarboxazide, Moclobemide, Phenelzine, Tranylcipromine.
Tetracyclics such as Mianserin, Mirtazapine.
Modified cyclic antidepressants such as Trazodone.
Aminoketone such as Bupropion (induced seizures).
Serotonin and norepinephrine reuptake inhibitor such as Duloxetine, Venlafaxine.
Opioid antagonist such as Naltrexone (Intended to alleviate addictive behaviors such as the
addictive drive to eat or binge eat).
Antiemetic such as Ondansetron (Used to give sensation of satiety and fullness).
Anticonvulsant such as Topiramate (May help regulate feeding behaviors).
Other such as Lithium carbonate (Used for patients who also have bipolar disorder, but may be
contraindicated for patients with substantial purging).
Autism spectrum disorders
 Autism spectrum disorders is a diagnostic category refers to a group of disorders characterized by
delays or impairments in communication, social behaviors, and cognitive development.
 Autism is a complex developmental disability that typically appears during the first 3 years of life.
 It is widely recognized as a neuro-developmental disorder that affects the functioning of the brain.
 Children with autism are unable to interpret the emotional states of others, failing to recognize
anger, sorrow or manipulative intent
 It impacts the normal development of the brain in the areas of social interaction and
communication skills.
 Children and adults with autism typically have difficulties in verbal and non-verbal communication,
social interactions, and leisure or play activities.
 Stereotypic (self-stimulatory) behaviors may be present.
 In some cases, aggressive and/or self-injurious behaviors might be present.
 It is not a behavioral, emotional, conduct disorder a mental illness.
 There are no medical tests that can be used to diagnose autism
Symptoms of children with autism
Communication
 Avoid eye contact
 Act as if deaf
 Develop language, then abruptly stop talking
 Fail to use spoken language, without compensating by gestur
Social relationships
 Act as if unaware of the coming and going of others
 Are inaccessible, as if in a shell
 Fail to seek comfort
 Fail to develop relationships with peers
 Have problems seeing things from another person’s perspective, leaving the child unable to
predict or understand other people’s actions
 Physically attack and injure others without provocation
Exploration of Environment
 Remain fixated on a single item or activity
 Practice strange actions like rocking or hand-flapping
 Sniff or lick toys
 Show no sensitivity to burns or bruises, and engage in self-mutilation
 Are intensely preoccupied with a single subject, activity or gesture
 Show distress over change
 Insist on routine or rituals with no purpose
 Lack fear
Symptoms of children with autism
Cause of autism
 A specific cause is not known, but current research links autism to biological and
neurological differences in the brain
 Studies of twins confirm that autism has a heritable compound but suggest that
environmental influences play a role as well (teratogens)
 By examining the inheritance of the disorder, researchers have shown that autism
does run in families, but not in a clear-cut way
 Siblings of people with autism have a 3 to 8 % chance of being diagnosed with the
same disorder
 Several lines of evidence point to synaptic dysfunction as a cause of autism. Some
rare mutations may lead to autism by disrupting some synaptic pathways, such as
those involved with cell adhesion.
 Autism is not caused by bad parenting or ‘refrigerator mothers’.
Treating Autism
Behavioral Interventions – research suggests that early, intensive behavioral interventions may
improve outcomes for children with autism and help the children achieve their maximum
potential.
Sensory Integration – integration and interpretation of sensory stimulation from the
environment enhances cognition.
Diet – people with autism are more susceptible to allergies and food sensitivities than the
average person. The most common food sensitivity in children with autism is to gluten and
casein.
Medical Therapy – there is no known medical cure for autism but behavioral issues, anxiety or
depression, mood swings (bipolar disorder), obsessive compulsive disorder, attentional issues and
hyperactivity symptoms can be treated.
Treating Autism
Treating Anxiety and Depression:
 SSRIs are prescribed for anxiety, depression, and/or obsessive-compulsive disorder. Of
these only Fluoxetine has been approved by the FDA for both OCD and depression in
children age 7 and older. Three that were approved for OCD are fluvoxamine, age 8 and
older; sertraline, age 6 and older; and clomipramine, age 10 and older. Bupropion is an
antidepressant that works differently from the SSRI class of antidepresants .
Treating Behavioral Problems:
 Many autistic children have significant behavioral problems. Some can be managed by nonpharmaceutical treatments such as Applied Behavior Analysis, Floortime, etc. But when
behaviors are out of control or dangerous, it may be time to consider antipsychotic
medications. These work by reducing the activity in the brain of the neurotransmitter
dopamine
Anti-Psychotic Medications:
 Older drugs as haloperidol, thioridazine, fluphenazine, and chlorpromazine, haloperidol may
be effective in treating serious behavioral problems. But all can have serious side effects such
as sedation, muscle stiffness, and abnormal movements.
 Newer "atypical" antipsychotics as risperdone, olanzapine and ziprasidone may be a better
choice, particularly for children.
Treating Autism
Treating Seizures:
 One in four people with ASD also have a seizure disorder. usually they are treated with
anticonvulsants such as carbamazepine, lamictal , topiramate or divalproex . Although
medication usually reduces the number of seizures, it cannot always eliminate them .
Treating Inattention and Hyperactivity:
 Stimulant medications such as methylphenidate used safely and effectively in persons with
ADHD, have also been prescribed for children with autism. These medications may decrease
impulsivity and hyperactivity in some children, especially those higher functioning children.
Adderall (amphetamine and dextroamphetamine) is a stimulant, and is often used in the same
way as methylphenidate to help with attention, focus and behavior issues.
Assessing Drug Options
All pharmaceuticals described in this article have the potential for side effects. Some, when
prescribed for autism, are prescribed "off label" (that is, for purposes other than that for which
they were approved). That means that no pharmaceutical intervention comes without risk.
Analgesics and Anti-inflammatory Drugs
Pain sensation can be influenced
or modified as follows:
 elimination of the cause of pain.
 suppression of transmission of
nociceptive impulses in the spinal
medulla (opioids).
 inhibition of pain perception
(opioids, general anesthetics).
 altering emotional responses to
pain, i.e., pain behavior
(antidepressants as “coanalgesics”).
 lowering of the sensitivity of
nociceptors (antipyretic
analgesics, local anesthetics).
 interrupting nociceptive
conduction in sensory nerves
(local anesthetics).
1. Opioid Analgesics
 Endogenous opioids
enkephalins, β-endorphin,
dynorphins.
 Exogenous opioids
morphone,
heroin,
pentazocine,
pethidine,
meperidine,
methadone,
fentanyl,
noscapine,
codeine,
tramadol.
 Opioid receptors are;
μ (Mu), delta (δ), Kappa (Ƙ).
 Mode of action of opioids
1. hyperpolarization (↑ K+).
2. ↓ release of excitatory
transmitters and ↓ synaptic
activity (↓ Ca2+).
Action of endogenous and exogenous opioids at opioid receptors
Effects of opioids
 Analgesic effect by inhibition of nociceptive impulse transmission and attenuation of impulse
spread and inhibition of pain perception → floating sensation and euphoria → dependence
 Antitussive effect by inhibition of the cough reflex.
 Emetic effect by stimulation of chemoreceptors but this effect disappears with repeated use.
 Miosis effect by stimulating the parasympathetic portion of the oculomotor nucleus → PPP
 Antidiarrheic effect through ↑ segmentation, ↓ propulsive peristalsis, ↑ tone of sphincters
Opioid Tolerance
 Rout of administrations: orally, parenterally, epidurally or intrathecally or transdermal.
 With repeated administration of opioids, their CNS effects can lose intensity (increased
Tolerance). In the course of therapy, progressively larger doses are needed to achieve the
same degree of pain relief.
 Development of tolerance does not involve the peripheral effects as locomotor stimulation
and constipation, so that persistent constipation during prolonged use may force a
discontinuation of analgesic therapy.
 Physiological tolerance involves changes in the binding of a drug to receptors or changes in
receptor transductional processes related to the drug of action.
 Person who is tolerant to morphine will also be cross-tolerant to the analgesic effect of
fentanyl, heroin, and other opioids. Note that a subject may be physically dependent on heroin
can also be administered another opioid such as methadone to prevent withdrawal reactions.
 Methadone has advantages of being more orally effective and of lasting longer than heroin.
 Methadone maintenance programs allow heroin users the opportunity to maintain a certain
level of functioning without the withdrawal reactions.
 Toxic effects of opioids are primarily from their respiratory depressant action and this effect
shows tolerance with repeated opioid use.
 Opioids might be considered “safer” in that a heroin addicts drug dosage would be fatal in a
first-time heroin user.
Opioid Dependence
 Physiological dependence occurs when the drug is necessary for normal physiological
functioning, this is demonstrated by the withdrawal reactions.
 Withdrawal reactions are usually the opposite of the physiological effects produced by the
drug.
 Acute withdrawal can be easily precipitated in drug dependent individuals by injecting an
opioid antagonist such as naloxone.
Acute Action
 Analgesia
 Respiratory Depression
 Euphoria
 Relaxation and sleep
 Tranquilization
 Decreased blood pressure
 Constipation
 Pupillary constriction
 Hypothermia
 Drying of secretions
 Reduced sex drive
 Flushed and warm skin
Withdrawal Sign
 Pain and irritability
 Hyperventilation
 Dysphoria and depression
 Restlessness and insomnia
 Fearfulness and hostility
 Increased blood pressure
 Diarrhea
 Pupillary dilation
 Hyperthermia
 Lacrimation, runny nose
 Spontaneous ejaculation
 Chilliness and “gooseflesh”
Morphine antagonists and partial agonists
 Pure Agonist: has affinity for binding plus efficacy.
 Pure Antagonist: has affinity for binding but no efficacy.
 Mixed Agonist-Antagonist: produces an agonist effect at one receptor and an antagonist
effect at another.
 Partial Agonist: has affinity for binding but low efficacy.
 The effects of opioids can be abolished by the antagonists naloxone or naltrexone. Given by
itself, neither has any effect in normal subjects; however, in opioid-dependent subjects, both
precipitate acute withdrawal signs.
 Naloxone is effective as antidote in the treatment of opioid-induced respiratory paralysis.
 Naltrexone may be used as an adjunct in withdrawal therapy.
 Buprenorphine behaves like a partial agonist/antagonist at μ-receptors. Pentazocine is an
antagonist at μ-receptors and an agonist at Ƙ-receptors. Both are classified as “low-ceiling”
opioids, because neither is capable of eliciting the maximal analgesic effect obtained with
morphine or meperidine.
2. Non-opioid Analgesics & Anti-inflammatory Drugs
Origin and effects of eicosanoids
Prostaglandins (D, E, F, G, H, or I),
Thromboxane (Platelet aggregation) COX
Prostacyclin (Vascular diameter),
Leukotrienes (Allergic reactions).
LPs
A. Antipyretic Analgesics
Acetaminophen (paracetamol)
Therapeutic doses 0.5-1.0 g.
Onset 30 min.
Duration 3 h.
Liver damage (↑ NAPQI→↓GSH) x NAC.
Impaired renal function ?
Acetylsalicylic acid (Aspirin)
Therapeutic doses 0.5-1.0 g.
t1/2 ~20 min.
Irreversible inhibitor of COX 1 and 2
Suitable as inhibitor of platelet aggregation.
Duration (depend on COX resynthesis).
Irritates the gastric mucosa.
Induces bronchoconstriction (pseudoallergy)
Induces impaired blood coagulation.
Reye’s syndrome (liver and brain damage).
Induces prolonged labor, bleeding tendency.
Dipyrone (Novalgen, Analgin)
Therapeutic doses 0.5-1.0 g.
t1/2 of 5 h.
fatal agranulocytosis (↓WBs count),
In sensitized subjects → cardiovascular collapse
B. Non-steroidal Anti-inflammatory Drugs (anti-rheumatic drugs)
Cyclooxygenase (COX) isozymes:
COX-1, a constitutive form present in
stomach and kidney.
COX-2, is induced in inflammatory cells
in response to appropriate stimuli. COX2-selective
agents
as
Celecoxib,
Rofecoxib is tolerated better but risk for
heart attack, thrombosis, and stroke have
been reported..
Aspirin at > 4 g/d (→ CNS toxicity)
Carbonic acids (diclofenac, ibuprofen)
Enolic acids (piroxicam, azapropazone).
Analgesic, antipyretic, antiinflammatory.
Reversible inhibitor of COXs.
Don’t inhibit platelet aggregation.
Highly bound to plasma proteins.
t1/2 - different speeds.
NSAIDs: adverse effects
Group-specific adverse effects
 Peptic ulceration (may be prevented by co-administration of the PG derivative, misoprostol).
 Asthma attacks (lack of bronchodilating PG and increased production of leukotrienes).
 Reduced renal blood flow and renal impairment.
 Edema and a rise in blood pressure.
Drug-specific side effects
 Indomethacin (CNS: drowsiness, headache, disorientation).
 Piroxicam (skin: photosensitization).
 Phenylbutazone (blood: agranulocytosis).
Thermoregulation
Heat production and heat loss
Disturbances of Thermoregulation and Antipyretics
 Neuroleptics (inactivate hypothalamic temperature controller without activating counterregulatory mechanisms). This can be used in hyperpyrexia or in open-chest surgery with
cardiac by-pass.
 Ethanol and barbiturates at higher doses (inactivate hypothalamic temperature controller
with impairment of other centers→ uncontrolled heat loss) thus allowing cooling of the
body to the point of death.
 Pyrogens (induce fever by ↑ the controller prostaglandins and interleukin-1).
 Antipyretics such as acetaminophen and acetylsalicylic acid return the set point to its
normal level and thus bring about a defervescence.