Pharmacology Chapter 13 (Unit 1)

Question 1

• This is a very complex system in the human body
• Many drugs work either work in the CNS or cause adverse effects in the CNS

-CNS activity is regulated by a “checks-and- balances system”
-Excitatory and inhibitory neurotransmitters
- Receptors in the CNS

-CNS Stimulation results from either excessive stimulation or excitatory neurons or blockade of inhibitory neurons

Answer 1

Central Nervous System

Question 2

• A broad class of drugs that stimulate specific areas of the brain or spinal cord
• Act by stimulating the excitatory neurons in the brain
• Neurons contain receptors for excitatory neurotransmitters, including dopamine (dopaminergic drugs), norepinephrine (adrenergic drugs), and serotonin (serotonergic drugs)
• Sympathomimetic drugs

Drugs are classified in 3 ways

1) Chemical structural similarities: amphetamines, serotonin agonists, symphomimetics, and xanthines

2) Site of therapeutic action in the CNS

3) Major therapeutic uses: anti-attention deficit disorders, antinarcoleptic, anorexiant, antimigraine, and analeptic drugs

Answer 2

CNS Stimulants

Question 3

• Most common psychiatric disorder in children, affecting 10.8% of school aged children
• Boys are affected more often than girls (but girls may be underdiagnosed)
• Primary symptoms of this are inappropriate ability to maintain attention span or the presence of hyperactivity and impulsivity
• Drug therapy for both childhood and adult this are the same
• May involve predominantly attention deficit, predominantly hyperactivity or impulsivity or a combination of both
• Usually diagnosed around 7 years of age with symptoms typically appearing between 3 and 6 years
• Officially be diagnosed when symptoms last at least six months and occur at least in two different settings

Answer 3

Attention deficit hyperactivity disorder (ADHD)

Question 4

• An incurable neurologic condition in which patients unexpectedly fall asleep in the middle of normal daily activities

-Known as “sleep attacks”

• Reportedly cause car accidents or near misses in 70% or more of patients
• Half of patients with this also experience migraine headaches

Answer 4

Narcolepsy

Question 5

• This is sudden acute skeletal muscle weakness
• Associated symptom in at least 70% of narcolepsy cases
• It is often associated with strong emotions (ex. joy, anger) and commonly the knees buckle in the individual falls to the floor while still awake

Answer 5

Cataplexy

Question 6

• According to the National Institutes of Health and the Centers for Disease Control and Prevention, approximately 42.2% of Americans are this
• Higher incidence in women and in minorities (Between ages 6-19 are most common)
• Being 20% or more above ones ideal body weight based on population statistics for height, body frame, and gender

-Having a BMI of 30 or greater

Health Risks include: Calorie excess, disordered metabolism, the risk for hypertension, dyslipidemia, coronary artery disease, stroke, type 2 diabetes mellitus, gallbladder disease, gout, osteoarthritis, sleep apnea, and certain types of cancer, including breast and colon cancer

-

Answer 6

Obesity

Question 7

• A common type of reoccurring headache, usually lasting from 4 to 72 hours

-Typical features: Pulsatile quality with pain that worsens with each pulse

• Most commonly unilateral but may occur on both sides of the head

-Symptoms include: Nausea, vomiting, photophobia (avoidance of light) and phonophobia (avoidance of sounds)

-Aura

Answer 7

Migraine

Question 8

Neonatal apnea
- Common in seventy percent of premature infants born before 34 weeks gestation

-Bronchopulmonary dysplasia

-Postanesthetic respiratory depression

• Treated with analeptic drugs such as theophylline, aminophylline, caffeine, and doxapram

Answer 8

Analeptic- Responsive Respiratory Depression Syndromes

Question 9

This condition occurs when a patient spontaneous respiratory drive does not resume adequately and in untimely manner after general anesthesia

Answer 9

Postanesthetic respiratory depression

Question 10

-CNS stimulants are first line drugs

• They are potent drugs with a strong potential for tolerance in a psychologic dependence

-Classified as schedule 2 drugs

• Two of the oldest known stimulants are cocaine and amphetamine which are pro typical drugs for this class of drugs

Amphetamines: methylphenidates

Nonamphetamine stimulants
- Modafinil
-Atomoxetine: nonstimulant drug that is used to treat this
- Lisdexamfetamine (Vyvanse) prodrug for dextroamphetamine

Answer 10

Drugs for attention deficit hyperactivity disorder (ADHD) and narcolepsy

Question 11

Armodafanil and Modafinil are examples of these stiulants

Answer 11

Nonamphetamine stimulants

Question 12

• A non stimulant drug that is also used to treat ADHD
• Selective nor epinephrine reuptake inhibitor

-Has a low incidence of insomnia and a lower abuse potential

Answer 12

Atomoxetine

Question 13

• A sulfate amphetamine derivative that was introduced for the treatment of hyperactivity in children in 1958
• Schedule 2 drug
• Used to treat ADHD and or narcolepsy

Answer 13

Methylphenidate

Question 14

• This drug is a prodrug for deoxtroamphetamine Meaning it is converted into the body into deoxtroamphetamine

Answer 14

Lidexamfetamine (Vyvanse)

Question 15

Mechanism of Action and drug effects

• Stimulate areas of the brain associated with mental alertness

CNS effects
- Mood elevation or euphoria

• Increased mental alertness and capacity for work
• Decreased fatigue and drowsiness
• Prolonged wakefulness

Respiratory effects

• Relaxation of bronchial smooth muscle
• Increased respiration
• Dilation of pulmonary arteries
• Increase the effects of norepinephrine and dopamine in CNS synapses by increasing their release and blocking their reuptake
• Both neurotransmitters are in contact with their receptors longer which lengthens their duration of action

Indications
- includes: ADHD, Narcolepsy, and Obesity

Contraindications
-Do not take known drug allergy, cardiac structural abnomralities, and recent MAIO

Adverse Effects

-Wide range; dose related

-Tend to “speed up” body systems

-effects include: Increased heart rate and blood pressure. As well as Angina, anxiety, insomnia, headache, trimmer, blurred vision, increased metabolic rate, gastrointestinal (GI) distress, dry mouth, and worsening of or new onset of psychiatric disorders, including mania, psychoses, and or aggression

• Common adverse effects associated with atomoxetine include headache, abdominal pain, vomiting, anorexia, and cough

-Available in prescription form only for oral use

Answer 15

Amphetamines

Question 16

• This drug is approved for treating ADHD in children older than 6 years and in adults

-Lacks addictive properties

• In September 2005 the FDA issued a warning describing cases of suicidal thinking and behavior in small numbers of adolescent patients receiving this medication

Answer 16

Atomoxetine (Strattera)

Question 17

• This drug was the first prescription drug indicated for ADHD and is also used for narcolepsy

-Extended-release dosage forms include Ritalin SR, Concerta, and Metadate CD

• This drug increases the release and blocks the reuptake of norepinephrine and dopamine
• Schedule 2 controlled drug

Answer 17

Methylphenidate (Ritalin)

Question 18

• This drug is used for improvement of wakefulness in patients with excessive daytime sleepiness associated with narcolepsy and with shift work sleep disorder
• Less abuse potential than amphetamines and methylphenidate
• Schedule 4 drug

-Armodafinil (Nuvigil): similar to this drug

Answer 18

Modafinil (Provigil)

Question 19

• Any substances that suppress appetite
• Used to promote weight loss and obesity. Whoever their effectiveness has not yet been proven

Ex:
Phentermine (lonamin)

Benzphetamine (Regimex)

Methamphetamine (Desoxyn)

Diethylpropion (Tenuate)

• Benzphetamine and Methamphetamine are the only amphetamines currently approved for treating obesity

Mechanism of Action
- Suppress appetite control centers in the brain

• Increase the body’s basal metabolic rate
• Mobilization of adipose tissue stores
• Enhanced cellular glucose uptake/ reduce dietary fat absorption

Indications

• Used to treat obesity along with behavioral modifications (diet, exercise)
• Most often used in higher risk patients

Contraindications
-Do not use: Drug allergy, severe cardiovascular disease,, uncontrolled hypertension, hyperthyroidism, eating disorders, MAOI usage

Adverse Effects
- effects include: Elevated blood pressure, heart palpitations, anxiety, agitation, dizziness, headache

Answer 19

Anorexiants

Question 20

• A anti-obesity drug that is not a CNS stimulant
• It works by inhibiting the enzyme lipase (Alli- OTC version) binds to gastric and pancreatic enzymes
• This results in reduced absorption of dietary fat from the intestinal tract and increased fat elimination in the feces
• Reduces fat absorption by roughly 30%
• Restricting dietary intake of fat to less than 30% of total calories can help reduce GI adverse effects which include oily spotting, flatulence, and fecal incontinence
• Decreases in serum concentrations of vitamins A, D, and E and beta carotene are seen as a result of blocking off fat absorption
• Supplement with fat soluble vitamins corrects this deficiency

Contraindications
Do not use: In cases of chronic malabsorption syndrome, Crohn’s disease, colitis, short bowel syndrome, and Cholestasis

Adverse Effects
effects include: Fecal incontinence with oily feces, sometimes referred to as explosive diarrhea

Answer 20

Orlistat (Xenical)

Question 21

• This drug is a Sympathomimetic anorexiant
• Structurally related to amphetamines
• Much lower abuse potential
• Classified as a schedule 4 drug

Answer 21

Phentermine (Ionamin)

Question 22

-Sumatriptan (Imitrex)

-Almotriptan (Axert)

-Eletriptan (Relpax)

-Naratriptan (Amerge)

-Rizatriptan (Maxalt)

-Zolmitriptan (Zomig)

• Frovatriptan (Frova)
• Lasmiditan (Reyvow)

Migraines are severe headaches thought to be due to vasodilation in the brain the (blank) stimulate (blank) causing vasoconstriction, helping to abort a migraine

Mechanism of Action

-Stimulates 5-HT receptors in cerebral arteries, causing vasoconstriction and reducing headache symptoms

-Reduce the production of inflammatory neuropeptides

• Abortive therapy for migraines

Adverse Effects
- Effects include: Vasoconstriction, coronary circulation, irritation at injection site, tingling, flushing (skin warmth and redness) and a congested feeling in the head or chest

Answer 22

Antimigraine/ serotonin agonists/ triptans

Question 23

• These drugs were the mainstay of treatment of migraine headaches but have been replaced by the triptans for first line therapy
• Dihydroergotamine mesylate (D.H.E. 45): injectable form and as a nasal spray (Migranal)
• Ergotamine tartrate with caffeine (Cafergot): tablet form

Mechanism of action
- Narrow or constrict blood vessels in the brain

Adverse Effects
- effects include: Nausea and vomiting, cold or clammy hands and feet, muscle pain, dizziness, numbness, vague feeling of anxiety, a bitter or foul taste in the mouth or throat, and irritation of the nose (with the nasal spray dosage form)

Answer 23

Antimigraine Drugs: Ergot Alkaloids

Question 24

-These drugs have recently been introduced for migraine prevention and treatment

• Work by blocking the effects of CGRP
• Given by injection: erenumab (Aimvoig), Galacanezumab (Emgality), Fremanezumab (Ajovy), Eptinezumab (Vyepti)

-Given orally for acute treatment: Rimegepant and Ubrogepant (Ubrelvy)

Answer 24

Antimigraine Drugs: Calcitonin Gene- related Peptide Inhibitors (CGRP inhibitors)

Question 25

• This drug can be used for chronic migraines
• It is injected by a health care provider every twelve weeks
• Has a black box warning regarding spread of the toxin on the site of injection that can result in dysphagia and breathing difficulties

Answer 25

Onabotulinumtoxin A (Botox)

Question 26

• These drugs are used to treat migraine headaches
• Can produce relief from moderate to severe migraines within two hours and 70% to 80% of patients
• They work by stimulating 5-HT 1 receptors in the brain and these drugs are sometimes referred to as this or Triptans’
• Available in oral, sublingual tablets, subcutaneous self injections, and nasal sprays
• Orally administered medications are not tolerated by some patients because of nausea and vomiting associated with migraines
• Non oral including sublingual forms are advantageous for this reason. Have a more rapid onset of action, producing relief in some patients in 10 to 15 minutes, compared with 1 to 2 hours for tablets taken orally

Answer 26

Serotonin Receptor agonist

Question 27

• This drug was the original prototype drug for this class
• Seven triptans
• Slight pharmacokinetic differences exist between some of these products

-Effects are comparable overall

Answer 27

Sumatriptan (Imitrex)

Question 28

• This drug is used in the treatment and Prevention of migraines but not as frequently

-Dihydroergotamine mesylate: available as an injectable or nasal spray (Migrannal)

• Ergotamine tartrate with caffeine (Cafegot) is available in tablet form

Answer 28

Ergotamine

Question 29

• These kinds of drugs work by stimulating areas of the CNS that control respiration, mainly the medulla and spinal cord
• Methylxanthine
• inhibit phosphodiesterase, leading to buildup of cyclic adenosine monophosphate (cAMP)

Caffeine
- antagonizes Adenosine receptors

Adverse Effects
- effects include:

-Vagal: Stimulation of gastric secretions, diarrhea, and reflex tachycardia

• Vasomotor: Flushing (warmth, redness) and sweating of the skin

-Respiratory: Elevated respiratory rate (usually the desired effect)

-Musculoskeletal: Muscular tension and tremors

-Neurologic: Reduced deep tendon relfexes

Answer 29

Analeptics

Question 30

• This is a prodrug and it is hydrolyzed to theophylline in the body. Metabolized to caffeine
• Helps to potentiate the effects of analgesics used for migraine therapy and has a diuretic effect
• The stimulant effects of caffeine are attributed to its antagonism (blocking) of adenosine receptors in the brain, which is associated with sleep promotion

Caffeine
Found in
- Over the counter drugs: NoDoz
- Combination prescription drugs: Fioricet, Fiorinal
- Food and beverages

Use with caution in patients with a history of:
- Peptic ulcer
- Recent myocardial infraction
-Dysrhythmias

Intravenous: Caffeine citrate in caffeine sodium benzoate

Answer 30

Aminophylline

Question 31

• This drug is used in the event of respiratory depression associated with anesthetic drugs and drug of abuse, C O P D induced hypercapnia
• Monitor deep tendon reflexes, In addition to vital signs and heart rhythm, to prevent overdose of this drug
• Has a greater stimulant effect in the area of the brain that senses carbon dioxide content. When the carbon dioxide content of the blood is high, the respiratory center in the brain is stimulated to induce deeper and faster breathing in an attempt to exchange more carbon dioxide for inhaled oxygen

Answer 31

Doxapram (Dopram)