Lecture 43

Question 1

Amphetamines

Answer 1

• CII
• Amphetamine, Dextroamphetamine, Methamphetamine
• Non-catecholaminic sympathomimetic agents
• Stimulates cate. release (displaces from vesicles)
• Inhibits reuptake (completes with cate. pumps)
• Affects NE and DA in CNS and PNS

Question 2

Adderall

Answer 2

• Onset: 30-60 minutes, half life: 6-10 hours
• Equivalent amount of mixed amphetamine salt combos
• XR: once daily
• Black box: high potential for abuse, can cause sudden death or severe CV reactions

Question 3

Adderall Uses

Answer 3

1. ADHD
2. Short-term Obesity
3. Narcolepsy

Question 4

ADHD

Answer 4

• Children: inattention, hyperactive, impulsive
• Adults: lack of organization and motivation
• Genetics: 80% in twin studies
• ADHD with comobid tics (10-35% of patients) may worsen with stimulants

Question 5

Adderall + ADHD

Answer 5

• Amphetamines improve attention and reduce distractability and impulsiveness
• Avoid giving near bedtime since insomnia and anorexia can occur
• Side effects decrease with time

Question 6

Adderall + Obesity

Answer 6

• Short term treatment: 3-6 weeks
• Suppresses appetite centers of hypothalamus
• Anorexic effects in the first few weeks (decline with time)

Question 7

Narcolepsy

Answer 7

• Transition from waking state to REM sleep

- Loses muscle tone (cataplexy), falls to ground, hypnogognic hallucinations

Question 8

Lisdexamfetamine

Answer 8

-Vyvanse
-Inactive prodrug of dextroamphetamine (covalently bonded to l-lysine)
-Hydrolyzed in intestine/first pass metabolism
-Limits abuse potential when used IV/intranasally
Uses: ADHD, moderate to severe binge eating disorder (FDA approved)

Question 9

Methamphetamine

Answer 9

• Desoxyn, Methampex
• CII
• Oral
• Uses: ADHD, exogenous obesity (short-term) when in refractory period of alternate therapy
• Black Box: High potential for abuse, use in weight reduction only when other therapies are ineffective, can cause sudden death and severe CV reactions

Question 10

Methylphenidate

Answer 10

• Ritalin, Concerta, Daytrana
• Dexmethylphenidate: D-enantiomer of methylphenidate (more active)
• Milder peripheral actions
• CII
• Used in ADHD, narcolepsy, and depression or post-stroke depression (off-label)
• *Many sustained release versions available**

Question 11

Phentermine

Answer 11

• Apidex-P
• Stimlant
• CIV
• Increases NE and DA release, inhibits uptake
• Used for short term obesity with dietary/behavior modifications and exercise
• Use in obese patients with BMI>30 or >27 in the presence of other risk factors

Question 12

Diethylpropion

Answer 12

• Tenuate
• Similar mechanism to amphetamine
• CIV
• Oral
• Manages exogenous obesity in those not responding to other therapies

Question 13

Bathsalts

Answer 13

1. Crystalline, scented substances added to bath water
2. Any of several catecholamine synthesized drugs used as stimulants and usually packages to look like cosmetics or household products

Question 14

Ephedrine

Answer 14

-Releases endogenous NE indirectly and directly acts on B-receptors

Uses

1. Acute bronchospasm
2. Hypotension in spinal anesthesia/overdoses of hypotensive causing drugs
3. Orthostatic hypotension
4. Nasal congestion

Question 15

Pseudophedrine

Answer 15

• Sudafed
• OTC, oral
• Indirect and direct effects on alpha receptors
• Treats nasal congestion (Cold and allergies) and prophylaxis for otitic barotrauma in air pressure changes
• *Combat Methamphetamine Epidemic Act of 2005**

Question 16

Nexafed

Answer 16

• New Sudafed drug to curb meth production

- Turns into thick gel when dissolved, makes Sudafed hader to extract

Question 17

Cocaine

Answer 17

• CII, high abuse potential
• Euphoria
• Reuptake inhibitor of NE, DA, 5-HT (indirect agonist)
• General sympathetic effect: increases HR/BP
• Local anesthetic on mucous membranes or in oral, laryngeal, and nasal cavities
• Vasoconstrictor action that decreases bleeding

Question 18

Stimulant Contraindications

Answer 18

• High potential for abuse, less so for CIV
• Not recommended for those with substance abuse problems
• Do not use in those with cardiac disease, hyperthyroidism, psychosis, and depression

Question 19

Drug Interactions with Stimulants

Answer 19

1. Enhances other sympathomimetics (CNS and PNS)
2. MAOIs, caution with L-DOPA
3. May counteract some antihypertensive agents
4. Antipsychotic drugs (D2 agonists) may block central stimulant action and decrease affects of drugs used for ADHD, narcolepsy, and appetite suppression

Question 20

Stimulant Adverse Reactions

Answer 20

1. Anxiety, headache, insomnia (lower doses or take drug holidays to reduce these)
2. High doses/overdoses: paranoia, psychosis, arrhythmias, seizures, coma, and death
3. Growth inhibition in children due to decreased appetite and altered GH secretion
4. CV: increased BP/HR
5. Reverse tolerance (sensitization)
6. Severe depressive symptoms, anxiety, and suicidal idealation
   * *During D/C, monitor patient and gradually reduce dose to minimize these effects**

Question 21

Modafinil

Answer 21

• Provigil
• Alternative narcolepsy treatment option
• CIV, low abuse potential
• Stimulant
• R isomer (active) = Armodafinil
• Minimal peripheral side effects, no tolerance development
• Improves wakeful-ness in those with narcolepsy, obstructive sleep apnea, and shift work disorder
• *Doesn’t cause agitation, aggression, etc.**

Question 22

Atomoxetime

Answer 22

• Strattera
• Treats ADHD in adults and children by blocking NE reuptake
• Doesn’t exacerbate tics
• Original two trials saw a 59-64% response when compared to the placebo
• Side effect: suppressed appetite
• Lacks abuse potential, so good for those with abuse history

Question 23

Drugs Removed from Market

Answer 23

1. Phenylpropanolamine - D/C 2000, stroke
2. Pemoline (Cylert) - D/C 2005, life threatening hepatic failure
3. Sibutramine (Merdine) - D/C 2010, increased CV risks

Question 24

Drugs NOT to use with LQTS

Answer 24

1. Amphetamine/dextroamphetamine (Adderall, Adderall XR)
2. Dextroamphetamine (Dexedrine)
3. Methamphetamine
4. Methylphenidate (Ritalin, Concerta)
5. Dexmethylphenidate (Focalin)
6. Lisdexamfetamine (Vyvanse)
7. Atomoxetine (Strattera)