Lecture 42

Question 1

Dobutamine

Answer 1

• Beta 1 Selective agonist
• Increases contractility and chronotropic (HR) effects): increases CO
• Systolic BP in elevated
• Diastolic BP and mean arterial pressure are unchanged
• NO effects on dopamine receptors
• Given IV, half life = 2 minutes

Question 2

Dobutamine Uses

Answer 2

1. Short term IV inotropic treatment in those with decompensated CHF and following heart surgery
   * *Only use for 48-72 hours due to desensitization with prolonged use**

Question 3

Dobutamine Contraindications/Adverse Effects

Answer 3

Contraindication: Hypertrophic subaortic stenosis

Adverse Effects: Angina, palpitations, N/V, hypertension

Question 4

Short Acting Beta 2 Agonists

Answer 4

• Albuterol (Proventil, Ventolin)
• Terbutaline (Brethaire)

Use to treat breakthrough symptoms and immediate prevention of exercise-induced bronchospasms

Question 5

Long Acting Beta 2 Agonists

Answer 5

• Salmeterol (Serevent) - onset 10-20 minutes
• Formoterol (Foradil) - onset 1-3 minutes
• Advair Diskus (Fluticasone/Salmeterol)

Use to treat moderate - severe, persistent asthma when symptoms aren’t controlled by corticosteroids alone

Question 6

Beta 2 Agonists

Answer 6

• Differ on selectivity and onset/durations
• Relax/dilate smooth muscle in lungs, uterus, and vasculature of skeletal muscle
• Stabilize mast cells (inhibit histamine and leukotriene release)

Question 7

Beta 2 Agonist Uses

Answer 7

1. Acute bronchospasm - in those with asthma and COPD
2. Bronchospasm prophylaxis - prevention of exercise-induced bronchospasm
   - Inhibition of uterine contraction in premature labor (off label)

Question 8

Metaproterenol

Answer 8

• Alupent
• Aerosol inhalation
• Onset - 1-30 minutes, peaks at 1 hour, duration 4 hours
• Treats acute bronchospasm in asthma/COPD

Question 9

Terbutaline

Answer 9

• Brethaire
• Administered via tablet or SC
• Used to reverse acute bronchospasm in asthma/COPD
• Inhibits uterine contractions for 48-72 hours as well (off label use)

Question 10

Terbutaline WARNING

Answer 10

• Do not use in pregnant women to prevent or prolong preterm labor for more than 48-72 hours
• Can cause serious, maternal heart problems and death

Question 11

Albuterol/Levalbuterol

Answer 11

• Albuterol = Proventil, Ventolin
• Levalbuterol = Xopenex, R-isomer of Albuterol (s-isomer has no effect)
• Combination: Duoneb or Combivent (Albuterol + Ipratropium)

Question 12

Albuterol

Answer 12

• Inhalation, tablets, solution
• Used to treat acute bronchospasms in asthma
• Also in breakthrough symptoms in asthmatics

Question 13

Levalbuterol

Answer 13

-Prevents bronchospasms in those 6 years old and older with reversible, obstructive airway disease

Question 14

Salmeterol

Answer 14

• Serevent
• Duration - 12 hours
• Combination: Advair (Salmeterol + Fluticasone) - maintenance inhaler for COPD/asthma

Question 15

Salmeterol Uses

Answer 15

1. Maintain/prevent astham with concomitant corticosteroids
2. Bronchospasm prophylaxis with COPD
3. Prevent exercise-induced bronchospasm

Question 16

Clenbuterol

Answer 16

• Vet use only
• B2 agonist
• Increases lean body mass and activates lipases through B-receptors
• Considered doping substance by most athletic organizations

Question 17

Formoterol

Answer 17

• Foridil
• Selective B2 agonist
• Quicker onset than Salmeterol with similar duration
• Same uses as Salmeterol

Question 18

Salmeterol and Formoterol

Answer 18

1. NOT indicated for acute asthma attacks or status asthmaticus
   * *Don’t take extra doses, use short acting B2 agonists for acute bronchospasms**
2. NOT substitute for corticosteroids
3. “Step Down Therapy” - D/C by reducing the dose by 25-50% every 3 months to the lowest dose possible

Question 19

LABA Black Box

Answer 19

• Increase the risk of asthma-related deaths
• Increase risk of asthma-related hospitalization
• Use with concomitant use of long-term asthma control medications (inhaled corticosteroids)
• Don’t use if controlled with corticosteroids
• Pediatric/adolescents who need this drug, preferably prescribe combination with corticosteroid to increase adherence of both

Question 20

Beta 2 Agonist Contraindications

Answer 20

• *Possible Beta 1 effects**
• Harmful scale: IV > IM = SC > Oral > Inhalation
  1. Hypertension, cardiac arrhythmias, cardiac disease due to possible beta 1 activation
  2. Hyperthyroidism - increases number of beta receptors in heart, dose related B1
  3. Diabetes Mellitus - Beta agonists increase blood glucose

Question 21

Selective Beta 3 Agonist

Answer 21

• Mirabegron (Myrbetriq)
• Bladder relaxation of detrusor muscle
• Increases bladder capacity
• At usual doses: selective for B3
• Adverse reaction: hypertension in 9-11%
• Combine with antimuscarinic drug if symptoms persist

Question 22

Seletive Alpha-1 Agonist

Answer 22

• Vasoconstrictors
• Direct or indirect sympathetic effects
• Used as decongestants and to increase BP

Question 23

Phenylephrine

Answer 23

• Neosynephrine
• Similar to epinephrine structurally
• Alpha 1 agonist, potent vasoconstrictor
• Tablet, liquid, sprays
• Mainly used in combination with antihistamine, dextromethorphan, or APAP
• Metabolized by MAO in liver/intestine
• Used for nasal congestion from cold and allergies

Recent studies found that, when taken orally, doses as high as 40 mg were no more beneficial than a placebo

Question 24

Midodrine

Answer 24

• Proamatine
• Alpha 1 agonist
• Oral
• Used for severe postural hypotension (titrate)
• Avoid near bedtime, can cause supine hypertension
• Contraindication: heart disease, renal disease, urinary retention
• Black box: increased supine BP
• *Use in those who can’t tolerate fludrocortisone or to treat intermittent symptoms if non-drug measures fail (water and sodium)**

Question 25

Alpha 1 Agonist Contraindications

Answer 25

1. Severe cardiac disease and arrhythmias 2. During labor 3. Hypertension 4. Hyperthyroidism, especially if they have an indirect action that could release NE onto the heart

Question 26

Selective Alpha 2 Agonists

Answer 26

- Anti-hypertensive effect - CNS activation on locus ceruleus/nucleus tractus solitarius - Central in origin: can't cross BBB, can't lower BP - Suppresses sympathetic NS activity, PNS predominates - Useful to treat anxiety, insomnia, pain, and opioid withdrawal (Clonidine patients ideally have all of this) - Rebound: rapid withdrawal can produce nervousness and anxiety and increase the BP

Question 27

Clonidine

Answer 27

- Catapres - Epidural, oral, patch - Side effect = sedation

Question 28

Clonidine Uses

Answer 28

1. Treat hypertension 2. Withdrawal from opioids, ethanol, and nicotine side effects: decrease sympathetic outflow 3. Treatment of severe pain in cancer patients; epidural produces analgesia (Duraclon - injection) 4. Treat ADHD, especially in those with sleep disturbances - Treat symptoms of anxiety if mainly SNS in nature

Question 29

Clonidine ADHD Treatment

Answer 29

- Clonidine ER (Kapvay) and Guanfacine (Intuniv) - Good alternatives for kids who can't tolerate stimulants - May be added on to stimulant therapy as well - FDA approved to be monotherapy or add-on - Withdrawal symptom: rebound hypertension

Question 30

Guanfacine

Answer 30

- Intuniv - More selective than Clonidine for alpha-2 - Less frequency and severe rebound - Use to treat hypertension (moderate to severe)

Question 31

Guanabenz

Answer 31

- Wytensin | - Treats moderate to severe hypertension

Question 32

Dexmedetomidine

Answer 32

- Precedex - Alpha 2 agonist - May produce sedation and decrease anxiety - Half life 2.5 hours, used for 2-30 days and no incidence of rebound tachycardia/hypertension reported upon withdrawal (unlike clonidine)

Question 33

Precedex Uses

Answer 33

1. Sedation of intubated and ventilated ICU patients 2. Sedation of non-intubated patients prior and during surgical procedures * *Inhibits SNS and allows less opioids to be needed, doesn't produce respiratory depression**

Question 34

Methyldopa

Answer 34

- Aldomet - Oral and parenteral - Therapy for moderate to severe hypertension - Converted to alpha-methylNE - Stimulates CNS alpha-2 receptors - BOX WARNING - When used to HCT, not for initial hypertension therapy, need to titrate patients specifically

Question 35

Brimonidine

Answer 35

- Alphagan - Ophthalmic solution - Treats increased IOP in open angle glaucoma or ocular hypertension - Decreases aqueous humor production and increases outflow via uveoscleral pathway (alpha 2 and prostaglandins open it) - 1000x more selective for alpha 2 than 1 (1 causes mydriasis which could further increase IOP)

Question 36

Combigan

Answer 36

Combination of Brimonidine + Timolol

Question 37

Apraclonidine

Answer 37

- Iopidine - Alpha 2 agonist - Ophthalmic solution - Less CV side effects - Similar uses as brimonidine, shorter duration

Question 38

Tizanidine

Answer 38

- Zanaflex - alpha 2 agonist - Decreases spasticity causes by MS or spinal injury - Corticospinal motor neurons transmit via glutamate in motor neurons of spinal cord, presynaptic alpha-2 receptors on these neurons inhibit the glutamate release

Question 39

Tramadol

Answer 39

- Ultram - Oral analgesic - Affinity for mu receptor: 30%, blocks NE receptors: 70% - Increases NE in synapse which activates alpha 2 presynaptic receptors - Inhibits calcium uptake into the neuron and decreases glutamate release, decreases transmission of pain pathway

Question 40

Tramadol Contraindications

Answer 40

1. Abrupt D/C - rebound hypertension, anxiety, nervousness 2. Don't use in those with heart or stroke disease, hypotensive effects may decrease perfusion and worsen ischemic conditions

Question 41

Tramadol Adverse Effects

Answer 41

- Sedation - Headache - Fatigue - Confusion - N/V - Ejaculation dysfunction - Hypotension