Lecture 42 Flashcards
Direct Acting Agonists
1
Q
Dobutamine
A
- 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
2
Q
Dobutamine Uses
A
- 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**
3
Q
Dobutamine Contraindications/Adverse Effects
A
Contraindication: Hypertrophic subaortic stenosis
Adverse Effects: Angina, palpitations, N/V, hypertension
4
Q
Short Acting Beta 2 Agonists
A
- Albuterol (Proventil, Ventolin)
- Terbutaline (Brethaire)
Use to treat breakthrough symptoms and immediate prevention of exercise-induced bronchospasms
5
Q
Long Acting Beta 2 Agonists
A
- 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
6
Q
Beta 2 Agonists
A
- 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)
7
Q
Beta 2 Agonist Uses
A
- Acute bronchospasm - in those with asthma and COPD
- Bronchospasm prophylaxis - prevention of exercise-induced bronchospasm
- Inhibition of uterine contraction in premature labor (off label)
8
Q
Metaproterenol
A
- Alupent
- Aerosol inhalation
- Onset - 1-30 minutes, peaks at 1 hour, duration 4 hours
- Treats acute bronchospasm in asthma/COPD
9
Q
Terbutaline
A
- 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)
10
Q
Terbutaline WARNING
A
- 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
11
Q
Albuterol/Levalbuterol
A
- Albuterol = Proventil, Ventolin
- Levalbuterol = Xopenex, R-isomer of Albuterol (s-isomer has no effect)
- Combination: Duoneb or Combivent (Albuterol + Ipratropium)
12
Q
Albuterol
A
- Inhalation, tablets, solution
- Used to treat acute bronchospasms in asthma
- Also in breakthrough symptoms in asthmatics
13
Q
Levalbuterol
A
-Prevents bronchospasms in those 6 years old and older with reversible, obstructive airway disease
14
Q
Salmeterol
A
- Serevent
- Duration - 12 hours
- Combination: Advair (Salmeterol + Fluticasone) - maintenance inhaler for COPD/asthma
15
Q
Salmeterol Uses
A
- Maintain/prevent astham with concomitant corticosteroids
- Bronchospasm prophylaxis with COPD
- Prevent exercise-induced bronchospasm
16
Q
Clenbuterol
A
- Vet use only
- B2 agonist
- Increases lean body mass and activates lipases through B-receptors
- Considered doping substance by most athletic organizations
17
Q
Formoterol
A
- Foridil
- Selective B2 agonist
- Quicker onset than Salmeterol with similar duration
- Same uses as Salmeterol
18
Q
Salmeterol and Formoterol
A
- NOT indicated for acute asthma attacks or status asthmaticus
* *Don’t take extra doses, use short acting B2 agonists for acute bronchospasms** - NOT substitute for corticosteroids
- “Step Down Therapy” - D/C by reducing the dose by 25-50% every 3 months to the lowest dose possible
19
Q
LABA Black Box
A
- 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
20
Q
Beta 2 Agonist Contraindications
A
- *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
21
Q
Selective Beta 3 Agonist
A
- 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
22
Q
Seletive Alpha-1 Agonist
A
- Vasoconstrictors
- Direct or indirect sympathetic effects
- Used as decongestants and to increase BP
23
Q
Phenylephrine
A
- 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
24
Q
Midodrine
A
- 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)**
25
Alpha 1 Agonist Contraindications
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
26
Selective Alpha 2 Agonists
- 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
27
Clonidine
- Catapres
- Epidural, oral, patch
- Side effect = sedation
28
Clonidine Uses
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
29
Clonidine ADHD Treatment
- 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
30
Guanfacine
- Intuniv
- More selective than Clonidine for alpha-2
- Less frequency and severe rebound
- Use to treat hypertension (moderate to severe)
31
Guanabenz
- Wytensin
| - Treats moderate to severe hypertension
32
Dexmedetomidine
- 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)
33
Precedex Uses
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**
34
Methyldopa
- 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
35
Brimonidine
- 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)
36
Combigan
Combination of Brimonidine + Timolol
37
Apraclonidine
- Iopidine
- Alpha 2 agonist
- Ophthalmic solution
- Less CV side effects
- Similar uses as brimonidine, shorter duration
38
Tizanidine
- 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
39
Tramadol
- 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
40
Tramadol Contraindications
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
41
Tramadol Adverse Effects
- Sedation
- Headache
- Fatigue
- Confusion
- N/V
- Ejaculation dysfunction
- Hypotension
