Exam 3 Flashcards
1
Q
- used for asthma, COPD, bronchitis, pneumonia, pulmonary HTN, cystic fibrosis, lung cancer
- drugs must reach required site of action
- advantages: ease and convenience of administration (targeted treatment), lower dose (because doesn’t distribute as much) and minimum systemic adverse effects, avoid degradation by GIT and liver (no first pass metabolism), quick onset of action for emergencies, target specific sites in the lungs (bronchioles, alveoli)
A
pulmonary drug delivery - local action
2
Q
- lungs as a route of administration (drug absorbed from the lungs into systemic circulation)
- inhalation products for induction and maintenance of general anesthetic for example, inhaled insulin, antipsychotics, anti-parkinson agent
A
pulmonary drug delivery - systemic effect
3
Q
what is Afrezza?
A
inhaled insulin
4
Q
what is Adasuve?
A
inhaled antipsychotic
5
Q
what is Inbrija?
A
inhaled anti-parkinson agent
6
Q
nebulizers, metered dose inhalers (MDI), dry powder inhalers (DPI)
A
aerosol/inhalation (oral inhalation)
7
Q
a tracheal tube (catheter) for establishing and maintaining an airway, can be used to administer medications (albuterol, atropine, epinephrine, ipratropium, lidocaine), deliver surfactant to premature infants
A
instillation/endotracheal administration
8
Q
- most aerosol preparations are either liquid or solid (nasal cavity filters and removes these aerosols)
- oral cavity is less sensitive to irritants as compared to the nose (irritation may lead to sneezing), increased inhalation volume (better drug delivery, breath-activated devices), shorter pathway to the lungs (less drug loss)
A
benefits of oral inhalation compared to nasal inhalation
9
Q
for asthma or COPD, do we want drugs to reach bronchi or alveoli?
A
bronchi
10
Q
for drugs to reach systemic circulation, do they have to target bronchi or alveoli?
A
alveoli
11
Q
which region of the lungs provides better drug absorption (air conducting region or gas exchange region) for systemic effect and why?
A
gas exchange region - this is where the exchange happens so drug can reach systemic circulation, needs to reach alveoli
12
Q
highly permeable, thin epithelial cells (about 0.1 micrometers), covered with pulmonary surfactant
A
alveolar epithelium
13
Q
what is the purpose of pulmonary surfactant in terms of drug absorption?
A
surfactants are good at dissolving both hydrophilic and lipophilic substances, anything can get absorbed
14
Q
mucus traps particles, cilia move the mucus and the particles back to the throat, they are swallowed
A
mucociliary escalator/clearance
15
Q
dissolution of drug in secretions (stability, solubility, diffusion, mucus or surfactant coated airways), particles must deposit on airway walls/alveolar sacs, major challenge though is getting particles to areas of maximum benefit/interest
A
pulmonary drug delivery - absorption/bioavailability
16
Q
what type of particle deposition is characterized by large particles/particles with high velocity (large momentum) and usually occurs in the upper tracheobronchial region (swallowed and leads to systemic adverse effects)?
A
inertial impaction
17
Q
what type of particle deposition is characterized by deposition due to gravitational force at low airflow velocity, holding breath after inhalation increases the deposition of particles, usually happens in bronchioles and alveolar region?
A
sedimentation
18
Q
what type of particle deposition is characterized by random movement and collision of particles, for small particles (1-5 microns, not too small because won’t have enough movement to collide with walls), deposition occurs in alveolar sacs and if not deposited they will be exhaled, holding breath after inhalation improves this type of deposition?
A
brownian diffusion
19
Q
what type of particle deposition is characterized by deposition due to the shape of the particles/fibers, small aerodynamic diameters relative to their size, “asbestos effect”
A
interception
20
Q
the diameter of a spherical particle that would have the same settling velocity in air as a particle of interest assuming both have the same density
A
aerodynamic diameter
21
Q
how big must particles be to have alveolar deposition?
A
1-5 micrometers
22
Q
- aerosol related: particle size/shape, propulsion, electrical charge, hygroscopicity
- formulation: oral vs nasal inhalation, properties of the inhaled carrier gas
- patient related: inhalation/breathing pattern (flow rate, inhalation volume), breath-holding ability, compliance
- lung disease related: airflow obstruction, types and severity of lung disease
A
factors affecting pulmonary deposition
23
Q
- exhaled (very small particles less than 1 micrometer)
- dissolved in aqueous layer followed by systemic absorption which is a loss for local drug delivery
- removed with mucus (mucociliary clearance, ciliary activity, change in viscosity of mucus due to lung disease)
- removed by macrophages in the lung
- removed by cough reflex during inhalation
A
fate of a drug after inhalation
24
Q
- inhaled through nose or mask/mouth
- oxygen, anesthetic gases (compressed gas/volatile solutions)
- for example: nitric oxide gas for inhalation, pulmonary vasodilator for hypoxic respiratory failure associated with pulmonary HTN, in neonates with ventilatory support, Inomax, Genosyl, Noxivent
A
gases and vapors
25
- drug in solution or suspension, sterile, isotonic, neutral pH
- generate fine aerosol/mist, compressed air/jet, ultrasonic, mesh, inhaled through a mouthpiece or face mask
nebulizers
26
aerosol droplets are produced through high frequency (1-3 MHz) vibrations of a piezoelectric crystal that converts electrical energy into mechanical energy that creates the vibrations, could affect the stability of drugs and drug products, suspensions not suitable for this because vibrations will crush particles
ultrasonic nebulizers
27
- inhaled corticosteroid for maintenance and prophylactic treatment of asthma in patients 1-8 years - not for relief of acute bronchospasm
- used with a jet nebulizer that is connected to an air compressor (not to be used with ultrasonic nebulizer)
- shake well before using, do not swallow, administer with mouthpiece/facemask, wash face if using mask, compatible with other medications (albuterol, ipratropium) at same time in nebulizer, rinse mouth with water following each treatment to avoid thrush/oral candidiasis
Pulmicort inhalation suspension
28
- nebulizers with vibrating mesh or membrane
- Omron MicroAir, Aeroneb GO, Altera, Lamira
mesh nebulizers
29
- monobactam antibacterial agent for cystic fibrosis
- single use vial of sterile lyophilized aztreonam to be reconstituted with an ampule of sterile diluent, powder for inhalation
- once reconstituted this drug is administered by oral inhalation using only Altera nebulizer system
- counseling points: pour the reconstituted solution into the handset of the nebulizer system, turn the unit on, place the mouthpiece in patient's mouth and encourage them to breathe normally through the mouth, administration time is usually 2-3 minutes, administer doses 4 hours apart, administer alone (do not mix with other nebulizer meds), administer a bronchodilator before administration
Cayston for inhalation solution
30
vibrating mesh system that monitors patients' breathing and releases the drug as the patient inhales
I-neb AAD (adaptive aerosol delivery) nebulizers
31
- prostaglandin (vasodilator), pulmonary arterial HTN, single use glass ampule that is preservative free
- AAD nebulizer solution
Ventavis inhalation solution
32
aqueous mist inhalation spray, sterile aqueous solution, metered dose, creates slow moving mist, "soft mist inhaler", Combivent, Spiriva, and Striverdi are all examples of this
Respimat
33
- aluminum canister
- sealed (pressurized, rubber gaskets to prevent propellant leaks)
- metering chamber that controls the volume released
- valve/actuator that generates aerosol
- mouthpiece for oral inhalation
MDIs - container and delivery system
34
- API (drug in solution or suspension)
- solvent/dispersion medium (propellant): HFA (used as a solvent and maintains pressure in canister), cosolvents/other excipients (water, ethanol, pH adjuster, isotonic agent)
MDIs - contents
35
example of this is Atrovent HFA - anticholinergic bronchodilator, HFA -134A, cosolvents ethanol and water, buffer/pH adjustment is citric acid, stabilizing agent, solvent partially evaporates after actuation (droplets/particles), not necessary to shake
MDI - solution
36
example of this is Xopenex HFA - micronized levalbuterol tartrate, selective beta 2 adrenergic receptor agonist, propellant is HFA-134A, dehydrated alcohol and oleic acid stabilize the drug and help to create a uniform aerosol/dispersing agent, shake well before using
MDI - suspension
37
- inverted, shake well if necessary
- prime valve of new MDI and put date on the canister
- exhale completely
- place lips around mouthpiece or hold near mouth
- start breathing slowly through the mouth
- actuate MDI
- take slow deep breath, hold for 5-10 seconds
- exhale slowly through the mouth
- rinse and dry mouthpiece
how to use MDIs
38
- loss of drug in mouth and back of throat leading to systemic adverse effects
- poor hand-mouth coordination (actuation and inhalation, children, geriatrics)
- deep inhalation needed which is difficult for sensitive/irritated airways
- could initiate cough reflex
difficulties with MDIs
39
- MDI is actuated in small plastic container, larger particles will settle out due to gravity which reduces oral and throat deposition (reduces thrush or swallowing), smaller particles will remain suspended so only small particles are inhaled, patient inhales contents soon after actuation so hand-mouth coordination is not necessary
- problems: must be cleaned regularly, electrostatic attraction to particles of walls of plastic, different drugs stick to different types of these differently so don't change spacer without consulting, dosage adjustment might be required if there is a change in type of this
MDI with spacer
40
- eliminates the need for hand-mouth coordination
- has a special valve that is activated or opened with an adequate airflow
- increased oropharyngeal deposition of drugs (disadvantage)
- example: QVAR RediHaler
breath actuated MDIs
41
- products are under pressure so do not puncture or heat
- propellant can leak which concentrates the product, store in a cool place
- gunk can accumulate on the mouthpiece which changes the flow of particles
- moisture can interfere with the aerosolization/actuation so dry thoroughly after washing, store in dry place, do not exhale into inhaler
problems with MDIs
42
- micronized particles (drug-excipient blend), size of drug about 1-5 micrometers
- may contain large particle-size diluents (lactose/mannitol) with small drug particles, interactive mixture, free flowing powder
- do not shake these, can separate drug from larger molecules in the inhaler when the drug should be separated outside the inhaler
dry powder inhalers (DPIs)
43
- short acting beta 2 agonist (rescue drug)
- aerosol powder breath-activated inhalation
- no spacer, no priming
multidose reservoir inhalers - ProAir RespiClick (or RespiClick in general)
44
- similar shape to an MDI but should not be shaken
- dose should be administered with a quick, forceful inhalation (breath-actuated)
- device is preloaded with set number of doses, when opened it automatically prepares a dose
- should not be used with a spacer
- do not take extra dose from inhaler even if you don't feel/taste medicine
- don't wash any part of the device in water
counseling points - RespiClick
45
- do not shake before use
- unit should be primed before first dose only, will not need to be primed again even if not used for a long time
- hold the inhaler in upright position to load the dose
- discard when dose indicator reads 0
- rinse mouth with water after each use (thrush risk)
- keep inhaler dry
- clean mouthpiece once weekly with dry tissue
counseling points - multidose reservoir inhalers - Flexhaler (Pulmicort Flexhaler)
46
- long acting anticholinergic agent for COPD, breath actuated multidose dry powder inhaler
- remove protective cap and prepare inhaler by pressing and releasing green button to load dose
- make sure control window goes from red to green
- breathe out completely, form tight seal with lips, and breath in
- will hear a clicking sound to ensure full dose has been given (might not hear)
- use the control window (green to red after inhalation) to make sure dose was inhaled correctly, if still green repeat inhalation steps
multidose reservoir inhaler - Pressair (Tudorza Pressair)
47
- hold the device in a level, horizontal position
- push the lever back until it clicks to prime, every time the lever is pushed back a dose is ready to be inhaled
- exhale deeply and completely
- hold the device level, do not shake/tilt/close the device
- put the mouthpiece to the lips and inhale steadily and deeply
- remove the device from the mouth, never breath into the device
- hold breath for 10s, breathe out slowly and close the device
- never take an extra dose even if don't feel/taste the medication
pre-measured multidose inhalers - Diskus (Advair Diskus, Wixela Inhub)
48
- antiviral agent for Influenza A/B, treatment and prevention, not for patients with airway disease, foil blister disk
- must be used with specific device
- foil blister disk containing medication should not be administered manipulated, solubilized or administered via nebulizer
- patients scheduled to use an inhaled bronchodilator at the same time as this should used the bronchodilator first
- administer at same time each day
pre-measured multidose inhaler - Relenza Diskhaler
49
- no need to shake inhaler
- each time the cover of the inhaler is opened a click should be heard and a dose is ready to be inhaled
- only open the cover when ready for administration
- opening and closing the device without inhaling will result in losing a dose
- do not close inhaler until dose has been inhaled
pre-measured multidose inhaler - Ellipta
50
- capsules packaged in blisters (foil protects from moisture), use the capsule immediately, if foil is accidentally opened discard the capsule, don't swallow capsule
- open dust cap and mouthpiece
- place the capsule in center chamber
- close mouthpiece until it clicks, dust cap off
- hold the device upright and press the piercing button, don't press more than once
- before inhaling powder breathe out completely
- put lips around the mouthpiece, breathe in slowly and deeply
- capsule vibration (rattle) could be heard within the device
- throw away capsule by tipping it into a trash can without touching it, do not leave in inhaler
- some powder left in capsule is normal
capsules for inhalation - Spiriva HandiHaler, Inbrija, Bronchitol, Tobi PodHaler
51
Tyvaso DPI and Afrezza are examples of this
cartridges for inhalation
52
- no need for hand-mouth coordination, breath-activated
- less impact at back of throat (easy-moving particles compared to other types of inhalers)
- no need for propellants and solvents, less allergy or bad taste from those excipients
- powder can irritate throat and lungs
- less convenient than other types of inhalers, more complex devices
- moisture/humidity major issue (particle agglomerate, reduce effectiveness, store in dry place, do not exhale into device, close device after use, don't wash or rinse, dry thoroughly if wet)
DPIs - advantages, disadvantages, issues
53
keratinized epithelium (skin) in the nasal cavity, relatively impermeable to drugs
nasal vestibule
54
about 90% of the nasal cavity, good for drug absorption, mucociliary clearance
respiratory region (ciliated mucosa)
55
provides direct nose to brain pathway, could be a potential route of administration of drugs to brain but no drugs on market yet that do this intentionally
olfactory region
56
rapid and almost complete absorption for lipophilic small molecules, absorption profile mimics IV administration for rapid onset of action
nasal drug delivery - absorption
57
- rapid onset of action comparable to IV administration
- ease of delivery: painless, noninvasive, needle-free, self-medication, caregivers
- improve bioavailability through bypassing GI and liver, lower dose, lower ADR
- suitable for patients with dysphagia, nausea, vomiting
advantages of nasal route
58
- rapid removal of drug from site of absorption (mucociliary clearance, swallowing, inhalation, dripping, sneezing)
- pathological conditions: nasal congestion, cold, allergies
- variability due to incorrect administration (incorrect placement or drug loss)
- bad taste or burning from medication (irritant API or excipients)
concerns/limitations with nasal route
59
how to increase nasal bioavailability?
increase nasal deposition, minimize swallowing, inhalation, etc.
60
- drugs for allergic rhinitis and nonallergic rhinitis: azelastine, olopatadine, ipratropium, cromolyn, nasal corticosteroids
- drugs for nasal decongestant: oxymetazoline, tetrahydrozoline
nasal drug products for local effect
61
- treatment of migraine: sumatriptan, dihydroergotamine, zolmitriptan, zavegepant
- acute active seizures: diazepam, midazolam
- NMDA receptor antagonist, depression: esketamine
- treatment of hypoglycemia: glucagon
- diabetes insipidus: desmopressin
- pain medication: opioid (butorphanol) or NSAID (ketorolac)
- opioid overdose: naloxone, nalmefene
- smoking cessation: nicotine
nasal drug products for systemic effect
62
- single dose nasal spray device for treatment of migraine, don't need to prime/test, buffered, sterile (even though nasal cavity not sterile, potential to reach lungs which is sterile) unit dose, no preservatives (no need to preserve because single dose)
- counseling points: blow nose, head upright and close one nostril, hold container with thumb supporting bottom and index/middle fingers on either side of nozzle, insert nozzle into nostril and angle outward, tilt head back and breathe slowly through nose while releasing spray into nostril by pressing plunger, remove from nostril and keep head level for 10-20s, gently breathe in through nose out through mouth, don't breathe deeply
Tosmyra (sumatriptan) nasal solution (spray)
63
- increase retention and comfort of nasal products
- temperature dependent, pH dependent, and mucoadhesive polymers
- example is a C-III drug, administered 3 times daily, hormone therapy for men with androgen deficiency syndromes, requires priming before first use
- counseling points: prime pump by niverting and depressing pump 10 times (discard this portion into sink), blow nose, insert actuator into nostril until pump reaches base of nose, tilt so tip is in contact with lateral wall of nostril, depress slowly until pump stops, press on nostrils and lightly massage, refrain from blowing or sniffing nose for 1 hour afterwards, wash hands
nasal gel - Natesto (testosterone)
64
for powders or liquids for nasal drug delivery, soft palate closes the nasal cavity during blowing air through mouth, example is Onzetra Xsail (exhaler powder)
breath-activated nasal delivery
65
- nasal implant indicated for treatment of nasal polyps
- expands into ethmoid sinus and delivers drug directly to nasal polyps, sustained drug release for 90 days
Sinuva nasal implant
66
highly perfused part of the eye, drug is absorbed into systemic circulation (nonproductive absorption, don't want this because want to stay in eye)
conjunctiva
67
transparent anterior refracting surface of the eye, contains five layers creating a barrier for corneal drug absorption, high concentration of nerve fibers so sensitive to pain and irritation, no blood vessels
cornea
68
bathes cornea and conjunctiva, lubricant, antibacterial, nutritional, cleansing, lacrimal glands in eyelid and conjunctiva, meibomian glands, goblet cells
tear film
69
excessive tear production due to allergies, disease, irritation, types of formulations (more viscous is better, suspensions favored because they stay longer), volume of ophthalmic product, rate of blinking, etc.
factors affecting ophthalmic drug delivery
70
sterile, non-irritating, isotonic, pH 6.5-8.5, viscosity increases residence time, preserved if necessary
properties of ophthalmic products
71
increase tear production in patients with dry eyes, preservative free (single use vial, discard remaining contents after use), contains cremophor EL which is a vehicle to dissolve the drug
Cequa - ophthalmic solution
72
- used to treat eye infections and reduce swelling due to inflammation (antibiotic and corticosteroid), has a preservative because multidose bottle
- counseling points: for topical ophthalmic use only, shake before use, tilt head back and place into conjunctival sac and close eyes, do not touch container tip to eyelids to keep sterile, apply light finger pressure for 1 minute following instillation
Blephamide - ophthalmic suspension
73
sterile, preservative free single dose for dry eyes (increases ability to produce tears), white slightly translucent, shake well before use
Restasis, Verkazia - ophthalmic emulsion
74
- sterile, preserved, clear, used to treat acute herpetic keratitis, herpes simplex virus, topical ophthalmic antiviral product
Zirgan - ophthalmic gel
75
corticosteroid intracanalicular insert placed in punctum and into canaliculus, treatment of inflammation and pain following ophthalmic surgery, designed to deliver drug to ocular surface for up to 30 days
Dextenza
76
intravitreal injection administration only, used to treat uveitis and ocular inflammatory conditions unresponsive to topical corticosteroids
Triesence
77
injected into suprachoroidal space using a microinjector
Xipere
78
inserted surgically or with special injector, release the drug over 6 months
Ozurdex
79
sustained release over 36 months, for diabetic macular edema, injectable microinsert
Iluvien
80
silicon encased tablet surgically placed in eye, extended release over 30 months
Retisert
