ADMET: Absorption: Administration Routes

ADMET Overview

Absorption: Why do we care about routes/Sites of Administration? (2)

- Ensuring that the drug gets to the site of action

- administering drug through an incorrect route is a common source of medication errors & can cause patient harm

Objective

What are the sites of enteral sites of administration?

Enteral:

- oral (PO)

Objective

What are the sites of parenteral sites of administration? (5)

Parenteral:

- Intramuscular (IM)

- Intrathecal (IT)

- Intravenous (IV)/Intraarterial (IA)

- Subcutaneous (SC, SubQ, SQ)

- Intraarticular injections

Objective

What are the sites of topical (mucus and other membranes) sites of administration? (9)

- Buccal/sublingual (SL)
- Intraaural/Auricular/Otic (AD, AS, AU)
- Intranasal (IN)
- Intraocular/Ophthalmic (OD, OS, OU)
- Intrauterine (IU)
- Intravaginal (PV)
- Pulmonary/Inhalation (Inh.)
- (Ano) Recta (PR)
- Transdermal/epidermal (TD)

Objective

Enteral/oral: The absorption pattern is ___________ and dependent upon many factors

Variable

The BA range of enteral/oral drugs

<1-100%

Enteral/oral drugs and BA examples (2)

Diazepam: 100% oral BA
Alendronate: <0.7% oral BA

Objective

Enteral/oral drugs: Special Utility

- Most ____________ and _________

- Usually the _______ route

- Best route for the treatment of ___________ diseases

- In most cases can be ________-administered

- most convenient & economical
- safest route
- GI diseases
- patient-administered

Objective

What are limitations and precautions of enteral/oral drugs? (4)

- Requires patient cooperation (antipsychotics and pediatrics)

- Poorly soluble, slowly absorbed, unstable

- extensive first-pass effect

- potential issues in vomiting/diarrhea

Example of what enteral/oral drugs can be used for

gastroesophageal reflux disease (GERD) & peptic ulcer disease (PUD) (omeprazole (Prilosec®), sucralfate (Carafate®))

Objective

Intramuscular: The absorption pattern is _______________ (from aqueous solutions)

prompt

Objective

Intramuscular: The absorption pattern is ________ (from repository/depot preparations)

slow

Intramuscular BA range

75-100% BA

Objective

Special utility: Intramuscular can be used with moderate (max 3 mL for adults)....

- volumes, oily vehicles, some irritants, depot (sustained-release) injections

Objective

Limitations/Precautions of IM:

- Usage may be limited during ____________ therapy

- May interfere with certain ____________ tests

- Most cases, require another _______ to administer

- limited during anticoagulant therapy

- diagnostic tests

- require another person to administer

IM drug examples

triptorelin pamoate (Trelstar Depot®), haloperidol decanoate (“Haldol® D”)

Objective

Intrathecal absorption pattern:

Very prompt

Intrathecal BA range

100% availability in the CNS

Objective

Intrathecal special utility

- Intrathecal provides a _______ & _______ _________ of pain perception

- allows for ____________ the drug concentration in the CNS

- fast & effective spinal block

- maximizing the drug concentration in the CNS

Objective

Limitations/precautions of Intrathecal

- caution of volumes/rate of administration due to increased ______________

- requires specialized _____________ for administration

- potential issues relating to ________ puncture, risk of ________, loss of ________, ___________, _________-

- increased intracranial pressure

- specialized medical assistance

- dural puncture, risk of infection, loss of pressure, headaches, dizziness

Examples of intrathecal drugs

- Epidural pain relief in birthing (e.g. bupivacaine HCl (Marcaine®), fentanyl citrate (Sublimaze®))

- Intrathecal administration of brain cancer treatments (Gliadel® wafers impregnated with carmustine/BCNU)

Objective

Intravenous/intraarterial absorption pattern: Avoids need for _________ and _________

- dissolution and absorption

What is the BA range of intravenous/intraarterial drugs?

100% BA

T/F: The effects of intravenous/intraarterial drugs can be slow

FALSE

their effects can be immediate (can be good or bad)

Objective

Intravenous/intraarterial special utility

- Intravenous/ intraarterial are one of the best routes for _________________

- can be used with larger _____________ and _________

- can be used for larger ________ and _________

- best routes for emergency medications

- larger volumes (liters) and irritants (diluted)

- larger peptides and proteins

Objective

Limitations/precautions of Intravenous/intraarterial

- Nor suitable for _________ soluble or _________ agents/vehicles

- most cases require ________ administration

- usually requires another person and _______________ for administration

- increased risk of ______________

- poorly soluble or insoluble agents/vehicles

- require slow administration

- medical supervision

- adverse events

Examples of Intravenous/intraarterial drugs

eptifibatide (Integrilin®), octreotide (e.g. Sandostatin®)

Objective

Subcutaneous absorption pattern: ___________ (from aqueous solutions)

Prompt

Objective

Subcutaneous absorption pattern: ___________ (from repository/depot preparations)

Slow

Subcutaneous BA range

75-100% BA

Objective (special utility)

T/F: Subcutaneous in most cases can be self-administered by patient with no other assistance needed

TRUE

Objective (special utility)

Subcutaneous can be used for some relatively ____________ suspensions and for ____________ of solid pellets (e.g. testosterone pellets (Testopel®))

- insoluble
- implantation

Objective

Limitations/precautions of subcutaneous

- Volumes are limited to ________ or less

- Possible injection site issues: ________, __________, _______, ________

- 2 mL or less

- irritation, infection, necrosis, pain

Examples of subcutaneous drugs

- recombinant human insulin (e.g. Novolin®, Humulin®)

- somatropin / recombinant human growth hormone (rhGH, Serostim®)

Objective

Absorption pattern of sublingual/buccal

Prompt

Sublingual/buccal BA range

60-80% BA

Objective

Sublingual/buccal special utility

- Sublingual/buccal can be ______-administered by patient

- can be used in patients who can't _______

- best route for the treatment of _____________________

- avoids ______-______ clearance

- self-administered

- can't swallow

- peridontal diseases

- avoids first-pass clearance

Objective

Limitations/precautions of sublingual/buccal:

- Volumes are ____________

- Potential for patient to ____________ medicaiton

- limited
- swallow medication

Examples of sublingual/buccal drugs

- Buprenorphine + naloxone buccal film, SL film, SL tablets (Suboxone®)

- Cyanocobalamin (vitamin B12) sublingual tablets & spray

- Nitroglycerin sublingual products (e.g. Nitrostat®)

Objective

Intraaural/otic absorption pattern: _________ (local) to ___________ (systemic)

- moderate (local)

- poor (systemic)

T/F: Intraaural/otic have a very unlimited BA

FALSE

Very limited bioavailability

Objective

Intraaural/otic Special utility:

- Best route for the treatment of......

ear-related diseases

(e.g. earaches, ear infections)

Objective

Limitations/precautions of intraaural/otic:

- Limited __________

- Potential for ___________

- Caution in patients with ___________ tubes

- May require ___________ for administration

- limited volumes (mLs)

- irritation

- myringotomoy tubes

- assistance

Examples of intraaural/otic drugs

- Ciprofloxacin + dexamethasone otic drops (Ciprodex®)

- Hydrocortisone + glacial acetic acid otic drops (Vosol HC®)

Objective

Intranasal absorption pattern

Prompt

Intranasal BA range: Depending on the agent, BA can be up to......

90%

Objective

Intranasal special utility

- Best route for the treatment of.......

- _____ for patients to administer

- nasopharyngeal diseases (e.g. sinus infections, congestion, allergies)

- easy

Limitations/precautions of Intranasal:

- _______ volumes (sprays/drops)

- Potential for ______ and _________

- limited volumes

- irritation & nosebleeds

Examples of intranasal

- Nasal steroid sprays for treatment of allergic rhinitis (triamcinolone acetate (Nasacort®), mometasone furoate (Nasonex®), etc.)

- Nasal decongestant sprays (e.g. oxymetazoline HCl (Afrin®))

- Miscellanous agents (desmopressin acetate (DDAVP® nasal spray))

Objective

Ocular absorption pattern

prompt

Ocular BA range: Depending on the agent, _____________ is usually very good, and systemic BA can be ________ than expected

- local absorprtion

- higher

Objective

Ocular special utility

- Ocular is the best route for treatment of _______________

- Usually easy for patients to __________

- treatment of ocular diseases (e.g. eye infections, allergies, conjunctivitis, glaucoma)

- self-administer

Objective

Limitations/precautions of Ocular:

- Limited ________ (drops)

- Potential for __________ and _________ issues

- Potential for __________ effects

- limited volumes

- irritation and visual issues

- systemic effects

Examples of ocular drugs

- Ophthalmic preparations for treatment of glaucoma (timolol maleate (Timoptic®))

- Anti-infective eye drops (tobramycin (Tobrex®))

- Ophthalmic drops for treatment of irritation (tetrahydrozoline HCl (e.g. Visine® Original eye drops))

Objective

Pulmonary/Inhalation absorption pattern

Prompt

Pulmonary/inhalation BA range: Depending on the agent, local absorption is usually very __________ and systemic BA can be ____________%

- very good

- 5-100%

Objective

Pulmonary/inhalation special utility

- Pulmonary/inhalation is the best route for the treatment of ____________

- depending on the _________ method and _______ of PT, can be easy for PT to self-administer

- treatment of pulmonary diseases (e.g. asthma, COPD)

- delivery method and age

Objective

Limitations/precautions of pulmonary/inhalation:

- Limited ______ (max of few mL (nebulizer))

- Possible __________

- Absorption----->__________ effects

- limited volumes

- irritation

- systemic effects

Examples of pulmonary/inhalations Part 1

- Inhaled beta-agonists & anticholinergics for the treatment of COPD (salmeterol xinafoate (Serevent®), tiotropium bromide (Spiriva®))

- Inhaled anesthetics (e.g. isoflurane (Forane®))

Examples of pulmonary/inhalations Part 2

- Inhaled steroids for the treatment of COPD (fluticasone propionate (Flovent®), triamcinolone acetonide (Azmacort®))

- Miscellanous agents (e.g. dornase alfa (Pulmozyme®))

Objective

(Ano) Rectal absorption pattern

Prompt

Rectal BA range: depending on the agent, local absorption is usually very _________, systemic BA can be ___________%

- very good

- 30-100%

Objective

Ano/rectal special utility

- Rectal is the best route for the treatment of ____________

- Provides an _____________ route when oral administration isn't feasible

- Avoids most of ________________ effect

- treatment of anorectal diseases (e.g. hemorrhoids)

- alternative route when oral administration isn’t feasible (unconscious, seizures, vomiting, etc.)

- Avoids most of first-pass effect

Objective

Limitations/precautions of rectal:

- Limited ___________

- Irritation

- Absorption---> __________ effects

- Absorption can be ___________ and __________

- difficult to administer if patient has _____________

- limited volumes

- irritation

- systemic effects

- irregular & incomplete

- diarrhea

Examples of rectal drugs

- Anorectal steroid products for irritation (hydrocortisone acetate + pramoxine HCl (e.g. Proctofoam-HC®))

- Antinausea suppositories (promethazine HCl (Phenergan®))

- Pediatric antipyretic products (acetaminophen (Tylenol®))

Objective

Intravaginal absorption pattern

Prompt

Intravaginal BA range: Depending on the agent, local absorption is very _________, and systemic BA can be up to ______%

- very good

- up to 100%

Objective

Intravaginal special utility:

- Intravaginal is the best route for the treatment of ____________

- usually can be _____-_____________ by PT

- treatment of vaginal diseases (e.g. vaginal infections, vaginal atrophy)

- self-administered

Objective

Limitations/precautions of intravaginal:

- Limited ______/____________ (grams)

- Possibility for ____________

- Absorption---->____________

- limited volumes/amounts

- irritation

- systemic effects

Examples of intravaginal drugs

- Vaginal anti-infective agents (miconazole nitrate vaginal cream (Monistat 7®))

- Topical hormone products for vaginal atrophy (progesterone vaginal gel (Crinone®))

Objective

Epidermal/transdermal Absorption Pattern: Can be _________, depending upon condition of _________

- What does the best absorption occur with?

- variable, depending on skin condition

- best absorption occurs with lipid-soluble agents

Epidermal/transdermal BA range: Depending on agent/formulation, BA can be as high as _______%

100%

Objective

Epidermal/transdermal special utility

- Epidermal/transdermal is the best route for the treatment of _____________

- usually can be ____-_______ by patient

- Convenience

- dermatalogical diseases (e.g. skin infections, psoriasis, rashes)

- self-adminsitered

- Convenience: transdermal multi-day patches

Objective

Limitations/precautions of epidermal/transdermal

- Limited _________/__________ (grams/drops)

- Possible __________

- _________ of patches

- Affected __________ area

- ____________ absorption reported for some patches

- limited volumes/amounts

- possible irritation

- detachment of patches

- affected surface area

- variable absorption

Epidermal/transdermal examples

- Topical steroid formulations (mometasone furoate (Elocon®))

- Topical antibiotics & antifungals (e.g. mupirocin (Bactroban®), miconazole (Micatin®))

- Transdermal patches (scopolamine (Transderm-Scop®), nitroglycerin (e.g. Nitrodisc®))

Choices for routes/sites of administration: Disease state

Put drug at site of action, if possible

Choices for routes/sites of administration: Urgency: quickest routes for drug delivery are...

Quickest routes for systemic drug delivery are typically IV, SL (also IM epinephrine)

Choices for routes/sites of administration: Sustained action (days-weeks)

IM depot injections, some transdermal patches, SC pellets

Choices for routes/sites of administration: Convenience and safety:

- PO (especially XL/XR/SR/ER dosage forms)
- transdermal/epidermal

Choices for routes/sites of administration: Avoiding first-pass effect

IV, SL, PR

Choices for routes/sites of administration: Larger (liter) volumes

IV