GI Salivary Flow Flashcards
**What two systemic drugs are used in the Rx of Xerostomia(dry mouth→no saliva)? (know these)
CPX (X=for Xerostomia)
1. Cevimeline
2. Pilocarpine
These are Muscarinic Agonists
When are Saliva Substitutes used?
Saliva substitutes are used when exocrine (salivary) glands are damaged and muscarinic agonists are not effective/cannot be used.
In what population is there reduced saliva production? Why is this important?
Saliva production decreases with AGE; therefore, elderly people often have difficulty swallowing pills.
Five questions about dryness to ask patients for which a positive answer is associated with a decrease in saliva? (don’t memorize)
- Does your mouth usually feel dry?
- Does your mouth feel dry when eating a meal?
- Do you have difficulty swallowing dry foods?
- Do you sip liquids to aid in swallowing dry foods?
- Is the amount of saliva in your mouth too little most of the time.
Patients may have xerostomia only at night/when they wake up because….?
Slept with their mouth open (mouth breathing) or a snoring problem
Non-pharmaceutical options to improve xerostomia? (2)
- Sugar-free gum→promote salivation
2. Citrus juices
What five classes of drugs can cause Xerostomia? (know the 1st one)
- ANTIHISTAMINES→ CHLORPHENIRAMINE→1st generations for coughs/colds due to ANTICHOLINERGIC effects
- Anticholinergics→SCOPOLAMINE
- Decongestants
- Anti-hypertensives
- Anti-depressants/Anti-psychotics
Medical causes (10) of Xerostomia? (don’t memorize)
- Temporary Hypofunction (4)→Short term drug use (Antihistamines), Viral infection (Mumps), Dehydration, Psychological conditions (Anxiety)
- Chronic Hypofunction (4)→Chronic drug use, Autoimmune disorders, Sjogrens Syndrome, Primary Biliary Cirrhosis
- Endocrine Disorders (DM, hypothyroidism)
- Infections (HIV, Hepatitis)
- Neurological disorders (Parkinson’s, Bell’s palsy)
- Genetic diseases (CF, Down Syndrome, Celiac disease)
- Nutritional deficiencies
- Head/Neck Radiation
- GVHD
- Bone Marrow Transplant
Consequences of Xerostomia? (7)
- Difficulty chewing, swallowing, and speaking
- Increased risk of mucosal, gingival, and tongue lesions
- Increased risk of candidiasis, dental caries, periodontal disease, and other oral fungal/bacterial infections
- Taste alteration→can lead to weight loss b/c don’t enjoy food
- Oral halitosis (bad breath)
- Increased fluid intake and interdialytic weight gain (for dialysis patients)
- Reduced QOL (quality of life)
What is Sjogren’s Syndrome?
Autoimmune disease w/ destruction of tear and salivary glands→dry eyes and dry mouth.
Signs/Symptoms of Sjogren’s Syndrome? (4)
- DRY EYES/MOUTH (Xerostomia)
- Fatigue, fever, swollen glands
- Change in color of hands or feet
- Joint pain/swelling
Rx for Sjogren’s Syndrome? (2) (don’t memorize)
- Symptomatic relief→DMARD’s (cyclosporine), artificial tears/eye lubrication, sip water/chew sugar-free gum), avoid medicines/alcohol that cause dryness, drugs that promote saliva production or saliva substititutes
- Enhanced dental care→saliva contains protective enzymes, antimicrobial factors, etc.
How does Ach stimulate salivation?
- Ach binds M3-R’s on salivary acinar cells
- M3→Gq→PLC→IP3→Increased Ca2+ (from ER)
- Ca-induced Ca release via IP3-R and RyR
- Increased Ca++ activates/opens apical Cl- channel and basal K+ channel
- Efflux/secretion of Cl- into acinar lumen→ Na+ and water follow passively→Na+ follows Cl- and water follows Na+ (osmotic gradient)
What autonomic receptors are responsible for salivary gland secretions and what are their effects?
- M3 and M2→↑↑↑’d K+ and Water secretion
- Alpha-1→↑’d K+ and Water secretion
M3 stimulation has much stronger effect than Alpha-1 stimulation
What autonomic receptors are responsible for salivary gland blood vessel tone and what are their effects?
- Alpha-1 and 2→constriction
2. M3→via NO release from endothelium→dilation
What is important about the M3-R’s involved in salivary gland blood vessel dilation?
These M3 are NOT innervated and respond only to EXOGENOUS muscarinic agonists in the circulation. Their activation causes endothelium to release NO→vasodilation.
What is another consideration (other than adrenergic/cholinergic effects) that must be considered concerning the tone of the salivary gland vasculature?
The glands themselves produce Kalikrein and other vasodilatory substances:
Increased Kallikrein→Increased Bradykinin→vasodilation→increased blood flow
How does parasympathetic-induced saliva secretion compare to sympathetic-induced?
- Parasympathetic: large/copious volume of protien-poor saliva
- Sympathetic: low/sparse volume of protein-rich (thicker) saliva
What substances mediate autonomic regulation of salivary gland secretion and blood flow? (3)
Secretion and blood flow are controlled by NE, Ach, and VIP (neuorpeptide released from Parasympathetic nerves).
PSNS→Ach+VIP→NO modulation→salivary vasodilation
Two Muscarinic Agonists used in Rx of Xerostomia?
- Cevimeline
2. Pilocarpine
How do the two Muscarinic Agonists differ (2)? What is the consequence of this?
- Cevimeline: acts on M3»>M1 (~specific for M3); does not cross BBB
- Pilocarpine: Nonselective→acts on ALL muscarininc receptors; can cross BBB
Therefore, Cevimeline will be better tolerated with less global ADE’s, particularly it will have less CNS toxicity.
ADEs/Contraindications (CI) of Cevimeline?
“BATH GAL”
B: B-Blockers→concurrent use→cardiac conduction disturbances
A: Asthma (CI),and precuation w/ COPD, bronchitis
T: Teratogen→pregnancy/breast-feeding
H: Heart Ds→angina, arrhythmias, MI
G: Glaucoma (closed angle), iritis, decreased visual acuity so don’t drive/operate machinery
A: Age extremes→precuation in geriatrics and kids
L: Lithiasis (both nephro and cholelithiasis)
Contrainidications are Asth,ma Closed angle glaucoma, iritis; the rest are ADEs/precautions
ADEs/Contraindications of Pilocarpine?
BATH GAL + Psychosis owing to greater CNS activity (b/c pilocarpine can cross BBB unlike Cevimeline)
What is the 3rd agent used in Rx of Xerostomia? When is it used and what is the effect? What is its mechanism? (NOT ON TEST)
Amifostine:
1. Given 15-30 minutes before head/neck radiation to protect from gland damage leading to xerostomia. Amifostine reduces associated acute and chronic xerostomia while preserving antitumor treatment efficacy.
(Also, given as nephroprotector w/ Cisplatin therapy)
2. MoA: scavenges free radicals that could damage exocrine glands
ADEs of Amifostine? (3) (NOT ON TEST)
- N/V
- Hypotension
- Allergic reactions
Important pharmacokinetic consideration for Cevimeline?
CYP3A3/3A4/2D6 interactions possible
What drug type are used in the Rx of Sialorrhea (hypersalivation? Example?
Anticholinergics→SCOPOLAMINE
Regarding Hx and PE of a pt w/ Hypersalivation (Sialorrhea) what is important to check as a possible cause?
Check their MEDICATIONS b/c many drugs used for many different conditions can cause hypersalivation.
When should a pt with sialorrhea (hypersalivation) be treated?
Only treat if the sialorrhea is NOT drug-related. If it is drug-related, look for an alternative drug.
