Sweatman - Salivary Flow

Question 1

What are the 3 drugs for salivary flow (incl. categories)?

Answer 1

• PARASYMPATHOMIMETICS:
  1. Cevimeline
  2. Pilocarpine
• RADIO-PROTECTOR:
  1. Amifostine: free radical scavenger used with radiotherapy of head and neck to protect salivary glands
• Remember: there are also saliva substitutes, but we are not responsible for these b/c no pharmacology

Question 2

What types of questions might you ask a patient with suspected xerostomia?

Answer 2

• Affirmative response to at least 1 of the 5 questions below shown to correlate with DEC in saliva:
  1. Does your mouth usually feel dry?
  2. Does your mouth feel dry when eating a meal?
  3. Do you have difficulty swallowing dry foods?
  4. Do you sip liquids to aid in swallowing dry foods?
  5. Is the amt of saliva in your mouth too little most of the time?
• Ask whether dryness is constant, or just at night, which may indicate the problem is related to mouth breathing or snoring problem

Question 3

What are some drugs that induce xerostomia?

Answer 3

• Antihistamines: Diphenhydramine
• Decongestants: Pseudoephedrine
• Antidepressants: Amitryptiline
• Antipsychotics: Haloperidol
• Anti-HTN: Methyldopa, Metoprolol, Furosemide, CCB’s
• Anti-cholinergics: Atropine, Scopolamine

Question 4

What are some medical causes of xerostomia?

Answer 4

• Primary biliary cirrhosis, Sjogren’s
• DM, hypothyroidism
• HIV, HCV, Mumps
• Parkinson’s
• CF, Down’s, Celiac
• Head and neck radiation, graft vs. host disease, bone marrow transplant

Question 5

Sjogren’s? Tx?

Answer 5

• Autoimmune disease w/destruction of tear and salivary glands, dry eyes and mouth
  1. Fatigue, fever, change in color of hands/feet, joint pain/swelling, swollen glands
• TX: relief of symptoms, enhanced dental care
  1. Artificial tears, plug tear drainage ducts
  2. DMARD’s
  3. Sipping water, chewing sugarless gum
  4. Saliva substitutes, drugs that help salivary glands make more saliva

Question 6

What are some of the consequences of xerostomia?

Answer 6

• Difficulties in chewing, swallowing, speaking
• INC risk of mucosal, gingival, tongue lesions
• INC risk of candidiasis, dental carries, periodontal disease, and other oral fungal/bac infections
• Taste alteration
• Oral halitosis, aka, bad breath
• INC fluid intake and interdialytic weight gain (pts on routine dialysis)
• Reduced QOL

Question 7

What is the mechanism for secretion of saliva?

Answer 7

• Cholinergic innervation: analogous to production of sweat -> Na+ and H₂O drawn into oral cavity by passive flow after efflux of Ca-mediated Cl- secretion
• Ach binds G-protein linked M3 receptor, which causes phospholipase C to generate IP3, leading to release of Ca -> INC Ca activates apical membrane Cl- channel, and basolateral K+ channel
• Efflux of Cl- into acinar lumen draws Na+ across cells, and osmotic gradient generates fluid secretion

Question 8

What receptors are involved in salivary secretion and blood vessel regulation?

Answer 8

• SECRETIONS: K+ and water secretion -> alpha-1, M₂ and M₃ (much more K+ and water via M2, M3)
  1. SYM also believed to stimulate motor responses that help expel saliva from gland
• BLOOD VESSELS: constriction via alpha-1,2 and dilation via M3
  1. Endo of most vessels releases NO in response to muscarinic stimuli -> not innervated, and respond only to exogenously added muscarinic agonists in circulation
  2. Glands also produce vasodilatory substances (kallikrein -> bradykinin), INC blood flow over resting levels
• NOTE: vasoactive intestinal peptide (VIP) also involved in vasodilation

Question 9

How is PARA-stimulated saliva different from SYM-stimulated?

Answer 9

• PARA: copious secretion relatively poor in protein
• SYM: sparse, but protein-rich saliva
• NOTE: secretion controlled by

Question 10

Cevimeline dose, receptor, and AE’s

Answer 10

• 30mg q8h PO; CYP3A3/4, 2D6 interaxns possible
• M3>>M1: receptor selectivity (M1 in CNS)
• CONTRAINDICATED: asthma, closed-angle glaucoma (constriction of pupil can exacerbate the problem of pressure in the eye), iritis
• PRECAUTIONS: angina, breast-feeding, pregnancy, bronchitis, cardiac arrhythmias/disease, children, cholelithiasis, COPD, driving/operating heavy machinery (DEC visual acuity), geriatric, MI, nephrolithiasis
• Administer w/caution in pts on beta-blockers b/c possibility of cardiac conduction disturbance

Question 11

Pilocarpine dose, receptor, AE’s

Answer 11

• 5mg q6-8h PO
• All muscarinic receptors
• CONTRAINDICATED: asthma, closed-angle glaucoma (constriction of pupil can exacerbate the problem of pressure in the eye), iritis
• PRECAUTIONS: angina, breast-feeding, pregnancy, bronchitis, cardiac arrhythmias/disease, children, cholelithiasis, COPD, driving/operating heavy machinery (DEC visual acuity), geriatric, MI, nephrolithiasis + PSYCHOSIS (owing to greater CNS activity than Cevimeline)
• Administer w/caution in pts on beta-blockers b/c possibility of cardiac conduction disturbance

Question 12

What is the indication of Amifostine? MOA?

Answer 12

• Destruction of salivary glands via irradiation of head and neck to treat unresectable cancers or as adjunctive tx following removal of primary tumor
  1. Bystander effect on adjacent tissue, leading to apoptotic/necrotic cell loss
• AMIFOSTINE: free radical scavenger indicated for radio-protection of head and neck where field is expected to include a substantial portion of the parotids
  1. Administered IV prior to radiation dose
  2. Some degree of tissue damage still endured
• Orphan drug for this indication: pharmaceutical agent that has been developed specifically to treat a rare medical condition

Question 13

Are saliva substitutes effective?

Answer 13

• No strong evidence, but no reason not to try these out in pts with no other tx options

Question 14

What is one option if a drug produces hypersalivation in a pt?

Answer 14

• Try another drug, or reduce dose
• Until proven otherwise, a drug is causing the effect you are concerned about (long list of drugs that can do this)

Question 15

What are some pharma txs for sialorrhea?

Answer 15

• Labeled anti-cholinergic: Glycopyrrolate
  1. Used in some neuro conditions like cerebral palsy
• Off-label drugs: botulinum toxin, Scopolamine
  1. Scopolamine: muscarinic antagonist effects, and also used for prevention of N/V assoc with motion sickness, reduction in salivation excess and bronchial secretions prior to surgery, reduction in spastic states in Parkinson’s, and to produce cycloplegic refraction and pupil dilation

Question 16

How should pts take meds (like tablets) that sink?

Answer 16

• Fill bottle with water
• Put tablet on tongue and close lips tightly around bottle opening
• Drink, keeping contact b/t bottle and lips by pursing and making sucking motion -> swallow water and pill right away
• Don’t let air into bottle as you swallow: you should feel bottle squeeze in on itself as you swallow
• REMEMBER: many ppl complain of difficulty taking pills, and inappropriate admin, or lodged pills can cause ulceration of the esophagus

Question 17

How dhoulf pts take products that float?

Answer 17

• Put capsule on tongue
• Take medium sip of water, but don’t swallow yet
• Bend head forward by tilting chin slightly toward chest
• Swallow capsule and water with head bent forward