Antihistamines

1. Antihistamines Chapter 69

2. Outcomes • Identify concepts related to medication classifications and application to manage allergic reactions, conditions of the upper respiratory system, acid indigestion and gastric reflux. • Choose nursing interventions related to the applied pharmacokinetics and pharmacodyanmics specific to these medications • Implement the nursing process in the administration of medication classes covered herein

3. Background • Histamines – (Predominantly H1) • Endogenous • Vessel effects • Bronchi effects • Stomach effects • Secretes Mucus • Greatest interest • Allergic reactions (mild / anaphylaxis) • PUD (Peptic Ulcer Disease)

4. Histamine Release • Allergic response • Requires IgE antibodies • Prior exposure to allergen • Non-allergic – direct stimulation of cells • Some drugs, chemicals, radiocontrast media, plasma expanders - require no prior exposure • Cell injury (histamines can cause)

5. Physio / Pharm Effects • H1 Stimulation • Vasodilation (If this, then?) BP drops, nose gets stuffy, edema, puffy eyes, etc. • Vessel wall cells contract (If this, then?) • Bronchoconstriction (If this, then?) Trouble breathing • Itching & pain • Mucus secretion • CNS effect – cognition / memory / sleep • H2 Stimulation • Secretion of gastric acid (If this, then?)

6. Allergies & Pharmacology • Mild Allergy • Hay fever, urticaria, mild transfusion rx. • Sxms caused by? histamines • TX? • Severe • Anaphylactic shock (bronchocontriction, hypotension, & edema of glottis) • Sxms caused by? leukotrienes • TX? (ch 17) Epi • Other Uses • Common cold – runny nose

7. Antihistamines: 1st Generation • H1 Antagonists (classic antihistamines) • No single prototype • dyphenhydramine [Benadryl] • Highly sedating • MOA • Blockers (1st Gen) • Selectively bind to histaminic receptors • Can also bind to nonhistaminic receptor (muscarinic)

8. Therapeutic Effects (TE) • Vessels (If blocks histamine, then ?) • Capillaries (If blocks, then ?) • Sensory nerves (If, then) – itching relief • Mucous membranes (If, then) • CNS • Therapeutic doses (If, then) - sedation • Overdose – stimulation, seizures – esp. in young • Other: relieve N & V, motion sickness

9. Clinical uses • Mild allergies, seasonal rhinitis, acute urticaria, allergic conjunctivitis, mild transfusion reactions • Some block muscarinic & H1 receptor sites – useful for motion sickness • promethazine [Phenergan] and dimenhydrinate [Dramamine] • Insomnia (diphenhydramine [Benadryl])

10. Adverse Effects • CNS • Sedation = to excess ETOH (If this, then?) • Dizziness, lack of coordination, confusion • Paradoxical: insomnia, excitation, tremors, convulsions • GI • N, V, Diarrhea / constipation, loss of appetite

11. Anticholinergic effects • Dry mouth, throat, nasal passages, thickened secretions, (cautions?) urinary hesitancy, constipation, palpitations • Cardiac Dysrhythmias w some 2nd Gen. • Torsades de pointes, V-fib • terfenadine [Seldane] & astemizole [Hismanal] • Contraindications – third trimester • Precautions: asthma, children/elderly, urinary retention, HTN, OA glaucoma, prostatic hypertrophy

12. D  D • ETOH, barbs/benzos/ opioids, antidepressants • Toxicity • Sxms similar to atropine poisoning (anticholinergic), hyperpyrexia (super fever, can kill children) • Can lead to death in children via excitation, hallucinations, convulsion, coma, CV collapse, death. • Tx: remove and support – may use charcoal followed with cathartics

13. Antihistamines: 2nd Generation • Prototypes - Fexofenadine [Allegra] - EXPENSIVE • MOA / TE – antagonists of histamine to relieve sxms of allergic rhinitis and urticarias • ADME - Do not readily cross B-B barrier therefore non-sedating w minimized anticholinergic SEs • Precautions – ETOH, drowsiness, liver, kidneys

14. Drugs for Treating Allergic Rhinitis, Coughs, Colds Ch 75

15. Allergic Rhinitis • Review of sxms • Commonly associated disorders • Seasonal vs. Perennial

16. Antihistamines • First line - oral • Prophylaxis first • No use against cold • Adverse effects • 1st gen - sedation, anticholinergic • 2nd gen - rare

17. Intranasal Glucocorticoids • Prototype: fluticasone (Flonase) • Action / Use • Predominantly local anti-inflammatory • First line - Most effective against all sxms • Adverse Effects • Drying, burning, or itching (when applied topically) • Rare - sore throat, epistaxis and HA • Rare - systemic – adrenal suppression / slowed growth in children • Dose: Adults – 2 sprays of 50 mcg. once daily

18. Intranasal Cromolyn • Prototype: cromolyn (NasalCrom) • Action / Use • Suppresses release of histamine • Best suited for prophylaxis • May not see results for week or more • Adverse effects • Negligible

19. Sympathomimetics (fight or flight) (Decongestants) • Prototype: phenylephrine (Neo-Synephrine) • Action / Uses - Reduce nasal congestion via ? • Topical - rapid and intense • Oral - prolonged, moderate, systemic effects • Also used in sinusitis and colds • Adverse effects • Rebound congestion • CNS stimulation • Cardiovascular • Hemorrhagic stroke w phenylporpanolamine • Abuse (pseudoephedrine and ephedrine)

20. Sympathamometics (cont’d) • Nasal sprays • 2 – 3 sprays every 4 hours needed – not to exceed 5 consecutive days (to reduce dependence) • What cocaine is

21. Anticholinergics • Prototype: ipratropium bromide (Atrovent) • Action / Use • Blocks cholinergic receptors and inhibits secretions to relieve rhinorrea in allergic rhinitis and asthma • No systemic effects • SEs: drying, irritation • Dry mouth, throat, etc.

22. Leukotriene Antagonist • Prototype: montelukast (Singulair) • Action / Uses; • Blocks binding of leukotrienes to receptors thereby relieving nasal congestion • Leukotrienes normally vasodilate and increase vascular permeability, causing congestion • Adverse Effects: None significant • Table 75-1 in book

23. Treatment of Coughs

24. Antitussives • Antitussives (cough suppressants) • Actions / use: elevate cough threshold in common cold and URTI • Opioid (codeine and hydrocodone) – best (stops cough in the brain) • Dosage: codeine 10 to 20 mg up to 6 times daily • Nonopioid (dextromethorphan) - best • Opioid derivative w/o euphoria or dependence • Can lead to mind-body dissociation equal to PCP

25. Expectorants • Prototype - guaifenesin (Mucinex) • MOA / Use – increases flow of respiratory tract secretions • Don’t use for COPD or something else… read the friggin book

26. Mucolytics • Prototype – acetylcysteine (Mucomyst) • Can also use hypertonic saline • MOA / Use – directly thins secretions • ADME • Inhalation delivery • Adverse effects • Can trigger bronchospasm • Antidote for tylenol!

27. Colds • Drug regimen • Symptomatic • Combination products • Decongestants • Antitussives • Analgesics • Antihistamines - anticholinergic to suppress mucus • Caffeine

28. Treatment of Severe Allergy Chapter 17

29. Adrenergic Agonist • Prototype - epinephrine • MOA/Use • Direct receptor binding ( 1&2, 1&2) mimicing the sympathetic nervous system • Also known as sympathomimetic & catecholamine (think of these to mean stimulation) • ADME • Broken down quickly in stomach & significant 1st pass effect (can’t take it PO) • Can’t cross blood-brain • Discolors (pink/brownish) as it degrades (If, then?) (Throw it away!)

30. TEs (Therapeutic Effects) • Vasoconstriction (most common use) • Hemostasis • Augments local anesthetic via vascontriction • Elevates blood pressure • Restores beating heart • Bronchodilates • TOC for anaphylactic shock • Mydriasis (rare use) • Adverse effects: • HTN, necrosis, bradycardia w HTN, tachycardia, tremor, chest pain, elevated blood sugar

31. Table 17-3 • D  D • MAOIs • TCAs • General anesthestics (myocardial effects) • Precautions • IV admin can cause potentially fatal effect – check concentrations! • Insure patent and healthy IV site (you don’t want epi going into the tissues The range can be from 1:100,000 to 1:1,000… make sure to read the label!!!!

32. EpiPen • Anaphylactic deaths • PCN, venoms & foods • Device: EpiPen & EpiPen Jr. • Storage & Replacement • Room temp – dark – do NOT refrigerate • Injection • Duration 10-20 mins • SEs

33. Selected Drugs for Peptic Ulcer Disease (PUD) Chapter 76

34. Histamine2-Receptor Antagonists • Prototype: cimetadine (Tagamet) • First choice for gastric / duodenal ulcers • Action / Uses: • Promote healing through acid reduction • GERD, Aspiration Pneumonitis (aspiration of acid in the lungs) in obese & gyne prior to anesthesia • Adverse effects • Low incidence of gynecomastia (breasts devlpmnt in men), reduced libido, impotence, CNS depression / excitement, pneumonia • D  D • Inhibits hepatic drug metabolism – therefore? • Major Drugs of concern – warfarin, phenytoin, theophylline, lidocaine

35. Famotidine (Pepsid) • For Heartburn, acid indigestion, sour stomach • Cut dose in renal compromise/failure • No antiandrogenic effects • No effect on hepatic metabolism of other drugs • Doesn’t cause a lot of the things that Tagamet does

36. Proton Pump Inhibitors • Prototype - omeprazole (Prilosec) • Action / Uses – suppress secretion of gastric acid • Irreversible - days - up to weeks after cessation • Superior to H2RAs • Adverse effects • HA, diarrhea, N & V • Long term may increase risk of CA • ADME – give 30 min before meal – once daily • DD, DF • Reduced absorption of atazanavir, ketocanazole and itracanazole – NOT recommended concurrently with atazanavir

37. Antacids • Prototypes - magnesium hydroxide / aluminum hydroxide • Action / Uses – alkaline agents that neutralize acid & decrease destruction of gut wall • And prophylactically to prevent aspiration pneumonia • ADME • Take regularly to promote healing • In PUD: 1 and 3 hr after each meal & at bedtime • Goal is gastric pH greater than 5

38. Adverse effects • Constipation (aluminum base) / Diarrhea (magnesium base) • Sodium “loading” • High levels in renal failure clients • DD – may interfere with absorption of other drugs