MEDS 301 - Pharmacotherapy of Gastrointestinal and Respiratory Disorders

Phases of digestion

1. Cephalic

2. Gastric

3. Intestinal

cephalic phase of digestion

Smell, sight, thought or initial taste of food stimulate the release of gastric juices before food even reaches the stomach

What cells are responsible for the release of gastric acid (HCL)

Parietal cells or oxyntic cells

these activate digestive enzyme pepsin so that food can actually be digested

Gastric phase of digestion

stomach distends due to the presence of chyme which triggers further release of gastric juices

Intestinal phase of digestion

the presence of acid and fat inhibit the release of HCL and pepsin as it could damage the GI tissue

Peptic uler 1

open sources which develop in the mucosal lining of the stomach and duodenum

typically caused by infection of (H. pylori)

thought to be acquired through contaminated water, unwashed food, or through saliva.

Could also be the result of long term NSAID use, hyperacidity, hyperchlorydria

Symptoms

- pain, nausea, vomiting, low appetite, heartburn

Treatment for managing GI disorders

1. Antibiotics for (H. pylori)

- typically a combination of two or more antibiotics and bismuth salts

2. Antiulcer therapy

- reduce gastric acidity

- enhance mucosal barrier

- involves the use of antisecretory drugs and antacids

Gastrointestinal Esophogeal Reflux Disease (GERD)

• Chronic disorder characterized by heartburn, condition is described as burning in chest or throat

Occurs due to regurgitation of digestive juices into the esophagus due to poor constriction of the lower esophageal sphincter

Lifestyle management for treating GI disorders

1. Quit smoking

2. Avoid caffeine and alcohol

3. lose weight (if overweight)

4. elevate head of the bed

Antisecretory drugs: Antihistamine (h2) antagonists

Histamine is a potent stimulator of gastric secretions. histamine is located in mast cells along the mucosa. drug binding prevents the secretion of acid or reduces the pH of acid being secreted.

treatment used in

- benign gastric ulcers

- duodenal ulcers

- GERD

Antisecretory drugs: Proton pump inhibitors (PPIs)

drugs which directly inhibit the release of HCL by inhibiting the ATPase exchange of H+ and K+ ions within parietal cells, which is necessary to form HCL

used to treat short term ulcers linked with H pylori

*drug class produces greater suppression of ulcer pain, faster healing than H2 receptor antagonists

Antisecretory drugs: Prostaglandins

prostaglandins are potent

inhibitors of histamine secretion and local vasodilators

that increase blood flow to injured cells and promote

healing. Drugs that inhibit prostaglandin synthesis,

such as NSAIDs, are known to induce gastric ulcers,

presumably by inhibition of the prostaglandin-mediated

secretions. Prostaglandins, therefore, are effective in

preventing NSAID-induced ulcers

prostaglandin receptors mediate the secretion of bicarbonate and mucus, promoting the protective barrier for the mucosa.

NSAIDs inhibit prostaglandin synthesis and can damage lining of the mucous

used to treat NSAID induced ulcers exclusively

administered orally

Antacids

neutralize the acids in the stomach

approved for the use in treating hyperacidity associated with peptic ulcers, heartburn, GERD.

act on HCL to form water and salt, increase the pH of the stomach

very short duration of action; 30 mins empty stomach

taken prior to meals

Barrier enhancers: Sucralfate

drug which forms a protective barrier over damaged regions of gastric mucosa to prevent further damage

Used in short term treatment for duodenal ulcers

Prokinetic drugs used to treat GERD: Metoclopramide

Drug induces contractions within upper GI to prevent reflux of acid into the esophagus and promote gastric emptying as well as contraction of lower esophageal sphincter to prevent reflux

used to treat mild heartburn and chemo induced vomiting

Management of emesis

emesis; vomiting

emesis in controlled through the: vomiting center (VC) and the chemoreceptor trigger zone (CTZ)

VC: pick ups information pertaining to balance and motion

CTZ: monitors for noxious chemicals in the blood

NT release in the VC and CTZ induces emesis

Antiemetics: serotonin antagonists (5-HT3)

Prevent the initiation of afferent signals to the CNS by blocking serotonin from reaching the CNS

also prevent serotonin from stimulating CTZ or VC

Antiemetics: Neurokinin-1 Receptor Antagonists (NK1)

drugs which bind to NK1-receptors and blocks the activity of substance P

No matter what the emetic stimulus is, substance P and its NK1-receptors are the final pathway that regulates vomiting.

Process of defecation

the movement of feces into the rectum increases rectal pressure. this region is under PNS control

internal anal sphincter relaxes and peristalsis moves feces into the anus

voluntary relaxation of the external sphincter permits defecation

diarrhea

symptom of increases intestinal activity.

acute: lasts less than 14 days

chronic: lasts longer than 30 days. can lead to electrolyte imbalances or dehydration due to excess water loss.

serious conditions may occur from this in children and the elderly or those in poor health

types of diarrhea

inflammatory/exudative

- induced by bacteria, virus, etc invading the GI tract

increased intestinal motility

- drug therapy can induce changes in motility, secretory, and osmosis within the GI

Treatment of simple diarrhea: absorbents

simple D. is usually linked with poor diet habits or stress.

treatment is often symptomatic, not curative as cause is often unknown.

absorbents act to remove irritants from GI by forming a complex with any potential irritants, carrying them into the feces.

used as a prophylactic

Treatment of simple diarrhea: anti-motility drugs

drugs which are used to treat D. by reducing peristalsis and constricting the sphincters

Causes of constipation

Poor dietary habits without sufficient fiber. fiber acts to increase water retention and do not produce sufficient distention to trigger defecation

Poor habits; ignoring the urge to defecate or voluntarily retaining can induce constipation

stress/anxiety; increases SNS activity and inhibits bowel movements

Treatment of simple diarrhea: anticholinergic drugs

act to inhibit postganglionic receptors of PNS nerves which control intestinal motility

constipation

Health care defines it by stool frequency of fewer than three bowel movements per week. Chronic constipation occurs when symptoms last more than 3 month

Laxatives and Cathartics

medications used to stimulate defecation

cathartics produce intense action on the bowel vs laxatives

both act directly on intestines to alter stool formation

respiratory disease is defined as:

any disease which interferes with gas exchange in the lungs, causing serious changes in the concentration of oxygen and c02 in the blood

COPD

chronic obstructive pulmonary disease

refers to a condition caused by emphysema and chronic bronchitis, both of which cause irreversible damage to the respiratory system

chronic bronchitis

inflammation of the bronchi persisting over a long time, caused by chronic irritation of the respiratory tract

induced by smoke, or environmental pollutants. results in a thickening of respiratory mucus secretions, interfering with gas exchange

symptoms:

- productive cough, difficulty breathing, restriction in physical activity, increased respiratory infection

Emphysema

a condition where alveoli become inflamed and destroyed.

protease enzymes which destroy alveoli are increased by pollutants, smoke, and irritants.

destruction causes enlargement of air spaces within the lungs and leads to hyperinflation

result is a difficult in expelling air from lungs, gas exchange is reduced, and SOB

Treatment for respiratory disease

respiratory exercises and breathing exercises

oxygen therapy

bronchodilators and anti-inflamatory agents

Asthma

inflammatory, respiratory condition characterized by bronchoconstriction, SOB, and wheezing

asthma is the result of hyper responsiveness to environmental factors such as allergens, pollutants, cold air, drugs, exercise, etc

chemical mediators during respiratory inflammatory reaction (4)

during inflammatory reaction, mediators are released from damaged cells

histamine

- induces bronchoconstriction and mucosal edema

ECF-A

- attracts eosinophils to site of irritant

Prostaglandins & leukotrienes

- induce bronchoconstriction, edema, and produce mucus

autonommic nervous system & bronchodilation

Bronchiolar smooth muscle tone and secretion of mucus are normally influenced by the sympathetic and parasympathetic divisions of the autonomic nervous system.

Parasympathetic

stimulation produces

bronchoconstriction and

increased mucus

secretion.

Sympathetic stimulation

produces bronchodilation.

Sympathomimetic drugs

decrease parasympathetic

activity.

Bronchodilator Drugs; beta adrenergic drugs

Nonselective beta-adrenergic drugs.

- stimulate both beta 1 and beta 2 receptors

- may induce tachycardia or arrhythmia

selective beta 2 drugs

- used as bronchodilators in chronic asthma and COPD

- prevent the release of mediators by mast cells

bronchodilator: Methlxanthines

promote bronchodilation by inhibiting phosphodiesterase, leading to increased cyclic AMP. cyclic AMP produces dilation and inhibits the release of mast cells from mediators

May induce Nausea and vomiting, flushing, vasodilation, and hypotension.

Bronchodilator Drugs: Anticholinergic drugs

act to promote bronchodilation by blocking action of ACh, lower production of respiratory secretions

PNS stimulation releases ACh which causes constriction and secretion.

first line of drugs used to treat COPD

anti-inflammatory Drugs: Corticosteroids

referred to as "controller" drugs because they reduce and control the inflammatory response

corticosteroid drugs are considered the most potent anti-inflammatory and antiallergic drugs available.

Corticosteroids inhibit the activity of inflammatory cells, the release of inflammatory mediators from mast cells, the production of allergic antibodies, edema, and many other anti-inflammatory actions

may induce Oral infections, hoarseness, and vocal cord disturbances.

Anti-Inflammatory Drugs: Leukotriene inhibitor

Prevent synthesis of leukotriene or block the leukotriene

receptor, which can cause constriction inflammation and mucus production in the bronchi

drug often used to treat chronic asthma

adverse effects: nausea, rash, headache

Antiallergic Agents: Cromolyn sodium:

prevents the release of mast cell mediators

Interleukin-5 Receptor Antagonists

reduce the production and

survival of eosinophils.

used to treat severe asthma with eosinophilic phenotype

Adverse effects include sore throat, myalgia, antibody

development and injection site reactions.

Mucolytics

agents that destroy or dissolve mucus, allowing for the removal of mucus by coughing or using suction

expectorants

liquefy respiratory secretions so that they are more easily dislodged during coughing episodes

allow for removal of thickened mucus from lungs

Allergies: role of histamine and mast cell degranulation

histamine is present within mast cells throughout the body

release of histamine from mast cells is the body's response to the presence of an allergen

repeat exposure to an allergen results in degranulation of mast cells

Antihistamines

prevent interaction between

histamines and histamine receptors.

Antiallergic

agents block the release of histamine

from mast cells.

histamine effect on blood vessels

temporary reduction in BP, hives When capillary leakage occurs in the skin

angioedema When the edema and swelling are beneath the skin rather than on the surface

histamine effect on cardiac

rapid heartbeat

histamine effects on extravascular smooth muscle

Intestinal disturbances.

Bronchoconstriction.

Antihistamine H1 Antagonists 1

Used to relieve the symptoms of allergic

reactions after histamine has already been

released

Block histamine from binding to the H1 receptors.

Categorized into first generation and second

generation.

available OTC

indications for Antihistamine H1 Antagonists

Itching.

• Local surface pain from insect bites.

• Urticaria.

• Hay fever.

• Rhinitis.

• Dermatitis.

• Motion sickness.

• Insomnia.

Mast cell stabilizers

drugs which block allergic reaction by preventing mast cells from releasing their contents.

drug acts by Blocking the H1 receptors.