pharmacology - git drugs

Pharmacology of the GIT system

2005

LECTURE Outline

• REVIEW the Anatomy of the GIT

• REVIEW the Physiology of the GIT

• Review common GI drugs in the following categories:– 1. Drugs affecting GI secretions– 2. Laxatives– 3. Anti-diarrheals– 4. Emetics and anti-emetics

Fig. 16.1

Fig. 16.10a

Fig. 16.10b

Fig. 16.11a

Fig. 16.11b

Fig. 16.12

Drugs affecting GI secretions

There are five types of drugs that affect gastric acid secretions and are useful for the treatment of peptic ulcer.

1. Histamine (H2) receptor antagonist/blockers

2. Antacids

3. Proton pump inhibitors

4. Mucosal protectants

5. Prostaglandin analogs

Drugs affecting secretions: anti ulcer

Anti-ulcer drugs Prototype

Histamine (H2) receptor antagonist/blockers

Cimetidine

Antacids AlOH and MgOH

Proton pump inhibitors Omeprazole

Mucosal protectants Sucralfate

Prostaglandin analog Misoprostol

General indication of the drugs affecting gastric acid secretion

• Peptic ulcer

• Gastritis

• Patient on NPO to prevent stress ulcer

General time of administration of the drugs affecting gastric acid secretion

Anti-ulcer drugs Prototype Best time to give

Histamine (H2) receptor antagonist/blockers

Cimetidine With FOOD or ONE

hour after ANTACID

Antacids AlOH and MgOH Usually after meals

Proton pump inhibitors

Omeprazole BEFORE MEALS

Mucosal protectants

Sucralfate BEFORE MEALS

Prostaglandin analog

Misoprostol WITH MEALS

Pharmacodynamics

Histamine (H2) receptor blockers

• These drugs BLOCK the release of hydrochloric acid in the stomach in response to gastrin

Drugs affecting GI secretions

Antacids

• These drugs interact with the gastric acids at the chemical level to neutralize them

Drugs affecting GI secretions

Proton pump inhibitors

• These drugs suppress the secretion of hydrochloric acid into the lumen of the stomach

Drugs affecting GI secretions

Mucosal protectants

• These are agents that coat any injured area in the stomach to prevent further injury from acid

Drugs affecting GI secretions

Prostaglandin analogs

• These are agents that inhibit the secretion of gastrin and

• increase the secretion of mucus lining of the stomach, providing a buffer.

The H2 Blockers- “tidines”

Prototype: Cimetidine

• 1. Ranitidine

• 2. Famotidine

• 3. Nizatidine

The H2 Blockers- “tidines”

Pharmacodynamics: Drug Action• The H2 blockers are antagonists at the

receptors in the parietal cells of the stomach.

• The blockage results to inhibition of the hormone gastrin.

• There will be decreased production of gastric acid from the parietal cells.

• Also, the chief cells will secrete less pepsinogen.

The H2 Blockers- “tidines”Therapeutic use of the H2 blockers• Short-term treatment of active duodenal

ulcer or benign gastric ulcer• Treatment of hypersecretory conditions like

the Zollinger-Ellison syndrome• Prevention of stress-induced ulcers and

acute GI bleeding• Treatment of erosive GERD (reflux disease)• Relief of Symptoms of heart burn and acid

indigestion

The H2 Blockers- “tidines”

Precautions and Contraindications• Any known allergy is a clear

contraindication to the use of the agents. • Conditions such as pregnancy, lactation,

renal dysfunction and hepatic dysfunction should warrant cautious use.

• Nizatidine can be used in hepatic dysfunction.

The H2 Blockers- “tidines”

Dynamics- Side effects/adverse effects

• GIT= diarrhea or constipation

• CNS= Dizziness, headache, drowsiness, confusion and hallucinations

• Cardio= arrhythmias, HYPOTENSION (related to H2 receptor blockage in the heart)

• Cimetidine= Gynecomastia and impotence in males

The H2 Blockers- “tidines”

Drug-drug Interactions• Cimetidine, Famotidine, Ranitidine

are metabolized in the liver- they can cause slowing of excretion of other drugs leading to their increased concentration.

The H2 Blockers- “tidines”

Drug-drug Interactions

These drugs can interact with CIMETIDINE

• Anticoagulants

• Phenytoin,

• Alcohol

• Antidepressants.

The H2 Blockers- “tidines”Nursing considerations:• Administer the drug WITH meals at

BEDTIME to ensure therapeutic level• One hour after Antacids• Stress the importance of the

continued use for the length of time prescribed

The H2 Blockers- “tidines”Nursing considerations• Monitor the cardiovascular status

especially if the drugs are given IV• Warn patient of the potential problems

of increased drug concentration if the H2 blockers are used with other drugs or OTC drugs. Advise consultation first!

The H2 Blockers- “tidines”

Nursing considerations:

• Provide comfort measures like analgesics for headache, assistance with ambulation and safety measures because of confusion

• Warn the patients taking cimetidine that drowsiness may pose a hazard if driving or operating delicate machines.

The H2 Blockers- “tidines”

Nursing considerations:

• Provide health teaching as to the dose, frequency, comfort measures to initiate when side-effects are intolerable

Evaluate the effectiveness

• Relief of symptoms of ulcer, heart burn and GERD

The Antacids

These are drugs or inorganic chemicals that have been used for years to neutralize acid in the stomach

The Antacids

The following are the common antacids that can be bought OTC:

• Aluminum salts (hydroxide)

• Calcium salts (carbonate)

• Magnesium salts (milk of magnesia)

• Sodium bicarbonate

• Magaldrate (aluminum and magnesium combination)

The Antacids

Pharmacodynamics: drug action

• These agents act to neutralize the acidic pH in the stomach.

• They do not affect the rate of gastric acid secretion.

The Antacids

Pharmacodynamics: drug action

• The administration of antacid may cause an acid rebound.

• Neutralizing the stomach content to an alkaline level stimulates gastrin production to cause an increase in acid production and return the stomach to its normal acidic state.

The Antacids

Therapeutic Indications

• Symptomatic relief of upset stomach associated with hyperacidity

• Hyperacidic conditions like peptic ulcer, gastritis, esophagitis and hiatal hernia

• Special use of AMPHOGEL (aluminum hydroxide): to BIND phosphate

The Antacids

Precautions of Antacid Use• Known allergy is a clear

contraindication• Caution should be instituted if used in

electrolyte imbalances, GI obstruction and renal dysfunction.

• Sodium bicarbonate is rarely used because of potential systemic absorption metabolic alkalosis!!!

The Antacids

Pharmacokinetics

• These agents are taken orally and act locally in the stomach

The AntacidsPharmacodynamics: Effects of drugs1. GIT= rebound acidity; alkalosis may

occur.• Calcium salts may lead to hypercalcemia • Magnesium salts can cause DIARRHEA• Aluminum salts may cause

CONSTIPATION and Hypophosphatemia by binding with phosphates in the GIT.

2. Fluid retention due to the high sodium content of the antacids.

The AntacidsNursing Considerations:• Administer the antacids apart from any

other medications by ONE hour before or TWO hours after- to ensure adequate absorption of the other medications

• Tell the patient to CHEW the tablet thoroughly before swallowing. Follow it with one glass of water

• Regularly monitor for manifestations of acid-base imbalances as well as electrolyte imbalances

The Antacids

Nursing Considerations:• Provide comfort measures to alleviate

constipation associated with aluminum and diarrhea associated with magnesium salts.

• Monitor for the side-effects, effectiveness of the comfort measures, patient’s response to the medication and the effectiveness of the health teachings

The Antacids

Nursing Considerations

Evaluate for effectiveness:

Decreased symptoms of ulcer and pyrosis

Decreased Phosphate level (Amphogel) in patients with chronic renal failure

The PPI

These are the newer agents for ulcer treatment

• The “prazoles”

Prototype: Omeprazole

• Lanisoprazole

• Esomeprazole

• Pantoprazole

The PPIPharmacodynamics: drug action

• They act at specific secretory surface receptors to prevent the final step of acid production and thus decrease the level of acid in the stomach.

• The “pump” in the parietal cell is the H-K ATPase enzyme system on the secretory surface of the gastric parietal cells

The PPIClinical use of the PPIs

• Short-term treatment of active duodenal ulcers, GERD, erosive esophagitis and benign gastric ulcer

• Long-term- maintenance therapy for healing of erosive disorders.

The PPIPrecautions with the use of the PPIs

• Known allergy is a clear contraindication

• Caution if patient is pregnant

The PPIPharmacodynamics: Adverse effects

• CNS- dizziness, headache, asthenia (loss of strength), vertigo, insomnia, apathy

• GIT- diarrhea, abdominal pain, nausea, vomiting, dry mouth and tongue atrophy

• Respi- cough, stuffy nose, hoarseness and epistaxis.

The PPI

Nursing considerations:• Administer the drug BEFORE meals.

Ensure that patient does not open, chew or crush the drug.

• Provide safety measures if CNS dysfunction happens.

• Arrange for a medical follow-up if symptoms are NOT resolved after 4-8 weeks of therapy.

The PPI

Nursing considerations:

• Provide health teaching as to drug name, dosages and frequency, safety measures to handle common problems.

• Monitor patient response to the drug, the effectiveness of the teaching plan and the measures to employ

The PPI

Nursing considerations:

Evaluate for effectiveness of the drug

• Healing of peptic ulcer

• Decreased symptoms of ulcer

The Mucosal Protectant

Sucralfate (Caralfate/ Iselpin)

• This is given to protect the eroded ulcer sites in the GIT from further damage by acid and digestive enzymes

Sucralfate

Pharmacodynamics: Action of drug

• It forms an ulcer-adherent complex at duodenal ulcer sites, protecting the sites against acid, pepsin and bile.

• This action prevents further breakdown of proteins in the area and promotes healing.

Sucralfate

Clinical use of sucralfate

• Short and long term management of duodenal ulcer.

• NSAIDs induced gastritis

• Prevention of stress ulcer

• Treatment of oral and esophageal ulcers due to radiation, chemotherapy or sclerotherapy.

Sucralfate

Precautions on the use of Sucralfate

• This agent should NOT be given to any person with known allergy to the drug, and to those patients with renal failure/dialysis because of build-up of aluminum may occur if used with aluminum containing products.

The Mucosal Protectant

Pharmacodynamics: Side-effects & adverse reactions

• Primarily GIT= CONSTIPATION, occasionally diarrhea, nausea, indigestion, gastric discomfort, and dry mouth may also occur

• CNS= dizziness, drowsiness, vertigo

• Others= rash and back pain

The Mucosal Protectant

Drug-drug interactions

• If used with aluminum salts= high risk of accumulation of aluminum and toxicity.

• If used with phenytoin, fluoroquinolones and penicillamines- decreased levels of these drugs when taken with sucralfate

The Mucosal Protectant

Nursing Considerations• Administer drug ON AN EMPTY stomach, 1

hour before meals , or 2 hour after meals and at BEDTIME

• Monitor for side-effects like constipation and GI upset

• Encourage intake of high-fiber foods and increased fluid intake

• Administer antacids BETWEEN doses of sucralfate, NOT WITHIN 30 minutes of sucralfate dose

The Mucosal Protectant

Nursing Considerations• Provide comfort measures if CNS

effects occur• Provide health teaching as to drug

name, dosages and frequency, safety measures to handle common problems.

• Monitor patient response to the drug, the effectiveness of the teaching plan and the measures employed

The Mucosal Protectant

Nursing Considerations

• Evaluate effectiveness of therapy

Healing of ulcer

No formation of ulcer

Prostaglandin analogue

Misoprostol

• This agent is a synthetic prostaglandin E1 analog that is employed to protect the lining of the mucosa of the stomach

Prostaglandin analogue

Misoprostol: Pharmacodynamics

• Being a prostaglandin analog, it inhibits gastric acid secretion to some degree

• It INCREASES mucus production in the stomach lining.

Prostaglandin analogue

Misoprostol: Clinical use

• NSAIDs-induced gastric ulcers

• Duodenal ulcers unresponsive to H2 antagonists

Prostaglandin analogue

Precautions of Misoprostol Use• This drug is CONTRAINDICATED during

pregnancy because it is an abortifacient.• Women should be advised to have a negative negative

pregnancy test within 2 weeks of beginning pregnancy test within 2 weeks of beginning therapy and should begin the drug on the therapy and should begin the drug on the second or third day of the next menstrual second or third day of the next menstrual cycle.cycle.

• They should be instructed in the use of contraceptives during therapy.

Prostaglandin analogue

Pharmacodynamic effects: drug reactions

• GIT= Nausea, diarrhea, abdominal pain, flatulence, vomiting, dyspepsia

• GU effects= miscarriages, excessive uterine CRAMPING and bleeding, spotting, hyper-menorrhea and menstrual disorders.

Prostaglandin analogueNursing Considerations• Administer to patients at risk for NSAIDs-induced

ulcers during the full course of NSAIDs therapy• Administer four times daily with meals and at

bedtime• Obtain pregnancy test within 2 weeks of

beginning therapy. • Begin the therapy on second or third day of

menstrual period to ensure that the woman is not pregnant

Prostaglandin analogue

Nursing Considerations• Provide patient with both written and oral

information regarding the associated risks of pregnancy

• Provide health teaching as to drug name, dosages and frequency, safety measures to handle common problems.

• Monitor patient response to the drug, the effectiveness of the teaching plan and the measures to employ

Laxatives

• Generally used to INCREASE the passage of the colonic contents

• The general classifications is as follows:

1. Chemical stimulants- irritants

2. Mechanical stimulants- hyperosmotic agents and saline cathartics

3. Lubricants and stool softeners

Laxatives

• They promote bowel evacuation for various purposes

• They are classified into their mode of action

Laxatives

Type Prototype Action

Chemical stimulants

Bisacodyl (Dulcolax)

Direct stimulation of the GIT nerves

Irritant laxatives

Mechanical (bulk) stimulants

Lactulose Increased fluid content of the fecal material causing stimulation of the local reflex

Lubricants Docusate

Mineral oil

Lubricating the intestinal material to promote passage through the GIT

Therapeutic Indications of the Laxatives

• SHORT term relief of ConstipationConstipation

• Prevention of strainingPrevention of straining in conditions like CHF, post-MI, post partum, post-op

• Preparation for diagnostic examinationdiagnostic examination

• Removal of poison or toxins

• Adjunct in anti-helminthic therapy

• To remove AMMONIA by use of lactulose

Contraindications in Laxative use

• ACUTE abdominal disorders

–AppendicitisAppendicitis

–DiverticulitisDiverticulitis

–Ulcerative colitisUlcerative colitis

Chemical Stimulant Cathartics

Prototype: Bisacodyl

Irritant laxatives:

• 1. Castor oil

• 2. Senna

• 3. Cascara

• 4. Phenolphthalein

Chemical Stimulant Cathartics

Pharmacodynamics

• These agents DIRECTLY stimulate the nerve plexus in the intestinal wall

• The result is INCREASED movement or motility of the colon

Mechanical Stimulant Cathartics

Prototype: LACTULOSE (Cephulac)

Bulk-forming laxatives

• 1. Magnesium (citrate, hydroxide, sulfate)- saline cathatic

• 2. Psyllium

• 3. Polycarbophil

Mechanical Stimulant Cathartics

Pharmacodynamics

• These agents are rapid-acting laxatives that INCREASE the GI motility by– Increasing the fluids in the colonic

material– Stimulating the local stretch receptors– Activating local defection reflex

Lubricants-Stool softener

Prototype: Docusate

• 1. Glycerin

• 2. Mineral oil

Lubricants-stool softeners

Pharmacodynamics

• Docusate increases the admixture of fat and water producing a softer stool

• Glycerin and Mineral oil form a slippery coat on the colonic contents

Pharmacokinetics: Common Side-effects of the Laxatives

• Diarrhea

• Abdominal cramping

• Nausea

• Fluid and electrolyte imbalance

• Sympathetic reactions- sweating, palpitations, flushing and fainting

• CATHARTIC dependence

The Nursing Process and Laxative

ASSESSMENT

• Nursing History- elicit allergy to any laxatives, elicit history of conditions like diverticulitis and ulcerative colitis

• Physical Examination- abdominal assessment

• Laboratory Test: fecalysis, electrolyte levels

The Nursing Process and Laxative

NURSING DIAGNOSIS

• Alteration in bowel pattern

• Alteration in comfort: pain

• Knowledge deficit

The Nursing Process and Laxative

IMPLEMENTATION

1. Emphasize that it is use on a SHORT term basis

2. Provide comfort and safety measures like ready access to the bathroom, side-rails

3. Administer with a full glass of water

The Nursing Process and Laxative

IMPLEMENTATION

4. Encourage fluid intake, high fiber diet and daily exercise

5. DO NOT administer if acute abdominal condition like appendicitis is present

6. Advise to change position slowly and avoid hazardous activities because of potential dizziness

The Nursing Process and Laxative

IMPLEMENTATION7. Record intake and output to assess

fluid alteration8. If possible, observe the character of

stools9. Caution the patient that chronic use

may promote dependence and use during pregnancy may cause uterine cramping and Vitamin deficiency

The Nursing Process and Laxative

EVALUATION of drug effectiveness

1. Evaluate relief of GI symptoms, absence of staining and increased evacuation of GI tract

2. For Lactulose: decreased ammonia

3. Nomal bowel fucntion is restored

The Anti-diarrheals

• These are agents used to calm the irritation of the GIT for the symptomatic relief of diarrhea

• General Classifications

1. Local anti-motility

2. Local reflex inhibition

3. Central action on the CNS

The Anti-diarrhealsType Prototype Action

Local reflex inhibitor

Bismuth subsalicylate

Locally coats the lining of the GIT to soothe irritation

Local anti-motility

Loperamide Directly inhibits the intestinal muscle activity to SLOW peristalsis

Central acting agent

Opium derivatives (paregoric)

Stops GIT spasm by CNS action

Clinical Indications of drug use

• Relief of symptoms of acute and chronic diarrhea

• Reduction of fecal volume discharges from ileostomies

• Prevention and treatment of traveler's diarrhea

Contraindications of anti-diarrheal Use

• Poisoning

• Drug allergy

• GI obstruction

• Acute abdominal conditions

Pharmacokinetics: Side effects

• Constipation

• Nausea, vomiting

• Abdominal distention and discomfort

• TOXIC MEGACOLON

Nursing process and anti-diarrheals

ASSESSMENT

• Nursing History – Elicit history of drug allergy, conditions like poisoning, GI obstruction and acute abdominal conditions

• Physical Examination- Abdominal examination

• Laboratory test- electrolyte levels

Nursing process and anti-diarrheals

NURSING DIAGNOSIS

• Alteration in bowel pattern

• Alteration in comfort: pain

Nursing process and anti-diarrheals

IMPLEMENTATION

1. Monitor patient response within 48 hours. Discontinue drug use if no effect

2. Provide comfort measures for pain

3. Provide teaching regarding its short term use only

Nursing process and anti-diarrheals

EVALUATION

1. Monitor effectiveness of drug- RELIEF of diarrhea

2. Monitor adverse effects, effectiveness of pain measures and effectiveness of teaching plan

Emetics and Anti-emetics

Emetic Agent• Syrup of Ipecac

Anti-emetics• 1. Phenothiazines• 2. Non-phenothiazines• 3. Anticholinergics/Antihistamines• 4. Serotonin receptor Blockers• 5. Miscellaneous

EMETIC

• Prototype: Ipecac Syrup

EMETIC

Pharmacodynamics

• Ipecac syrup irritates the GI mucosa locally, resulting to stimulation of the vomiting center

• It acts within 20 minutes

EMETIC

Clinical Use of ipecac

• To induce vomiting as a treatment for drug overdose and certain poisonings

EMETIC

Contraindications of Ipecac use

• Ingestion of CORROSIVE chemicals

• Ingestion of petroleum products

• Unconscious and convulsing patient

EMETIC

Pharmacokinetics: side effects of Ipecac

• Nausea

• Diarrhea

• GI upset

• Mild CNS depression

• CARDIOTOXICITY if large amounts are absorbed in the body

Nursing process and the EMETIC

ASSESSMENT

• Nursing History- elicit the exact nature of poisoning

• Physical Examination- CNS status and abdominal exam

Nursing process and the EMETIC

IMPLEMENTATION1. Administer to conscious patient only2. Administer ipecac as soon as

possible3. Administer with a large amount of

water4. Vomiting should occur within 20

minutes of the first dose. Repeat the dose and expect vomiting to occur with 20 minutes

Nursing process and the EMETIC

IMPLEMENTATION

5. Provide comfort measures like ready access to bathroom, assistance with ambulation

6. Offer support

Nursing process and the EMETIC

EVALUATION

1. Evaluate patient response within 20 minutes of drug ingestion

2. Monitor for adverse effects

3. Evaluate effectiveness of comfort measures and teaching plan

ANTI-EMETICS

• These are agents used to manage nausea and vomiting

• They act either locally or centrally• In general, they may inhibit the

chemoreceptor trigger zone in the medulla by blocking DOPAMINE receptor

• Others act by decreasing the sensitivity of the vestibular apparatus

ANTIEMETICS

Anti-emetic types Common examples

Phenothiazines Prochlorperazine, Promethazine

Non-phenothiazines Metoclopramide

Anticholinergics and Antihistaminics

Meclizine, buclizine

Serotonin Receptor blockers

“setron”- dolasetron

Miscellaneous Dronabinol, hydroxyzine

ANTIEMETICSTypes Pharmacodynamics

Phenothiazines Centrally block the vomiting center in the medulla

Non-phenothiazine Reduces the responsiveness of the nerve cell in the medulla; also blocks the dopamine receptors

Anticholinergics Block the transmission of the impulses to the medulla

Serotonin receptor blockers

Centrally and locally inhibits the serotonin receptors

Miscellaneous Act in the CNS , either in the medulla or in the cortex

ANTIEMETICSTypes Clinical Use

Phenothiazines N/V associated with anesthesia, intractable hiccups

Non-phenothiazine N/V associated with chemical stimulation

Anticholinergics N/V associated with motion sickness

Serotonin-receptor Blockers

N/V associated with chemotherapy

Miscellaneous N/V associated with chemotherapy

ANTIEMETICS

Indications

• 1. Prevention and treatment of vomiting

• 2. Motion sickness

ANTIEMETICS

Contraindications

• 1. Severe CNS depression

• 2. Severe liver dysfunction

ANTIEMETICS

Pharmacokinetics:

• Oral absorption is good if vomiting is not present

• IV drugs can be given if vomiting is active

• Most drugs are metabolized in the liver excreted in the kidneys

ANTIEMETICS

Pharmacokinetics: Side-effects1. PHOTHOSENSITIVITY2. Drowsiness, dizziness, weakness and

tremors and DEHYDRATON3. Phenothiazines= autonomic anti-

cholinergic effects like dry mouth, nasal congestion and urinary retention

Metoclopramide= EPS due to dopamine receptor blockage

Nursing Process and the ANTIEMETICS

ASSESSMENT

• Nursing History- elicit allergy, impaired hepatic function and CNS depression

• Physical Examination- CNS status and abdominal examination

• Laboratory test- Liver function studies

Nursing Process and the ANTIEMETICS

NURSING DIAGNOSIS

1. Alteration in comfort: pain

2. High risk for injury

3. Knowledge deficit

Nursing Process and the ANTIEMETICS

IMPLEMENTATION

1. Assess patient’s intake of other drugs that may cause dangerous drug interaction

2. Emphasize that this is given on a short term basis

Nursing Process and the ANTIEMETICS

IMPLEMENTATION

3. Provide comfort and safety measures– Advise to change position slowly– Avoid hazardous activities– Provide mouth care and ice chips– Monitor for dehydration and offer fluids if

it occurs

Nursing Process and the ANTIEMETICS

IMPLEMENTATION

4. Protect from sun exposure– Sunscreens – Protective covering

5. Provide health teaching

Nursing Process and the ANTIEMETICS

EVALUATION

1. Monitor for the drug effectiveness• Relief of nausea and vomiting

2. Monitor for adverse effects

3. Evaluate effectiveness of comfort measures and teaching plan