Clinical Considerations in Urinary Retention

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Questions and Answers

What is one consequence of increased tone of the urinary sphincter?

Increased urinary frequency

Enhanced urine flow

Urinary retention (correct)

Decreased bladder capacity

What commonly occurs in relation to urinary retention postoperatively?

Frequent urination

Spontaneous resolution without intervention

Increased risk of urinary infections (correct)

Decreased muscle tone of the sphincter

Which smooth muscle's tone is primarily affected leading to urinary retention?

Bladder detrusor muscle

Ureter muscle

Renal pelvis muscle

Urinary sphincter (correct)

What is the primary issue associated with urinary retention in a clinical setting?

Increased pressure in the bladder Signup and view all the answers

Which of the following statements is true regarding postoperative urinary retention?

It is frequently encountered after surgery. Signup and view all the answers

Why are repeated subcutaneous injections of morphine avoided in patients who are in shock?

They may lead to improved absorption after shock reversal. Signup and view all the answers

In the context of shock, what is the potential risk associated with the use of morphine via subcutaneous injection?

Increased risk of overdose due to enhanced absorption. Signup and view all the answers

What is the recommended route for administering morphine in patients experiencing shock?

Intravenous. Signup and view all the answers

What is a key reason why subcutaneous morphine is not recommended in shocked patients?

Its absorption can significantly increase after shock has been resolved. Signup and view all the answers

Which factor contributes to the recommendation against using subcutaneous morphine during shock?

The altered physiological state can change drug absorption. Signup and view all the answers

What is currently preferred for treating severe diarrhea instead of crude opium?

Meperidine analogues Signup and view all the answers

Which of the following is a non-addicting meperidine analogue used for severe diarrhea?

Loperamide Signup and view all the answers

Which statement is true regarding the treatment of severe diarrhea?

Meperidine analogues include drugs like Loperamide. Signup and view all the answers

What distinguishes Loperamide from crude opium in the context of diarrhea treatment?

Loperamide is a meperidine analogue. Signup and view all the answers

Why are non-addicting meperidine analogues preferred for severe diarrhea treatment?

They are non-addictive. Signup and view all the answers

What is the primary reinforcement factor associated with the patient's drug use?

Euphoria Signup and view all the answers

Which of the following sensations is commonly reported by addicts during drug use?

Warm flushing skin Signup and view all the answers

What term is used to describe the intense sensation in the lower abdomen that addicts may experience?

Rush Signup and view all the answers

What emotional state serves as a significant factor in reinforcing the drug's use?

Euphoria Signup and view all the answers

How might an addict describe the sensation experienced during drug use in the lower abdomen?

Similar to sexual orgasm Signup and view all the answers

What is true about the development of tolerance and physical dependence?

They develop slowly over time. Signup and view all the answers

How do withdrawal symptoms compare to those from morphine?

Withdrawal symptoms are milder than those from morphine. Signup and view all the answers

What can be said about the sedative effects compared to morphine?

Sedative effects are less intense than morphine. Signup and view all the answers

Which statement accurately describes the relationship between tolerance and dependence?

Tolerance and dependence develop slowly over time. Signup and view all the answers

Which statement is true regarding the severity of withdrawal symptoms in relation to morphine?

They are less intense compared to morphine withdrawal symptoms. Signup and view all the answers

How does naltrexone differ from naloxone in terms of administration?

It is used only orally. Signup and view all the answers

What is the duration of action for naltrexone?

24 hours Signup and view all the answers

In comparison to naloxone, how is naltrexone characterized in terms of potency?

It is more potent. Signup and view all the answers

Which of the following statements is true regarding naltrexone's administration route?

Its primary route of administration is oral. Signup and view all the answers

What advantage does naltrexone have over naloxone regarding treatment duration?

Longer duration of action. Signup and view all the answers

Study Notes

Opioid Analgesics

Opioid analgesics are commonly used pain killers.
Other pain killers include NSAIDs and local anesthetics, as well as some antiepileptics and antidepressants.
Opiates are agents derived from opium poppy, which include natural alkaloids (e.g., morphine, codeine) and semisynthetic derivatives (e.g., heroin).
Opioids include any substance with morphine-like actions, and their effects are blocked by antagonists such as naloxone.
Opioid analgesics relieve pain but can cause drowsiness, mood changes, and mental clouding.
Opiopeptides are naturally occurring ligands that act on opioid receptors. Examples are endorphins, dynorphins, and enkephalins.

Classification of Opioids

Classification is based on their action on opioid receptors.
Pure opioid agonists: Drugs that act as agonists on opioid receptors and produce morphine-like effects.
- Includes morphine and its analogs (morphine, codeine, tramadol, heroin), meperidine and its analogs (meperidine, fentanyl, sufentanil), and methadone and its analogs (methadone, propoxyphene).
Pure opioid antagonists: Drugs acting as antagonists on opioid receptors, preventing the effects of opioid agonists.
- Examples are naloxone and naltrexone.
Mixed agonists/antagonists: Act as agonists at some opioid receptors and antagonists at others.
- Examples are nalbuphine, pentazocine, and buprenorphine.

Classification Based on Analgesic Efficacy

A chart showing different opioids and their relative analgesic efficacy (high, moderate, low).
- Opioids vary in their ability to relieve pain.

Mechanism of Action of Opioids

Opioids bind to endogenous opioid receptors (mu, kappa, delta) in the central nervous system (CNS) and extra-cerebral tissues, which are G-protein coupled receptors.
Their mechanisms of action include inhibiting adenylyl cyclase, which reduces cAMP, opening potassium channels, and blocking voltage-sensitive calcium channels.
These actions ultimately reduce the transmission of pain signals.

Opioid Receptors

Different opioid receptors mediate different effects.
μ (mu): Supraspinal analgesia, respiratory depression, sedation, euphoria, miosis, decreased GIT motility (constipation).
κ (kappa): Spinal analgesia, dysphoria, sedation & respiratory depression (less than mu).
δ (delta): Analgesia at both spinal and supraspinal levels.

Endogenous Opiopeptides

Endogenous peptides that interact with opioid receptors are called opiopeptides.
They cause analgesia and pain sensation modulation.
Examples are endorphins, enkephalins, and dynorphins; they are strong analgesics and widely distributed in the CNS and GI tract.
However, they do not cross the blood-brain barrier (BBB), so their effectiveness is limited.

I- Morphine

Pharmacological actions: Affect the central nervous system, cardiovascular system, gastrointestinal tract, other smooth muscles, and metabolism.
Specific CNS effects: Analgesia, sedation, hypnosis, clouding of consciousness, euphoria, miosis, respiratory depression, antitussive effects, nausea, vomiting.
Mechanism of analgesia: Interfering with pain perception and modifying emotional reactions to pain through euphoria.
Euphoria: False sense of well-being, particularly in the presence of pain, anxiety, or addiction. This is thought to be related to the inhibition of locus ceruleus (LC) activity, which contains dopaminergic neurons.
Sedation/hypnosis: Results from CNS depression by morphine, causing drowsiness, decreased physical activity, and mental apathy.
Respiratory depression: Morphine suppresses all stages of respiratory activity.
Other effects (miosis, vomiting): Morphine constricts pupils (miosis) and stimulates nausea and vomiting by triggering the chemoreceptor trigger zone (CTZ) in the medulla.

I- Morphine & its Congeners

Lists specific examples of morphine and its related drugs: morphine, codeine, and tramadol.
Briefly describes how they are collected or synthesized.

1. Morphine: CNS Effects details

It causes analgesia, sedation, hypnosis, clouding of consciousness, euphoria, miosis, respiratory depression, antitussive effects, nausea and vomiting.

2. GIT effects

Morphine increases smooth muscle tone in the intestines and anal sphincters, decrease motility, and reduces gastrointestinal secretions (saliva, gastric, intestinal and pancreatic).
It can cause constipation (no tolerance).
Morphine can cause biliary spasm, increasing pressure in the biliary tract due to Oddi's sphincter spasm and biliary colics, and this can be reduced by concurrent use with atropine or nitrates (e.g., Nitroglycerin - more acceptable than atropine).

3. Effects on other smooth muscles

Morphine causes urinary retention due to increased tone in the urinary sphincter, and postoperative urinary retention is a frequently encountered condition.
In asthmatics, morphine is contraindicated due to a potentially harmful bronchoconstrictor effect induced by histamine release.

4. Effect of Morphine on CVS

Morphine causes vasodilation (VD) leading to orthostatic hypotension (fainting on standing up). Morphine also relieves pulmonary congestion.

5. Neuroendocrine Effects of Morphine

Increased ADH release → urinary retention.
Block of testosterone release → impotence.
Blockage of gonadotropin release from pituitary → hypogonadism and infertility.
ACTH release → hyperglycemia.

6. Effect of Morphine on Histamine Release

Morphine stimulates histamine release
- Leading to hypotension, itching, and bronchospasm, contraindicated in asthmatics.

I- Morphine Pharmacokinetics

Summarizing how morphine is absorbed (oral, parenteral, rectal), distributed (CNS & placenta), metabolized, and excreted (via bile and kidneys).

Morphine Metabolism

Morphine glucuronide conjugation in the liver transforms morphine.
Morphine-6-glucuronide is more active than morphine, with a prolonged effect from chronic dosing.
Morphine-3-glucuronide exhibits minimal analgesic activity.

Metabolic Pathways of Morphine

Illustrates the metabolic pathways of morphine and codeine. Showing enzymatic pathways and metabolites, emphasizing the role of liver enzymes and their metabolites for elimination.
Differentiates active analgesics from those without analgesic activity

Therapeutic Uses of Morphine

Uses of morphine which include:
- Pain relief in severe acute pain.
- Cardiac asthma with pulmonary edema.
- Pre-anesthetic medication in individuals with preoperative pain.
- Treating dry cough, as an antitussive.
- Treating severe diarrhea.

Therapeutic Uses of Morphine: Detailed

Analgesic: Treatment for severe acute constant pain (burns, postoperative pain, fracture pain, biliary/renal colic, acute MI, cancer pain). The use must be carefully managed in the context of shock
Cardiac Asthma (pulmonary edema): Relieves anxiety, reducing preload and afterload to address dyspnea (shortness of breath).
Antitussive: Effective in dry, non-productive coughs, even though other less-addictive treatment could be used.
Diarrhea: (Historical treatment use – now less common) Non-addicting meperidine analogues (e.g., Loperamide and Diphenoxylate) are now preferred.
Pre-anesthetic Medication: Used for its sedative properties, anxiolytic (reducing anxiety), and analgesic properties for managing preoperative pain.

Precautions of Morphine

Lists factors that may be relative contraindications.
- Asthma and head injury
- Conditions during pregnancy or labor delivery.
- Patients with severe hepatic or renal dysfunction. Patients with circulatory collapse due to severe blood loss.
- Alcoholism, Epilepsy, and pregnancy.
- Patients with acute abdomen (e.g., appendicitis, ectopic pregnancy).
- Elderly and infants, susceptible to adverse effects.

Acute Toxicity of Morphine

Summarizing manifestations of acute morphine poisoning.
- Respiratory depression, postural hypotension, constipation, nausea and vomiting, urinary retention, increased intracranial pressure, itching, and urticaria.

Triad Symptoms of Acute Morphine Poisoning

Lists the critical triad (co-occurring) symptoms: Coma, Depressed Respiration, Pinpoint Pupils.

Treatments for Acute Morphine Poisoning

Treatments for acute poisoning in non-addicts (e.g., intravenous naloxone).
Treatments for acute poisoning in addicts (e.g., naltrexone or naloxone with cautious use.)

Chronic Toxicity (ADRs) of Morphine

Morphine dependence (physical and psychic), compulsive and habitual use as a result of its effects.
Euphoria as the reinforcement factor, warm flushing skin, and sensations described by the addict as similar to sexual orgasm (rush, kick).
Tolerance and withdrawal symptoms.
Outcomes of dependence associated with social problems (e.g., divorce) and other factors (e.g., impotence).

ADRs (Cont.)

Morphine tolerance (decreasing response to the drug with increasing doses).
Withdrawal syndrome (with sudden withdrawal or use of antagonists like naloxone.)
Manifestations are a response against morphine actions like autonomic hyperactivity (sweating, dilated pupils, etc.), psychological hyper-excitability (anxiety, restlessness), and motor hyperactivity (muscle/joint pain).

TTT of Morphine Dependence

Gradual morphine withdrawal.
Methadone as a replacement therapy for morphine addiction.
Use of clonidine (a2-agonist) to control autonomic hyperactivity.
Use of partial opioid agonists (e.g., buprenorphine) to suppress withdrawal and decrease cravings.
Methylnaltrexone to treat morphine-related constipation.
Psychotherapeutic treatment.

Morphine Derivatives: Codeine

Codeine is a methylmorphine derivative acting as a weak µ-agonist.
Codeine has a lower analgesic potency (1/12 of morphine).
Codeine is used for mild pain not relieved by NSAIDs. It is often combined with aspirin or paracetamol for analgesia, has high effectiveness orally, and has a limited first-pass effect (useful for oral use.)
Codeine has a relatively low risk of addiction and withdrawal.

Morphine Derivatives: Tramadol

Tramadol is a synthetic codeine analogue with weak µ agonist activity. Tramadol has the advantage of inhibiting the reuptake of norepinephrine and serotonin in the CNS.
It has an active metabolite (O-demethylated) with greater potency than tramadol itself.
Naloxone can reduce the analgesic effect of Tramadol somewhat.
Tramadol is effective for mild to moderate pain, but less effective than morphine for chronic/severe pain.
It does not usually cause severe respiratory depression or cardiovascular (CVS) side effects, but may cause convulsions.

Morphine Derivatives: Heroin

Heroin is a diacetylmorphine derivative with a high addiction potential and is not used in clinical practice.
It has twice the analgesic effect compared to morphine.

II- Meperidine (Pethidine)

Meperidine has 1/10th the analgesic potency of morphine.
Disadvantages include tachycardia caused by antimuscarinic activity (harmful in certain cardiac conditions). While initially believed to have low addiction, this is not the case.
NOT used IV or SC due to local irritation / tissue damage , but used IM.
Advantages:
- Less spasmodic action on smooth muscles (than morphine), useful in smooth muscle spasm disorders (such as biliary colics).
- Safer in patients with asthma.
- Does not cause respiratory depression to the same extent as morphine.
Potential for CNS excitation, potentially producing seizures. Physical Dependence is common.

Meperidine Derivatives: Fentanyl, Alfentanil, Remifentanil, Sufentanil

Fentanyl, alfentanil, remifentanil, and sufentanil are meperidine derivatives with high μ-receptor agonist potency (100x+ compared to morphine).
Used in general anesthesia and postoperative pain relief. High potent dosages could result in muscle rigidity. Fentanyl transdermal patch is used in chronic cancer pain for longer lasting effects.

Meperidine Derivatives: Diphenoxylate & Loperamide

Non-addicting opioids used for managing diarrhea.
Diphenoxylate often used in combination with atropine, decreasing intestinal motility and secretions.
Contraindicated in children and individuals with amebic, or bacillary dysentery, due to potential complications (e.g., paralytic ileus, respiratory depression).

III- Methadone

Acting as a µ agonist
Used to treat morphine addiction due to longer duration of action, lower addiction potential, smoother withdrawal treatment, and less intense sedative effects compared to morphine.
Administered orally
Methadone has a cross-dependence with morphine.

IV- Mixed Agonist-Antagonists

Pentazocine: Partial agonist at kappa receptors, weak antagonist at mu receptors.
Butorphanol: Partial agonist at kappa receptors, weak antagonist at mu receptors.
Nalbuphine: Partial agonist at kappa receptors, weak antagonist at mu receptors.
Buprenorphine: Partial agonist at mu receptors, with no action at kappa receptors. It's less potent than other opioid agonists.

V- Pure opioid antagonists

Naloxone: Competitive pure antagonist at mu receptors, less potent at kappa receptors. Used to reverse opioid overdose in non-addicts and as a treatment for neonatal asphyxia.
Naltrexone: Bioavailable oral form of naloxone, longer duration of action (24 hours), stronger than naloxone.

A higher potency is usually indicated by needing lower amounts of the drug for the intended effect, with a risk of greater side effects and dependence from high frequency use.

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Description

This quiz explores key concepts related to urinary retention, particularly in postoperative patients. It covers the implications of urinary sphincter tone and the management of pain relief in clinical shock situations. Testing your knowledge on these topics will enhance your understanding of patient care and the use of medications like morphine.