Membrane Sweep Mucus Plug

The absorption of drugs is determined by the physicochemical properties of the drug, the formulation and the method of administration. Dosage forms (e.g. tablet, capsule, solution), which are composed of the active substance and other components, are each formulated for specific types of application (e.g. oral, buccal, sublingual, rectal, parenteral, topical, inhalation). Regardless of the dosage form, drugs must be dissolved in order to be absorbed. Therefore, solid formulations (e.g., tablets) must be able to disintegrate and dissolve. Unless given IV, a drug must cross several semi-permeable cell membranes before reaching the large circulation. Cell membranes are biological barriers that selectively inhibit the passage of drug molecules. Membranes are primarily composed of a bimolecular lipid matrix that determines the permeability properties of the membrane. Drugs can cross cell membranes through

  • Passive diffusion
  • Facilitated passive diffusion
  • Active transport
  • Pinocytosis

Sometimes various globular proteins embedded in the matrix act as receptors and help transport molecules across the membrane. Drugs diffuse across a cell membrane from a region of higher concentration (e.g., gastrointestinal fluids) to one of lower concentration (e.g., blood). The rate of diffusion is directly proportional to the gradient, but also depends on the lipid solubility of the molecule, the molecular size, the degree of ionization, and the size of the absorbing surface. Because the cell membrane is lipoid, lipid-soluble drugs diffuse most rapidly. Small molecules tend to penetrate membranes faster than larger ones. Most drugs are weak organic acids or bases that exist in aqueous environments in nonionized or ionized forms. The nonionized form is usually fat soluble (lipophilic) and diffuses readily across cell membranes. The ionized form has low lipid solubility (whereas it has high water solubility – is hydrophilic, for example) and high electrical resistance, and therefore has difficulty penetrating cell membranes. The proportion of the non-ionized form present (and thus the ability of the drug to pass through a cell membrane) is determined by the ambient pH and the pKa (pKs value, acid dissociation constant) of the drug. The pKa is the pH at which the concentrations of the ionized and non-ionized forms are equal. When the pH is lower than the pKa, the non-ionized form of a weak acid predominates, whereas the ionized form of a weak base predominates. In gastric juice (pH 1.4), the ratio is reversed (1000:1). Therefore, in plasma (pH 7.4) for a weak acid (e.g. with a pKa of 4.4), a ratio of non-ionized to ionized form of 1:1000 is present. Therefore, when a weak acid is administered orally, most of the drug is present in the stomach in the nonionized form, which promotes diffusion through the gastric mucosa. The majority of the drug is present in the stomach in ionized form. For a weak base with a pKa of 4.4, the result is reversed. Certain molecules with low lipid solubility (e.g., glucose) cross membranes faster than expected. One theory for this is facilitated passive diffusion: a transport molecule (carrier) in the membrane reversibly binds the substrate molecule outside the cell membrane, diffuses rapidly across the membrane as a carrier-substrate complex, and releases the substrate at the inner surface. In these cases, the membrane transports only substrates with a relatively specific molecular configuration, and the availability of transport molecules limits the process. This process does not require energy, and transport against the concentration gradient is not possible. Active transport is selective, requires energy, and may involve transport against the concentration gradient. Active transport appears to be limited to drugs that are structurally similar to endogenous substances (e.g., ions, vitamins, sugars, amino acids). These drugs are usually absorbed at specific sites in the small intestine. In pinocytosis, fluids or particles are “engulfed” by the cell. The cell membrane invaginates, enclosing the liquid or particle, then fuses again, forming a vesicle that later detaches and migrates to the interior of the cell. Energy must be expended for this to occur. With the exception of protein drugs, pinocytosis probably plays a minor role in drug transport. To be absorbed, an orally given drug must survive contact with low pH and numerous gastrointestinal secretions, including potentially degrading enzymes. Peptide drugs (e.g., insulin) are particularly susceptible to degradation and are not used orally. Absorption of oral drugs includes transport through membranes of epithelial cells in the gastrointestinal tract. Absorption is influenced by

  • Differences with respect to pH along the gastrointestinal lumen.
  • Size of surface area per gastrointestinal volume
  • Blood flow
  • Presence of bile and mucus
  • The nature of the epithelial membranes

However, contact with the mucosa is usually too brief for substantial absorption. The oral mucosa has a thin epithelium and is rich in vessels, which promotes absorption. A drug pushed between the gums and cheeks (buccal administration) or given under the tongue (sublingual administration) lingers longer, which increases absorption. The stomach is usually the first organ in which intensive contact takes place between an orally administered drug and the fluids of the gastrointestinal tract (for an overview, see [ 1 General information The absorption of drugs is determined by the physicochemical properties of the drug, the formulation and the method of administration. Dosage forms (e.g., tablet, capsule… Learn more ]). Although the stomach has a relatively large epithelial surface area, its thick mucus layer and short residence time limit drug absorption. These characteristics of the stomach may influence drug composition and behavior. Because absorption occurs predominantly in the small intestine, gastric emptying is often the rate-determining step. Food intake, especially high-fat foods, delays gastric emptying (and the rate of drug absorption), which explains why taking some drugs on an empty stomach accelerates absorption. Drugs that affect gastric emptying (e.g., parasympatholytics) simultaneously affect the absorption rate of other drugs. Food intake may increase the rate of absorption for poorly soluble drugs (e.g., griseofulvin), decrease it for drugs that are broken down in the stomach (e.g., penicillin G), or have little or no effect. The small intestine has the largest surface area for absorption of drugs in the gastrointestinal tract, and its membranes have higher permeability than those in the stomach. For these reasons, most drugs are primarily absorbed in the small intestine, and acids are absorbed more rapidly in the intestine than in the stomach, although as nonionized drugs they may pass more easily through membranes (For an overview, see [ 1 General Note The absorption of drugs is determined by the physicochemical properties of the drug, the formulation, and the route of administration. Dosage forms (e.g., tablet, capsule,… Learn More ] The pH in the intestinal lumen ranges from 4 to 5 in the duodenum, but becomes progressively more alkaline, reaching approximately 8 in the lower ileum. Gastrointestinal microflora may decrease absorption. Decreased blood flow (e.g., shock) may lower the concentration gradient along the intestinal mucosa and reduce absorption by passive diffusion. The duration of intestinal transit may also affect drug absorption, particularly for those drugs that are absorbed via active transport (e.g., B vitamins), those that dissolve slowly (e.g., griseofulvin), and those that are polar (i.e., with low lipid solubility, e.g., numerous antibiotics). To ensure continued use as much as possible, physicians should prescribe oral suspensions and chewable tablets for children under 8 years of age. In adolescents and adults, most drugs are administered orally as tablets or capsules, primarily for reasons of convenience, economy, stability, and patient acceptance. Because solid drug formulations must first dissolve for absorption to occur, the rate of dissolution determines the availability of the drug for absorption. If dissolution is slower than absorption, the dissolution process becomes the rate-determining step. Modification of the formulation (e.g., drug form as salt, crystal, or hydrate) can alter the dissolution rate and thus control overall absorption.

  • 1. Vertzoni M, Augustijns P, Grimm M, et al: Impact of regional differences along the gastrointestinal tract of healthy adults on oral drug absorption: An UNGAP review. Eur J Pharm Sci 134:153-175, 2019. doi:10.1016/j.ejps.2019.04.013.

Drugs administered IV enter the major circulation directly. However, drugs that are injected intramuscularly or subcutaneously must cross one or more biological membranes to enter the large circulation. When proteins with a molecular weight > 20,000 g/mol are injected i.m. or subcutaneously, they pass through capillary membranes so slowly that most of the absorption occurs through the lymphatic system. In such cases, the drug enters the large circulation slowly and, because of first-pass metabolism (metabolism of a drug before it reaches the large circulation) by proteolytic enzymes in the lymphatic vessels, often incompletely. Blood flow (blood flow/g tissue) strongly influences capillary absorption of small molecules injected i.m. or subcutaneously. Therefore, the injection site may affect the rate of absorption. In salts of poorly soluble bases and acids (e.g., parenteral forms of phenytoin) and in patients with poor peripheral circulation (e.g., hypotension or shock), absorption may be delayed or uneven after i.m. or subcutaneous injections. Controlled release formulations are being developed to reduce the frequency of use for drugs with a short elimination half-life and duration of action. These formulations also limit fluctuations in the plasma concentration of the drug, resulting in a more consistent therapeutic effect while minimizing adverse effects. The rate of absorption can be slowed by coating drug particles with wax or other water-insoluble materials, by embedding them in a matrix that releases the drug during passage through the gastrointestinal tract, or by complexing them with ion-exchange resin. With these formulations, the majority of absorption occurs in the colon. Crushing or otherwise destroying a controlled-release tablet or capsule can often be dangerous. Transdermal controlled release systems are designed to release drugs over extended periods of time, sometimes over several days. For transdermal administration, drugs must have suitable characteristics in terms of skin penetration properties, as well as high potency, because the penetration rate and application area are limited. Many non-intravenous parenteral formulations are developed to maintain the plasma concentration of the drug. The absorption of antibiotics may be prolonged if they are injected i.m. in the form of their relatively insoluble salt (e.g., penicillin G, benzathine). For other drugs, suspensions or solutions in nonaqueous vehicles are developed to delay absorption (e.g., crystalline suspensions for insulin). Atelectasis is a collapsed section or lobe of the lung that is no longer filled with air.

  • A common cause of atelectasis is occlusion of a large bronchus.
  • Shortness of breath may occur with low oxygen saturation or pneumonia.
  • Diagnosis is confirmed by chest x-rays.
  • Treatment may include ensuring deep breathing and/or reducing airway obstructions.

The main function of the lungs is to take oxygen from the surrounding air into the bloodstream and to release carbon dioxide from the blood into the air we breathe (gas exchange – see Gas exchange between alveoli and capillaries Gas exchange between alveolar spaces and capillaries ). For this gas exchange to take place, the small alveoli (air sacs) must be open and filled with air. This happens thanks to the elastic structure of the lungs and their surface active substance (surfactant). The surfactant counteracts the natural tendency of the alveoli and prevents them from closing. Regular deep breaths, which we take unconsciously, and coughing also keep the alveoli open. Coughing expels mucus and other secretions that could block the airways leading to the alveoli. If the alveoli close for any reason, they can no longer participate in gas exchange. The more alveoli are closed, the less gas exchange occurs. So atelectasis can lower the oxygen level in the blood. Our body compensates for minor atelectasis by narrowing the blood vessels in the affected areas. This narrowing (constriction) diverts blood flow to those alveoli that are still open, allowing gas exchange to continue. Common causes of atelectasis are usually the following:

  • Obstruction of one of the major bronchi leading from the trachea (windpipe) to the lungs
  • Conditions that decrease deep breathing or suppress the patient’s ability to cough

When a bronchial or smaller airway (a bronchiole) is constricted, air from the alveoli beyond the constriction is absorbed into the bloodstream, causing the alveoli to shrink and eventually collapse. The collapsed lung tissue is susceptible to infection because bacteria and white blood cells can accumulate behind the obstruction. The risk of infection is especially high if atelectasis persists for several days or even longer. If atelectasis persists for months, the lungs are unlikely to inflate as easily. Certain neurological disorders, immobility, and chest deformities can limit chest mobility, as can abdominal distension, all of which can contribute to shallow breathing. People who are severely or morbidly obese are also at increased risk for atelectasis. Atelectasis does not present with symptoms except for occasional shortness of breath. The occurrence and extent of shortness of breath depend on how quickly atelectasis develops and which parts of the lungs are affected. If atelectasis affects only a limited portion of the lungs or if it develops slowly, only very mild symptoms may occur, sometimes not even noticed. If a large number of the alveoli are affected, and especially if atelectasis develops rapidly, severe shortness of breath may occur.

  • X-ray of the chest

Smokers can lower their surgery-related atelectasis risk by quitting smoking six to eight weeks before surgery Smoking cessation Although challenging, quitting is one of the most important things a smoker can do for his or her health. Smoking cessation brings immediate… Learn More . After surgery, all patients are encouraged to breathe deeply, cough regularly and exercise as soon as possible. Also, through devices that patients voluntarily to deep breathing, called stimulation spirometry breathing exercises Physiotherapy for the chest uses mechanical techniques such as chest tapping, drainage positioning and vibration to clear secretions from the lungs. Respiratory therapists… Learn More , animate, and certain exercises with postures that facilitate the expectoration of mucus and other secretions from the lungs can prevent atelectasis. In general, atelectasis can be prevented by ensuring that deep breathing is performed. Circumstances in which only shallow breathing occurs for prolonged periods should be remedied if possible.

  • Deep breathing and coughing
  • Relief of airway obstruction by suctioning or bronchoscopy.

Treatment of atelectasis may include ensuring deep breathing and/or reducing airway obstructions. Atelectasis may require treatment of both symptoms and complications. Patients may require the following:

  • supplemental oxygen
  • Antibiotics if a bacterial infection is suspected.

The following is an English language resource that may be useful. Please note that the MANUAL is not responsible for the content of this resource. Using the diaphragm as a contraceptive method, women can prevent pregnancy relatively safely. It has the greatest reliability when combined with a chemical contraceptive – usually a spermicide. A pessary, also called a diaphragm, is made of a latex membrane with a flexible wire ring and looks like a hat with a small brim. There are different sizes and models – among other things, the reliability of contraception depends on the correct fit. The pessary size should also be checked every one to two years, and in young women even every six months. After childbirth or weight changes of more than 3 kilos, the pessary must be readjusted.

Use of the diaphragm

Before sexual intercourse, the diaphragm is inserted with the front end deep into the vagina. It must sit firmly between the posterior vaginal vault and the pubic bone, so that it completely covers the cervix like a seal for sperm defense. It is advisable to perform some dry exercises beforehand when using it for the first time; this increases safety and reassures.

The most important rules for successful use of a pessary:

  • the best time to insert the pessary is about half an hour before sexual intercourse, it should not be more than 2 hours ago.
  • the diaphragm should be rubbed with a sperm-killing gel beforehand, as this increases safety.
  • after insertion, the woman should feel whether the diaphragm is properly positioned over the cervix. It must be palpable through the rubber skin.
  • the diaphragm should be removed no earlier than 8 hours after the last intercourse, but should not be left in the vagina for more than 12 hours.
  • after each use, it should be thoroughly cleaned with soap and water, so it can be kept for up to 5 years.
  • the pessary should be regularly checked by the woman herself for small tears or holes.

Safety of the diaphragm

The Pearl Index ranges from 1 to 20 and depends very much on the age, experience of the user and exact fitting. In combination with a spermicidal cream it is even slightly safer.

For whom is a diaphragm suitable?

  • for women who do not want to use contraception permanently and have sexual intercourse only occasionally
  • for women who cannot tolerate hormonal contraception for health reasons
  • for women who have a special relationship with their body; however, insertion and proper fit of the pessary require practice and experience

Advantages of the diaphragm

  • use only when necessary
  • does not interfere with the body’s hormonal system
  • easy to insert and remove
  • easy to carry, fits in any handbag

Disadvantages of the diaphragm

  • no protection against sexually transmitted diseases
  • adjustment by a doctor necessary
  • in case of repeated sexual intercourse in a row, spermicidal gel has to be inserted again
  • removal 6 to 8 hours after sexual intercourse at the earliest, as sperm survive at least that long
  • reliability depends on exact fit
  • does not allow much spontaneity during sex
  • not suitable for women who are in childbed, suffer from malformations of the genital organs or have severe uterine prolapse.

Possible side effects of the diaphragm

  • if the diaphragm remains in the vagina for more than 24 hours, there is a risk of discharge and vaginal inflammation
  • susceptibility to bladder infections may increase
  • Skin irritation or allergic reactions in the woman or her partner are rare.

Cost of the diaphragm

Approx. 30 euros per piece, spermicide cream or gel approx. 8-12 euros, non-prescription. Membrane Sweep Mucus Plug.

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