NEET MDS Synopsis
Odontogenic Cysts
Oral Pathology
Odontogenic cysts
Odontogenic cysts are lined with epithelium derived from the following tooth development structures:
• rests of Malassez: radicular cyst, residual cyst
• reduced enamel epithelium: dentigerous cyst, eruption cyst
• Remnants of the dental lamina: Odontogenic keratocyst, lateral periodontal cyst, gingival cyst of adult, glandular odontogenic cyst
Radicular cyst
Radiology
- A well-defined, round or ovoid radiolucency is associated with the root apex or, less commonly in the lateral position, of a heavily restored or grossly carious tooth.
- A corticated margin is continuous with the lamina dura of the root of the affected tooth.
- The appearances are similar to those of an apical granuloma, but lesions with a diameter exceeding 10 mm are more likely to be cystic
Pathology
The cyst lumen is lined by a layer of simple squamous epithelium of variable thickness, which may display areas of discontinuity where it is replaced by granulation tissue.
Arcades and strands of epithelium may extend into the cyst capsule, which is composed of granulation tissue infiltrated by a mixture of acute and chronic inflammatory cells.
This infiltrate reduces in intensity as the more peripheral areas of the cyst capsule are approached, where mature fibrous tissue replaces the
granulation tissue
Several features associated with inflammatory odontogenic cysts may be present in the cyst lumen, lining and capsule: cholesterol clefts, foamy macrophages, haemosiderin and Rushton's bodies.
Residual cyst
Radiology
The residual cyst has a well-defined, round/ovoid radiolucency in an edentulous area. Occasionally flecks of calcification may be seen.
Pathology
The lining and capsule are similar to the radicular cyst; however, both appear more mature, with the former lacking the arcades and strands of epithelium extending into the capsule.
Keratocystic odontogenic tumor-(Odontogenic keratocyst)
The orthokeratinizing odontogenic cyst is considered an unrelated entity without risk of recurrence or aggressive growth or association with Nevoid basal cell carcinoma syndrome
Epidemiology
- 4 - 12% of all odontogenic cysts (often compared to odontogenic cysts even though WHO classifies as tumor)
- Peaks in second and third decade of life, but can occur over wide age range
- 90% are solitary
- Multiple tumors seen in Nevoid Basal Cell Carcinoma Syndrome / Gorlin Syndrome
Sites
- Mandible most commonly involved (65 - 85% of KCOT)
- Most common site: posterior mandible
- Not uncommonly, but not exclusively associated with impacted teeth
- Rarely occurs in soft tissue
Pathophysiology
- Thought to arise from dental lamina
- Two-hit mechanism results in bi-allelic loss of PTCH ("patched") tumor suppressor on 9q22.3-q31 causing dysregulation of p53 and cyclin D1 oncoproteins
- The presence of daughter cysts within the capsule is a well-recognised finding, particularly in those odontogenic keratocysts arising as a component of the basal cell naevus syndrome.
Clinical features
- Often asymptomatic, incidentally discovered on Xray
- Can cause symptomatic swelling
- Symptoms of pain and drainage if secondarily infected
- Can cause local bone and soft tissue destruction, but usually spares teeth and roots
Radiology
- Small lesions often unilocular radiolucent lesion, variable sclerotic margins
- Larger lesions often multilocular, variable scalloped margins
Dentigerous cyst
Radiology
In dentigerous cysts, there is a pericoronal radiolucency greater than 3-4 mm in width that is suggestive of cyst formation in a dental follicle. The well-defined, corticated radiolucency is associated with the crown of an unerupted tooth. Classically the associated crown of the tooth lies centrally within the cyst, but lateral types occur .
Pathology
The defining feature of a dentigerous cyst is the site of attachment of the cyst to the involved tooth. This must be at the level of the amelocemental junction. The lining of the cyst is composed of a thin layer of epithelium, either cuboidal or squamous in nature, some 2-5 cells thick . This lining is of even thickness and may include mucous cells along with focal areas of keratinisation of the superficial epithelial cells. The cyst capsule is, classically, free from inflammation. However, in common with the odontogenic keratocyst, the normal features of the epithelial lining may be distorted when an inflammatory infiltrate is present.
Eruption cyst
Radiology
The extra-bony position of the eruption cyst means that the only radiological sign is likely to be a soft tissue mass.
Pathology
An eruption cyst is basically a dentigerous cyst in soft tissue over an erupting tooth. The histological features are similar to those of the dentigerous cyst, though reduced enamel epithelium is often seen.
Gingival cysts
Gingival cysts are commonly found in neonates but are rarely encountered after 3 months of age.
Many appear to undergo spontaneous resolution.
White keratinous nodules are seen on the gingivae and these are referred to as Bohn's nodules or Epstein's pearls.
Arise from epithelial rests of dental lamina epithelium (rests of Serres) within soft tissue
Many open into the oral cavity forming clefts from which the keratin exudes.
Radiology
Cyst may cause a superficial "cupping out" of alveolar bone, usually not detected on a radiograph but apparent when cyst is excised
Histology of the Pulp
Dental Anatomy
Histology of the Pulp
PARTICIPATING CELLS
1. Odontoblasts (body and process)
Most distinctive cells of the pulp
Single layer
The cells are columnar in the coronal portion, cuboidal in the middle portion, flat in the apical portion
Individual odontoblasts communicate with each other via junctions. The number of odontoblasts corresponds to the number of dentinal tubules.
The lifespan of an odontoblast equals the one of a vital tooth.
The morphology of the odontoblasts reflects their functional activity.
(There are three stages that reflect the functional activity of a cell: active, transitional and resting)
The odontoblastic process
2. Fibroblasts
Most numerous cells
Produce collagen fibers and ground substance
Ground substance consists of: proteoglycans and glycoproteins
Again, active and resting cells
Fibroblasts have also capability to degrade collagen
3. Undifferentiated mesenchymal cells A pool of cells from which connective tissue cells can derive.
They are reduced with age.
4. Endothelial cells, Schwann cells, pericytes and immunocompetent cells
MATRIX
It is composed of fibers and ground substance
55% of the fibers are Type I collagen. 45% of the fibers are Type III collagen.
The ground substance is gelatinous in the coronal aspect and more fibrous in the apical.
VASCULARITY
Superior and inferior alveolar arteries that derive from the external carotids
Afferent side of the circulation: arterioles
Efferent side of the circulation: venules
Lymphatics
Small, blind, thin-walled vessels in the coronal region of the pulp and exit via one or two larger vessels.
Antianginal Drugs
Pharmacology
Antianginal Drugs
Organic Nitrates :
Short acting: Glyceryl trinitrate (Nitroglycerine, GTN), Amyl Nitrate
Long Acting: Isosrbide dinitrate (Short acting by sublingual route), Erythrityl tetranitrate, penta erythrityl tetranitrate
Beta-adrenergic blocking agents : Propanolol, Metoprolol
Calcium channel blockers Verapamil, Nifedipine, Dipyridamole
Mechanism of action
– Decrease myocardial demand
– increase blood supply to the myocardium
Primary Retention Form
Conservative DentistryPrimary Retention Form in Dental Restorations
Primary retention form refers to the geometric shape or design of a prepared
cavity that helps resist the displacement or removal of a restoration due to
tipping or lifting forces. Understanding the primary retention form is crucial
for ensuring the longevity and stability of various types of dental
restorations. Below is an overview of primary retention forms for different
types of restorations.
1. Amalgam Restorations
A. Class I & II Restorations
Primary Retention Form:
Occlusally Converging External Walls: The walls of
the cavity preparation converge towards the occlusal surface, which
helps resist displacement.
Occlusal Dovetail: In Class II restorations, an
occlusal dovetail is often included to enhance retention by providing
additional resistance to displacement.
B. Class III & V Restorations
Primary Retention Form:
Diverging External Walls: The external walls
diverge outward, which can reduce retention.
Retention Grooves or Coves: These features are
added to enhance retention by providing mechanical interlocking and
resistance to displacement.
2. Composite Restorations
A. Primary Retention Form
Mechanical Bond:
Acid Etching: The enamel and dentin surfaces are
etched to create a roughened surface that enhances mechanical retention.
Dentin Bonding Agents: These agents infiltrate the
demineralized dentin and create a hybrid layer, providing a strong bond
between the composite material and the tooth structure.
3. Cast Metal Inlays
A. Primary Retention Form
Parallel Longitudinal Walls: The cavity preparation
features parallel walls that help resist displacement.
Small Angle of Divergence: A divergence of 2-5 degrees
may be used to facilitate the seating of the inlay while still providing
adequate retention.
4. Additional Considerations
A. Occlusal Dovetail and Secondary Retention Grooves
Function: These features aid in preventing the proximal
displacement of restorations by occlusal forces, enhancing the overall
retention of the restoration.
B. Converging Axial Walls
Function: Converging axial walls help prevent occlusal
displacement of the restoration, ensuring that the restoration remains
securely in place during function.
Thrombosis
General Pathology
Thrombosis
Definition-The formation from constituents of the blood, of a mass within the venous or arterial vasculature of a living animal. Natural defense of the body to acute vascular injury.
Pathologic thrombosis includes deep venous thrombosis (DVT), pulmonary embolism (PE), coronary artery thrombosis leading to myocardial infarct and cerebrovascular thrombosis leading to stroke.
Coagulated blood- clots formed
Clot – formation of solid mass of blood components formed outside the vascular tree
Thrombosis with resulting embolic phenomena is important cause of morbidity and mortality.
Haemostatic system allows blood to remain in fluid form under normal conditions and causes the development of temporary thrombus at site of vascular injury.
Components of haemostatic system:
1. Platelets
2. Vascular endothelium
3. Procoagulant plasma protein clotting factors
4. Natural anticoagulants
5. Fibrinolytic proteins
6. Antifibrinolytic proteins
Normal haemostasis:
1. Primary haemostasis-platelet plug formation
2. Secondary haemostasis-stable plug or thrombus
3. Natural anticoagulants-confines thrombus site and size to maintain blood flow
4. Fibrinolysis-degrades fibrin , limits thrombus size and dissolves thrombus once vessel injury is repaired
Changes in any of these factors may result in pathologic thrombosis.
Pathophysiology of thrombosis:
Virchow’s Triad-Thrombosis results from a) decreased blood flow b) vascular endothelial injury and c) alterations in the components of blood.
Vessel wall:
EC (intima), smooth muscle cells (media) and the connective tissue (adventitia).Vascular endothelium is thromboresistant. EC injury leads to TF expression and thrombosis.
Vessel wall has antiplatelet, anticoagulant and fibrinolytic activities which make it thromboresistant.
Antiplatelet activities:
1. Prostacyclin synthesized by EC in response to thrombin. Inhibits platelet adhesion as well as causes vasodilation
2. NO regulates vascular tone as well as functioning as inhibitor of platelet adhesion. Constitutive expression as well as induced expression by EC in response to cytokines
3. Ectozymes which metabolize ADP and ATP to AMP and adenosine. Adenosine inhibits platelet function, ADP is platelet agonist
Anticoagulant activities:
1. Synthesis of heparin like GAG which inactivate activated clotting factors
2. Protein C and S and thrombomodulin-Thrombin generated binds to thrombomodulin which activates protein C which then binds to Protein S and this inhibits coagulation by its proteolytic effect on Factors Va and VIIIa
3. TFPI is synthesized by EC and regulates TF-VIIa activation of Factor X. Also inhibits vascular cell proliferation
Fibrinolytic activities:
1. Secretion and synthesis of plasminogen activators TPA in response to thrombin and vasoactive stimulants such as vasopressin and histamine
2. Synthesis of urokinase in response to inflammatory cytokines
3. FDP’s generated have antiplatelet and antithrombin activity
4. Secretion of PAI
Prothrombotic properties of vascular endothelium promote coagulation with appropriates stimuli.
EC exposure to stimuli such as trauma, cytokines, atherogenic stimuli, endotoxins and immune complexes result in increased TF expression, reduced Protein C activation and reduced fibrinolysis so converting an antithrombotic surface to a prothrombotic surface.
Inherited conditions which result in abnormalities of EC derived or regulated proteins will cause thrombosis.
Arterial thrombosis:
1. Abnormal vessel wall due to atherosclerotic plaque rupture, arterial outflow obstruction, vessel dissection EC injury promote platelet adhesion and activation
2. Release of contents of platelet granules cause recruitment and activation of additional platelets
3. Thromboxane synthesis induces platelet aggregation
4. Thrombin generation due to presence of PL
Platelets are pathogenetically more important in arterial thrombi thus antiplatelet agents are very important in arterial thrombosis management.
Venous thrombosis:
1. Vessel wall is usually normal except if there is direct vessel trauma, extrinsic venous compression or damage due to drugs like chemotherapy
2. Reduction in venous tone is important in pathophysiology
Venous thrombi can be of two types.
A. Phlebo thrombosis
This is thrombus formation in an uninflammed vein usually due to stasis or changes in coagulability of blood. This occurs mostly in deep calf veins and varicose veins in the legs originating near valve pockets. They may propagate to extend to popliteal ,femoral and iliac-veins. These are a common source of massive emboli ‘Phlegmasia alba dolens’ (painful white leg) is a condition seen in late pregnancy and puerperium. In this condition, in addition to iliofemoral thrombosis , there is arterial spasm
B Thrombophlebitis:
In this condition venous wall is inflamed and initiates thrombosis. This is more firmly attached to the vessel wall and also there is much less tendency for propagation Hence there is little chance or embolism.
Cardiac Thrombosis
Intra cardiac thrombus formation can be at 3 sites
• Valvular: as in endocarditis
• Atrial : as in atrial fibrilation ('ball valve thrombus") over MacCallum’s patch is Rheumatic Fever.
• Ventricular mural thrombus over site of MI
Fate of Thrombus
- Resolution : if small, the thrombus is rapidly covered by endothelial cells. Then it can Resolved by a combination of retraction, phgocytosis , platelet autolysis, and fibrinolysis
- Organisation: there is in growth of vascular granulation tissue. This can result in
a. recanalisation
b. collagenisation and-scarring
- Detachment resulting in thromboembolism
Danger Space
Oral and Maxillofacial SurgeryDanger Space: Anatomy and Clinical Significance
The danger space is an anatomical potential space located
between the alar fascia and the prevertebral fascia.
Understanding this space is crucial in the context of infections and their
potential spread within the neck and thoracic regions.
Anatomical Extent
Location: The danger space extends from the base
of the skull down to the posterior mediastinum,
reaching as far as the diaphragm. This extensive reach
makes it a significant pathway for the spread of infections.
Pathway for Infection Spread
Oropharyngeal Infections: Infections originating in the
oropharynx can spread to the danger space through the retropharyngeal
space. The retropharyngeal space is a potential space located
behind the pharynx and is clinically relevant in the context of infections,
particularly in children.
Connection to the Posterior Mediastinum: The danger
space is continuous with the posterior mediastinum, allowing for the
potential spread of infections from the neck to the thoracic cavity.
Mechanism of Infection Spread
Retropharyngeal Space: The spread of infection from the
retropharyngeal space to the danger space typically occurs at the junction
where the alar fascia and visceral fascia fuse,
particularly between the cervical vertebrae C6 and T4.
Rupture of Alar Fascia: Infection can spread by
rupturing through the alar fascia, which can lead to serious complications,
including mediastinitis, if the infection reaches the posterior mediastinum.
Clinical Implications
Infection Management: Awareness of the danger space is
critical for healthcare providers when evaluating and managing infections of
the head and neck. Prompt recognition and treatment of oropharyngeal
infections are essential to prevent their spread to the danger space and
beyond.
Surgical Considerations: Surgeons must be cautious
during procedures involving the neck to avoid inadvertently introducing
infections into the danger space or to recognize the potential for infection
spread during surgical interventions.
Bacterial infectious diseases
General Medicine
Bacterial infectious diseases
Anthrax
- an acute infectious disease caused by the bacteria Bacillus anthracis
- Anthrax can enter the human body through the intestines (ingestion), lungs (inhalation), or skin (cutaneous).
1. Pulmonary (pneumonic, respiratory, or inhalation) anthrax
Respiratory infection initially presents with cold or flu-like symptoms for several days, followed by severe (and often fatal) respiratory collapse.
A lethal dose of anthrax is reported to result from inhalation of 10,000-20,000 spores. This form of the disease is also known as Woolsorters' disease or as Ragpickers' disease.
2. Gastrointestinal (gastroenteric) anthrax
Gastrointestinal infection often presents with serious gastrointestinal difficulty, vomiting of blood, and severe diarrhea. Untreated intestinal infections result in 25-65% mortality.
3. Cutaneous (skin) anthrax
Cutaneous infection often presents with large, painless necrotic ulcers (beginning as an irritating and itchy skin lesion or blister that is dark and usually concentrated as a black dot, somewhat resembling bread mold) at the site of infection.
Treatment
- large doses of intravenous and oral antibiotics, such as penicillin, ciprofloxacin, doxycycline, erythromycin, and vancomycin.
- Antibiotic prophylaxis is crucial in cases of pulmonary anthrax to prevent death.
Cholera
- a water-borne disease caused by the bacterium Vibrio cholerae, which are typically ingested by drinking contaminated water, or by eating improperly cooked fish, especially shellfish.
Symptoms
- general GI tract upset: profuse diarrhea (eg 1L/hour), abdominal cramping, fever, nausea and vomiting.
- Dehydration
- severe metabolic acidosis with potassium depletion, anuria, circulatory collapse and cyanosis
- Death is through circulatory volume shock (massive loss of fluid and electrolytes)
Treatment
- rehydration and replacement of electrolytes
- Tetracycline antibiotics may have a role in reducing the duration and severity of cholera
Diphtheria
- Diphtheria is an upper respiratory tract illness characterized by sore throat, low-grade fever, and an adherent membrane (a pseudomembrane) on the tonsil(s), pharynx, and/or nose
Signs and symptoms
- Incubation time of 1-4 days
- Symptoms include fatigue, fever, a mild sore throat and problems swallowing
- Children infected have symptoms that include nausea, vomiting, chills, and a high fever,
Treatment
- Antibiotics are used in patients or carriers to eradicate C. diphtheriae and prevent its transmission to others
- Erythromycin (orally or by injection) for 14 days (40 mg/kg per day with a maximum of 2 g/d), or
- Procaine penicillin G given intramuscularly for 14 days (300,000 U/d for patients weighing <10 kg and 600,000 U/d for those weighing >10 kg).
- Patients with allergies to penicillin G or erythromycin can use rifampin or clindamycin.
- In more severe cases lymph nodes in the neck may swell, and breathing and swallowing will be more difficult throat may require intubation or a tracheotomy
Pertussis
- Pertussis, also known as "whooping cough", is a highly contagious disease caused by certain species of the bacterium Bordetella—usually B. pertussis
- The disease is characterized initially by mild respiratory infections symptoms such as cough, sneezing, and runny nose (catarrhal stage).
- After one to two weeks the cough changes character, with paroxysms of coughing followed by an inspiratory "whooping" sound (paroxysmal stage)
- Other complications of the disease include pneumonia, encephalitis, pulmonary hypertension, and secondary bacterial superinfection.
- The disease is spread by contact with airborne discharges from the mucous membranes of infected people.
- Laboratory diagnosis include; Calcium alginate throat swab, culture on Bordet-Gengou medium, immunofluorescence and serological methods.
-Treatment of the disease with antibiotics (often erythromycin, azithromycin, clarithromycin or trimethoprim-sulfamethoxazole)
- Vaccination in children as preventive measure . The immunizations are often given in combination with tetanus and diphtheria immunizations, at ages 2, 4, and 6 months, and later at 15–18 months and 4–6 years
Tetanus
Tetanus is a serious and often fatal disease caused by the neurotoxin tetanospasmin which is produced by the Gram-positive, obligate anaerobic bacterium Clostridium tetani.
Symptoms
-The incubation period for tetanus is 3 days to as long as 15 weeks
- For neonates, the incubation period is 4 to 14 days, with 7 days being the average
- The first sign of tetanus is a mild jaw muscle spasm called lockjaw (trismus), followed by stiffness of the neck and back, risus sardonicus, difficulty swallowing, and muscle rigidity in the abdomen.
- Typical signs of tetanus include an increase in body temperature by 2 to 4°C, diaphoresis (excessive sweating), an elevated blood pressure, and an episodic rapid heart rate
Treatment
- Penicillin and metronidazole
- Human anti-tetanospasmin immunoglobulin should be given.
- Diazepam and DPT vaccine booster are also given
Syphilis
- a sexually transmitted disease (STD) that is caused by a spirochaete bacterium, Treponema pallidum
- The route of transmission for syphilis is almost invariably by sexual contact
Stages of syphilis
1.Primary syphilis
Chancres on penis due to primary syphilitic infection
Primary syphilis is manifested after an incubation period of 10-90 days (the average is 21 days) with a primary sore.
During the initial incubation period, individuals are asymptomatic.
The sore, called a chancre, is a firm, painless skin ulceration localized at the point of initial exposure to the bacterium, often on the penis, vagina or rectum.
Local lymph node swelling can occur. The primary lesion may persist for 4 to 6 weeks and then heal spontaneously.
2. Secondary syphilis
characterized by a skin rash that appears 1-6 months (commonly 6 to 8 weeks) after the primary infection
This is a symmetrical reddish-pink non-itchy rash on the trunk and extremities , nvolves the palms of the hands and the soles of the feet
in moist areas of the body the rash becomes flat broad whitish lesions called condylomata lata. Mucous patches may also appear on the genitals or in the mouth
common other symptoms include fever, sore throat, malaise, weight loss, headache, meningismus, and enlarged lymph nodes
3. Tertiary syphilis
occurs from as early as one year after the initial infection but can take up to ten years to manifest
This stage is characterised by gummas, soft, tumor-like growths, readily seen in the skin and mucous membranes, but which can occur almost anywhere in the body, often in the skeleton
Other characteristics of untreated syphilis include Charcot's joints (joint deformity),
Clutton's joints (bilateral knee effusions).
The more severe manifestations include neurosyphilis and cardiovascular syphilis.
Cardiovascular complications include aortic aortitis, aortic aneurysm, aneurysm of sinus of Valsalva, and aortic regurgitation, and are a frequent cause of death
Syphilitic aortitis can cause de Musset's sign
4.Congenital syphilis
Congenital syphilis is syphilis present in utero and at birth, and occurs when a child is born to a mother with secondary or tertiary syphilis.
Manifestations of congenital syphilis include abnormal x-rays; Hutchinson's teeth (centrally notched, widely-spaced peg-shaped upper central incisors);
mulberry molars (sixth year molars with multiple poorly developed cusps);
frontal bossing; saddle nose; poorly developed maxillae; enlarged liver; enlarged spleen; petechiae;
other skin rash; anemia; lymph node enlargement; jaundice; pseudoparalysis; and snuffles, the name given to rhinitis in this situation.
Rhagades, linear scars at the angles of the mouth and nose result from bacterial infection of skin lesions.
Death from congenital syphilis is usually through pulmonary hemorrhage.
Diagnosis
First effective test for syphilis, the Wassermann test
Rapid Plasma Reagin (RPR) and Venereal Disease Research Laboratory (VDRL) test are not as effective
Newer tests based on monoclonal antibodies and immunofluorescence, including Treponema pallidum haemagglutination assay (TPHA) and Fluorescent Treponemal Antibody Absorption (FTA-ABS) are more specific, but are still unable to rule out non-syphillis Treponomal infections such as Yaws and Pinta.
Microscopy of chancre fluid using dark ground illumination can be extremely quick and effective.
Treatment
first choice treatment for syphilis remains penicillin, in the form of benzathine penicillin G or aqueous procaine penicillin G injections
oral tetracyclines. In patients allergic to penicillins
Typhoid fever
- Typhoid fever (Enteric fever) is an illness caused by the bacterium Salmonella typhi
Symptoms
After infection, symptoms include:
a high fever from 39 °C to 40 °C (103 °F to 104 °F) that rises slowly
chills
bradycardia (slow heart rate)
weakness
diarrhea
headaches
myalgia (muscle pain)
lack of appetite
constipation
stomach pains
in some cases, a rash of flat, rose-colored spots called "rose spots"
extreme symptoms such as intestinal perforation or hemorrhage, delusions and confusion are also possible.
Diagnosis
Widal test (demonstration of salmonella antibodies against antigens O-somatic and H-flagellar)
Treatment
Antibiotics, such as ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, and ciprofloxacin, are commonly used to treat typhoid fever in developed countries
Usage of Ofloxacin along with Lactobacillus acidophilus is also recommended.
Sympathomimetics -Adrenergic Agents
Pharmacology
Sympathomimetics -Adrenergic Agents
The sympathomimetic or adrenergic or adrenomimetic drugs mimic the effects of adrenergic sympathetic nerve stimulation.
These are the important group of therapeutic agents which may be used to maintain blood pressure and in certain cases of severe bronchial asthma.
Mechanism of Action and Adrenoceptors
The catecholamines produce their action by direct combination with receptors located on the cell membrane. The adrenergic receptors are divided into two main groups – alpha and beta.
alpha receptor - stimulation produces excitatory effect and
beta receptor -stimulation usually produces inhibitory effect.
Alpha receptors: There are two major groups of alpha receptors, α1 and α2.
Activation of postsynaptic α1 receptors increases the intracellular concentration of calcium by activation of a phospholipase C in the cell membrane via G protein.
α2 receptor is responsible for inhibition of renin release from the kidney and for central aadrenergically mediated blood pressure depression.
Beta receptors:
a. Beta 1 receptors have approximately equal affinity for adrenaline and noradrenaline and are responsible for myocardial stimulation and renin release.
b. Beta 2 - receptors have a higher affinity for adrenaline than for noradrenaline and are responsible for bronchial muscle relaxation, skeletal muscle vasodilatation and uterine relaxation.
c. Dopamine receptors: The D1 receptor is typically associated with the stimulation of adenylyl cyclase. The important agonist of dopamine receptors is fenoldopam (D1) and bromocriptine (D2) and antagonist is clozapine (D4) .
Adrenergic drugs can also be classified into:
a. Direct sympathomimetics: These act directly on a or/and b adrenoceptors e.g. adrenaline, noradrenaline, isoprenaline, phenylephrine, methoxamine salbutamol etc.
b. Indirect sympathomimetics: They act on adrenergic neurones to release noradrenaline e.g. tyramine.
c. Mixed action sympathomimetics: They act directly as well as indirectly e.g. ephedrine, amphetamine, mephentermine etc.
Pharmacological Action of Sympathomimetics
Heart: Direct effects on the heart are determined largely by β1 receptors.
Adrenaline increases the heart rate, force of myocardial contraction and cardiac output
Blood vessels: Adrenaline and noradrenaline constrict the blood vessels of skin and mucous membranes.
Adrenaline also dilates the blood vessels of the skeletal muscles on account of the preponderance of β2 receptor
Blood pressure: Because of vasoconstriction (α1) and vasodilatation (β2) action of adrenaline, the net result is decrease in total peripheral resistance.
Noradrenaline causes rise in systolic, diastolic and mean blood pressure and does not cause vasodilatation (because of no action on β2 receptors) and increase in peripheral resistance due to its a action.
Isoprenaline causes rise in systolic blood pressure (because of β1 cardiac stimulant action) but marked fall in diastolic blood pressure (because of b2 vasodilatation action) but mean blood pressure generally falls.
GIT: Adrenaline causes relaxation of smooth muscles of GIT and reduce its motility.
Respiratory system: The presence of β2 receptors in bronchial smooth muscle causes relaxation and activation of these receptors by β2 agonists cause bronchodilatation.
Uterus: The response of the uterus to the atecholamines varies according to species
Eye: Mydriasis occur due to contraction of radial muscles of iris, intraocular tension is lowered due to less production of the aqueous humor secondary to vasoconstriction and conjunctival ischemia due to constriction of conjunctival blood vessels.
a. Urinary bladder: Detrusor is relaxed (b) and trigone is constricted (a) and both the actions tend to inhibit
micturition.
b. Spleen: In animals, it causes contraction (due to its a action) of the splenic capsule resulting in increase in number of RBCs in circulation.
c. It also cause contraction of retractor penis, seminal vesicles and vas deferens.
d. Adrenaline causes lacrimation and salivary glands are stimulated.
e. Adrenaline increases the blood sugar level by enhancing hepatic glycogenolysis and also by decreasing the uptake of glucose by peripheral tissues.
Adrenaline inhibits insulin release by its a-receptor stimulant action whereas it stimulates glycogenolysis by its b receptor stimulant action.
f. Adrenaline produces leucocytosis and eosinopenia and accelerates blood coagulation and also stimulates platelet aggregation.
Adverse Effects
Restlessness, anxiety, tremor, headache.
Both adrenaline and noradrenaline cause sudden increase in blood pressure, precipitating sub-arachnoid haemorrhage and occasionally hemiplegia, and ventricular arrhythmias.
May produce anginal pain in patients with ischemic heart disease.
Contraindications
a. In patients with hyperthyroidism.
b. Hypertension.
c. During anaesthesia with halothane and cyclopropane.
d. In angina pectoris.
Therapeutic Uses
Allergic reaction: Adrenaline is drug of choice in the treatment of various acute allergic disorders by acting as a physiological antagonist of histamine (a known mediator of many hypersensitivity reactions). It is used in bronchial asthma, acute angioneurotic edema, acute hypersensitivity reaction to drugs and in the treatment of anaphylactic shock.
Bronchial asthma: When given subcutaneously or by inhalation, adrenaline is a potent drug in the treatment of status asthmaticus.
Cardiac uses: Adrenaline may be used to stimulate the heart in cardiac arrest.
Adrenaline can also be used in Stokes-Adam syndrome, which is a cardiac arrest occurring at the transition of partial to complete heart block. Isoprenaline or orciprenaline may be used for the temporary treatment of partial or complete AV block.
Miscellaneous uses:
a. Phenylephrine is used in fundus examination as mydriatic agent.
b. Amphetamines are sometime used as adjuvant and to counteract sedation caused by antiepileptics.
c. Anoretic drugs can help the obese people.
d. Amphetamine may be useful in nocturnal enuresis in children.
e. Isoxsuprine (uterine relaxant) has been used in threatened abortion and dysmenorrhoea.