NEET MDS Synopsis
Selective serotonin reuptake inhibitors
Pharmacology
Selective serotonin reuptake inhibitors (SSRIs)
e.g. fluoxetine, paroxetine, citalopram, and sertraline
- Most commonly used antidepressant category
- Less likely to cause anticholinergic side effects
- Relatively safest antidepressant group in overdose
- Selectively inhibits reuptake of serotonin(5-HT)
Mode of Action;
- Well absorbed when given orally
- Plasma half-lives of 18-24 h allowing once daily dosagedaily dosage
- Metabolised through CYP450 system and most SSRIs inhibit some CYP isoforms
- Therapeutic effect is delayed for 2-4 weeks
ADVERSE DRUG REACTIONS
- Insomnia, increased anxiety, irritability
- Decreased libido
- Erectile dysfunction, anorgasmia, and ejaculatory delay
- Bleeding disorders
- Withdrawal syndrome
Malignant Diseases of Skin
General Pathology
Malignant Diseases of Skin
1. Bowen's disease refers to a carcinoma in situ on sun-exposed skin or on the vulva, glans a penis, or oral mucosa which has an association, in some cases, with a visceral malignancy.
2. Skin cancers associated with ultraviolet light damage include basal cell carcinoma, squamous cell carcinoma, and malignant melanoma.
3. A basal cell carcinoma is the MC malignant tumor of the skin and occurs on sunexposed, hair-bearing surfaces.
- Locally aggressive, infiltrating cancers arising from the basal cell layer of the epidermis and infiltrate the underlying superficial dermis.
- they do not metastasize
- BCC are commonly located on the face on the inner aspect of the nose, around the orbit and the upper lip where they appear as raised nodules containing a central crater with a pearly-colored skin surface and vascular channels.
- microscopically, they have cords of basophilic staining cells originating from the basal cell layer infiltrating the dermis.
- they commonly recur if they are not totally excised, because they are frequently multifocal.
- the basal cell nevus syndrome is an autosomal-dominant disorder characterized by the development of basal cell carcinomas early in life with associated abnormalities of bone, skin, nervous system, eyes, and reproductive system.
Peutz-Jeghers syndrome
General Pathology
Peutz-Jeghers syndrome
1. Lesions appear as small, melanotic, and freckle-like. They can be found on the skin, oral mucosa, lips, feet, and hands.
2. May also present with intestinal polyps, which may develop into a gastrointestinal carcinoma.
3. Genetic transmission: autosomal dominant.
Maintenance of Homeostasis
Physiology
Maintenance of Homeostasis
The kidneys maintain the homeostasis of several important internal conditions by controlling the excretion of substances out of the body.
Ions. The kidney can control the excretion of potassium, sodium, calcium, magnesium, phosphate, and chloride ions into urine. In cases where these ions reach a higher than normal concentration, the kidneys can increase their excretion out of the body to return them to a normal level. Conversely, the kidneys can conserve these ions when they are present in lower than normal levels by allowing the ions to be reabsorbed into the blood during filtration. (See more about ions.)
pH. The kidneys monitor and regulate the levels of hydrogen ions (H+) and bicarbonate ions in the blood to control blood pH. H+ ions are produced as a natural byproduct of the metabolism of dietary proteins and accumulate in the blood over time. The kidneys excrete excess H+ ions into urine for elimination from the body. The kidneys also conserve bicarbonate ions, which act as important pH buffers in the blood.
Osmolarity. The cells of the body need to grow in an isotonic environment in order to maintain their fluid and electrolyte balance. The kidneys maintain the body’s osmotic balance by controlling the amount of water that is filtered out of the blood and excreted into urine. When a person consumes a large amount of water, the kidneys reduce their reabsorption of water to allow the excess water to be excreted in urine. This results in the production of dilute, watery urine. In the case of the body being dehydrated, the kidneys reabsorb as much water as possible back into the blood to produce highly concentrated urine full of excreted ions and wastes. The changes in excretion of water are controlled by antidiuretic hormone (ADH). ADH is produced in the hypothalamus and released by the posterior pituitary gland to help the body retain water.
Blood Pressure. The kidneys monitor the body’s blood pressure to help maintain homeostasis. When blood pressure is elevated, the kidneys can help to reduce blood pressure by reducing the volume of blood in the body. The kidneys are able to reduce blood volume by reducing the reabsorption of water into the blood and producing watery, dilute urine. When blood pressure becomes too low, the kidneys can produce the enzyme renin to constrict blood vessels and produce concentrated urine, which allows more water to remain in the blood.
HYPERTROPHY
General Pathology
HYPERTROPHY
Increase in the size of an organ or tissue due to increase in the size of its Constituent cells.
1. Skeletal muscle due to -exercise.
2. Cardiac muscle of:
- Left ventricle in:
o Hypertension.
o Aortic valvular lesion.
o Severe anaemia.
- Right ventricle in :
o Mitral stenosis
o Cor pulmonale
3. Smooth muscle of:
- GIT proximal to strictures.
- Uterus in pregnancy.
Types of Brain Injury
General SurgeryTypes of Brain Injury
Brain injuries can be classified into two main categories: primary and
secondary injuries. Understanding these types is crucial for effective diagnosis
and management.
1. Primary Brain Injury
Definition: Primary brain injury occurs at the moment
of impact. It results from the initial mechanical forces applied to the
brain and can lead to immediate damage.
Examples:
Contusions: Bruising of brain tissue.
Lacerations: Tears in brain tissue.
Concussions: A temporary loss of function due to trauma.
Diffuse axonal injury: Widespread damage to the brain's white
matter.
2. Secondary Brain Injury
Definition: Secondary brain injury occurs after the
initial impact and is often preventable. It results from a cascade of
physiological processes that can exacerbate the initial injury.
Principal Causes:
Hypoxia: Reduced oxygen supply to the brain, which
can worsen brain injury.
Hypotension: Low blood pressure can lead to
inadequate cerebral perfusion.
Raised Intracranial Pressure (ICP): Increased
pressure within the skull can compress brain tissue and reduce blood
flow.
Reduced Cerebral Perfusion Pressure (CPP):
Insufficient blood flow to the brain can lead to ischemia.
Pyrexia: Elevated body temperature can increase
metabolic demands and worsen brain injury.
Glasgow Coma Scale (GCS)
The Glasgow Coma Scale is a clinical tool used to assess a patient's level of
consciousness and neurological function. It consists of three components: eye
opening, verbal response, and motor response.
Eye Opening (E)
Spontaneous: 4
To verbal command: 3
To pain stimuli: 2
No eye opening: 1
Verbal Response (V)
Normal, oriented: 5
Confused: 4
Inappropriate words: 3
Sounds only: 2
No sounds: 1
Motor Response (M)
Obeys commands: 6
Localizes to pain: 5
Withdrawal flexion: 4
Abnormal flexion (decorticate): 3
Extension (decerebrate): 2
No motor response: 1
Scoring
Best Possible Score: 15/15 (fully alert and oriented)
Worst Possible Score: 3/15 (deep coma or death)
Intubated Cases: For patients who are intubated, the
verbal score is recorded as "T."
Intubation Indication: Intubation should be performed
if the GCS score is less than or equal to 8.
Additional Assessments
Pupil Examination
Pupil Reflex: Assess size and light response.
Uncal Herniation: In cases of mass effect on the
ipsilateral side, partial third nerve dysfunction may be noted,
characterized by a larger pupil with sluggish reflex.
Hutchinson Pupil: As third nerve compromise increases,
the ipsilateral pupil may become fixed and dilated.
Signs of Base of Skull Fracture
Raccoon Eyes: Bilateral periorbital hematoma,
indicating possible skull base fracture.
Battle’s Sign: Bruising over the mastoid process,
suggesting a fracture of the temporal bone.
CSF Rhinorrhea or Otorrhea: Leakage of cerebrospinal
fluid from the nose or ear, indicating a breach in the skull base.
Hemotympanum: Blood in the tympanic cavity, often seen
with ear bleeding.
THROMBOPHLEBITIS AND PHLEBOTHROMBOSIS
General Pathology
THROMBOPHLEBITIS AND PHLEBOTHROMBOSIS
- The deep leg veins account for more than 90% of cases (DVT)
- the most important clinical predispositions are: congestive heart failure, neoplasia, pregnancy, obesity, the postoperative state, and prolonged bed rest or immobilization
- local manifestations: distal edema, cyanosis, superficial vein dilation, heat, tenderness, redness, swelling, and pain
- migratory thrombophlebitis (Trousseau sign): hypercoagulability occurs as a paraneoplastic syndrome related to tumor elaboration of procoagulant factors
TRICYCLIC ANTIDEPRESSANTS
Pharmacology
TRICYCLIC ANTIDEPRESSANTS
e.g. amitriptyline, imipramine, nortriptyline
Belong to first generation antidepressants
ACTION:
Inhibit 5-HT(5-hydroxytryptamine) and norepinephrine reuptake
slow clearance of norepinephrine & 5-HT from the synapse
enhance norepinephrine & 5-HT neuro-transmission
MODE OF ACTIONMODE OF ACTION
TCAs also block
– muscarinic acetylcholine receptors
– histamine receptors
– 5-HT receptors
– α1 adrenoceptors
Onset of antidepressant activity takes 2-3 weeks
PHARMACOKINETICS
- Readily absorbed from the gastro-intestinal tract
- Bind strongly to plasma albumin
- Has a large volume of distribution(as a result of binding to extravascular tissues)
- Undergo liver CYP metabolism into biologically active metabolites
- These metabolites are inactivated via glucuronidation and excreted in urine
ADVERSE DRUG REACTIONS
Antimuscarinic - dry mouth, blurred vision, constipation and urinary retention
Antihistamine – drowsiness
adrenoceptor blockage(+/- central effect) postural hypotension
Reduce seizure threshold
Testicular enlargement, gynaecomastia, galactorrhoea
AV-conduction blocks and cardiac arrhythmias
TOXICITY
- Fatal in toxicity
- Most important toxic effect is, slowing of depolarisation of the cardiac action potential by blocking fast sodium channels ("quinidine-like" effect)
- delays propagation of depolarisation through both myocardium and conducting tissue
- prolongation of the QRS complex and the PR/QT intervals
- predisposition to cardiac arrhythmias
DRUG INTERACTIONS
Pharmacodynamic:
– ↑ sedation with antihistamines, alcohol
– ↑ antimuscarinic effects with anticholinergics– ↑ antimuscarinic effects with anticholinergics
– Hypertension and arrhythmias with MAOIs- should be given at least 14 days apart
Pharmacokinetic (via altering CYP metabolism)
– ↓ plasma concentration of TCA by- carbamazepine, rifampicin
– ↑ plasma concentration of TCA by- cimetidine, calcium channel blockers,fluoxetine
OTHER CLINICAL USES OF AMITRIPTYLINE
- Treatment of nocturnal enuresis in children
- Treatment of neuropathic pain
- Migraine prophylaxis