BTR OFFLINE Day 3 PDF - Hematology, Cardiovascular, and Neurology

INTEGRATED HEMATOLOGY RBC shapes and disorders Mulberry/Mott cells Flame cells Russel body- Dutcher body- B2 microglobulin Microcytic Anemia...

INTEGRATED HEMATOLOGY RBC shapes and disorders Mulberry/Mott cells Flame cells Russel body- Dutcher body- B2 microglobulin Microcytic Anemia IDA vs Thalassemia minor Serum iron ↓ ↓ ↑ Mentzer index Transferrin or TIBC ↑ ↓ ↓ RDW: Ferritin ↓ ↑ ↑ Confirmatory test for thalassemia minor: % transferrin saturation ↓↓ ↓ ↑↑ Glu -> Valine: SICKLE CELL ANEMIA: Glu -> Lysine Glutamic acid Chr 16 deletion: Hydroxyurea Chr 11 Splicing mutation: Voxelotor Crizanlizumab Intravascular hemolysis Pancytopenia Thrombosis-Budd Chiari syndrome LAP score low Aplastic anemia, Leukemia Rx-Eculizumab WBCs Approach to Pancytopenia HSM + HSM - HYPERCELLULAR DRY TAP + HYPERCELLULAR DRY TAP + MARROW MARROW BMB: Approach to Leukemia CHRONIC ACUTE Lymphocytic Myeloid origin ADULT CHILD 10yr Pre B cell T cell –Acid phosphatase + L1 Mediastinum, Brain, Testes Hyperdiploidy L2 t 12;21 Hypodiploidy t (9;22) t (4;11) MC in children: SPLENOMEGALY + PANCYTOPENIA MC in down syndrome: DRY TAP + MC in downs (6% Aggregation Immature Abn Platelet 75 y 2 points D Diabetes 1 point S2 Stroke 2 points V Vascular disease 1 point A Age>65 y 1 point Sc Sex category, female 1 point DOC-Verapamil ESC 2010 Anticoagulation Recommendations: Score=1 Aspirin Score> 2 oral anticoagulation. Unstable-Cardioversion 25-50J Stable-Esmolol/Ibutilide Anticoagulation Carotid sinus massage Iv adenosine Unstable-Cardioversion Unstable-Defibrillation Stable-IV Amiodarone DOC-Lignocaine Romano-Ward: Jerwell-Lange-Nelson: DOC-MgSO4 Important ECG Digitalis: Shortening of QT interval, Flattened T waves Scooped ST depressions-Hockey stick/ Salvador Dali moustache PR increased Serum Possible ECG abnormalities potassium Mild (5.5-6.5 Peaked T waves mEq/L) Prolonged PR segment Moderate Loss of P wave (6.5-8.0 Prolonged QRS complex mEq/L) ST-segment elevation Ectopic beats Severe (>8.0 Sine wave mEq/L) Ventricular fibrillation Asystole ST-elevation Changes in MI: Acute chest pain + Pericardial rub Ventricular aneurysm Prinzmetal angina-transient Takotsubo CMP  Prinzmetal Stable Unstable angina NSTEMI STEMI Angina Angina PAIN TROPONIN LEVEL ECG INFARCTION Management JVP Heart sounds Murmurs Systolic Crescendo-decrescendo ejection murmur, loudest at heart base, radiates to carotids Holosystolic, high-pitched “blowing” murmur MR: Loudest at apex, radiates toward axilla TR: loudest at tricuspid area Late crescendo murmur with midsystolic click (MC) that occurs after carotid pulse Best heard over apex Holosystolic, harsh-sounding murmur Loudest at tricuspid area Diastolic Early diastolic, decrescendo, high-pitched “blowing” murmur Follows opening snap (OS) Delayed rumbling mid-to-late murmur (↓ interval between S2 and OS correlates with ↑ severity) Continuous Continuous machine like murmur, best heard at left infraclavicular area Murmurs Preload reduce ( Valsalva/Standing/Nitroglycerin): Preload increase ( Passive leg raise / Squatting/Phenylephrine): Afterload reduce ( amyl nitrite): Afterload increase (Handgrip): Inspiration: Pressure-volume curves  Cardiac Pathology JAI VIGYAN MISSION MODE PROJECT CVS Pharmacology DYSLIPIDEMIC DRUGS: NEW DRUGS Statins-HMG coA reductase inhibitor Ivabradine: Ezitimibe-Absorption – Nicorandil: Fibrates-PPAR alpha – Rho kinase inhibitor: Niacin-HSL – Neprilysin+ ACE inhibitor: Alirocumab, Evolocumab-PCSK9- S/e: Evinacumab: AL3p Neprilysin inhibitor: Metabolic modulators: Bainbridge reflex MM + Late inward Na blocker: Bezold-Jarisch reflex J reflex Postural hypotension: SBP-DBP-within 3min of standing  CCB Hydralazine Nitroprusside Digoxin ACE-: ARB: Nitrates Captopril, Losartan, Amlodipine, nifedipine, Diltiazem, Lisinopril, Valsartan nimodipine verapamil Enalapril S/E: S/E: Reflex tachycardia Hyperkalemia S/E: S/E: AV block Flushing Cholinergic Hyperkalemia Constipation Yellow vision Cough Pedal edema Ventricular bigeminy MC Angioedema Gingival hyperplasia Hyperprolactinemia ATP binding casette PPAR-y agonist Uric acid excretion increase TxA2 inhibition Clonidine: Rebound hypertension Antiarrhythmic drugs I IA: K-: Quinidine, Procainamine, Disopyramide IB: K +: Lignocaine, Phenytoin IC: K no: Fleicanide, Propafenone II III-Amiodarone, Ibulitide Dofetilide, Sotalol IV Adenosine Amiodarone: Pls Check PFT LFT TFT ANATOMY Cranial Nerve Columns “SAVE VA SAVE VASE” Cranial nerve Preganglionic Ganglion Postganglionic Structure Medial to lateral: nucleus parasympathetic parasympathetic Edinger-Westphal CN III Ciliary ganglion Nasociliary nerve Ciliary muscles GVA-SVA-GSA-SSA nucleus Short ciliary nerves Superior CN VII Pterygopalatine Maxillary nerve Lacrimal gland salivatory nucleus ganglion Sublingual and Submandibular Lingual nerve submandibular ganglion glands Inferior salivatory CN IX Otic ganglion Auriculotemporal Parotid gland nucleus nerve) Dorsal motor CN X - Vagal Nerve Heart, lungs upper GI nucleus Cranial foramina Cranial foramina and CN Dorsal origin RULE OF 17: Internal decussation Longest intracranial course Thinnest, smallest Longest intradural course Longest intraosseous course Neuroanatomy COMMISURAL: ASSOCIATION: PROJECTION: FORNIX: Head and neck ILN ILN All muscles supplied by except Safety muscle: Depressor: Chorda tympani Lingual N All muscles supplied by except All elevators except All protractors except Attached to articular disc of TMJ: Accessory masticator muscle: EMBRYOLOGY NEURAL CREST MOTEL PASSES GU system Adrenal cortex Gonads Dura SOMITES: SOMATOPLEURIC: Nucleus pulposus Axial skeleton Dermis of anterior torso, limbs Tectorial membrane Dermis of back Appendicular skeleton Skeletal muscles Tongue / EOM SPLANCHNOPLEURIC: Cardiac muscles Smooth Muscles RES-Spleen, Microglia Adrenal cortex- Dura- Serosa, endothelium Adrenal medulla- Leptomeninges- UROGENITAL SYSTEM MESONEPHRIC DUCT= PARAMESONEPHRIC DUCT= Caudal end-Ureteric bud: Males: Males: Females: Females: P E Urinary system G VS Gartner duct cyst- Kidney (Till DCT) Collecting system- Trigone- UB- Urethra- Prostate- Pharyngeal cleft-pouch derivatives Cleft Adult derivatives 1st External auditory meatus, tympanic membrane 2nd – 4th Cervical sinus- obliterates; Persist as Brachial cyst/sinus Pouch Adult derivatives 1st Middle ear cavity, Eustachian tube, Mastoid, Tympanic membrane 2nd Epithelial lining of crypts of palatine tonsil; including crypta magna 3rd Thymus, Inferior parathyroid glands 4th Superior parathyroid glands Ultimobranchial body (5th remnant) Pharyngeal arch derivatives Pharyngea Bones Muscles Nerve Artery l arch 1st Meckel’s cartilage, Maxilla, Muscles of mastication, V3 Maxillary artery Mandible, Malleus and incus, Mylohyoid, zygoMatic bone, sphenoMandibular Anterior belly of digastric, Tensor ligament veli palatini, 2nd Reichert’s cartilage Muscles of facial expression, VII Stapedial artery Stapes, Styloid process, LeSSer horn Stylohyoid, Stapedius,Buccinator, of hyoid bone, Platysma, Stylohyoid ligament Posterior belly of digastric 3rd Hyoid bone (Body and greater horn) Stylopharyngeus IX Common carotid and internal carotid 4th Laryngeal cartilages Cricothyroid, Vagus nerve (X) Left: Aortic arch Levator palatini, Superior Laryngeal Right: Proximal right subclavian Pharyngeal constrictors nerve artery (+ 7TH intersegmental artery + Dorsal Aorta) 6th All intrinsic muscles of larynx Vagus nerve (X) PA (except cricothyroid) Recurrent laryngeal DA Cricopharyngeus nerve Pharyngeal arch derivatives Pharynge Bones Muscles Nerve Artery al arch 1st Meckel’s cartilage, Maxilla, Muscles of mastication, V3 Maxillary artery Mandible, Malleus and incus, Mylohyoid, zygoMatic bone, Anterior belly of digastric, sphenoMandibular ligament Tensor veli palatini, 2nd Reichert’s cartilage Muscles of facial expression, VII Stapedial artery Stapes, Styloid process, Stylohyoid, LeSSer horn of hyoid bone, Stapedius,Buccinator, Stylohyoid ligament Platysma, Posterior belly of digastric 3rd Hyoid bone (Body and Stylopharyngeus IX Common carotid and greater horn) internal carotid 4th Laryngeal cartilages Cricothyroid, Vagus nerve (X) Left: Aortic arch Levator palatini, Superior Right: Proximal right Pharyngeal constrictors Laryngeal nerve subclavian artery (+ 7TH intersegmental artery + Dorsal Aorta) 6th All intrinsic muscles of Vagus nerve (X) PA larynx (except cricothyroid) Recurrent DA Cricopharyngeus laryngeal nerve Ventral mesentery derivatives Dorsal mesentery derivatives Lesser omentum (Hepatogastric Greater omentum and Hepatoduodenal ligament) Falciform ligament Gastrosplenic ligament Triangular ligament of liver Lienorenal ligament Coronary ligament of liver Gastrophrenic ligament Mesentery of small intestine and mesoappendix Transverse and sigmoid mesocolon Changes After Birth: Closing of Shunts Shunt Functional Anatomical closure closure Ductus 2-3d 2 – 3 wks arteriosus (10-15hrs) Formamen Within mins One year ovale Ductus Within mins 3 – 7 days venosus UMBILICAL LIGAMENTS MEDIAN- MEDIAL- LATERAL- Left Umbilical vein- Diaphragm A. B. C. D. Abdomen Couinaud’s liver segments Gluteus maximus: Function: Gover sign Iliotibial tract: Gluteus minimus, medius: Function: Upper limb Spiral/twisted: Axillary sheath: Continuation of Upper trunk: Ant to Scalenus anterior: Inter-scalene triangle: Lower trunk: HISTOLOGY JOINTS-SYNOVIAL Incus-stapes Malleus-incus Atlanto- Atlanto- TMJ Ankle Intercarpal Hip 1st CMC occipital axial Knee Elbow Intertarsal Shoulder Calcaneo-cuboid IP Acromio- Talo- Sterno-clavicular clavicular calcaneo- Costo- navicular transverse Costo- vertebral Sterno-costal except 1st Reticulin fibres absent in: Ligamentum flavum rich in: Dense irregular collagen in: Reticular fibres absent in: Ligamentum flavum is rich in: Dense irregular collagen in: Superficial posterior compartment of leg: Ansa cervicalis: CCA division at the level of: Transverse facial artery: Parallel arrangement: Thyrohyoid, Sternohyoid, Rectus abdominis, Fusiform: Biceps brachii, digastric INTEGRATED NEUROLOGY  Sensory Receptors RECEPTOR ADAPTATION REMARKS FAST Most numerous Non-hairy skin only Fast moving touch, two point discriminatopn FAST Largest receptor Most sensitive HIGH FREQUENCY VIBRATION FAST Hair movement SLOW Epidermis- Edge BRAILLE SLOW Skin stretch, pressure Maximum in joint capsule SLOW Itching, Slow pain (Substance P) Erlanger-Grasser: Nerve fibres Fiber type Functions Conduction Diameter Cold sensation: velocity (µm) (m/sec) Warm, burning pain and freezing pain: A Alpha Proprioception; somatic motor 70-120 12-20 Local anaesthetic: Ag and Ad>> Beta Touch, pressure 30-70 8 Aα and Aβ >> B >>C Gamma Efferent to muscle spindles 15-30 5 Pressure: Delta Fast Pain, temperature (cold) 12-30 2-5 Hypoxia: B Preganglionic autonomic 3-12 3 C Slow Pain, temperature (warm), 0.5-2 1 Postganglionic sympathetic SLEEP PHYSIOLOGY Awake (eyes open) Beta Awake (eyes closed) Alpha Stage N1 (5%) Theta Stage N2 (45%) Sleep spindles and K complexes Stage N3 (25%) Delta REM sleep (25%) Beta, PGO Nightmares: Night-terrors Reduced REM Latency: Elderly: Low REM, Low N3  Basal Ganglia Caudate Putamen Gpi Gpe SNpr SNpc STN Tremor increases with activity Decreases with alcohol Familial DOC:  Hypothalamic nuclei Lateral nucleus Ventromedial nucleus Anterior nucleus Posterior nucleus Suprachiasmatic nucleus Supraoptic nucleus Paraventricular nuclei Preoptic nucleus Cerebellum Intention tremor Dysdiadochokinesia Pendular knee jerk IMPORTANT RADIOLOGY IMAGES  COLOUR WBC GLUCOSE PROTEIN OPENING Layers punctured for LP: (cells/ul) (mg/dl) (mg/dl) PRESSURE mm H20 Normal Clear 0-5 40-70 personality changes Apo E2 Apo E4 Mild: Donepezil Severe: Memantine Lecanemab, Aducanumab Transdermal patch: Stepwise decline Deep white matter changes on neuroimaging Early personality changes Apathy, disinhibition & compulsive behavior Visual hallucinations Spontaneous parkinsonism Fluctuating cognition, REM behaviour disorder Wet-Wacky-Wobbly Shuffling gait with preserved arm swing Behavioral changes, Myoclonus Rapidly progressive 14-3-3 in CSF, Periodic sharp wave EEG STROKE LOCALISATION Contralateral paralysis and sensory loss—lower limb + Urinary incontinence + Personality changes Contralateral paralysis and sensory loss—face and upper limb + Aphasia Contralateral paralysis and sensory loss—face and upper limb + C/l hemianopia + Denial of blindness + Alexia without agraphia (Dominant) Agraphia, acalculia, finger agnosia, R-L disorientation Contralateral hemisensory loss followed by an agonizing, burning pain in the affected areas EPILEPSY SYNDROMES Infant + Global -Transient loss of MC in Adolescent developmental delay consciousness (1-2s) Early morning ”clumsy” Multifocal sz -No loss of postural 3-6 Hz generalized polyspike Anti-dsDNA Anti-histone Anti-Sm Anti-U1 RNP Anti-Ro/SS-A Anti-La/SS-B Anti-Jo1 Anti-Mi2 Anti-topoisomerase 1 / Anti-scl-70 Anti-centromere TSI (thyroid stimulating Ig) p-ANCA c-ANCA RF GOUT-PSEUDOGOUT Acute Gout NSAIDS Colchicine Chronic gout DOC: HLA B5*801 AVOID WITH:  Management of RA RA: DOC in pregnancy: BIOLOGICALS in RA TNF-apha inhibitors: Adalimumab Certolizumab Etanercept Infliximab Golimumab IL-1R Antagonist: IL-6 inhibitor: B-cell depletor/CD20-: Co-stimulation inhibitor/CTLA4-: JAK inhibitors: Tofacitinib, Baricitinib Vasculitis Granulomas ANCA IMMUNE COMPLEX Diagnosis: DOC:  INTEGRATED RENAL SYSTEM RENAL PHYSIOLOGY Clearance= GFR= RPF= Filtration fraction= Clearance: PAH > Creatinine > Inulin > Urea > Na > Glucose Macula Densa: TUBULAR DISORDERS K Ca pH Nephrolithiasis DEPOSITS TYPE IV COLLAGEN IgG, IgM, IgA, C3, C1q NEPHRITIC SYNDROME Hematuria, Oliguria, Hypertension Child Adult Rapid progressive Hematuria 10-21d after Hematuria 3d after pharyngitis pharyngitis/impetigo Recurrent gross hematuria Sparsentan: ARB- + Endothelin - NEPHROTIC SYNDROME Proteinuria >3g/d, Edema, frothy urine Child Adults Adult MC in elderly Prior URTI/ Heroin / HIV HBV/HCV /malaria Adenoca lung / colon/ immunisation Reflux nephropathy melanoma NSAIDS, Hodgkin’s Obesity PLAR2 lymphoma Sickle cell anemia Nephrin NPHS1-Finnish type AKI Pre renal Acute Tubular necrosis Biomarkers of AKI: Cause Cystatin C KIM-1 NGAL Fractional excretion of Na TIMP2 IGFBP7 Urine Na Urine Osmolality Urine casts CKD MCC of death: Anemia: Bone disease: Calciphylaxis: Acid-base: Uremia: Pericarditis P.Edema Ph 6.5 Encephalopathy Dialysis disequilibrium syndrome DOC: Acid-base imbalance pH Co2 HCo3- pH PRIMARY CHANGE COMPENSATION METABOLIC ACIDOSIS METABOLIC ALKALOSIS RESPIRATORY ACIDOSIS RESPIRATORY ALKALOSIS On laboratory investigations in a patient, pH=7.3, pCO2=35 mm Hg, What is the likely acid base imbalance? A. Respiratory acidosis B. Metabolic acidosis C. Metabolic alkalosis D. Respiratory alkalosis A patient is having pH-7.12, HCO3-28 and PCO2-50 mm Hg. What is the acid base disorder in this patient? A. Metabolic acidosis with respiratory compensation B. Metabolic alkalosis with respiratory compensation C. Respiratory acidosis with renal compensation D. Respiratory alkalosis with renal compensation A patient who is a known case of CKD has complaints of vomiting. His ABG reports are as follows: pH-7.40, pCO2- 40, HCO3-25. Na-145, chloride-100. What is the metabolic abnormality? A. Normal anion gap metabolic acidosis B. High anion gap metabolic acidosis C. No acid base abnormality D. High anion gap metabolic acidosis with metabolic alkalosis High Anion-Gap Metabolic Acidosis Anion Gap: 12+/-4 Anion gap= (Na + K) - (HCO3 + CI) NAGMA= Hyperchloremic acidosis: Causes of NAGMA Renal tubular acidosis Diarrhea Carbonic anhydrase inhibitors Ureteral diversion (e.g., ileal loop)  INTEGRATED RESPIRATORY SYSTEM SPIROMETRY Helium dilution Nitrogen washout Body plethysmography  Surfactant: Compliance Coughing: Surface tension Deep inspiration -> forced expiration against closed glottis -> sudden Shape: glottis opening Positive co-operativity P50: Sneeze: forced expiration against open glottis  Chest infections CURB-65 Scoring Symptom Points OP Amoxicillin +/- Macrolides / Doxycycline Confusion 1 0-1 Urea: BUN>19 mg/dL (>7 mmol/L) 1 IP FQ / BL+ Azithral/Doxy Respiratory rate>30 breaths /min 1 2 Systolic BP 0.3 Paracentral scotoma Siedel’s scotoma Bjerrum/ Arcute scotoma Ring/Double arcuate Roenne’s nasal step Loss of central vision Temporal crescent loss Anti-Glaucoma Drugs Decrease Aqueous Increase Trabecular Increase Uveoscleral Production Outflow Outflow Ocular Beta Blockers Cholinomimetic Drugs PGF2∝ Analogues 1. Timolol Pilocarpine 1. Lantanoprost 2. Betaxolol 2. Bimatoprost 3. Levobunolol 4. Carteolol Nonselective Alpha Agonist Rho kinase inhibitor Dipivefrine Netrasudil Alpha-2 Agonist 1. Apraclonidine 2. Brimonidine Carbonic Anhydrase Inhibitors 1. Acetazolamide 2. Brinzolamide 3. Dorzolamide Cataract Nuclear Cataract-Index myopia ; second sight phenomenon MC delayed complication: Endophthalmitis-most common cause Early onset- Late onset- SQUINT HERRING: SHERRINGTON: Eso- Exo- Hyper- Hypo- 2 > 1 deviation: 1= 2 deviation: Ptosis + dilated pupil: Ptosis + constricted pupil: Trauma Penetrating trauma-Ciliary body Granulomatous panuveitis Enucleation Evisceration GTCS Exenteration Posterior subscapular cataract Miscellaneous Blepharospasm/ Superotemporal: Lacrimation/Photophobia Inferonasal: Striae: Eye drop -> ointment Microspherophakia: Corneal diameter>13mm Bulbar-Palpebral conjunctiva fused: Superior-inferior eyelid fused: Integrated GI / HPB GI MOTILITY ELECTRICAL MECHANICAL Segmentation Peristalsis MMC ASCITES Spontaneous bacterial peritonitis: < Ascitic protein Ascitic protein <  DIARRHEA CHRONIC: ACUTE Secretory: OSMOTIC 7 % >6HRS D-xylose - /N D-xylose +/Abn Travelers: Rice water: SHELLFISH: Camping/persistent/malabsorption: Acute RIF pain: Antibiotics ++ BLOODY: -Poultry and eggs -Severe dehydration, febrile seizures: -GBS, Reiter syndrome: -Uremia / Anemia: HLA-DQ2 -Flask shaped ulcer: Biopsy: Duodenum -Longitudinal ulcers: -Transverse ulcers: POLYPS Non-neoplastic Neoplastic Rectal bleeding 4yr old with rectal mucus discharge bleeding 11yr old with intussusception  IBD Ulcerative colitis Crohn’s disease Wall layer MC site Stricture, Fistula, Abscess Skip lesions Antibody H/P Earliest imaging finding Management Hepatobiliary path Alcoholic + CK 8/18 Intermediate filaments ANA, SMA: LKM-1, SLA, LC: Maddrey’s discriminant function >32: Steroids HBsAg Anti-HBs Anti-HBc HBeAg Anti- Anti- Anti- HCV Anti-HEV HBe HDV HCV RNA + - IgM + - - - - - + - IgG + - - - - - + - IgG - + - - - - + - IgM + - + - - - + - IgG + - + - - IgM + - - - - - - + IgG - + - - - - - + - - - - - - - - - - - - - + - - - - - - - - + + - - - - - - - - - +  INTEGRATED ENDOCRINE SYSTEM Hormone Actions - GPCR G-protein pathway Receptor and ligand Second messenger G- protein (Gq-alpha subunit) “Hav1 M and M -GOT” ↑IP3 ↑DAG G-protein (Gs-alpha subunit) FSH, LH, ACTH, TSH, ↑cAMP CRH, hCG, ADH-V2, MSH, PTH, Calcitonin, H2, Glucagon, GHRH All B receptors G-protein (Gi-alpha subunit) MAD 2 ↓cAMP Receptor Guanyl cyclase “BAN” ↑cGMP STEROIDS PREP TV INSULIN PIFE PIGGLET Osteoporosis treatment Inhibit Osteoclasts Stimulate Osteoblasts Dual Action BISPHOSPHONATES: Adverse effect- 1. PTH 1-34 Romosozumab 2. Teriparatide 3. Abaloparatide Max: 2yrs Longest acting- Strontium SERM Denosumab Calcitonin: Intranasal Cinacalcet-CasR agonist Used in HyperPTH DM Metabolic syndrome: NCEP-ATP III 1. Central obesity: Degludec: longest >102 cm (India-90cm) in men >88 cm (India-80cm) in women 2. Elevated triglycerides: >150 mg/dL 3. HDL < 40 mg/dL in men < 50 mg/dL in women. 4. Blood pressure: >130/85 mm Hg 5. Fasting glucose: >100 mg/dL OHG Agent Mechanism of action Side effects Sulfonylureas Increases insulin secretion by inhibiting B- Hypoglycemia , Weight gain Chlorpropamide cell K+ ATP channels Chlorpropamide: Glipizide, Glyburide Meglitinides Repaglinide, Nateglinide Biguanides Stimulates AMP kinase, decreasing insulin Lactic acidosis, Weight loss, Vit B12 deficiency Metformin resistance Max reduction in HbA1c Thiazolidinediones Activates transcription regulator PPAR-g, Weight gain, Heart failure, Hepatotoxic, Fractures Pioglitazone decreasing insulin resistance Risk of bladder cancer - Rosiglitazone MI- GLP-1 agonists Increases glucose- dependent insulin Increase satiety, Weight loss Exenatide, Liraglutide-SC secretion, decreases glucagon secretion, Pancreatitis – Semaglutide-Oral delays gastric emptying MTC DPP4 inhibitors : ORAL GLP-2 agonist: Nasopharyngitis- Sitagliptin, Saxagliptin, Linagliptin DPP4 - : CI in renal failure except: Amylin Analogue Decreases glucagon secretion, delays Increase satiety Pramlintide gastric emptying α-glucoside inhibitors Reduces intestinal disaccharide absorption Diarrhea, Flatulence Acarbose , Miglitol CI in IBD SGLT2 Inhibitors Increases renal glucose excretion Urinary tract infections , Polyuria (osmotic diuresis) Canagliflozin, Dapagliflozin Weight loss  Anterior Pituitary Amenorrhea, Post-partum Fatigue/ infertility, Hypoglycemia/ galactorrhea, Failure to lactate / hot flashes Amenorrhea Neutrophil: Eosinphil: Lymphocytes: IOC to confirm: IOC for pituitary origin: Posterior Pituitary Polydipsia-Polyuria SIADH Central DI Nephrogenic DI Primary polydipsia Diabetes mellitus Urine Osm Plasma Osm Serum Na Diagnosis Water loading Water deprivation Water deprivation Water deprivation - test: ADH high test: Osm low test: Osm low test: Osm increases Management SIADH causes: Chlorpropamide, Oxcarbamazepine, Cyclophosphamide, Vincristine, SSRI Small cell ca lung, Pneumonia, Encephalitis GENERAL PHARMACOLOGY Formulae: Loading dose: Target conc x Vd Maintanence dose: Target conc x CL Therapeutic index TI= Median toxic dose /median effective dose = TD50/ED50 General Pharmacology Enzyme inducers Enzyme inhibitors CYP2C19: Griseofulvin Valproate CLOPIDOGREL Phenobarbitone Ketoconazole CYP2C9: Phenytoin Cimetidine WARFARIN Rifampicin Ciprofloxacin PHENYTOIN Carbamazepine Erythromycin, Clarithromycin Smoking, Ethanol INH Aminophylline: Gynecomastia Essential drugs : Schedules: PDE-4 inhibition Under medical supervision: PDE-3 inhibition Cost effective With prescription only: Adenosine antagonism Prevalent diseases Cannot be treated: Histone deacetylase activation Available easily Addictive potential: No combination Category: X: 500mg PCM containing only 200mg PCM: Potency VS Efficacy Competitive antagonist: Non-competitive: ANS DOC Septic shock, Neurogenic shock Cardiogenic shock-refractory Cardiogenic shock Cardiogenic shock + oliguria CPR, Anaphylactic shock Postural hypotension Spinal induced hypotension  Antimicrobials Safe in renal failure: PMT Cyp inh, QT prolong, tendons Cyp inh, QT prolong, Prokinetic, Jaundice Vancomycin: Transglycosylase Matzke normogram B lactams: Transpeptidase CONDOM No cross-reactivity: DOC: Syphilis, Actinomyces Listeria Mastitis SSI Neisseria, Lyme disease (complicated), Enteric fever Enterobacter, Acinetobacter Plague,Tularemia Ricketsia, Cholera Atypical pneumonia, Legionella, Mycoplasma, Chlamydia, Pertussis, Diphtheria Nocardia, PCP, Burkholderia, Cyclospora, Isospora Meningococcal, Anthrax, UTI, Travelers diarrhea Ceftriaxone, Cefoperazone: Imipenem+ Cilastatin: Bile excretion  TABLE OF DRUGS NOT EFFECTIVE AGAINST MICROORGANISMS MYCOPLASMA Cell wall inhibitors (beta-lactams, vancomycin) PSEUDOMONAS Vancomycin ANAEROBES Aminoglycosides MRSA Beta lactams (except fifth generation cephalosporins) SALMONELLA Aminoglycosides VRSA: CIDAL DRUGS Linezolid BEVAFA STREPTOGRAMINS Daptomycin Quinpristine-Dalfopristine Ceftarolin ATT Mycolic acid synthesis inhibitor, CYP inh, Hepatotoxic, Neuropathy, Sideroblastic anemia, Lupus FA synthesis inhibitor, Hepatotoxic, Hyperuricemia: Arabinogalactan synthesis inhibitor, Red-green colour blindness: Max cidal action, inducer of enzymes, Pulmonary syndrome, orange urine: Pseudojaundice, uveitis, min inducer of enzyme: Hepatotoxic, Hypothyroidism: QT prolongation: ATP synthase inhibitor: Max CSF action, Prodrug, Safest in pregnancy: PROPHYLAXIS: Household contacts , AntiTNF/ immunosupressants, Dialysis , Silicosis Rifapentin+INH x 3mon weekly  Anti-Viral drugs gp120- Fostemsavir (oral) gp41- Enfuviritide CD4: Tenofovir 300 mg+ Lamivudine 300 mg + Dolutegravir 50 mg Ibalizumab CCR5: Maraviroc (oral) Max neuropathy- Max pancreatitis- BM suppression, Hepatotoxic- Nephrotoxic- MI- Pigmentation in palms and soles- Safest- Hep B- Best to prevent vertical transmission- Teratogenic, Vivid dreams- Min lipodystrophy- Stones, hyperbilirubinemia- Intracranial hemorrhage-  Hemorrhagic cystitis Compound: Prevention: Treatment: Cyclophosphamide Busulfan Bleomycin Carmustine Methotrexate Amiodarone Vincristine Bleomycin L-aspararginase ribonucleotide reductase DHF reductase Fludarabine Mitomycin C Temozolamide Nephrotoxic ; DOC to reduce: Ototoxic Anthracycline s/e: Most emetogenic Prevention: DOC early- DOC delayed-  Anticancer small molecule inhibitors NEW DRUGS Alectinib, crizotinib ALK Non-small cell lung Vismodegib cancer Osimertinib : T790M mutation Erlotinib, gefitinib, EGFR Non-small cell lung Belimumab: afatinib L858R mutation cancer Teprotumumab: Imatinib, dasatinib, BCR-ABL CML, ALL, GISTs Elacestrant, Fluvestrant: nilotinib Teplizumab: Ruxolitinib JAK1/2 Polycythemia vera Omavexolone: Bortezomib, Proteasome Multiple myeloma, Ravulizumab, Rozanolixizumab: ixazomib, carfilzomib (induce G2-M mantle cell Daprodustat: arrest -> lymphoma Vanoprazan: apoptosis) Palivizumab Vemurafenib, BRAF Melanoma Cetuximab, Panitumumab encorafenib, Emicizumab dabrafenib Palbociclib Cyclin- Breast cancer Natalizumab dependent IFN-α kinase 4/6 IFN-β (induces arrest IFN-γ at GI-S phase → Aldesleukin apoptosis) Olaparib Poly(ADP-ribose) Breast, ovarian, Ixekizumab, Secukikumab polymerase (↓ pancreatic and Risankizumab, Guselkumab, Tildrakizumab DNA repair) prostate cancers Ustekinumab ALEMTUZUMAB CD52 CLL General Physiology Muscle reflex Reflex Type Stimulus Afferent Response Stretch reflex/ Spindle Golgi tendon During contraction: Prominent- Disappear- Shorten- Constant- Nerst equation-Equilibrium potential Na: +60 mV Carrageenan theory: Ca: +100 mV Bitter taste transmitted by: Cl: -70mV TENS: K: -90V ` FEEDBACK: Baroreceptor reflex: Parturition, Clotting, LH surge: Gibbs Donnan : Diffusion of permeable ions Salivation on thinking about food, Exercise, changes due to large impermeable molecule Temperature : Radiology FOREIGN BODIES Type Most sensitive Least sensitive Cell Type Organ Blood cell Cell cycle phase Tissue Structure of eye TUMORS Acute radiation syndrome INVERSE SQUARE LAW Psychiatry General Psychiatry Delusion is a disorder of thought- Obsession is a disorder of thought- Hallucination is a disorder of- Derailment is a disorder of- MC delusion: ORIENTATION ATTENTION CONCENTRATION Capgras- Digit span test Serial 7 subtraction Fregoli - Othello syndrome- Cotard syndrome- Ganser syndrome- Transference MC obsession: MC compulsion: Association of OCD, anorexia: Short term memory: Giving clues: Distractibility Irresponsibility Grandiosity Flight of ideas Activity increased Sleep decreased Talkativeness GOOD PROGNOSTIC FACTORS BAD PROGNOSTIC FACTORS Acute onset or abrupt onset Insidious onset Advanced age at onset (>35 yrs) Early onset (6mon: Precontemplation -> Contemplation -> Preparation Gene: -> Action -> Maintainence -> Relapse Drug: Regression in any gender >2yrs:  Personality disorders Cluster A personality disorders Pervasive distrust, suspiciousness Voluntary social withdrawal, content with social isolation (vs avoidant) Odd beliefs or magical thinking Cluster B personality disorders Criminality, impulsivity, hostility ≥18 years old Unstable interpersonal relationships, impulsivity, suicidality. Females > males. Splitting , Dialectical BT Attention-seeking, dramatic speech and emotions Grandiosity, sense of entitlement, requires excessive admiration Cluster C personality disorders Hypersensitive to rejection and criticism, socially inhibited Preoccupation with order, perfectionism, and control; ego-syntonic Excessive need for support, low self-confidence  Other disorders Anorexia Bulimia Reduced REM latency Hypnagogic/ pompic hallucinations, Cataplexy BMI Hypocretin / orexin Distorted body image DOC: Amenorrhea, Osteoporosis Parotitis, Tooth decay Hypo Cl, K Metabolic alkalosis Russel sign UNINTENTIONAL INTENTIONAL Secondary Stressor gain Preoccupation of Excessive Unexplainable + - having DIAGNOSIS of preoccupation with 1 neurological serious illness or more symptoms disorder No/ mild symptoms Stressor + Stressor + - - Consistently negative Ix > 6months La Belle >6 months Indifference Antipsychotics -Max EPS : -Min EPS, DOC for refractory psychoses: -Max metabolic s/e, Sialorrhea, Seizure, Myocarditis, Agranulocytosis: -QT prolongation: -PD induced psychosis DOC: -Longest acting: -Technique for depot injections: -Catatonia DOC: -Catatonia TOC/ Depression + suicide / stupor : Anesthetic agent of choice: -D2 partial agonist: Extrapyramidal symptoms Treatment Sudden, sustained contraction Torticollis, trismus, oculogyric crisis restlessness, inability to sit still Gradual-onset tremor, rigidity, bradykinesia Dyskinesia of the mouth, face, trunk, extremities: Rabbit syndrome Antidepressants: -Mc side effect of SSRI: -SIADH, vivid dreams, dry mouth, sweating: -DOC for severe depression -S/e: Hypertension, Discontinuation syndrome -Min sexual s/e: -Min wt gain, sedation, Seizures in bulimic, Anti-smoking: -Priapism: TCA MOA: -TCA toxicity DOC: Hemodialysis: --Drugs with anti-suicide ability: -Antidepressant of choice in pregnancy: -Approved for Postpartum depression: -Black box warning for anti-depressants: -Novel antidepressant: Agonist at 5HT1a, antagonist at 5HT3: -Clonus, diarrhea, altered mental status on antidepressants: Mood Stabilizers Levels: Prophylaxis- DOC in acute mania/BPD- Acute Mania- DOC in prophylaxis of BPD- Toxicity- DOC in rapid cyclers- Dialysis- DOC in pregnancy- T1/2: Measurement: Adverse Effects of Lithium Tremors Nephrogenic diabetes insipidus DOC: R/F: Volume loss/ AKI, ACE inhibitors, thiazide Thyroid dysfunction diuretics, NSAIDs Hyperparathyroidism Nausea, vomiting, slurred speech, hyperreflexia, Acne, Psoriasis seizures, ataxia Weight gain Leukocytosis Teratogenic: