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BIOCHEM AND PHARMA

*SAM- S Adenosine Methionine

*Carnitine- Transports Fatty acids in to the mitochondria for Beta-oxidation to acetyl


CoA.

- Impaired in Alcoholism.

*Amanita Toxin - Binds to DNA dependent RNA Polymerase II, halts mRNA synthesis.

- Accumulates in rapidly dividing cells, thus cause more damage to these


cells / organs. (eg. hepatocytes, Intestinal cells, renal cells).

*Ricin (from castor oil) - Halts Protein Synthesis.

*STOP CODON - Codes for Releasing Factor 1.

*Colchicine - Impairs Neutrophil migration and phagocytosis by interfering with


microtubule formation.

- Decreases tyrosin kinase activity thus decreased Neutrophil activation.

*Osteopetrosis - Increased bone thickness and density

d/t- Impaired osteoclast activity

*anti-CCP antibody - RA Specific.

*RF - Antibodies against Fc portions of IgG. Found inRA, but non-specific.

*anti-Centromere antibody - CREST Syndrome

*anti-dsDNA - SLE.

*anti-Phospholipid antibodies - SLE & Antiphospholipid antibody syndrome.

*Glycine - M/C (every third) amino acid in collagen fibers. D/t its smallest size, it
gets fit into the restricted space of triple helix.

*Proline - essential for alpha helix in collagen fibers, as it's ring structure produces a
bend into polypeptide chains.

*Ketogenic Amino acids - Leucine and lysine

*Pyruvate Carboxylase - converts Pyruvate to OAA, requires Biotin

*Enhancer region - can be located anywhere upstream/ downstream/ within the


introns or may be thousands of bases away from the gene.
*Promotor - 25 Bases (TATA/Hogness box) or 70 bases (CAAT Box) upstream of the
gene. These are the sites for attachment of Polymerase II.

*Coenzymes required for Pyruvate Dehydrogenase (PDH) and Ketoglutarate


Dehydrogenase - thymine, lipoic acid, Fad, Nad, CoA( Active form of Pentothenic
acid)

*CoA - Pentothenic acid to CoA - ATP dependent phosphorylation

- In SYnthesis of Vit A, D, Cholesterol, Steroids, Heme A, Fatty Acids, Amino Acids


and Proteins.

*Citrullinemia - Urea cycle disorder,

- d/t deficiency of Arginosuccinate synthatse (ATP is a cofactor)

*Methylmalonic acidemia Deficiency of Methylmalonate Mutase ( Vit. B12)

*Homocystinuria - Premature Atherosclerosis (MI in very young), Def. of


cystathionine synthase.

*Homocysteine to cysteine - Cystathionin synthase & Cystathionase(B6 Required)

*Homocysteine to Methionine - Folate & Vit. B12 dependent process.

*Ketone Body Utilizing parts- Skeletal Muscles, Cardiac muscles, Renal Cortex, Brain.

*Ketone bodies cant be utilized by - RBCs ( no Mitochondira, so no use of


acetoacetate), Liver Cells (lacks Succinyl CoA-Acetoacetate CoA Transferase
(thiophorase) which is required to convert acetoacetate to acetoacetyle CoA)

*Guanosine capping- 5' 7-methyl guanosine

*Poly A tail - at 3' end. Gene has consensus sequence (AAUAAA) at 3' end, after
which poly A tail is added.

- it protects mRNA in cytoplasm from degradation.

*Introns - Non-coding sequences in mRNA (Intruders).

*Propionyl CoA - produced by Valine, Isoleusine, Methionine, Threonin, odd


numbered Fatty acids and cholesterol side chain.

*Lead - Inhibits d-amino levulinate Dehydratase & Ferrochelatase

*Tetrahydrobiopterin - cofactor in the synthesis of Tyrosine, dopa, serotonin & Nitric


Oxide.
*Maple syrup urine - Defective oxidative decarboxylation of branched chain amino
acids ( leucine, isoleucine, Valine) by branched chain a-ketoacid dehydrogenase
enzyme.

*Homocystienuria - Methionin restriction and cystiene supplementation is T/t.

*Branched chain a- ketoacid dehydrogenase, Pyruvate dehydrogenase & a-


ketoglutarate dehydrogenase require 5 cofactors - Thiamiane pyrophosphate,
Lipoate, CoA, FAD, NAd( Tender Loving Care For Nancy).

*Only Vit. B12 & folate are reserved in Liver in sufficient amount to last for YEARS.
Other Vit. (Viz. A,E,K) last only for few months.

*Vit. K Stores last 1-3 Weeks only.

*Heme -> -ve Feedback on d-ala Synthatase.

*HbF- Replaced by HbA in 6 months.

*UDP Glucuronyl Transferase - -nt in Criggler-Najjar, Low in Gilbert & Infants.

- unconjugated jaundice.

*Defective secretion of Conjugated Bilirubin - Rotor Syndrome, Dubin Johnson Syn.

*Tumor lysis syndrome - large quantity of Uric acid is produced which can cause
Acute Renal Failure.

*Rasburicase - Recombinant Urate Oxidase. Converts uric acid to allantoin which is


5-10 times more water soluble than urate. given for tumor lysis syndrome.

*Imperforate Anus - A/w GUT malformations.

*Infantile hydrocele is equivalent to adult Indirect Hernia. (Hydrocoele n Indirect


hernia are formed through the same mechanism through tubovaginalis (?))

*Late division of Monozygotic twins results in 1 amniotic sac and 1 chorionic sac.

*Sertoli cells will inhibit the involution of Mullerian (paramesonephric) ducts. Thus
inhibiting the development of internal female genitalia.

*Leydig cells produce testosterone, thus developing wullfian duct and male external
genetalia.

*Leydig cells produce Testosterone, which gives negative feedback to LH.

*Sertoli cells produce Inhibin b, which gives negative feedback to FSH.

*The hormones that regulate the synthesis of surfactantinclude are - Glucocoticodes


( Max Effect), prolactin, insulin, estrogen, androgen, thyroid and catecholamines.
*Neural Crest Cells- Form Submucosal (Meisner's) and Myenteric (Auerbech"s) Plexi.

*hCG - Glycoprotein Hormone Produced by the placenta, which resembles LH, FSH &
TSH.

- THE MAIN function of hCG is to support Corpus Lutium, to produce progesterone.

*Triple Test - afp, hcg & estriol levels. B/w 16-18 weeks.

- If triple test is abnorml, then usg. If usg is consistent with pregnancy dates
n there r no anatomic abnormalities, then Amniocentesis.

*True Diverticulum - Meckle's Diverticulum, Normal Appendix

*Pseudo-diverticulum - Zenker's Diverticulum, Commomn Colon Ticks

*Mackel's Diverticulum - Remnant of Omphalomesentric (vitelline) duct.

Connected to Ileum, 2 feet from iliocoecal valve.

M/c ectopic Mucosa - Gastric Mucosa F/B Pancreatic tissue.

*Freckles - Ephelides

*M/C congenital anomaly - Accessory nipples.

*Ureteric Bud Derivatives - Collecting system of kidney, including collecting tubules


& ducts, Major and minor callyces, Renal Pelvis and Ureter.

*Metanephric Blastema derivatives - Glomeruli, Bowman's Space, Proximal Tubule,


Loop of henle And Distal Collecting tubules.

*Alpha Fetoproteins (AFP) and Acetylcholinestrase - Neural Tube Defects

*The secondary Oocytes remain frozen until fertilization occurs in Fallopian tube.

*Dorsal Pancreatic Bud - Forms Tail, body and most of head of pancreas along with
dorsal (accessory) Pancreatic duct of Santorini.

*Vetral Pancreatic Bud - Uncinate process, Inferior/posterior portion of head and


major pancreatic duct (of wirsung).

- Both, Ventral and dorsal buds are derived from the duodenal portion of the
foregut.
*Vit. A overdose in pregnancy - Craniofacial Deformity, Posterior fossa CNS Defects,
Auditory defects and abnormalities of great vessels. (similar to DiGeorge
Syndrome).

*Cleft Lip - d/t non-fusion of Maxillary prominence with intermaxillary Segment.

*Cleft Palate - Non-fusion of Palatine shelves growing from maxillary prominences


with one another n intermaxillary segment (primary Palate).

*Melanoma - Commonly migrates to Brain, Intestine, bone, liver and Lungs.

- Malignancy of Melanocytes, which are derived from Neural crest cells.

*Kallman's Syndrome - Failure of migration of GnRH secreting neurons from


Olfactory lobe to Hypothalamus.

*Apple Peel Atresia - Atresia of small intestine in neonate d/t SMA obstruction.

- This menifests as a blind-ending proximal jejunum with absence of a long


length of small bowell and dorsal mysentery. The terminal ileum distal to atresia
assumes a spiral configuration around an ileocolic vessel.

*Polyhydramnios causes -

1. Decreased Fetal Swallowing ( GIT Obstruction eg. Duodenal,


Esophageal, Intestinal atresia) or anencephaly.

2. Increased fetal Urination [High Cardiac Output (eg. Anemia)] or twin


to twin transfusion syndrome.

*Vancomycin induced RED MAN Syndrome - Mediated by Histamin

*Substance P - 11-amino acid polypeptide. pain neurotransmitter in both peripheral


and central nervous system.

- Capsaicin - reduces pain by decreasing it's level in Peripheral nervous


System.

- in CNS, It's also thought to regulate mood, anxiety, and stress behavior.

*Niacin - Causes flushing mediated by Prostaglandin. T/t- Aspirin

- Antihyperlipidimic action- Decreases Cholesterol-> VLDL, VLDL->LDL.

- It also increases HDL by 25-30%.

- Potentiates the effect of some Antihypertensive meds d/t its vasodilatory


effect.

- increases Insulin resistance. Worsens DM.


*Segmental Glomerulosclerosis - Heroin and pamidronate

*Membranous Glomerulopathy - Gold

*Tubular Necrosis - Aminoglycosides, Foscarnet, Radio Contrast, amphotericin B and


Cisplatin.

*Drug induced tubular obstruction - Sulfonamides, Methotrexate, I/V Acyclovir and


triamterene.

*Acute Interstitial infiltration - Methicillin (M/C), NSAIDs, Acetazolamide, allopurinol,


Cisplatin and Sulfonamides.

*Chronic Interstitial Nephritis - Li, Cyclosporin.

*ACEI - cause decrease in GFR by reducing efferent arteriole vasoconstriction, thus


increasing Serum Creat. by 30% in 2-5 days.

*Nitropruside - Antihypertensive with mixed arterial and venous vasodilatory


actions.

ADR - Nitropruside ->Cynide. accumulation of cynide causes poisoning.

Cyanide via liver rhodanase-> thiosynate.

Antidote - Sodium thiosulfate. it gives additional Sulfur to liver rhodanase to


enhance metabolism and detoxification of cyanide to thiocyanate.

*Fenoldopam - Benzapine derivative of Dpamine, which has selective effect on D1


receptor.

- Indicated in hypertensive emergencies only.

MOA - 1.) D1 receptor activation -> activayes adenylyl cyclase ->raises cyclic
AMP -> Arterial dilatation (espacially Renal, Coronary and mesenteric) -> decreases
SVR

2.) D1 receptor in kedneys increses water and Sodium excretion.

- Only I/v drug that improves renal perfusion, so beneficial in renal


insufficiency.

*During continuous infusion of a drug metabolized by first order kinetics, the steady
state concentration is reached in 4-5 lives.

*Dopamine -

1.) Low dose - Stimulate D1 receptor in renal and mesenteric vessels->


vasodilation and increased blood flow at these sites.
2.) Higher doses - Stimulation of cardiac beta-1 receptor-> increased cardiac
output

3.) still higher doses - generalised vasoconstriction by alpha-1 adrenergic


effect.

*Nor-epinephrine - I/v may cause Indurations and pallor of the surrounding tissue,
D/t extravasation of NE-> intense alpha1 mediated vasoconstriction which can lead
to local tissue necrosis.

T/t- infiltration of affected area with 5-10 mg of phentolamine mesylate(alpha


receptor blocker) in 10-15 cc NaCl, with-in 12 hours of extravasation.

*Isoproterenol - beta-2 agonist, acts particularly in striated muscles, renal and


mesenteric vascular beds.

*Enzyme Inducers:- Carbamazepine, Phenobarbitol, phenytoin, rifampin,


Griseofulvin, nevirapine, Chr. ALchohol abuse, St. Johns wart.

*Enzyme Inhibitor:- Cimetidine, Ciprofloxacin, Macrolide(except Azithromycin), Azole


antifungals, Grapefruit juice, Isoniazid, Ritonavir(PI), Quinidine.

*Statins - lower LDL

*Fibrates - lower Triglycerides

*Niacin - increases HDL (ADR - Increase Uric acid Level)

*STATINS have smaller but significant effect in lowering triglycerides. So used in


mild-moderate hyperlipidemia.

*Statins reduce serum cholesterol concentration by inhibiting HMG CoA reductase,


thus causing an increase in LDL Receptors on hepatocytes, which reduces serum
LDL concentration.

*Statins are metabolized in the liver (except Pravastatin) by Cyt3A4. So, enzyme
inhibitors will increase their Concentration and enzyme inducers will decrease their
concentration.

-ADR- Heptitis and Myopathy. Myopathy is maximally caused by simvastatin.


When given with Fibrates, its dosage must not exceed 10mg.

*Fibrates cause myopathy by:-

1. Gemfibrozil- Increases the concentration of statins.

2. Fenofibrates- Causes myopathy itself.

*Use of medications to raise HDL doesn't improve cardiovascular outcomes.


*Pharmacological treatment of patients with low HDL levels should focus on
lowering LDL cholesterol with Statins, as these are the most effective lipid lowering
drugs for preventing cardiovascular events.

*HDL - in reverse cholesterol transport i.e. transport of cholesterol from peripheral


tissues to liver.

1.)- Direct pathway- HDL delivers cholesterol ester to hepatocytes by


scavenger receptors (SCARB1) on hepatocyte membranes.

2.)- Indirect pathway- transfer cholesterol to LDL & VLDL by cholesterol


transfer proteins.

*Hydrocholothiazide - I line T/t for HTN with osteoporosis (since it increases the
Serum calcium) and Isolated Systolic HTN.

*Epinephrine - Alpha1, Beta1 & Beta2 agonist.

*Nor-epinephrine - Alpha1, Beta1 Agonist.

*Niacin MOA - 1.) decreases the synthesis of hepatic triglycerides and VLDL ->
SUPPRESSED RELEASE of free fatty acids from peripheral tissues.

- 2.) decreases VLDL conversion TO LDL, thus decreasing LDL.

ADR - Flushing, Itching, increased Uric acid level, Hepatotoxicity, increased


insulin Resistance.

*Fibric acid derivative ADR- Gallstones, Myopathy.

*Fibrates and niacin - decrease hepatic VLDL production. Thus mainstay of T/t for
Primary hypertriglyceridemia (increased VLDL).

*EZETIMIBE - decrease absorption of dietary cholesterol-> decrease serum LDL.

*ApoB 100 - Apoprotein on VLDL &LDL. Decreased serum concentration of these will
cause decreased ApoB 100.

*Bile acid binding resins ADR- GI Upset, Hypertriglceridemia, Malabsorption.

*Isolated Systolic HTN T/t -

in Non-diabetics -Thiazide diuretics, Dihydropyridine CCBs

in Diabetics- ACE-I or ARBs

*Verapamil - diphenylalkylamine CCB.

- For rate control in AF with rapid ventricular response d/t ability to slow
conduction through the AV node.
ADR- Constipation and gingival hyperplasia.

*Nor-epinephrine-

MOA- 1. alpha-1 mediated Increased IP3 in visceral & cutaneous


vessels causes vasoconstriction, causing decreased blood flow to renal and hepatic
circulation n increased venous return.

2. beta-1 mediated cAMP increase in heart muscles through Gs


receptor mediated coupling. It increases cardiac muscle contractility, conduction
and heart rate.

*Terazosin, Doxazosin - Alpha-1blocker. Cause relaxation of smooth muscles in


arterial and venous walls-> decreases TPR.

ADR- first dose orthostatic hypotension & vertigo.

Hydrocholorthiazide - acts at DCt, prevents the reabsorption of sodium , chloride


and water by blocking Na/Cl cotransporter.

ADR- elevation of glucose, calcium and uric acid.

*Cardio selective beta blocker - pts. With coronary artery Ds. with CHF and HTN

*ACE-I - increase in Serum creatinine by 30% within 2-5 days is common, which
stabilizes in 2-3 weeks.

*Phentolamine - non-specific alpha-1 and alpha-2 blocker

*Atropin - competitive antagoinst at post junctional muscarinic receptors in the


heart. Atropin increases the heart rate by blocking vagal influences.

*Epinephrine - Increases Systolic BP- Alpha-1 & Beta-1

- decreases Heart rate - Beta-1

- decreases diastolic b.p. (low dose) - alpha-1<beta-2

- increases distolic b.p. (high dose) - alpha-1>beta-2

*Cilostazol & Dipyridamol- decreases the activity of platelet phosphodiesterase->


decreases the breakdown of cyclic AMP-> increased platelet cyclic AMP-> decrease
platelet aggregation by preventing platelet shape change and granule release.

- Cilostazol is also arterial vasodilator.

- cilostazol is approved for T/t of intermittent claudication.

*Ticlopidine & Clopidogrel - block platelet ADP receptor-> disllow GP IIb/IIIa receptor-
> inhibit platelet aggregation.
*Abciximab - monoclonal antibody that inhibits platelet aggregation by targeting the
platelet IIb/IIIa receptor.

- used prior to percutaneus coronary intervention.

*Bile acid binding resin (Cholestyramine) increases the bile acid production, thus
increasing hepatic triglyceride & VLDL production.

*Tachyphylaxis - rapidly declining effect of a drug after few days of use.

eg.- 1.) alpha adrenergic agents used as nasal decongestant. use >3 days
causes negative feedback, resulting in decreased norepinephrine synthesis and
release from nerve endings, resulting in relative vasodilation. It is rebound
rhinorrhoea/ rhinitis medicamentosa.

2.) Nitroglycerine- decrease in effect d/t diminished release of NO from target


cells. drug free intervals of 8-10 hours should be maintained during the use of
nitroglycerine to prevent tachyphylaxis.

*ACE-I - angioedema d/t Kinin accumulation is rare but serious ADr.

*Urticaria - IgE mediated mast cell degranulation.

*Regulation of RAAS involves 3 major pathways:- macula densa, intrarenal


baroreceptor and beta-adrenergic receptor pathway. in particular, the beta-
adrenergic pathway is mediated through sympathetic stimulation of beta-1
receptors located on Juxta glomerular cells. norepinephrine binds to beta-1
receptors and stimulates rennin release.

*Beta blocker- lowers b.p. by reducing cardiac output secondary to negative


chronotropic and inotropic activity.

*Loperamide- Opiate antimotillity drug, for travelers diarrhea, where there is no


fever or blood in stool.

*Erythromycin- for Campylobacter jejuni. in lieu of fluoroquinolones.

*Types of collagen - Strong, Slippery, Bloody and BM

1. Strong:- bone, Muscle, Fascia, cornea, Tendon, skin. Dentin.


2. Slippery:- Cartilage, Vitreous
3. Bloody:- Blood vessels, granulation tissue, Uterus, Fetal tissue
4. BM:- Basement Membrane/ Basal lamina.

*Glucocorticoids- High doses are used for ophthalmopathy A/w Graves Disease.
They are helpful in decreasing the severity of inflammation and decreasing
extraocular volume. Conventional antithyroid drugs do not improve
ophthalmopathy.
* SERMs- Tamoxifen, Raloxifen. Agonist in Uterus and antagonist in Breast.

- Antagonist in breast, thus, doesnt cause breast cancer.

-Agonist in Uterus thus can cause endometrial hyperplasia, endometrial


carcinoma and endometrial polyps. Thus the pt is advised to have annual
gynecological examination.

- Also improve the lipid levels and partial agonist to bone, thus increase BMD.

* Thiazolidinediones (TZD):- decreases insulin resistance by binding to peroxisome


proliferator activated receptor Gamma (PPAR-gamma), which is a transcriptional
regulator of genes involved in glucose and lipid metabolism.

- PPAR-Gamma belongs to nuclear receptor superfamily, which that includes


thyroid hormones also.

- TZDs take days to weeks to show significant effect.

TZD ADR- fluid retention causing CHF and weight gain.

Transactivation- when TZD binds to PPAR-gamma, a conformational change


ensues, which allows another co-activator to attach. This complex then binds to
transcriptional regulatory sequence of genes responsible for glucose and lipid
metabolism. This whole process is called Transactivation.

-Adiponectin (Adipocytokinin) levels are low in type 2 DM. T/t with TZDs
increases its levels.

*Important genes that are altered by PPAR-gamma :-

W Increases Adiponectin
W increases fatty acid transport protein
W increases insulin receptor substrate
W increases glucose transporter-4 (Glut-4)

*Desmopressin:- To treat Central DI and nocturnal enuresis.

- increases circulating levels of von Wille brand factor (factor VII:R) and
promote the coagulant activity of factor VII:C.

*Neutrophil count increases post corticosteroid administration, as a result of


demargination of leucocytes previously attached to the vessel wall.

*Glucocorticoids decrease eosinophil, basophil and lymphocyte count.

-T Lymphocytes are reduced more than B lymphocytes.


- reduction in lymphocytes occur by redistribution of lymphocytes from the
intravascular compartment to the spleen, lymph nodes and bone marrow. Also,
direct inhibition of immunoglobulin synthesis and stimulation of lymphocyte
apoptosis.

* Premature Ovarian Failure- amenorrhoea, hypoestrogenism and elevated serum


gonadotropin levels in women age<40.

* Glucocorticoids increase liver protein synthesis, specifically the enzymes involved


in gluconeogenesis and glycogenesis.

* Glucosidase inhibitor decrease the activity of disaccharides on the intestinal


brush borders.

Eg.- Acarbose, Miglitol.

*Glucagon like polypeptide-1 (GLP-1) Incretin hormone secreted by intestinal L


cells in response to food intake. It decreases glucose by inducing satiety, decreasing
gastric emptying and increasing insulin resistance.

- acts through G-protein coupled cell surface receptor, which act by adenylate
cyclase activation.

* Biguanides eg. Metformin. Increases glycolysis and inhibits gluconeogenesis.

th* Amiodaron ADR:- Thyroid dysfunction, corneal micro-deposits, blue-grey skin


discoloration, drug related hepatitis and pulmonary fibrosis.

* Amiodaron induced HypOthyroidism- in iodine-sufficient regions.

T/t- levothyroxin and amiodaron continued as such.

*Amiodaron induced thyrotoxicosis- d/t excessive production of thyroid hormone.

- Primarily seen in iodine-deficient regions.

* NPH (neutral protamine Hagedorn) Insulin- intermediate acting insulin.

- crystalline suspension of insulin with protamine and Zinc, which prolongs


the duration of absorption of insulin. Thus increasing its duration of action.

- starts working in 2 hours, peaks in 4-12 hrs and lasts about 18 hours.

* Detemir- Long acting insulin analogue with a fatty acid bound to 1 of the lysine
amino acid on the insulin molecule. This fatty acid side chain allows the detemir to
bind to albumin and slowly dissociate afterwards, resulting in prolonged action.

- it usually starts working in with-in 2 Hours, peaks in 3-9 hours and lasts
about 24 hours.
*Beta-blocker- initially increases the PVR as it blocks beta2

*Metoprolol- Beta-1 blocker. inhibits renin release

*NO-> stimulates gunylate cyclase to convert GTP to cGMP-> decreased


intracellular Calcium concentration-> decreased activity of myosin light chain
kinase-> myosin light chain dephosphorylation-> smooth muscle relaxation.

*QRS complex corresponds to ventricular depolarization, in which rapid Na


movement in cardiac myocyte.

*ANti arrhythimic drugs do not affect phase 4 (the resting membrane potential) of
myocyte, but these do affect the phase 4 of pacemaker cell action potential, which
is mediated by Na influx.

*Digitalis ADR- fatigue, blurry vision, changes in color perception, nausea &
vomiting, diarrhoea, abdominal pain, headache, confusion, dizziness and delirium.

*Digoxin-> Stimulates Vagus-> increased parasympathetic tone-> decreased rate of


AV conduction-> AF controlled

*Methotrexate- ADR- Stomatitis( mouth ulcer), hepatotoxicity, myelosuppression,


increased risk of opertunistic infection, B-cell lymphoma and pulmonary fibrosis.

*Agents inhibiting purine and pyrimidine synthesis- MTX, leflunomide, azathioprine.

*After conversion to Dihydrotestosterone, androgens promote both follicular


epidermal hyperproliferation and excessive sebum production.

*Drugs causing acne - Androgens, epidermal growth factor receptor inhibitors and
Lithium.

*Estrogen is main hormone responsible for groethh and development of malignant


Breast Cancer

- aromatase inhibitors(Anastrozole, Letrozole, Exemestane) are superior than


Tamoxifen for it's T/t.

*lactic acidosis - Metformin ADR

*Agranulocytosis - Sulfonyl urea ADR

*postural/orthostatic hypotension- Insulin

*lung fibrosis- Amiodarone, bleomycin, Mitomycin C, busulphan and methysergide.

*Adrenal Crisis- hypotension, Tachycardia and hypoglycemia with a history


consistent with adrenal isufficiency (vomiting, abdominal pain, weight loss and
hyperpigmentation).
T/t- stress doses of corticosteroids.

*T/t of DKA- preffered insulin is I/V Regular insulin.

*Levothyroxin- synthetic form of T4.

*Hirsutism- terminal hair growth in male pattern in female.

Causes- PCOs, Cushing syndrome, ovarian and adrenal tumour and idiopathic.

T/t-Anti-androgens (spironolactone), Flutamide(testosterone receptor


antagonist) and finastride (5-alpha reductase)

*Virilization- Hirsutism, in association with clitoromegaly, increased acne, muscle


mass, increased libido and voice deepening.

*Mitotane- adrenolytic drug used primarily for treatment of adrenocortical


carcinoma.

*Metformin- decreases blood glucose by increasing glycolysis, decreasing


gastrointestinal glucose absorption and decreasing blood sugar gluconeogenesis.

ADR- GI upset and lactic acidosis.

C/I- renal failure, hepatic insufficiecy and hypersensitivity to metformin.

-should be avoided in CHF and alcoholics, as because of increased risk of


development of lactic acidosis.

*Antithyroid drugs MOA- Oxidation of iodine in thyroid gland, iodination of tyrosine


residues and coupling of iodotyrosine molecules (i.e. iodine organification and
coupling). All done by thyroid peroxidase.

eg.-Propylthiouracil, Methimazol.

ADR- Agranulocytosis(usually within first few weeks of therapy)

Management- drug is immediately discontinued and a white cell count with


diffrential is drown.

*PTU- decreases peripheral conversion of T4->T3, has a shorter half-life and is the
drug of choice in pregnancy.

*Propranolol- Beta blocker with additional peripheral T4->T3 conversion blocking


facility.

*Flutamide- non-steroid antiandrogen that comppetes with testosterone and DHT for
testosterone receptors.

-used with GnRH agonists for Prostate cancer.


*GnRH Agonists(leuprolide, Goserelin, Nafarelin and histrelin)- Decrease synthesis of
LH and FSH-> decrease stimulation of Leydig cells.

*Ketoconazole- weak antiandrogenthat decrease the synthesis of steroid hormones


in gonads and adrenal.

*Anastrozole- non-steroidal aromatase inhibitor.

- decreases peripheral androgen aromatization

- for postmenopausal women with breast cancer in whom greater source of


estrogen is the conversion of androstenedione from adrenal to estrogen, in liver,
muscles and fat.

*Ocular manifestation of Grave's thyrotoxicosis sometimes respond to corticosteroid


therapy, but not to beta-blocker therapy.

*Clindamycin- Against Bacteroides and Gr. +Ve cocci

ADR- Pseudomembranous colitis

*Gentamicin ADR- Vestibular and cochlear toxicity, Nephrotoxicity and


neuromuscular paralysis( with large doses or intrapleural administration).

*MTZ ADR- GI ad neurological(paresthesia and dizziness).

*Chloramphenicol- can lead to dose related (reversible) or dose independent(often


irreversible) pancytopenia.

*Heparin- binds and activates antithrombin III

*Cryoprecipitate- contains FactorVIII,XIII,vonWillebrand's factor and fibrinogen.

*Protamine sulphate- Heparin overdose.

*Rat Poison- Brodifacoun ( 4-hydroxycoumarin derivative)

*Lepirudin and Argatroban- Direct thrombin inhibitor, used for Mx of heparin induced
thrombocytopenia

*Ticlopidine ADR- neutropenia, fever and mouth ulcer.

-CBC is monitored biweekly for first 3 months

*Unfractionated heparin has pentasaccharide chain long enough (>18 saccharide


units) to bind to both antithrombin and thrombin.

*Gardos channel ( calcium dependent K ion channel) blockers hinder the efflux of
potasium and water from the cell, preventing dehydration of erythrocytes and
reducing the polymerization of HbS.
*Hyroxyurea icreases fetal hemoglobin (HbF) synthesis by an unknown mechanism.

- HYdroxyurea is reserved for Pts. with frequent pain crisis.

*Cimetidine, Metronidazole, cotrimoxazoland warfarin inhibit the metabolism of


warfarin, so dose need to be reduced.

*Rifampin, Phenytoin and phenobarbitol are enzyme enhancer.

*At low doses, aspirin inhibits COX1 alone, whereas at high doses, it inhibits both
isoenzymes irreversibly.

*NSAIDs produce REVERSIBLE COX inhibition.

*Abciximab, Eptifibatide and tirofiban- Inhibits binding of platelet GP II/IIIa surface


receptors with fibrinogen and fibronectin i.e. the final step in platelet aggregation.

*Ticlopidine and Clopitogrel - inhibit ADP mediated platelet aggregation.

Uses- Following PCI and T/t of unstable angina and non-Q wave myocardial
infarction.

*Heparin Induced Thrombocytopenia (HIT) T/t- Direct thrombin Inhibitor eg.Hirudin,


Lepirudin and Argatroban. Inhibition of all Heparins.

*nON-nUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITOR (NNRTI)- eg. Nevirapine,


Efavirenz and Delaverdine.

- Dont need phosphorylation intracellularly to get activated.

ADR- Hepatotoxicity with encephalitis(In first 6 weeks of initiating medication)


and life threatening SKin

reactions eg. Stevens -Johnson, Toxic Epidermal Necrolysis(in first 18 weeks).

*Protease Inhibitor- prevents assembly and maturation of the virus.

*Enfuvirtide- HIV Fusion Inhibitor. Binds to the envelope GP41 of HIV-1 and blocks
conformational changes necessary for the fusion of viral and cellular membrane.

*Heparin increases thromboxinIII activity-> Activated Antithrombin III binds to


thrombin(Factor II), Factor Xa etc.

*LMWH has more activity against Xa than Unfractionated Heparin.

*CLopidorel and Ticlopidin- Inhibit ADP mediated platelet aggregation.

*Age-related Macular degeneration- T/t- VEGF inhibitor [ eg.Ranibizumab(prefferred


Humanized recombinant antibody), Pegaptanib]; laser therapy and phototherapy.
*Epidermal Growth Factor receptor inhibitor (eg. erlotinib, Gefitinib) - for T/t of Non-
small-cell lung cancer.

*Rituximab- Monoclonal Antibody against Glycoprotein CD20.

Uses- B-cell Lymphoma, Rheumatoid Arthritis

*Infliximab- Chimeric IgG1 monoclonal antibody to TNF-alpha.

Uses-Rheumatoid arthritis, ANkylosing spondylitis and Fistulizing Crohn's


disease.

*Interlukin-2 - Cytokin that aids in maturation and diffrentiation of T-cells to aid in


tumor cell destruction.

Uses- RCC and Melanoma.

*CML - cells express BCR/ABL.

*Imatinib- inhibits BCR/ABL protein Tyrosin kinase. thus inhibits the cellular
proliferation of BCR/ABL cells without inducing apoptosis.

- ORAL medication.

*Naturally occuring negative coagulants- Protein C, Protein S, Antithrombin III and


Tissue Pathway Factor Inhibitor(TPFI).

*Protamine- binds and chemically inactivates heparin.

*G6PD Deficiency anemia Precipitating factors:-

1.Infections

2.Drugs- Dapsone,Antimalarials,Sulfonamides

3.DKA

4.Favism

*Raltegravir- Integrase inhibitor. Disrupts the ability of HIV to integrate it's genome
into the host cell's chromosomes, thus preventing host cellular machinery from
being used to synthesize HIv mRNA.

*Fusion inhibitor - Attaches to gp41 and ihibits virus entry into CD4+ cells.

eg.Enfuvirtide- binds to heptad repeat-1 (HR1) of gp41.

*HIV attachment to target cells is mediated by the binding of viral envelope protein
gp120 to the CD4 membrane protein of T-helper cells.
*RT inhibitor- HIV DNA Synthesis from RNA Template.

*Protease inhibitor- inhibits HIV polyprotein cleavage catalyzed by HIV VIral


protease.

*Integrase Inhibitor- inhibits HIV DNA integration into host genome.

*Aminocaroic acid and tranexamic acid- inhibit fibrinolysis. they inhibit plasminogen
activation.

*Ganciclovir - intgerfers to Human DNA, more tha acyclovir.

Use- CMV infection

ADR- Neutropenia, anemia, thrombocytopenia and renal dysfunction.

*AZT- can bind to and inhibit some mammalian cellularand mitochondrial DNA
polymerases, particularly beta and gamma polymerases.

ADR- Bone marrow suppression, causing anema, neutropenia.

*Samter's triad- asthma, aspirin hypersensitivity and nasal polyposis

- these symptoms occur due to the overproduction of leukotienes. As aspirin


blocks the Cyloxygenase pathway causing arachidonic acid metabolites to be
diverted into lipoxygenase pathway.

*Aspirin - at lowere doses increases uric acid levels.

- at high doses is uricosuric.

*Ascorbic acid - absorbed in distal small bowel by active transport

*pyridoxine (B6) - Jejunum, by passive diffusion

*Biotin (B7) & Pantothenic acid (B5) - via sodium dependent multivitamin
transporter.

*Atrial Natriuretic Peptide & NO- act via cGMP.

*Penicillin - inhibits transpeptidase, the enzyme that catalyzes the final crosslinking
step in peptidoglycan cellwall formation.

*Penicillins - structural analogue to D-ala-D-ala

*Sulfonamides - compete with Para Aminobenzoic Acid (PABA) for incorporation into
folic acid.

*Cmompetitive antagoinist- Chnage ED50 to shift right, no change in Emax


*Non-Competitive antagonist- Change Emax to shift down, but no change in ED50

*Drugs with high intrinsic hepatic clearance tend to have high lipophilicity and a
high volume of distribution, with penetrance into the CNS and other tissues.

*NAPQI- N-acetyl-p-benzoquinoneimine, a Toxic and highly reactive metabolite of


Paracetamol by oxidation by Cyt P450. It is reduced by Glutathion.

N-acetyl cysteine(NAC)- Paracetamol poisoning Antidote. It acts as


glutathione substitute to bind to NAPQI.

- It also provides sulfhydryl groups to enhance the non-toxic sulfation


elimination of acetaminophen.

*MU Opiod Analgesic-> contraction of smooth muscle cells-> -> constriction and
spasm of of the Sphincter of Oddi-> Increased CBD pressure-> increased Gall
bladder pressure-> Billiary colic.

*Indinavir ADR- Lipodystrophy, Hyperglycemia and inhibition of CYP P450,


Nephrotoxicity and Nephrolithiasis.

*Foscarnet ADR-> Nephrotoxicity, Electrolyte imbalance(eg. Hypocalcemia,


hypomagnesemia and hypokalemia).

*Acyclovir ADR- Nephrotoxicity.

*TMP-SMX ADR- Megaloblastic Anemia, Stevens-Johnson Syndrome and TEN.

*the risk of CVA due to OCPs is very much increased in smokers and >35 Yrs.

*Absolute C/I for OCPs-

1. Prior H/o CVA or thromboembolic event

2. H/o estrogen dependent tumor

3. >35 Yrs. age

4. Hypertriglyceridemia

5. Pregnancy

6. DEcompensated or active liver diease(would impair steroid metabolism)

*Lead Poisoning-

1.Colicky abdominal Pain, constipation,headaches, impaired concentration


and deficits in short term memory.

2. Bluish pigmentation at the gum-tooth line.


3. Wrist drop d/t neuropathy

4. Microcytic hypochromic anemia and basophilic stippling on peripheral


smear.

Dx- blood lead level >10micro grams/ dL(0.48 micromol/L) on a venous


sample.

*Arsenic Poisoning- nausea, vomiting, abdominal pain, diarrhoea, decreased level of


consciuosness, hypotension, tachycardia and Garlic odor of breath.

T/t- Dimercaprol, which displaces arsenic ions from the sulfhydryl group of
enzymes.

*DImercaprol- narrow therapeutic range.

ADR- nephrotoxicity and Hypertension.

*CaNa2EDTA- Acute lead and mercury poisoning

*Methylene blue- Methemoglobinemia.

*OCPs- Primary mode of action is suppression of synthesis of the gonadotropins FSH


and LH, which there by leads to inhibition of ovulation.

- minorly, It also thickens the cervicle mucus making spermpenetration


difficult and progestrin prevents growth of the endometrium making it unsuitable for
implantation of embryo.

*Diphenoxylate- opiate anti-diarrhoeal. binds to GI Mu receptors and lowers motility.

ADR- Bloating and mild sedation.

*Octreotide- Helpful in secretory diarrhoea.

*Amantadine- impairs uncoating of Influenza-A virion after host cell endocytosis.

Ribivirin MOA- Lethal Hypermutation, inhibiting RNA polymerase and IMP (depleting
GTP), causing defective 5'-cap formation on viral mRNA transcript and modulating a
more effective immune response.

*Bioavailability = Area under the oral curve* IV dose/ area under the IV curve*oral
dose

*Lyme disease vaccine- contains aa recombinant outer surface protein from Borrelia
burgdorferi bacteria

*Gout and pseudogout- WBC count <20,000

*Septic/Gonococcal arthritis- acute monoarticular arthrtis, with WBC count >50,000.


*Rheumatoid Arthritis- swelling, pain and morning stiffness in multiple joints for >6
months.

T/t- Acute- Corticosteroids and NSAIDs.

Chronic- Methotrexate. It takes weeks to show effect.

*Hydrochlrothiazide- it increases the absorption of calcium from DCT within


nephrones. Thus causing Hypercalcemia and hypoclciuria.

*Etambutol ADR- optic neuritis causing visual acuity, central scotoma or color
blindness.

*Aminoglycosides & Vancomycin ADR- direct damage to the 8th cranial nerve.
Therefore can cause deafness, vertigo and tinnitus.

*Aminoglycosides ADR- ototoxicity,Renal toxicity(Acute Tubular necrosis) and flaccid


paralysis due to neuromuscular blockade.

*CBC to be monitored in- Chloramphenicol(aplastic anemia),


Dapsone(agranulocytosis) and TMP-SMX(Megaloblastic Anemia)

*Bosentan- competitive antagonist of endothelin receptors.

- used for Primary Pulmonary HTN

*Etanercept- humanized monoclonal antibody against TNF-alpha

-anti-inflammatory agent indicated for treatment of Rheumatoid arthritis,


Psoriasis and Psoriatic Arthritis.

*N-acetylcysteine- a mucolytic agent that loosens the thick sputum by cleaving


disulfide bonds within mucus glycoproteins.

*Antimuscarinic agents (ipratropium,tiotropium) only reverse Vagally-mediated


bronchoconstriction.

*Methylxanthines(theophylline,aminophylline) cause bronchodilation by decreasing


phosphodiesterase enzyme activity, thereby increasing intracellular cAMP.

*Mycobacterium Avium Complex (MAC) T/t- Rifampin, Ethambutol and a


macrolide(azi or clarithromycin).

*Staphylococcal endocarditis- Penicillin and aminoglycoside

MRSA- Vancomycin, Rifampicin/aminoglycoside.

*Rifampin Monotherapy in exposure/carrier state of N. Meningitis.


*for Rifampin monotherapy bacteria rapidly acquire resistance through spontaneous
genetic mutations of the bacterial DNA-dependent RNA polymerase.

*aerosolised Ribavirin- for RSV infection, espacially in infants and children who are
at risk for disease progression.

*Oseltamivir- SIalic acid analogue inhibitor of Influenza A and B viral


Neuraminidases.

*Ganciclovir- Anti-CMV guanine nucleoside analogue.

*Isoniazid MOA- inhibition of mycolic acid synthesis after activation by bacterial


catalase.

Resistance- through non-expression of the catalase-peroxidase enzzyme or


through genetic modification of it's binding site on mycolic acid synthesizing
enzyme.

*Ethambutol- MOA-> inhibits with bacterial cellwall.

Resistance- Mycobacteria increase production of arabinosyl transferase (an


enzyme that polymerizes arabinose-> arabinan-> arabinogalactan)

*Pyrazinamide- converted to pyrazinamic acid, causing acterial environment to


become acidic.

Resistance- decreased activity of mycobacterial enzyme pyrazinamidase.

*Amphotericin B- MOA- binds to ergosterol with higher affinity than with cholesterol.

Toxicity- 1. Acute infusion related reactions. these decrease with subsequent


infusions.

2. dose dependent nephrotoxicity- coz it decreases the glomerular filtration


rate. KFT should be closely monitored.

3. HYpomagnesemia and hypokalemia. within first week of infection.

4. Anemia- d/t decreased renal erythropoietin synthesis. severe with AZT.

5. Thrombophlebitis.

*C. dephtheriae- causes bacterial toxin mediated axonal damage.

*Isoniazide is structurally similar to pyridoxin (B6). as a result it increases the


urinary excretion of B6. also, it competes with B6 binding sites, leading to the
defective synthesis of neurotransmitters like GABA.
*Antibiotics that act on 50S ribosomal subunit- chloramphenicol, clindamycin,
linezolid and macrolides.

*Antibiotics that act upon 30S subunit- Tetracyclins, doxyxycline and


aminoglycosides.

*Varenicline- Partial agonist of alpha4 beta2- nicotinic acetylcholine receptor.

- reduces withdrawal cravings and attenuating the rewarding effects of


nicotine.

*MAc infection- <50 CD4 cells.

-more involvement of RES causing Fever, weight loss diarrhoea, anemia,


hepatosplenomegaly, and elevated LDH and ALP levels.

- MAC grows well at higher temperature(unlike TB)

T/t- Azithro/clarithro with rifabutin/ethambutol.

Prophylaxis- weekly Azithro and pharamcological HIV T/t to bring CD4 cells
>200.

*Cromolyn and nidocromil- for prophylaxis in seasonal asthma, exercise induced


asthma and aspirin hypersensitivity.

*Lukasts- chronic asthma prophylaxis.

*Mycolic acid- long branched chain saturated fatty acid that contain aproximately
ninety carbon molecules.

*Polyenes(Amphotericin B and Nystatin):- bind ergosterol molecules in fungal cell


membrane, forming pores and causing cell lysis.

*Triazoles(keto,itra,flu and voriconazole):- inhibit ergosterol synthesis.

*Echinocandins(Caspofungin and micafungin):- inhibit 1,3-beta-d-glucan synthesis, a


component of fungal cellwall.

- Maximum activity against Candida and aspergillus, limited activity against


mucor and rhizopus and no activity against Cryptococcous neoformans.

*pyrimidines (Flucytosine):- convorted to 5FU and interferes with fungal RNA and
protein synthesis.

*Griseofulvin- enters fungal cells, binds microtubules and inhibits mitosis.

-effective only against dermatophytes, as it gets accumulated in keratin


containing tissues.
*Terbinafin- inhibits squalene-2,3-epoxidase, which ultimately results in in decreased
synthesis of ergosterol.

*Pyrazinamide- Acts in acidic media, so works better on intracellular organism


engulfed by macrophages.

*Isoniazid, ethambutol and rifampin - activity against extracellular organisms.

*Theophyllin Toxicity- abdominal pain, vomiting,, diarrhoea, cardiac


arrhythmias(tachyarrhythmias) and seizures(major cause of morbidity and
mortality).

T/t- beta-blockers for tachyarrhythmias.

- theophyllin induced seizures are very difficult to treat. BZD and


Barbiturates are used.

*Stretomycn- Uses-> Plague, Tularemia and TB.

*Medications causing Seizures- Bupropion( with H/o seizures and bulimea/anorexia


Nervosa), Ciproflox, Clozapine(antipsychotic, at high doses), Isoniazid( anti-
ttubercular, if given without pyridoxin) and imipenem.

* Clozapine ADR- Agranulocytosis

*Bone Marrow suppression - by Carbamazepine and Valproate.

*Lamotrigine- Rash, may even cause Stevens-Johnson.

*Olanzapine- Wt. gain.

*Sexual dysfunction - SSRI.

*Malignant hyperthermia- AD trait. Abnirmal ryanodine receptor, which are Ca


channels. these kept open in influence of some agents-> high influx of Calcium ion-
> excessive consumption of ATP-> excessive generation of heat-> both these slong
with ATP depletion cause muscle damage(rhabdomyolysis)-> releases potassium,
myoglobin and creatin kinase in the circulation.

Causative agents- Inhalation Anaesthetic(esp. Halothane) and muscle


relaxant Succinylcholine.

T/t- Dantrolin.

*Myasthenia Gravis- Dx- edrophonium

T/t- Neostigmine, pyridostigmine

*ADPKD- may have Berry aneurysm.


*No earlier than 3 days post SAH (usually 7-8days), pt may show signs and
symptoms of cerebral vasospams i.e. altered mental status and focal neuronal
deficit.

T/t- Nimodipine as preventive medicine.

*Physostigmine- Tertiary amine, which can cross BBB and reverse the anti-
muscarinic effect of Atropin.

*Neostigmine and edrophonium- quarternary amines, so can not cross BBB.

*Diazepam- Used as muscle relaxant to to stop spasticity caused by UMN disorders


(eg. MS, Strokes, Spinal cord trauma) and tetanus.

*BZDs- should not be co-administered with alcohol, barbiturates, neuroleptics and


Igeneration antihistamines.

*Penicillines irreversibly bind to PBPs eg. transpeptidases.

*Opiods- No tolerance to Mitosis and Constipation.

*Phenytoin -> MOA- inhibits neuronal high frequency firing by reducing the ability if
sodium channels to recover from inactivation, increasing the refractory period.

uses- tonic-clonic and psychomotor seizures. seizure Prophylaxis after head


trauma and before neurosurgery.

ADR- Generalized Lymphadenopathy(Pseudolymphoma), cosmetic


effects( Hirsutism, coarsening of facial features, acneiform skin rash and GINGIVAL
HYPERPLASIA).

*Carbamazepine- Uses- GTCS, Partial Seizures, pain relief in trigeminal and diabetic
neuropathy and bipolar disorder.

ADR- Agranulocytosis.

*Valproate- ADR-> Hepatotoxicity.

*Phenobarbitol ADR- Acute Intermitent Porphyria.

in toxic doses- sedation or cardiovascular and respiratory depression.

*Vitamin B6 increases the peripheral metabolism of Levodopa decreasing its


efficacy.

*Serotonin Syndrome- COnfusion, agitation, Tremor, Tachycardia, Hypertension,


Clonus, Hyperreflexia, Hyperthermia and Diaphoresis.

Causes- COmbination of SSRIs and MAO-Inhibitors, High doses of SSRI.


T/t-Supportive Care, Cyprohepatidine, a first generation histamine antagonist
with non-specifi 5HT1 and 5HT2 receptor antagonist properties.

-Short acting antihypertensives acn be used to treat hypertension a/w


serotonin syndrome. HYpertensive agents with longer half lives, should be avoided
d/t risk of developing hypotension and shock.

Haloperidol- antipsychotic. it's adverse reaction is similar to Serotonin


syndrome.

BZD- used to releive agitation, mildly reduce HR and b.p.

*Aged Pt.s with H/o falls etc., should not be given first generation antihistamines.

*Alzheimer's Disease- CNS NMDA receptor overstimulstion by glutsmate may


contribute to AD.

T/t- Cholinesterase Inhibitor(Donepezil), Antioxidents( Vit. E) and NMDA


receptor Antagonist( Mementine).

*GABA- BZDs bind to allosterically to gaba chloride ion channel and increase the
frequency of Cl ion channel opening. Thus facilitates GABA actions.

-Barbiturates- prolong the duration of ion gate opening in response to GABA.


AT higher concentration, they open the ion gates without need of GABA.

*Bupropion- ANtidepressant that doesn't cause sexual dysfunction.

ADR- agitation,insomnia and seizures.

-doen't significantly influence serotonin, Ach or histamine.

Uses- depression with accociated psychomotor retardatio or hypersomnia.

-Also effective in treatment of nicotine dependence.

*Ethosuximide - Absence Seizures.

- blocks T-type calcium ion channels that trigger and sustain rhythmic pulsed
discharges in thalamic neurons.

*Phenytoin - GTCS, STatus epilepticus.

- inhibits neuronal firing of action potentials by blocking Sodium ion channels

*Carbamazepine- COmplex Partial seizures and GTCS.

ADR- Apllastic Anemia and Agranulocytosis.

*Entacapon- Peripheral Catechol-o-methyl-Transferase (COMT) inhibitor.


*Talcapon- Peripheral and central COMT inhibitor.

- Hepatotoxic.

*Selegiline- inhibitor of brain's MAO-B, decreases central dopamine degeneration.

*Anti-cholinergics, like Trihexyphenidyl and Benztropine, inhibit central muscarinic


receptors.

-Mainly used for Parkinson's Disease.

*TCAs ADR- Urinary Retention (competitively block Ach on muscarinic receptors of


bladder),Cardiac arrhythmia(quinidine like effect, QRS and QT prolongation),
Seizures (in CLomipramine), Orthostatic Hypotension (through alpha-adrenergic
blockade) & sedation (d/t bloackade of Histamine receptors)

* Seizures - ADR of CLomipramine and Bupropione( DOpamine-Norepinephrine


reuptake inhibitor)

- D/t antihistaminic, antimuscarinicand anaesthetic properties.

*MAO Inhibitors- Tranylcypromine, phenelzine, Selegiline.

*Drug Induced parkinsonism- By Dopamine(D2) Receptor blockade in the


nigrostriatal pathway. Usually occur with first generation anti-psychotics.

T/t- Anticholinergics (like Benztropine, Trihexyphenidyl).

- Levodopa and dopamine agonist can exacerbate Psychosis, so C/I in drug


induced parkinsonism

*Buspiron- Selective agonist of the 5HT1a receptor.

-Anxiolytic with Minimal to no Hypnotic, sedative or euphoric effects.

- Dependence doesn't occur, even with chronic use.thus can be used in Pts.
with h/o of abuse of anti-anxiety drugs.

- Clinic response strats in 2 weeks.

*Negative symptoms of Schizophrenia respond poorly to the antipsychotic


medication. Psychosocial treatments, such as congnitive behavior therapy are
effective in treating these.

*TCAs- Used for Diabetic Neuropathy

*Bupropion- Uses- Major depression, tobacco dependence and hypoactive sexual


disorder.
-Structurally related to amphetamine and inhibit presynaptic reuptake of
Dopamine and NE, with greater effect on Dopamine.

ADR- Seizures, esp.in pts with H/o seizures, bulimia/anorexia.

* Cisplatin- MOA- forms a reactive oxygen species that can form Crosslinks.

ADR- Acute Tubular Injury.

Amifostine - a thiol based cytoprotective free radical scavenging agent


used to decrease the cumulative nephrotoicity associated with platinum containing
agents.