PHARMACOLOGY

Drugs used in Gastrointestinal System

1. Drugs for peptic ulcer H2 receptor antagonist cimetidine Proton pump inhibitor omeprazole Prostaglandin analogue misoprostol Mucosal protective agents sulcralfate i) Cimetidine Competitively blocking the binding of histamine to H2 receptors, reducing CAMP, thus decr secretion of gastric acid ii) Proton pump inhibitor inhibit H+/K+ATPase enzymes & inactivate it irreversibly, suppressing secretion of H+ into the gastric lumen b) Treatment of H.pylori infection Bismuth + metronidazole + amoxicillin / tetracycline Omeprazole + amoxicillin + clarythromycin 2. Drugs for peptic ulcer a) 4 types of drugs and exmples. [4] -H2 receptor antogonist cimetidine -Proton-pump inhibitor omeprazol -Prostaglandin analogue misoprostol -Mucosal protective agents sucralfote -Antimuscarinic agents pirenzepine b) Choose 1 drug, describe mechanism of action. [4] Cimetidine competitively blocking the binding of Histamine to H2 receptor, reducing cAMP, thus decrease secretion of gastric acid Proton pump inhibitor inhibit H+/K+ATPase enzyme & inactivate it irreversibly, suppressing the secretion oh H+ into the gastric lumen. c) Give the treatment for H. pylori infection [2] -Bismuth + metronidazole + amoxicillin/tetracycline -omeprazole + amoxilin + clarythromycin/metronidazole d)Choose 2 drugs from above and explain their mechanism of action. [6m] - Analogue of PGE - Increase HCO3- and mucus production - Increase HCL production - pH >4.0 - Decrease H. pylori growth

Drugs Used in Hemodynamic Disorder, Thromboembolitic & Shock

3. Warfarin Inhibit vit K epoxide reductase needed to regenerate vit K for carboxylation for factor II, VII, IX, & X Or, vit K is needed as a cofactor in the carboxilation of glutamic acid residues of factor II, VII, IX & X Thus warfarin results in the formation of inactive clotting factors

Cimetidine, metronidazole inhibit P450 system enzyme thus decrease metabolism of warfarin causing drug toxicity, increase bleeding

b) Pharmacokinetic Effects takes longer time bcoz preformed clotting 1st takes time to degrade Heparin acts on antithrombin III to inactivate clotting factors c) Contraindicated Aspirin harmful: antiplatelet effect of aspirin causing bleeding. Displacement of warfarin from plasma binding site increase warfarin Cimetine harmful: inhibition of microsomal enzymes decrease warfarin metabolism bleeding d) Treatment of overdose Stopping using the drug Administration of large doses of vit K, fresh frozen plasma or coagulation factor concentration 4.warfarin a) describe its pharamacological action(5) - inhibit vit. K epoxide reductase.(KER) - the enzyme is needed to regenerate vit K. - vit K is needed as a cofactor in the carboxylation of glutamic acid residue of factor 2,7,9 ,10. - results in the formation of inactive clotting factor. b) why its onset is much slower than heparin?(4) - effects take longer bcz preformed clotting first takes to degrade.heparin acts directly on antithrombin 3 to inactive clotting factors. c) explain whether it is harmful/beneficial interaction with (4) - aspirin - antiplatelet effect if asprinbleeding - displacement of warfarin from plasma binding site(albumin)increase warfarin concentrationincrease warfarin activity - cimetidine -inhibition of microsomal enzymeswarfarin metabolismbleeding d) what drug can be used to reverse the overdose(3) - large dose of vit K(phytonadione) - prothrombin complex concentrates,recombinant 7a n 4 - give fresh frozen plasma. - stop drug 5. anticoagulant agents a) Give 2 anticoagulant and their action b) Compare their duration, onset, route of administration, and drug for overdose Heparin unfractionated H (12-15 kD) LMWH (4.5 kD) Warfarin Heparin UFH LMWH Accelerater action of antithrombin III antithrombin III neutralizes factors IIa, IXa. Xa, XIa, XIIa Warfarin Inhibits reductase & so interferes with synthesis of vit. K dependent clotting factors (II, VII, IX,

Action

X) in liver

RoA & onset

i)iv subcutaneously Onset 12-16 hrs immediate after administration onset RoA oral ii)subcutaneous delayed onset up to 60mins Duration & t T = to 2 Longer t Action last 4-5 days hrs compare to T -3 days UFH elimination Zero order 1st order kinetics kinetics (linear) Plasma protein Binds no 99% bound to binding extensively to plasma protein PP & Thus, low Vd endomedial cells Neutralization yes Resist by platelet factor 4 Placenta/breast Does not cross Cross placenta & milk appear in breast milk Metabolized RES & liver Mixed function oxidase p450 Monitoring nPTT (1.5-2,5 X control) Prothrombin time (2-4X normal value) Antidote for Protamine suphate (basic) i)vit K (phytona ??) overdosing ii)free frozen plasma/? Blood - if theres bleeding Adverse effects i)hemorrhage i)hemorrhage ii) thrombocytopenia ?? ii) necrosis thrombosis iii) teratogenic iii) osteoporosis

6. Warfarin a) Mechanism of action. (4M) b) How is the a. oral route (1M) - 100% BA b. plasma protein binding (1M) - 99% bound c. metabolism (1M) - liver (P450 cytochrome) c) Why onset slow? (require several days) (3M) d) Drug interaction with a. Aspirin (4M) Compete for the same binding site on albumin, displace warfarin as it has higher affinity for albumin [ warfarin] pl bleeding. Inhibit COX1 pathway TXA form platelet inhibit platelet aggregation bleeding

b. Tetracycline (3M) Kill NF synthesis vitamin K vitamin K d. CF warfarin e)If overdose, what is the drug to counteract its action? (1M) Phytanadione Barbiturates Rifampicin f) Name one monitoring method. (2M) - prothrombin time 20-25% more than normal value. 7. Haematinics a) Give 2 reasons for iron deficiency. [2m] - Chronic GI bleeding - Decrease intake of iron/ B12 vitamin - Increase demand caused by pregnancy/lactation b) Give 2 drugs administered orally and 2 drugs administered i.v. [2m] Oral Ferrous sulfate Ferrous fumarate i.v. Iron dextran Iron sorbitol

c) Folate deficiency is associated with what kind of anemia? [1m] - Megaloblastic anaemia d)What drug will interfere metabolism of folate, explain. [2m] - Methotrexate Inhibit dihydrofolate reductase - So, dihydrofolate can not convert to tetrahydrofolate - This will inhibit nucleoside synthesis. e)Give 2 enzymes that vitamin B12 act as cofactor. [2m] - Methylmalonyl CoA-reductase f)Give the natural form and clinical form of vitamin B12. [1m] - natural methylcobalamin, deoxyadenosylcobalamin - clinical-hydroycobalamin, cyanocobalamin

Drugs Used in Treating Hypertension

8. A patient came into A&E with hypertensive crisis. He was given infusion of antihypertensive and the BP was successfully controlled. However, later he presented with signs of convulsion, tinnitus, hallucination, weakness and nausea a) What was the drug given and state your reasons. [4] Propranolol usually cause CNS side effects like hallucination, nausea, weakness because it is a highly lipid soluble drug that can cross the blood brain barrier easily. b) Briefly give the mode of action of this drug.[4] Block receptor, decrease contractility & HR Decrease CO, decrease BP Block receptor, decrease sympathetic outflow & release of renin, decrease angiotensin II & aldosteron, decrease retention of NA & H2O Bock pre-synaptic -adrenoceptors, block release of noradrenaline c) Give another drug that can be used. [2] - diuretics like hydrochlorothiazide (Antihypertensive)

9. Potassium-sparing diuretic a) Name 1 potassium-sparing diuretic [1] Amiloride b) Mechanism of action [3] Blocks Na+ channels in apical membrane of late distal tubule and cortical collecting tubule, thereby causing K+ retention at the same time as mild natriuresis. c) Discuss 2 clinical uses [4] Used with frusemide in patient with heart failure With thiazide for hypertension In both cases, amiloride prevent hypokalaemia due to loss of K+ when increase Na+ reaches the distal tubule in patients treated with frusemide and thiazide d) Give adverse effects [2] Nausea and vomiting Hyperkalaemia 10. ACE inhibitors a) 2 drugs that prevent formation of Angiotensin II Captopril Enalapril b) Action Prevent the conversion of AngT I to AngT II Inhibit d converting enzyme peptidyl dipeptidase which hydrolyzes angT I to angT II Inactivates bradykinin (vasoD) Dilates both arterioles & veins Reducing pre- & afterload c) Uses Hypertension, congestive heart failure d) Adverse effects Dry cough: ACE diminishes the rate of inactivation of bradykinin thus resulting in accumulation of bradykinin in the bronchial mucosa e) Contraindications Bilateral renal artery stenosis Patients treated with potassium sparing diuretics 11. Diuretics a) Name 1 potassium sparing diuretic Amiloride, Spironolactone b) Mechanism of action - Amiloride Blocks Na+ channels in apical membrane of late distal tubule & collecting tubule, thereby causing K+ retention at the same time as mild natriuresis c) 2 clinical uses Used with frusemide inpatients with heart failure With thiazide for hypertention In both cases, amiloride pevent hypokalemia due to loss K+ when Increase Na+ reaches the distal tubule in patients treated with frusemide & thiazide

d) AE Nausea & vomiting Hyperkalaemia

Drugs used in Endocrine System

12. Drugs affecting pituitary function a) Bromocriptine A: lower circulating prolactin levels & shrink pituitary prolactin-secreting tumors AE: N, V, H, Postural hypotension b) Desmopressin (V2 selective- renal tubule) Analogue vasopressin (ADH) Increase water permeability & water reabsorption in collecting tubule U: for DI & nocturnal enuresis (involuntary discharge of urine during sleep at night)

13. Anti-thyroid drugs a) MOA of these drugs & their AE i) Prophylthiouracil A: prevent T3 & T4 synthesis by *inhibiting the thyroid peroxidase catalyzed reactions to block iodine organification *blocks coupling of iodotyrosines Inhibiting deiodination of T4 to T3 in peripheral tissue Preferable in pregnancy bcoz strongly protein bound AE: allergic reaction ii) carbimazole A: prevent T3 & T4 synthesis by *inhibiting the thyroid peroxidase catalyzed reactions to block iodine organification *blocks coupling of iodotyrosines Rapidly converted to methimazole AE: granulocytopenia, maculopapular pruritic rash, caution in pregnancy iii) Radioactive iodine A: destroys thyroids cells by emits both B & gamma rays AE: not admin in pregnant women iv) Lugols solution A: Inhibit iodination of thyrosine residues on thyroglobulin, possibly by inhibiting H2O2 generation Inhibit thyroid hormone release by inhibition of thyroglobulin proteolysis Decrease size & vascularity of hyperplastic gland Used 4 surgery & thyroid storm Should not be used alone bcoz withdrawal may produce severe exacerbation of thyrotoxicosis in an iodine-enriched gland AE: allergic reaction, avoid in pregnancy v) Propranol given to decrease sign & symptoms of hyperthyroidism 14. man going for radioiodine therapy a) what is another drug used b4 treatment to decrease signs and symptom propanolol b) discuss mechanism of action

propanolol is a b-blocker.Thyroid hormone cause the sign and symptoms by increase proliferation of b-R and inhibit catecholamine induced symptom c) Llist 2 benefit of radioiodine - long T1/2 - effective,rapidly absorbed d) disadvantages - cytotoxix - may cross placenta and appear in breast milk 15. Glucocorticoid a) Mechanism of action Produces responds to stress by raising blood glucose levels through breakdown of protein & fats Suppresses immune response & inhibit inflammatory effects by inhibiting cytokines synthesis & decreasing activity of leukocytes b) AE Suppression of response to infection or injury Adrenal suppression (suppression of endogenous GC synthesis) Metabolic effects causing sodium retention & potassium loss Osteoporosis Iatrogenic Cushing syndrome Impaired glucose tolerance Peptic ulcer

c) 2 eg of GC wt root of action + usage Drugs ROA Hydrocortisone Oral Beclomethaxone Inhalation

Therapeutic usage Replacement therapy Asthma

16. Glucocorticoid (Metabolic effect & anti-inflammatory effect) a) Action on i) Carbohydrate Decrease tissue uptake & utilization of glucose Increase in gluconeogenesis in liver & muscles hyperglycemia Increase glycogen storage dt increase insulin in response to increase glucose ii) Protein Stimulation of protein catabolism & decr protein synthesis iii) Lipid Permissive effect on lypolytic response to catecholamine redistribution of fat to neck & trunk iv) Increase resistance to stress by raising plasma glucose & Enhance vasoC v) anti-inflammatory & suppression of immunological action *inhibit mononuclear cells & neutrophils migration & their adhesion *inhibit transcription of genes for synthesis of COX-2 & inflammatory cytokines vi) Ions Mineralocorticoid actions sodium retention & potassium loss Decr Ca2+ absorption & Incr excretion osteoporosis

b) 4 adverse effects of long term use Impaired glu tolerance & DM Suppression of response to infection Suppression of endogenous glucocorticoid synthesis Osteoporosis Iatrogenic Cushings syndrome Peptic ulcer Growth suppress in children c) Preparation Iv Name of drug Hydrocortisone Therapeutic use Replacement therapy in Addisons disease Severe acute allergy / asthma Inflammatory bowel disease Asthma Transplant rejection Cerebral edema Acute asthma or HS

Inhalation Parenteral Oral @ Parenteral Oral

Beclomethaxone Methyl prednisolone Dexamethasone Prednisolone

c) Fludrocortisone mineralcorticoides Use as replacement therapy wt defective aldosterone production (Addisons disease) Raised BP in postural hypotension by expension of blood volume 17. Drugs for treating NIDDM type2 c) Give 1 sulphonylurea & MOA eg. Glibenclamide: stimulate insulin secretion by blocking ATP sensitive K+ channel depolarization CA2+ entry *stimulation of endogenous insulin release from beta cells of pancreas *reduction of serum glucagons levels *increase binding of insulin to target tissue & receptors *decrease breakdown of insulin & increase density of insulin receptors on the cells d) 1 oral antidiabetic that directly increases sensitivity of insulin R Biguanides eg. Metformin decrease hepatic glu production MOA:*decrease hepatic glucose production by inhibiting gluconeogenesis *increase insulin sensitivity *direct stimulation of glycolysis in tissue, wt increase glucose removal from blood *slowing glu absorption form GIT e) Drugs that increase glu uptake Thiazolidinedione (TZD) eg. Rosiglitazone MOA: * promotes insulin-dependent glu uptake & metabolism in skeletal muscle & adipose tissue *reduced hepatic gluconeogenesis f) a-glucoside inhibitor: Acarbose MOA:* inhibits intestinal enzyme (a-glucosidase) in the intestinal brush border that responsible for digestion of complex carbohydrate to monosaccharides b4 being absorbed in duodenum & upper jejunum

18. Insulin a) Name 3 forms of preparations Rapid acting: soluble insulin Intermediate: amorphous insulin zink suspension Long: crystalline insulin Zn suspension

b) Effects of insulin on i) Liver: *inhibit glycogenolysis *inhibit coversion of FA & aa to keto acids *inhibit conversion of aa to glucose *promotes glucose storage as glycogens *increase TG synthesis & VLDL formation ii) Muscle:*increase protein synthesis by increase aa transport *Increase glycogens synthesis by induces glycogens synthase & inhibit iii) Adipose tissue:*increase TG storage *induced lipoprotein lipase hydrolyze TG from lipoprotein *inhibit intracellular lipase c) 2 common AE Hypoglycemia : results of imbalance between glu intake Insulin allergy: results from histamine release from tissue mast cells sensitized by antiinsulin IgE Ab Lipodystrophy at site of injection phosphorylase

Drugs used in Pregnancy

19. Drugs that contraindicated in pregnancy Methotrexate antineoplastic agent Thalidomide malformation of legs & arms (4th to 7th weeks of gestation) Warfarin oral anticoagulants -1,2,3rd trimester during brain devp Phenytoin, carbamazepine, sodium valporate anticonvulsant Androgens, estrogens sex hormone Tetracycline Alcohol, smoking (nicotine) b) Factors determining the transfer of drugs Molecular size *small molecular size easy transfer, LMS difficult Lipid solubility *lipid soluble easy; polar compound hard Degree of ionization *non charged molecule easy Degree of protein binding c) Factors interferes the transfer Maternal obesity lipid soluble drugs sequestered in mothers fat Maternal hypoproteinemia less protein bound more free form go to fetus Presence of drugs metabolizing enzyme in placental tissue Fetal drugs metabolism drugs enter liver of fetus being metabolized 20. Combine Oral Contraceptives a) Mechanism of action Estrogen: inhibit release of FSH on anterior pituitary prevent development of ovarian follicle Progestogen: *Inhibit release of LH & prevent ovulation *causes changes in cervical mucus & decrease its penetrability by spermatozoa *Changes in endometrium to discourage implantation b) 2 common AE

Mild: nausea, weight gain, acne, amenorrhoea, breast engorgement, irritability Hypertension bcos Es incr circulating rennin & angiotensin Na+ & H2O retention Thromboembolism bcoz Es Incr clotting factors in d blood & incr platelet aggregation + Decr antithrombin III DVT, pulmonary embolism,MI Cholestatic jaundice & gallstone (reduces bile flow & Decr solubility of choles in bile) Impaired glucose tolerance reduce absorption of carbohydrate from GI & Pgsincrease basal insulin level Increase risk of liver tumor, cervical tumor

c) Advantage of COC wt POP More effect Decr menstrual irregularity & menorrhagia Decr menstrual blood & thus less iron deficiency anemia Decr risk of ovarian ca & endometrium ca Decr risk benign breast disease Incr bone density Lower incidence ectopic pregnancy Es incr HDL & lower LDL d) Progestogen-only oral contraceptive Less effective than COC More likely breakthrough bleeding & menstrual irregularities Do not suppress lactation Antifertility action bcoz thickening of cervical mucus & impairment of implantation e) Post-coital oral contraceptive Progestogen only or combine wt estrogen within 72 hr after unprotected intercourse Eg. Levonorgestrel

Drugs used in Central Nervous System

21. Morphine a) Onset of action & duration iv Onset: < 10 min Duratn: > 80 min If oral admin paek after 30 45 min b) MOA Opioid receptor agonist. Stimulation of opioid receptors may inhibit sensory pain transmission along spinothalamic tract & raise pain threshold c) Give mean time onset different between morphine vs saline & aspirin vs saline d) Is d experiment is to test d analgesic effect of aspirin? Give reason Low dose of aspirin Pain does not involved inflammation MOA: morphine act on opiate receptor (analgesic effect) while aspirin act through inhibition of COX enzyme (prevent inflammation) morphine more effective

22. Morphine a) 2 CNS actions Analgesia: Inhibit dorsal horn pain transmission. / inhibit sensory pain transmission along spinothalamic tract Respiratory depression: reduction of sensitivity of respiratory center neuron to CO2 Euphoria: powerful sense of contentment & well-being Depression of cough reflex: also for codeine, have anti-tussive properties Miosis: pin-point pupil. Important diagnostically to differentiate between morphine used or other caused of coma & resp depression b) Why pethidine given during childbirth Pethidine is short acting & have less effect in uterine tone analgesia during labour c) 2 drugs 2 reverse respiratory depression caused by morphine & why? Naloxone & naltrexone opioid receptor antagonists. Rapidly displaces all receptor-bound opioid molecules. d) Why use methadone to help drug addicts Methadone used for detoxification same potency like morphine Tolerance & dependence develop more slowly Withdrawal signs & symptoms milder Longer duration released slowly from binding protein 23. Benzodiazepine (BDZ) a) MOA Binds to different sites (alpha subunit) of GABAA receptor channel & enhance binding affinity of GABA to its receptor Increase Cl- permeability into channel hyperpolarisation of the neuronal cells Inhibition of neuronal activation b) Calcifications??? Conditions Short T1/2 Intermediate T1/2 Long T1/3 Myoclonic epilepsy Terminating status epilepticus Fast onset hypnotic BDZ/ sleep onset Anaesthesia Early morning awakening Sedative agent Spasmolytic Insomnia Anxiolytic action only Non-BDZ hypnotic Management of drug withdrawal @ drug abstinence Drugs Triazolam, Midazolam Oxazepam, Lorazepam Diazepam, Nitrazepam, Flurazepam Clonozepam iv of Diazepam & Lorazepam Triazolam iv of Midazolam & Diazepam Diazepam, Nitrazepam Midazolam Diazepam esp in cerebral palsy, multiple sclerosis, mechanical injuries dt brain/ sc Triazolam, Nitrazepam Flurazepam (anti-anxiety agent) Zolpidem Diazepam

c) 3 reasons why midazolam iv is better than diazepam Water soluble Short duration More potent d) AE Drowsiness & confusion Cognitive impairment (decr long-term recall & acquisition of new knowledge)

Impaired coordination, diminished motor skills esp driving Ataxia (high doses) Anterograde amnesia Psychological & physiological dependence

24. Antiepileptic a) Which drug mandatory monitoring is necessary? Phenytoin b) Why Metabolism shows saturation kinetics meaning the rate of inactivation does not increase in proportion to d plasma concentration There is also large interindividual variation of metabolism of phenytoin T incr as dose incr, thus steady state mean plasma [ ] varies disproportionately wt d dose Narrow therapeutic index toxicity c) AE Acute: nystagmus (eye), ataxia, diplopia, drowsiness, vertigo Chronic: hyperplasia of gums, hirsutism, osteomalacia, megaloblastic anemia Pregnant lady: fetal hydantoin syndrome

25. Carbamazepine antiepileptic drugs a) MOA inhibit Na+ channels, prolong the inactivation stage of Na+ channels b) Treating what type of epilepsy partial seizures, tonic clonic c) 3 AE Nystagmus Diplopia Agranulocytosis & anaplastic anemia d) 3 non-epileptic function Treat trigeminal neuralgia Manic depressive patient Sedative hypnotic drugs 26. Anti-parkinsonism drugs a) Levodopa wt carbidopa actions Levodopa precursor of dopamine, can replenish dopamine content in CNS. Carbidopa is dopa decarboxylase inhibitor to prevent metabolism of levodopa at periphery b) AE of levodopa N. v Orthostatic hypotension Arrhytmias & tachycardia Dyskinesia Depression, anxiety, insomnia, hallucinations

c) Action of benzhexol antimuscarinic drugs. Efficacious against tremor & rigidity d) AE of Benzhexol Drowsiness Slowness

Confusion Agitations Hallucinations Avoided in prostatic hypertrophy & angle closure glaucoma

27. Migraine - Ergotamine a) Pathological action of ergotamine Partial 5HT1D receptor agonist Stimulation of 5HT1D receptor on trigeminal N inhibits release of substance P & CGRP Thus preventing vascular dilatation (vasoconstriction) & neurogenic inflammation b) Action of caffeine on ergotamine Caffeine promotes absorptn of ergotamine (ergotamine poor absorbtion in GIT) c) AE Nausea & vomiting Rebound headache Peripheral vasoconstriction including coronary vessels Uterus contraction fetal damage Overdose/ prolong used ergotism (distal paresthesia/abnormal sensation & gangrene of limbs)

28. Name 2 abortive drugs 4 migraine Sumatriptan *Stimulate 5HT1B/1D receptor (full agonist) * inhibit release of tachykinins (SP & CGRP) *Selectively constrict cranial BV *Block trigeminal activation & constrict blood vessels AE: Tingling sensation

Ergotamine *Partial 5HT1D agonist * inhibit release of tachykinins (SP & CGRP) *preventing vascular dilatation & neurogenic inflammation *Block trigeminal nerve activation AE: Nausea & vomiting

b) Why metoclopramide is given with analgesics (paracetamol, aspirin) in migraine Enhance gastric emptying & promotes their absorption Prevent nausea & vomiting by blocking central D2 receptor at CTZ c) Give 2 prophylactic medications of migraine Propranol, metoprolol (B blocker) Flunarizine (Ca channel blocker): block PG synthesis & Ca2+ dependent release of tachykinins from trigeminal N

Non-Steroidal Anti-Inflammatory Drugs

29. Cyclooxygenase enzymes a) Difference between COX-1 & COX-2 COX enzyme convert arachidonic acid to prostagladins COX-1 is constitutive & involved in platelet aggregation, protection of gastric mucosa & sensation of peripheral pain COX-2 is inducible increase during inflammation b) What group of drugs inhibits COX? NSAIDs c) Explain 3 pharmacological actions of this drugs & AE Reversible, non-selective inhibitors of COX except aspirin- irreversible

Antipyretic effects - Lower set points of temperature regulating centre by inhibiting PG Analgesic effects effective against pain assct wt inflammation & tissue damage bcoz they decrease PG that sensitize nocioceptors to bradykinin & cytokines Anti-inflammatory effects suppress pain, tenderness, swelling, vasoD Anti-thrombotic inhibit platelet aggregations & inhibit TXA2 (proaggregatory) Indomethacin used to close ductus arteriosus

d) Give 2 COX-2 inhibitors Celexocib Meloxicam Rofecoxib e) What drug irreversibly inhibit COX Aspirin f) Why cannot be given 2 children? In what condition induce Rayes syndrome in children wt viral infection. Avoided during full term pregnancy bcoz may cause premature closure of ductus arteriosus & increase bleeding during caesarian delivery 30. NSAIDs a) Why aspirin better than other salicylates as anti thrombotic action Causes irreversible inactivation of COX by acetylating the same residue in it & decr production of thromboxane A2 that involves in platelet aggregation Other NSAIDs bind to other sites & does not causes covalent modification of enzymes b) 3 feature of salicylates intoxication Tinnitus (high-pitches buzzing noise) Vertigo (spinning & deafness) Nausea & vomiting c) Effects of aspirin on i) Warfarin Aspirin displaces warfarin from plasma protein binding sites. Incr free warfarin thus inhibits platelet aggregation & increase risk of bleeding ii) Misoprostol PG E1 analogue. Can prevent gastric ulcers induced by NSAID PG inhibits acid productn + protects gastric mucosa 31. NSAID (COX inhibitors) a) 4 NSAID other than aspirin Ibuprofen: least risk GI problems diclofenac Ketoprofen: also inhibit lipoxygenase Indomethacin: most potent COX inhibitors, pmn mgrtn, T n B cell proliferation treat acute gout attack, closure of ductus arteriosus Piroxicam: - cox, pmn migration, oxgen radical production, lymphocyte fcntn Celecoxib: selective COX-II inhibitors b) Primary action of aspirin Inhibit cyclooxygenase irreversibly by acetylating it c) Action of aspirin in relation to i) Anti-inflammatory Aspirin inhibit inflammation by inhibiting vasodilatation. (edema & inflammation) through *inhibit chemotaxis

*down regulate IL-1 production *decr production free redical & peroxide (decr component of inflammatory & immune response) *interfere wt Ca-mediated IC events ii) Analgesia Aspirin decr PGs that sensitize nocioceptors to bradykinin & cytokines & other chemical mediators iii) Antipyretic In fever, cytokines formation enhanced so increase PGE2 synthesis PGE2 then elevates set point of T regulating centre in hypothalamus Aspirin decr PG that elevate temperature set point in hypothalamus iv) Antithrombotic Aspirin inhibit platelet aggregation by decreasing synthesis of thromboxane A2 (a preaggregator) Aspirin reduces risk of MI & stroke d) 2 AE Dyspepsia, nausea & vomiting, gastritis & bleeding except paracetamol Skin rashes, urticaria Gout (decr uric acid secretn dt inhibit secretion) Bleeding impaired platelet function through inhibition TXA2 Reyes syndrome Prolong labour Precipitate asthma Peptic ulcer Hepatitis Salicylism tinnitus, deafness, vertigo e) 3 conditions where aspirin should not be given @ given wt cautions Peptic ulcer Pregnancy Reyes syndrome Patients with CHF (aspirin cause water retention) Bleeding disorder Children wt viral infection Elderly gout 32. NSAIDS a) Name 2 NSAIDS Aspirin,ibuprofen b) discuss its action in terms of - antipyeretic NSAIDS causes reversible/irreV inhibition of COX enzyme-low pyrogen induced by PGI2-low IL-1 effect on hypokalaemia-low set point of temperature-increase dissipitation of heat by vasaD and sweating - anti-inflammatory NSAIDS inhibit chemotaxis,cause down regulation of IL-1 inhibut production of toxic free radicals and superoxide interfere with Ca mediated intraC events - antiplatelet NSAIDS irreV inhibit COX-1 enzyme-inhibit production of thromboxane in platelet Platelet no nucleus-no resynthesized thromboxane-inhibit platelet aggregation-antithrombotic

c) action of NSAIDS on kidney - can cause acute renal insufficient ~ esp in patient with CAF,hepatic cirrhosis with ascites ~ this patient depends on kidney produce PG production-vasoD to maintain renal blood flow-low GFR d) action of NSAIDS on causing gastric damage - PGI2-inhibit gastric a production - PGE2 and F2 increase bicarbonate and mucus production-increase sub mucosa BF e) name drug to counter NSAIDS in gastric damage Misoprostol

Drugs used treating Gout

33. Acute gout attack given indomethacin a) Mechanism of action of indomethacin Inhibit cyclooxygenase enzyme anti-inflammatory & analgesic action by decr production of PG b) Can allopurinol given at this point No. allopurinol causes urate crystal mobility. This will further aggravate acute gouty arthritis by inducing more inflammation c) Mechanism of action of Allopurinol Reduce uric acid level (very insoluble) by inhibiting xanthine oxidase Incr concentration of more soluble xanthines & hypoxanthines Decr concentration of urates in tissue plasma Decr deposition of urate crystal in tissue in reversed + formation of renal stone d) Name 1 uricosuric agent: Probenecid & sulfinpyrazone MOA: block proximal tubular resorption of uric acid

34. Antigout a) Colchicine Prevent migration of neutrophils/ granulocytes into joints by binding to tubulin, resulting in depolymerisation & interfering wt cell motility to affected area Block cell division by binding to mitotic spindle Inhibit synthesis & release of leukotries b) Indomethacin Inhibit COX enzyme Anti-inflammatory action c) Allopurinol Reduces synthesis of uric acid by inhibiting xanthine oxidase Deposition of urate crystal is reversed d) Probenecid Prevents reabsorbtion of uric acid in proximal convulated tubule 35. 1 drugs 4 chronic tophaceous (sandy) gout a) Allopurinol

b) MOA Reduced uric acid level by blocking its production Allopurinol & its metabolite (alloxanthine) inhibit the effects of xanthine oxidase c) In initial period, what problem arise & how 2 solve it Reabsorption of tophi is more rapid & causes motility of urate crystals worsen acute gouty arthritis NSAID or colchicines given concurrently d) 2 drugs interactions Reduced oxidation of mercaptopurine (anticancer agent) & azathioprine (immunosuppresion), requiring reduction in dosage of these drugs Given wt uricosuric, increase urate excretion, decrease inhibition of alloxanthine Given wt thiazide, increase incidence of toxicity Ampicillin + allopurinol skin rashes Allopurinol inhibit metabolizing enzymes & increase effects of warfarin, azathioprine & mercaptopurine

Drugs used in Chemotheraphy

36. Antineoplastic agent a) MOPP mecrhiorethamine, vincristine, procarbazine, prednisolone b) Advantage of d combination Additive or potentiated cytotoxic effects No overlapping host toxicities Slow or prevent d development or resistant cell lines Broader range of cell lines 37. a) label the cell cycle b) vincristine (M phase) & paclitaxel (S phase) plant alkaloids CCS methotrexate antimetabolites - CCS S-phase doxorubin antibiotic (except pleomycin) CCNS G1 phase, G0

Drugs to Drugs Interactions

38. Warfarin a) Describe the change in the plasma [ ] of warfarin after admin of Drug A Plasma [ ] of warfarin decr after admin of drug A b) Explanation Drug A induce hepatic P450 which increase degradation of warfarin c) Suggest Drug A Rifampicin, carbamazepine, barbiturates, griseofulvin, phenobarbitone d) State clinical condition for warfarin was given. What would be the possible consequences of above observation? Thrombosis. Effects of Warfarin decrease, incr in coagulation factor synthesis blood clot causing MI, stroke, DVT 39.

Agonist (Ach) Agonist + Antagonist

40.

Atropine Reversible competitive Parallel shift of agonist Log [ ] effect without Decr in max

Agonist (Nor) Antagonist

Phenoxybenzamne Irreversible competitive Decr effect in max xoncentration & effect cannot be reverse by Incr concentration of agonist