P drugs 21.10.22.pptx and everything about it.

Pharmacology

1. PH 3.5 p-drugs

2. SKILL-Clinical Pharmacology OBJECTIVE: At the end of the class, the student shall be able to To prepare and explain a list of P-drugs for a given case/condition

3. P( ersonal ) Drug Concept ?? P-drugs: that are chosen to be prescribed regularly for a given indication by a prescriber Not just the name of drug, also includes the dosage form, dosage schedule and duration of treatment

4. P drug concept Will differ from country-to- country and between doctors. In general, national list of essential drugs contain many more drugs than you, as a doctor, are likely to use regularly Most doctors use only 40-60 drugs routinely - Useful to make own selection from these lists, and to make this selection in a rational way

5. WHY SHOULD YOU COMPILE YOUR OWN LIST OF P-DRUGS ? 1. You have final responsibility for your patient's well-being and you cannot pass this on to others. While you can and should draw on expert opinion and consensus guidelines, you should always think for yourself. 2. You will learn how to handle pharmacological concepts and data . 3. You will know the alternatives when your P-drug choice cannot be used. 4. You will regularly receive information on new drugs, new side effects, new indications, etc. However, the latest and the most expensive drug is not necessarily the best, the safest or the most cost-effective .

6. How to select a P-drug!

7. Exercise… A 50 year-old male patient complains of bloody, mucoid stools and abdominal pain. There is no history of alcohol abuse. You have diagnosed it as a case of acute amoebic dysentery . Choose an appropriate drug and mention its dosage schedule and duration of treatment.

8. Step 1: Diagnosis acute amoebic dysentery Step 2: Therapeutic objectives treat the signs and symptoms, eradicate the disease and prevent transmission of the disease and further complications

9. Step 3: Make an inventory of effective groups of drugs Drugs with antiamoebic activity Nitroimidazoles [   e.g  , metronidazole, tinidazole , secnidazole , satranidazole ornidazole ] Alkaloids [   e.g  , emetine, dehydroemetine ] Amide [   e.g  , diloxanide furoate ] 8-Hydroxyquinolines [   e.g  , iodochlorohydroxyquin , diiodohydroxyquin ] Antibiotics [   e.g ,   tetracyclines , paromomycin ]

10. Step 4: Choose an effective group according to criteria Drug Group Efficacy Safety Suitability Nitroimidazoles +++ +++ +++ Alkaloids +++ ++ + Amides + ++ ++ 8-hydroxyquinolones + ++ ++ Antibiotics ++ +++ +++

11. Tablet metronidazole 400 mg tds X 5 days

12. Group Task -1 You are working as a private practitioner in a village 25 km from Pondicherry with a population of 5,000 mostly fishermen. Prepare your 'p’ list of drugs for hypertension and mention the rationale for your choice

13. 1. Define the diagnosis: Essential Hypertension 2. Therapeutic objectives : To achieve the target BP level with therapy For < 60 yrs , diabetics, CKD pts : <140/90 mmHg For > 60 y : 150/90 mm Hg To prevent life- threatening morbidities like myocardial infarction, CVA, etc.

14. 3. Make an inventory of effective groups of drugs ANTI-HYPERTENSIVES Diuretics (Hydrochlorothiazide, indapamide ) ACE Inhibitors ( Enalapril , Lisinopril) ARB (Losartan, telmisartan ) Calcium channel blockers (Amlodipine, nifedipine ) Beta- blockers ( Metoprolol , atenolol)

15. Efficacy Safety Suitability Thiazide-type diuretics Pharmacodynamics Decrease in CO; decrease Na +  dec. vessel wall stiffness Pharmacokinetics Good oral absorption Longer but variable duration of action Less hepatic metabolism Side effects Hypokalemia, hyperuricaemia , hyperglycemia, hyperlipidaemia , hypercalcaemia Contraindictions Diabetes mellitus, Gout, hypersensitivity to sulphur -containing drugs. Suitable for Elderly, isolated systolic hypertension Economical ACEIs Pharmacodynamics Inhibit ACE  abolish pressor response of AT-I Pharmacokinetics F = 70%; Duration: 6 – 12 hours Food interferes absorption Side effects angioedema hypotension, hyperkalemia, cough, rashes, dysgeusia , fetopathic Contraindictions Bilateral renal artery stenosis, pregnancy Suitable for Young patients, dyslipidemic , diabetic

16. Efficacy Safety Suitability Angiotensin receptor blockers Pharmacodynamics Antagonist of Angiotensin- II, VSMC relaxation Pharmacokinetics BA- 30-50% Potent- Olmesartan Good BA- Irbesartan Side effects Hypotension, headache, dizziness, URI, diarrhea, dry mouth, teratogenicity Alternative to ACE Inhibitors Calcium channel blockers Blocks L-TYPE Ca channel, decrease Ca entry into cardiac muscle, decreases contraction Pharmacokinetics 90-100% oral abdorption Amlo- Good BA, Nifedipine-Fast onset, Benidipine -Long acting Side effects Nausea, headache, hypotension, drowsiness, ankle edema, palpitation Not suitable for elderly- difficulty in micturition & GERD, IHD, Post MI, BPH Suitable for Elderly, asthma, COPD, pregnant hypertensive, daibetic

17. 4. Choose an effective group according to criteria Drug Group Efficacy Safety Suitability Cost Diuretics +++ ++ ++ +++ Calcium channel blockers +++ +++ ++ + ACE Inhibitors +++ +++ ++ + ARBs +++ +++ ++ + Beta blockers ++ ++ ++ ++

18. 5. ‘p’ LIST OF DRUGS FOR HYPERTENSION Drug Group Efficacy Safety Suitability Cost Hydrochlorothiazide +++ ++ ++ +++ Enalapril +++ +++ ++ + Losartan +++ +++ ++ + Amlodipine +++ +++ ++ + Atenolol ++ +++ ++ ++

19. Conclusion Drug Dose Dosage form Freq-uency Duration Hydrochlorothiazide 12.5 mg tablet od 3 weeks Enalapril 5mg tablet od 3 weeks Losartan 50 mg tablet od 3 weeks Amlodipine 5 mg tablet od 3 weeks Atenolol 25mg tablet od 3 weeks

20. TASK 2 You are working as a physician in a multispecialty corporate hospital in Hyderabad mostly focussing on endocrine disorders. Prepare your 'p' list of drugs for diabetes and mention the rationale for your choice

21. 1. Define the diagnosis: Type 2 diabetes mellitus 2. Therapeutic objectives : To achieve blood glucose level of 90-130 mg/dl, 180mg/dl and 150 mg/dl during fasting, 1h and 2h post-meal testing respectively. To achieve HbA1C value of < 7% To prevent both micro and macro vascular complications of diabetes.

22. 3. Make an inventory of effective groups of drugs ORAL HYPOGLYCEMIC AGENTS: Biguanides (Metformin) Sulfonylurea ( Glibenclamide , glimepiride) Thiazolidinediones (Pioglitazone) DPP-4 inhibitors ( Sitagliptin ) GLP-1 agonists ( Liraglutide )

23. COMPARISON OF ANTIDIABETIC DRUGS

24. RESEARCH SOCIETY FOR THE STUDY OF DIABETES IN INDIA 2020 RECOMMENDATIONS

25. 4. Choose an effective group according to criteria Drug Group Efficacy Safety Suitability Cost Biguanides +++ +++ +++ +++ Sulfonyl urea +++ ++ ++ ++ Thiazolidinediones ++ ++ ++ + DPP-4 Inhibitors ++ ++ ++ + GLP-1 agonists ++ ++ + +

26. 5. ‘p’ LIST OF DRUGS FOR TYPE 2 DIABETES MELLITUS Drug Group Efficacy Safety Suitability Cost Metformin +++ +++ +++ +++ Glimepiride +++ ++ ++ ++ Pioglitazone ++ ++ ++ + Sitagliptin ++ ++ ++ + Liraglutide ++ ++ + +

27. Conclusion Drug Dose Dosage form Freq-uency Dura- tion Metformin 500mg tablet bd 3 weeks Glimepiride 1mg tablet od 3 weeks Pioglitazone 15mg tablet od 3 weeks Sitagliptin 100mg tablet od 3 weeks Liraglutide 0.6mg Injection s.c. od 3 weeks

28. Task 3 Prescribe for a 30 year old male diagnosed with generalised tonic- clonic seizures and mention the rationale of your choice based on p-drug concept.

29. Task 3 Step 1 : GTCS Step 2 : reduction of seizure episodes Step 3 : Inventory of group of drugs effective in GTCS valproate lamotrigine topiramate carbamazepine oxcarbamazepine phenytoin

30. Efficacy Safety Suitability Valproate Pharmacodynamics Acts on Na, Ca & GABA channels Pharmacokinetics Good oral absorption hepatic metabolism Side effects anorexia, vomiting, drowsiness, ataxia, tremor, alopecia, curling of hair, increased blood ammonia Contraindications Hypersensitivity, liver disease, pregnancy Lamotrigine Pharmacodynamics Prolongs the inactivated state of Na + channels  decrease s the high frequency discharges Pharmacokinetics Good oral absorption Complete hepatic metabolism Side effects Sleepiness, dizziness, diplopia, ataxia, vomiting Contraindications hypersensitivity

31. Efficacy Safety Suitability Phenytoin Pharmacodynamics Prolongs the inactivated state of Na+ channels  decrease s the high frequency discharges Pharmacokinetics Poor oral absorption Longer duration of action (t1/2- 12-24hrs) hepatic metabolism (capacity limited kinetics first order changes to zero order) Side effects Gum hypertrophy, hirsutism, coarsening of facial features, acne, megaloblastic anaemia , osteomalacia , hyperglycemia Contraindications Pregnancy, Diabetes mellitus, anaemia , hypersensitivity, young girls. Topiramate Pharmacodynamics Acts on Na + channels, GABA & glutamate receptors Side effects Renal stones , Weight loss, Sedation, Speech or language problems, Fatigue, Paresthesias Contraindications hypersensitivity

32. Carbamazepine Pharmacodynamics Prolongs the inactivated state of Na + channels  decrease s the high frequency discharges Pharmacokinetics Poor oral absorption Longer duration of action (t1/2- 20-40 hrs ) hepatic metabolism Side effects Sedation, vertigo, dizziness, diplopia and ataxia. Vomiting diarrhoea worsening of seizures. Minor teratogenic. Contraindications Pregnancy, hypersensitivity, history of bone marrow suppression

33. Conclusion Valproate Valtec (200 mg; 10 tablets): Rs . 19.25 Tds  Rs . 173.25 (per month) Encorate (200 mg/ 5mL; 100 mL syrup): Rs . 63.50 Tds  Rs . 317.50 (per month) Lamotrigine Lamogin (50 mg; 10 tablets): Rs . 37.50 tds  Rs . 337.50 (per month) Topiramate Epimate (25 mg; 10 tablets): Rs . 26 BD  Rs . 156 (per month)

34. Drug Group Efficacy Safety Suitability Cost Valproate +++ +++ +++ +++ Lamotrigine +++ ++ ++ + Phenytoin ++ + ++ ++ Topiramate +++ ++ ++ ++ Carbamazepine ++ ++ ++ ++ ‘p’ LIST OF DRUGS FOR TYPE 2 GENERALISED TONIC CLONIC SEIZURES

35. P-drug for this patient Tab. VALPROATE 200 mg TDS for 1month