This document discusses the impact of Ramadan fasting on medication use and the impact of medications on fasting during Ramadan. It addresses how the absorption, distribution, and timing of medication administration can be affected by fasting and circadian rhythms. Specifically, it notes that medication pharmacokinetics and dynamics can vary between day and night even with the same dose. It also reviews recent literature demonstrating that optimizing medication timing based on circadian rhythms (chronotherapy) can improve outcomes for conditions like hypertension, cancer, and epilepsy.
This document discusses the pharmacology of postoperative pain management. It outlines various tools for pain assessment and factors to consider when evaluating a patient in pain. It then covers the principles of multimodal analgesia, including both pharmacological and non-pharmacological modalities. The major drug classes discussed are NSAIDs, opioids, and various adjuvants. Risks and guidelines for use are provided for different analgesic classes.
Ppi for bleeding ulcers intermittent vs continuousHassan Al tomy
in last few years there is emergent data on use of intermittent PPI in bleeding ulcers compared to continous infusion
in this meta-analysis the invistigator select 13 randomized controlled trial
Intermittent PPI regimens are comparable to continuous PPIinfusion regimens in patients with bleeding ulcers and high risk endoscopic findings
Because of ease of use and lower cost and resource utilization, intermittent PPI therapy may be the regimen of choice after endoscopic therapy in such patients
This systematic review and meta-analysis examined whether intermittent PPI therapy is noninferior to continuous intravenous PPI infusion for patients with high-risk bleeding ulcers after endoscopic treatment. The analysis found that intermittent PPI therapy was noninferior to continuous infusion, with an absolute risk difference of recurrent bleeding within 7 days of -0.28%, below the predefined noninferiority margin of 3%. Secondary outcomes of bleeding within 3 and 30 days also showed noninferiority of intermittent PPI therapy. Thus, intermittent PPI therapy is an acceptable alternative to continuous infusion for these high-risk patients.
Proton pump inhibitor : what new studies say on side effectsPAWAN V. KULKARNI
Proton pump inhibitors are among the most frequently prescribed drugs in the world and are generally considered safe. However, there is growing concern regarding their safety. World's leading journals say PPIs are not as safe as thought to be.
Proton-pump inhibitors (PPIs) are a widely prescribed class of medications used to treat acid-related disorders and its use has significantly increased over the last few decades. PPIs are often inappropriately prescribed; since they have been in the market. According to one study, it was observed that 46.7% of patients taking PPIs were ≥ 65 years of age who have compromised renal functions. Additionally, in approximately 40% of older adults, there was no indication for long-term PPI use identified. Adding to it, patients continue consuming PPIs way beyond the doctor’s advice. A number of post-marketing studies have been published in the past demonstrating associations between longer duration of PPI therapy and a number of adverse effects that are a concern. PPIs have been associated with an increased risk of a number of adverse effects including AIN, CKD, KIDNEY DISEASE, ESRD osteoporotic-related fractures, Clostridium difficile infection, community-acquired pneumonia, vitamin B12 deficiency.
Finasteride riduce la progressione clinica della IPB in pazienti con ingrossa...Merqurio
1) This study examined the long-term effects of finasteride versus placebo on clinical progression of benign prostatic hyperplasia (BPH) in men with different baseline prostate volumes.
2) In men with a baseline prostate volume ≥30ml, finasteride significantly reduced clinical progression of BPH compared to placebo. However, in men with a baseline prostate volume <30ml, finasteride did not significantly affect clinical progression compared to placebo.
3) Finasteride also significantly improved American Urological Association symptom index scores and maximum urinary flow rates compared to placebo in men with a baseline prostate volume ≥30ml, but not in men with a baseline volume <30ml.
This document discusses proton pump inhibitors (PPIs) and their interaction with the blood thinner clopidogrel. It notes that PPIs and clopidogrel are among the most commonly prescribed medications. Studies have shown that the PPI omeprazole can reduce the effectiveness of clopidogrel by inhibiting the enzyme CYP2C19 needed to activate clopidogrel. Regulatory agencies now warn against combined use of clopidogrel and omeprazole. Alternative PPIs like pantoprazole may be safer options, and future research is still needed.
This document discusses the pharmacology of postoperative pain management. It outlines various tools for pain assessment and factors to consider when evaluating a patient in pain. It then covers the principles of multimodal analgesia, including both pharmacological and non-pharmacological modalities. The major drug classes discussed are NSAIDs, opioids, and various adjuvants. Risks and guidelines for use are provided for different analgesic classes.
Ppi for bleeding ulcers intermittent vs continuousHassan Al tomy
in last few years there is emergent data on use of intermittent PPI in bleeding ulcers compared to continous infusion
in this meta-analysis the invistigator select 13 randomized controlled trial
Intermittent PPI regimens are comparable to continuous PPIinfusion regimens in patients with bleeding ulcers and high risk endoscopic findings
Because of ease of use and lower cost and resource utilization, intermittent PPI therapy may be the regimen of choice after endoscopic therapy in such patients
This systematic review and meta-analysis examined whether intermittent PPI therapy is noninferior to continuous intravenous PPI infusion for patients with high-risk bleeding ulcers after endoscopic treatment. The analysis found that intermittent PPI therapy was noninferior to continuous infusion, with an absolute risk difference of recurrent bleeding within 7 days of -0.28%, below the predefined noninferiority margin of 3%. Secondary outcomes of bleeding within 3 and 30 days also showed noninferiority of intermittent PPI therapy. Thus, intermittent PPI therapy is an acceptable alternative to continuous infusion for these high-risk patients.
Proton pump inhibitor : what new studies say on side effectsPAWAN V. KULKARNI
Proton pump inhibitors are among the most frequently prescribed drugs in the world and are generally considered safe. However, there is growing concern regarding their safety. World's leading journals say PPIs are not as safe as thought to be.
Proton-pump inhibitors (PPIs) are a widely prescribed class of medications used to treat acid-related disorders and its use has significantly increased over the last few decades. PPIs are often inappropriately prescribed; since they have been in the market. According to one study, it was observed that 46.7% of patients taking PPIs were ≥ 65 years of age who have compromised renal functions. Additionally, in approximately 40% of older adults, there was no indication for long-term PPI use identified. Adding to it, patients continue consuming PPIs way beyond the doctor’s advice. A number of post-marketing studies have been published in the past demonstrating associations between longer duration of PPI therapy and a number of adverse effects that are a concern. PPIs have been associated with an increased risk of a number of adverse effects including AIN, CKD, KIDNEY DISEASE, ESRD osteoporotic-related fractures, Clostridium difficile infection, community-acquired pneumonia, vitamin B12 deficiency.
Finasteride riduce la progressione clinica della IPB in pazienti con ingrossa...Merqurio
1) This study examined the long-term effects of finasteride versus placebo on clinical progression of benign prostatic hyperplasia (BPH) in men with different baseline prostate volumes.
2) In men with a baseline prostate volume ≥30ml, finasteride significantly reduced clinical progression of BPH compared to placebo. However, in men with a baseline prostate volume <30ml, finasteride did not significantly affect clinical progression compared to placebo.
3) Finasteride also significantly improved American Urological Association symptom index scores and maximum urinary flow rates compared to placebo in men with a baseline prostate volume ≥30ml, but not in men with a baseline volume <30ml.
This document discusses proton pump inhibitors (PPIs) and their interaction with the blood thinner clopidogrel. It notes that PPIs and clopidogrel are among the most commonly prescribed medications. Studies have shown that the PPI omeprazole can reduce the effectiveness of clopidogrel by inhibiting the enzyme CYP2C19 needed to activate clopidogrel. Regulatory agencies now warn against combined use of clopidogrel and omeprazole. Alternative PPIs like pantoprazole may be safer options, and future research is still needed.
This document discusses the classical and long-term indications for PPI use, including GERD, Barrett's esophagus, use with NSAIDs, use with anti-platelets, and non-ulcer dyspepsia. For GERD, guidelines recommend daily PPI for erosive esophagitis but intermittent PPI courses may be sufficient for many patients. For Barrett's esophagus, the absolute cancer risk reduction with daily PPI is low. For NSAID and anti-platelet users at high risk of bleeding, the benefits of daily PPI are well documented. Intermittent PPI courses are often sufficient for non-ulcer dyspepsia, though some patients may require long-
This document summarizes research on obesity hypoventilation syndrome (OHS). It finds that compared to other obese patient groups, patients with OHS have higher healthcare costs and risks of serious cardiovascular disease leading to early mortality. However, diagnosis and treatment of OHS is often late. Non-invasive ventilation can improve symptoms and gas exchange in OHS, but more research is needed comparing non-invasive ventilation to other treatments like CPAP. Weight loss through bariatric surgery may reverse the effects of OHS, but long-term data is limited. Overall, the document examines the morbidity, mortality and treatment options for OHS.
This document discusses metastatic prostate cancer and androgen deprivation therapy (ADT). It is presented by the Department of Urology at Govt Royapettah Hospital and Kilpauk Medical College in Chennai. The document covers various aspects of ADT including ablation of androgen sources through bilateral orchidectomy or anti-androgens, inhibition of LHRH or LH through agonists or antagonists, and inhibition of androgen synthesis through drugs like abiraterone. It also discusses adverse effects of ADT, monitoring of PSA levels, and management of issues like osteoporosis and hot flashes.
The document discusses various treatment options for managing vaginal dryness and sexual pain in cancer survivors. It includes both nonprescription options like lubricants and moisturizers as well as prescription therapies. Nonprescription options are used as needed for sexual activity or to maintain vaginal moisture. Prescription therapies include topical lidocaine, which provides temporary pain relief, and topical estrogen, which is the most effective but has safety concerns for some cancer survivors. Other options discussed include laser therapy, vaginal dilators, and cognitive behavioral therapy.
LT, a 46-year-old woman with sarcoma, experienced severe chemotherapy-induced nausea and vomiting (CINV) with her first two cycles of doxorubicin and ifosfamide chemotherapy. For her third cycle, she was given aprepitant, a neurokinin-1 receptor antagonist, in addition to a 5HT3 antagonist and dexamethasone for CINV prevention. Clinical trials show that a triple therapy approach including aprepitant improves control of both acute and delayed CINV compared to doublet therapy alone. Aprepitant works by blocking substance P signaling, an important mediator of nausea and vomiting, without affecting other antiemetic pathways.
Should we give a PPI IV before endoscopy in patients with upper GI bleeding?Waleed Mahrous
Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding - SIGN , BSG , NICE , ACG , AGA , ASGE Guidelines
Should we give a PPI IV before endoscopy in patients with upper GI bleeding?
This document discusses the management of low risk prostate cancer. It outlines the natural history of untreated low risk prostate cancer and the problems of overdiagnosis and overtreatment. Active surveillance is presented as a management option for low risk prostate cancer, with the rationale being to avoid unnecessary treatment and preserve quality of life. Results from active surveillance studies show low rates of cancer progression and metastasis, with 62% free from intervention at 10 years in one study. Triggers for intervention on active surveillance like rising PSA, grade progression, or tumor volume increase are discussed.
The document summarizes updated 2006 recommendations from ASCO for the use of hematopoietic colony-stimulating factors (CSFs). Key recommendations include:
- Primary CSF prophylaxis is recommended when the risk of febrile neutropenia is 20% or higher.
- Secondary CSF prophylaxis is recommended for patients who experienced a prior neutropenic complication.
- Therapeutic CSF use should be reserved for high-risk patients with fever and neutropenia.
- CSF can increase dose-dense chemotherapy but should only be used in clinical trials.
Advances in pharmacology applied to maxillofacial anaesthesiashabeel pn
1. PONV has a significant impact on patients despite being a minor medical issue, with an incidence of approximately 25%. Risk factors include female gender, previous history, surgery type and anesthetic drugs used.
2. For effective PONV prophylaxis, it is best to reduce baseline risk when possible and use a combination of antiemetic drugs including a steroid, 5-HT3 antagonist, and D2 antagonist for high risk patients.
3. New analgesic drugs and delivery methods show promise, including intravenous paracetamol, COX-2 inhibitors, and opioid-sparing multimodal analgesia techniques. Developments in anesthetic drugs also continue with new propofol formulations and antie
The document summarizes a clinical trial that evaluated the efficacy of NEPA (netupitant and palonosetron) compared to palonosetron alone or in combination with other antiemetics for preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy. The randomized, double-blind trial involved 694 patients receiving cisplatin chemotherapy who were assigned to receive either NEPA plus dexamethasone, palonosetron plus dexamethasone, aprepitant plus palonosetron and dexamethasone, or dexamethasone alone. The primary endpoint was complete response, defined as no emesis and no use of rescue medications during
1. A study found that adalimumab was more effective than azathioprine and mesalamine at preventing postoperative recurrence of Crohn's disease.
2. A study found that diagnostic delay in Crohn's disease is associated with a more complicated disease course and increased operation rate.
3. Vedolizumab was found to be an effective new option for induction and maintenance therapy for ulcerative colitis and is anticipated to be approved in the US in 2014.
This document discusses approaches to adjusting drug dosages for patients with impaired renal or hepatic function. It outlines three main approaches to adjusting dosage based on total body clearance, elimination rate constant or half-life, and methods used in renal failure. It also discusses dose adjustment considerations for obese, pediatric, elderly, and individual patients based on pharmacokinetic variability between individuals. The document emphasizes monitoring drug therapy through therapeutic drug monitoring to evaluate patient response and adjust dosages accordingly.
This randomized controlled trial assessed the efficacy and tolerability of pregabalin (75, 300, 600 mg/day) compared to placebo in treating pain from diabetic peripheral neuropathy. Patients receiving 300 and 600 mg/day of pregabalin showed significant improvements in pain scores and sleep interference compared to placebo. Improvements were seen as early as the first week and were sustained throughout the 5-week study. Pregabalin was well tolerated with few side effects, demonstrating its potential as an effective treatment for neuropathic pain associated with diabetes.
Journal club presentation, Randomised control trial, nephrotic syndromeDr. Md Yaqub
Daily administration of prednisolone during infections significantly reduced relapse rates in children with frequently relapsing nephrotic syndrome compared to alternate day dosing. The intervention group had 44 relapses compared to 76 in the control group, with daily dosing reducing relapse rates by 59%. Poisson regression analysis found daily dosing reduced the mean number of relapses per infection from 0.35 to 0.13. The number needed to treat was 6, indicating daily dosing during infections effectively reduced relapse frequency.
Drug interactions in pharmacy related practice j. boltPASaskatchewan
This document discusses drug-drug interactions in pharmacy practice. It begins by stating that over 2500 pairs of medications can potentially interact and that drug interactions are the second most common preventable adverse drug reaction. It then examines case studies of potential clinically significant interactions between rivaroxaban, HIV antiretrovirals, and antibiotics when added to a patient's medication regimen. The document stresses that pharmacists must be aware of high risk scenarios and populations to recommend appropriate management strategies for mitigating interaction risks.
Interstitial cystitis (IC), also known as bladder pain syndrome, is a chronic condition characterized by pelvic pain perceived to be related to the bladder along with urinary symptoms. The cause is multifactorial and likely includes alterations in bladder permeability and neurogenic inflammation. Diagnosis involves ruling out other causes through history, exam, cystoscopy, and urine testing. Treatment is individualized and may include conservative measures, oral medications like amitriptyline, intravesical therapies, minimally invasive procedures, and rarely surgery. Management aims to control symptoms and improve quality of life through a stepwise approach utilizing various options.
Journal club- Enteral Paracetamol or IV Indomethacin for closure of PDAZaheen Zehra
This randomized controlled trial compared the efficacy of enteral paracetamol and intravenous indomethacin for closing a patent ductus arteriosus (PDA) in preterm neonates. 77 preterm infants were randomly assigned to receive either paracetamol drops through a feeding tube every 6 hours for 7 days, or intravenous indomethacin once daily for 3 days. The primary outcome was PDA closure rate assessed by echocardiography. There was no significant difference in PDA closure rates or secondary outcomes like renal impairment between the two groups. The study concluded that oral paracetamol is safe but not superior to intravenous indomethacin for closing a PDA in preterm neonates
Clinical pharmacokinetics and its application--
1)definition
2) APPLICATIONS OF CLINICAL PHARMACOKINETICS
Design of dosage regimens:
a) Nomograms and Tabulations in designing dosage regimen,
b) Conversion from intravenous to oral dosing,
c) Determination of dose and dosing intervals,
d) Drug dosing in the elderly and pediatrics and obese patients.
Pharmacokinetics of Drug Interaction:
a) Pharmacokinetic drug interactions
b) Inhibition and Induction of Drug metabolism
c) Inhibition of Biliary Excretion.
Therapeutic Drug monitoring:
a) Introduction
b) Individualization of drug dosage regimen (Variability – Genetic, Age and Weight, disease, Interacting drugs).
c) Indications for TDM. Protocol for TDM.
d) Pharmacokinetic/Pharmacodynamic Correlation in drug therapy.
e) TDM of drugs used in the following disease conditions: cardiovascular disease, Seizure disorders, Psychiatric conditions, and Organ transplantations
Dosage adjustment in Renal and Hepatic Disease.
a. Renal impairment
b. Pharmacokinetic considerations
c. General approach for dosage adjustment in renal disease.
d. Measurement of Glomerular Filtration rate and creatinine clearance.
e. Dosage adjustment for uremic patients.
f. Extracorporeal removal of drugs.
g. Effect of Hepatic disease on pharmacokinetics.
Population Pharmacokinetics.
a) Introduction to Bayesian Theory.
b) Adaptive method or Dosing with feedback.
c) Analysis of Population pharmacokinetic Data
This document discusses women's and men's health issues related to infections. It presents a case study of a 68-year-old male admitted with community-acquired pneumonia and discusses appropriate treatment including continued empiric antibiotics. It also discusses a case of a 46-year-old female presenting with menopausal symptoms and recommends treatment options focusing on lifestyle modifications and medications to address her symptoms and elevated blood pressure.
Clinical pharmacokinetics is the application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual patient. Primary goals of clinical pharmacokinetics include enhancing efficacy and decreasing toxicity of a patient's drug therapy.
This document discusses the classical and long-term indications for PPI use, including GERD, Barrett's esophagus, use with NSAIDs, use with anti-platelets, and non-ulcer dyspepsia. For GERD, guidelines recommend daily PPI for erosive esophagitis but intermittent PPI courses may be sufficient for many patients. For Barrett's esophagus, the absolute cancer risk reduction with daily PPI is low. For NSAID and anti-platelet users at high risk of bleeding, the benefits of daily PPI are well documented. Intermittent PPI courses are often sufficient for non-ulcer dyspepsia, though some patients may require long-
This document summarizes research on obesity hypoventilation syndrome (OHS). It finds that compared to other obese patient groups, patients with OHS have higher healthcare costs and risks of serious cardiovascular disease leading to early mortality. However, diagnosis and treatment of OHS is often late. Non-invasive ventilation can improve symptoms and gas exchange in OHS, but more research is needed comparing non-invasive ventilation to other treatments like CPAP. Weight loss through bariatric surgery may reverse the effects of OHS, but long-term data is limited. Overall, the document examines the morbidity, mortality and treatment options for OHS.
This document discusses metastatic prostate cancer and androgen deprivation therapy (ADT). It is presented by the Department of Urology at Govt Royapettah Hospital and Kilpauk Medical College in Chennai. The document covers various aspects of ADT including ablation of androgen sources through bilateral orchidectomy or anti-androgens, inhibition of LHRH or LH through agonists or antagonists, and inhibition of androgen synthesis through drugs like abiraterone. It also discusses adverse effects of ADT, monitoring of PSA levels, and management of issues like osteoporosis and hot flashes.
The document discusses various treatment options for managing vaginal dryness and sexual pain in cancer survivors. It includes both nonprescription options like lubricants and moisturizers as well as prescription therapies. Nonprescription options are used as needed for sexual activity or to maintain vaginal moisture. Prescription therapies include topical lidocaine, which provides temporary pain relief, and topical estrogen, which is the most effective but has safety concerns for some cancer survivors. Other options discussed include laser therapy, vaginal dilators, and cognitive behavioral therapy.
LT, a 46-year-old woman with sarcoma, experienced severe chemotherapy-induced nausea and vomiting (CINV) with her first two cycles of doxorubicin and ifosfamide chemotherapy. For her third cycle, she was given aprepitant, a neurokinin-1 receptor antagonist, in addition to a 5HT3 antagonist and dexamethasone for CINV prevention. Clinical trials show that a triple therapy approach including aprepitant improves control of both acute and delayed CINV compared to doublet therapy alone. Aprepitant works by blocking substance P signaling, an important mediator of nausea and vomiting, without affecting other antiemetic pathways.
Should we give a PPI IV before endoscopy in patients with upper GI bleeding?Waleed Mahrous
Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding - SIGN , BSG , NICE , ACG , AGA , ASGE Guidelines
Should we give a PPI IV before endoscopy in patients with upper GI bleeding?
This document discusses the management of low risk prostate cancer. It outlines the natural history of untreated low risk prostate cancer and the problems of overdiagnosis and overtreatment. Active surveillance is presented as a management option for low risk prostate cancer, with the rationale being to avoid unnecessary treatment and preserve quality of life. Results from active surveillance studies show low rates of cancer progression and metastasis, with 62% free from intervention at 10 years in one study. Triggers for intervention on active surveillance like rising PSA, grade progression, or tumor volume increase are discussed.
The document summarizes updated 2006 recommendations from ASCO for the use of hematopoietic colony-stimulating factors (CSFs). Key recommendations include:
- Primary CSF prophylaxis is recommended when the risk of febrile neutropenia is 20% or higher.
- Secondary CSF prophylaxis is recommended for patients who experienced a prior neutropenic complication.
- Therapeutic CSF use should be reserved for high-risk patients with fever and neutropenia.
- CSF can increase dose-dense chemotherapy but should only be used in clinical trials.
Advances in pharmacology applied to maxillofacial anaesthesiashabeel pn
1. PONV has a significant impact on patients despite being a minor medical issue, with an incidence of approximately 25%. Risk factors include female gender, previous history, surgery type and anesthetic drugs used.
2. For effective PONV prophylaxis, it is best to reduce baseline risk when possible and use a combination of antiemetic drugs including a steroid, 5-HT3 antagonist, and D2 antagonist for high risk patients.
3. New analgesic drugs and delivery methods show promise, including intravenous paracetamol, COX-2 inhibitors, and opioid-sparing multimodal analgesia techniques. Developments in anesthetic drugs also continue with new propofol formulations and antie
The document summarizes a clinical trial that evaluated the efficacy of NEPA (netupitant and palonosetron) compared to palonosetron alone or in combination with other antiemetics for preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy. The randomized, double-blind trial involved 694 patients receiving cisplatin chemotherapy who were assigned to receive either NEPA plus dexamethasone, palonosetron plus dexamethasone, aprepitant plus palonosetron and dexamethasone, or dexamethasone alone. The primary endpoint was complete response, defined as no emesis and no use of rescue medications during
1. A study found that adalimumab was more effective than azathioprine and mesalamine at preventing postoperative recurrence of Crohn's disease.
2. A study found that diagnostic delay in Crohn's disease is associated with a more complicated disease course and increased operation rate.
3. Vedolizumab was found to be an effective new option for induction and maintenance therapy for ulcerative colitis and is anticipated to be approved in the US in 2014.
This document discusses approaches to adjusting drug dosages for patients with impaired renal or hepatic function. It outlines three main approaches to adjusting dosage based on total body clearance, elimination rate constant or half-life, and methods used in renal failure. It also discusses dose adjustment considerations for obese, pediatric, elderly, and individual patients based on pharmacokinetic variability between individuals. The document emphasizes monitoring drug therapy through therapeutic drug monitoring to evaluate patient response and adjust dosages accordingly.
This randomized controlled trial assessed the efficacy and tolerability of pregabalin (75, 300, 600 mg/day) compared to placebo in treating pain from diabetic peripheral neuropathy. Patients receiving 300 and 600 mg/day of pregabalin showed significant improvements in pain scores and sleep interference compared to placebo. Improvements were seen as early as the first week and were sustained throughout the 5-week study. Pregabalin was well tolerated with few side effects, demonstrating its potential as an effective treatment for neuropathic pain associated with diabetes.
Journal club presentation, Randomised control trial, nephrotic syndromeDr. Md Yaqub
Daily administration of prednisolone during infections significantly reduced relapse rates in children with frequently relapsing nephrotic syndrome compared to alternate day dosing. The intervention group had 44 relapses compared to 76 in the control group, with daily dosing reducing relapse rates by 59%. Poisson regression analysis found daily dosing reduced the mean number of relapses per infection from 0.35 to 0.13. The number needed to treat was 6, indicating daily dosing during infections effectively reduced relapse frequency.
Drug interactions in pharmacy related practice j. boltPASaskatchewan
This document discusses drug-drug interactions in pharmacy practice. It begins by stating that over 2500 pairs of medications can potentially interact and that drug interactions are the second most common preventable adverse drug reaction. It then examines case studies of potential clinically significant interactions between rivaroxaban, HIV antiretrovirals, and antibiotics when added to a patient's medication regimen. The document stresses that pharmacists must be aware of high risk scenarios and populations to recommend appropriate management strategies for mitigating interaction risks.
Interstitial cystitis (IC), also known as bladder pain syndrome, is a chronic condition characterized by pelvic pain perceived to be related to the bladder along with urinary symptoms. The cause is multifactorial and likely includes alterations in bladder permeability and neurogenic inflammation. Diagnosis involves ruling out other causes through history, exam, cystoscopy, and urine testing. Treatment is individualized and may include conservative measures, oral medications like amitriptyline, intravesical therapies, minimally invasive procedures, and rarely surgery. Management aims to control symptoms and improve quality of life through a stepwise approach utilizing various options.
Journal club- Enteral Paracetamol or IV Indomethacin for closure of PDAZaheen Zehra
This randomized controlled trial compared the efficacy of enteral paracetamol and intravenous indomethacin for closing a patent ductus arteriosus (PDA) in preterm neonates. 77 preterm infants were randomly assigned to receive either paracetamol drops through a feeding tube every 6 hours for 7 days, or intravenous indomethacin once daily for 3 days. The primary outcome was PDA closure rate assessed by echocardiography. There was no significant difference in PDA closure rates or secondary outcomes like renal impairment between the two groups. The study concluded that oral paracetamol is safe but not superior to intravenous indomethacin for closing a PDA in preterm neonates
Clinical pharmacokinetics and its application--
1)definition
2) APPLICATIONS OF CLINICAL PHARMACOKINETICS
Design of dosage regimens:
a) Nomograms and Tabulations in designing dosage regimen,
b) Conversion from intravenous to oral dosing,
c) Determination of dose and dosing intervals,
d) Drug dosing in the elderly and pediatrics and obese patients.
Pharmacokinetics of Drug Interaction:
a) Pharmacokinetic drug interactions
b) Inhibition and Induction of Drug metabolism
c) Inhibition of Biliary Excretion.
Therapeutic Drug monitoring:
a) Introduction
b) Individualization of drug dosage regimen (Variability – Genetic, Age and Weight, disease, Interacting drugs).
c) Indications for TDM. Protocol for TDM.
d) Pharmacokinetic/Pharmacodynamic Correlation in drug therapy.
e) TDM of drugs used in the following disease conditions: cardiovascular disease, Seizure disorders, Psychiatric conditions, and Organ transplantations
Dosage adjustment in Renal and Hepatic Disease.
a. Renal impairment
b. Pharmacokinetic considerations
c. General approach for dosage adjustment in renal disease.
d. Measurement of Glomerular Filtration rate and creatinine clearance.
e. Dosage adjustment for uremic patients.
f. Extracorporeal removal of drugs.
g. Effect of Hepatic disease on pharmacokinetics.
Population Pharmacokinetics.
a) Introduction to Bayesian Theory.
b) Adaptive method or Dosing with feedback.
c) Analysis of Population pharmacokinetic Data
This document discusses women's and men's health issues related to infections. It presents a case study of a 68-year-old male admitted with community-acquired pneumonia and discusses appropriate treatment including continued empiric antibiotics. It also discusses a case of a 46-year-old female presenting with menopausal symptoms and recommends treatment options focusing on lifestyle modifications and medications to address her symptoms and elevated blood pressure.
Clinical pharmacokinetics is the application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual patient. Primary goals of clinical pharmacokinetics include enhancing efficacy and decreasing toxicity of a patient's drug therapy.
The success of drug therapy is highly dependent on the choice of the drug, the drug product, and the design of the dosage regimen. The choice of the drug is generally made by the physician after careful patient diagnosis and physical assessment.
Individualisation and optimization of drug dosing regimenJyoti Nautiyal
Drug dosing regimen, dosing frequency, individualisation, Steps Involved in Individualization of Dosage Regimen, optimization, variability, Clinical experience with individualization and optimization based on plasma drug levels.
This document discusses population pharmacokinetics and describes a study analyzing methylphenidate (MP) pharmacokinetics in children with ADHD. The study used a population approach to model MP concentrations in 273 children based on single blood samples. Key findings included higher total daily MP doses in children receiving the drug three times daily compared to twice daily, and clearance proportional to body weight as expected. The model explained 43% of variability in MP concentrations and supported weight-based MP dosing in children.
This document discusses therapeutic drug monitoring (TDM), which refers to measuring drug concentrations in biological fluids to optimize drug therapy. TDM aims to maintain drug levels within the therapeutic window to maximize efficacy and minimize toxicity. It is useful for drugs with a narrow therapeutic index, large inter-individual variability, or in patients with organ dysfunction. Common drugs monitored include digoxin, aminoglycosides, phenytoin, and lithium. Factors like absorption, distribution, metabolism, excretion, drug interactions, and compliance can impact drug levels and require consideration during TDM interpretation. The document outlines the need, suitable/unsuitable drugs, therapeutic ranges, testing methods, and factors affecting TDM.
Metoclopramide for nausea and vomiting prophylaxis during andMohd Mudassir
This meta-analysis reviewed 11 randomized controlled trials involving 702 patients undergoing cesarean section to determine the effectiveness of metoclopramide in reducing intra-operative and post-operative nausea and vomiting. The analysis found that metoclopramide was effective at reducing nausea and vomiting when given before or after spinal/epidural anesthesia with no significant side effects reported. Specifically, metoclopramide reduced the incidence of intra-operative nausea and vomiting by 63% when given before anesthesia, and by 62% when given after delivery via neuraxial anesthesia. It also reduced the need for rescue antiemetics and the incidence of early post-operative nausea and vomiting. The review concluded that a 10mg dose of met
Nejm journal watch practice changing articles 2014Jaime dehais
This document provides a compilation of summaries of the latest practice-changing articles from NEJM Journal Watch. It includes summaries of articles on topics such as delayed or no antibiotic prescriptions for respiratory infections, physical therapy being beneficial for knee osteoarthritis, low-dose steroids being better than high-dose for COPD exacerbations, a diagnostic algorithm for upper-extremity deep vein thrombosis, evidence that meniscal tears may not require surgery, improvements in mental health with smoking cessation, doubts cast on flu drugs by meta-analyses, the 2014 recommended childhood immunization schedule, sentinel lymph node biopsies for thin melanomas, age-specific d-dimer cutoffs for pulmonary embolism, evidence that FOD
Therapy of focal or diffuse proliferative lupus nephritis, Moh'd sharshirMoh'd sharshir
Immunosuppressive therapy is recommended for patients with diffuse or focal proliferative lupus nephritis (LN). The standard induction therapies are cyclophosphamide or mycophenolate mofetil combined with glucocorticoids. Mycophenolate mofetil may be preferred in certain groups due to its comparable efficacy and better safety profile. Rituximab combined with mycophenolate mofetil and glucocorticoids has also shown efficacy in treating proliferative LN. Calcineurin inhibitors and other novel agents are being studied but cyclophosphamide and mycophenolate mofetil remain the standard of care.
This document summarizes a seminar on applying pharmacokinetics in new drug development and dosage form design. It discusses how pharmacokinetic parameters can be used to design dosage regimens, predict and explain drug interactions, and individualize treatment for special populations. Factors like dose size, dosing frequency, hepatic and renal function, age, weight, and disease states are considered when designing optimized dosage regimens. Therapeutic drug monitoring is also discussed as a way to evaluate patient response and adjust treatment as needed.
Pharmacokinetic and pharmacodynamic considerations are very much important while choosing any antibiotic specially in presence of comorbidities like chronic renal failure as the renal elimination is compromised in those patients and handling of antibiotics which excrete through kidney are altered hence needs judicious antibiotic selection and dose calculation.In this venture calculating eGFR through different online calculators make the physicians more aware of the underlying disease state and improve dose adjustment of the antibiotics. Examples are MDRD or CKD-EPI or Cockroft-Gault formula.
This document summarizes challenges in anesthetizing compromised patients and provides practical guidance. It notes that while drug selection is important, excellent patient management throughout the entire anesthetic period is even more critical. A thorough pre-anesthetic exam and stabilization of any medical issues is emphasized. The document recommends focusing support on the body systems most compromised for a given patient, rather than believing drug choice alone determines outcome. It stresses the importance of supporting vital organ function, especially circulation, during all anesthetic phases.
Lupus Nephritis Dilemma - Prof. Mohsen El KosiMNDU net
This document discusses Lupus Nephritis (LN), a common complication of Systemic Lupus Erythematosus (SLE) that affects the kidneys. It covers the epidemiology and diagnostic criteria of SLE, outlines current treatment options for LN including steroids, immunosuppressants, and biologics, and discusses ongoing clinical trials. It also examines challenges in LN management such as variability in histological classification systems and lack of consensus on treatment protocols. Overall, the document provides an overview of LN as a complex condition with ongoing efforts to improve diagnosis and outcomes.
1) The study investigated whether adherence to lipid-lowering medications predicts initial adherence to CPAP therapy for obstructive sleep apnea.
2) The study found that higher adherence to lipid-lowering medications, as measured by medication refill rates in the previous year, closely predicted higher rates of at least 4 hours per night of CPAP use in the first week of therapy.
3) Demographic and clinical factors like age, race, apnea severity, and obesity did not predict initial CPAP adherence, but adherence to lipid medications did, suggesting a "healthy user bias" may confound studies linking poor CPAP adherence to health outcomes.
This study examined the relationship between oral contraceptive pill (OCP) use and hypertension. 165 women aged under 40 who used OCPs for at least one year were studied. Their blood pressure and weight were measured at the start of OCP use and 6 months and 1 year after. Results showed a significant increase in systolic blood pressure 1 year after starting OCPs compared to baseline. This increase was greater for those using low-dose OCPs versus triphasic pills. No significant changes were found in diastolic blood pressure. The study concludes that while current lower-dose OCPs have little effect on blood pressure, monitoring is still recommended to identify potential high risk cases.
Chronopharmacology is the study of how biological rhythms affect medication. It considers how the effects and pharmacokinetics of drugs vary based on the time of day they are administered. Proper timing of medication can maximize benefits and minimize side effects by matching drug delivery to circadian rhythms in conditions like cardiovascular disease, respiratory disease, and endocrine disorders. For example, inhaled corticosteroids administered in the evening are nearly as effective as multiple daily doses for asthma, and beta blockers taken at night better prevent morning heart attacks. Chronopharmacology aims to deliver medications when the body's need or the disease's symptoms are greatest.
Proton Pump Inhibitors and Risk of Acute and Chronic Kidney Disease: A Retros...KhalafAlGhamdi
This document summarizes a study presented at a nephrology journal club that examined the association between proton pump inhibitor (PPI) use and the risk of acute kidney injury (AKI) and chronic kidney disease (CKD) using a large health insurance database. The study found that PPI use was associated with a 4-fold higher risk of AKI and a 20% higher risk of CKD compared to non-users. While the results strengthen evidence of this association, limitations include potential residual confounding and inability to account for over-the-counter medication use. The conclusion calls for provider education and deprescribing initiatives to reduce PPI overuse and potential kidney risks.
This document discusses chronopharmacotherapy and drug delivery systems that target the colon. It defines chronopharmacotherapy as using controlled drug delivery according to circadian rhythms to enhance therapeutic outcomes. It describes several colon-targeting drug delivery systems, including pulsatile systems, pressure-controlled capsules, and osmotically controlled systems. These systems aim to protect drugs from degradation in the upper GI tract and release them in the colon according to circadian rhythms to treat diseases like asthma, arthritis, cancer and diabetes.
This document discusses the impact of Ramadan fasting on medication use and the impact of medications on fasting during Ramadan. It addresses how the absorption, distribution, and timing of medication administration can be affected by fasting and circadian rhythms. Specifically, it notes that medication pharmacokinetics and dynamics can vary between day and night even with the same dose. It also reviews recent literature demonstrating that optimizing medication timing based on circadian rhythms (chronotherapy) can improve outcomes for conditions like hypertension, cancer, and epilepsy.
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxwalterHu5
In some case, your chronic prostatitis may be related to over-masturbation. Generally, natural medicine Diuretic and Anti-inflammatory Pill can help mee get a cure.
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kol...rightmanforbloodline
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Versio
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Version
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Version
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Kat...rightmanforbloodline
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
2. Fès, le 20 Juillet 2013
Pr KHABBAL YoussefGénéralités
3. Fès, le 20 Juillet 2013
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Deux approches
oImpact du RAMADAN sur la prise des médicaments
oImpact des médicaments sur RAMADAN
4. Fès, le 20 Juillet 2013
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Impact des médicaments sur Ramadan Voies d’administrationBut pharmacologique
Thérapeutique
Alimentaire
5. Fès, le 20 Juillet 2013
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Impact du ramadan sur la prise des médicaments
Interaction médicament et jeûne
Influence de la fréquence d’administration
Changement de l’horaire d’administration
6. Fès, le 20 Juillet 2013
Pr KHABBAL YoussefInteraction jeûne et médicamentEstomac vide ou plein Le comportement alimentaire → teneur en graisse
7. Fès, le 20 Juillet 2013
Pr KHABBAL YoussefInfluence de la fréquence d’administrationLes repères temporels: le lever, les trois repas et le coucherDurant ramadan: Deux repasMédicaments temps dépendants
8. Fès, le 20 Juillet 2013
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Horaire de prise médicamenteuseReport des prisesRythme circadien
9. Fès, le 20 Juillet 2013
Pr KHABBAL YoussefPreuves tangibles que toutes les fonctions du corps y compris ceux qui influencent les paramètres cinétiques tels que le système cardio- vasculaires , hépatique et rénale sont organisés dans le temps et ont des variations quotidiennes importantes
10. Fès, le 20 Juillet 2013
Pr KHABBAL YoussefLITTÉRATURE RÉCENTE
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RÉSULTATS: un total de 192 articles de journaux, 41 L'hypothèse spécifique pour l’impact de la chronothérapie :
chronoeffectiveness (n = 34),
chronopharmacocinétique (n = 5),
chronopharmacodynamics (n = 2).
Les résultats de deux tiers (n = 27) des études examinées, appuient l'idée de la chronothérapie.
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Perspectives on the chronotherapy of hypertension based on the results of the MAPEC study. Portaluppi F,Smolensky MH.Chronobiol Int.2010 Sep;27(8):1652-67. AbstractAppreciation of chronotherapy in hypertension continues to lag, despite clear demonstrations by many studies of (i) clinically relevant dosing-time differences of the beneficial and adverse effects of most blood pressure (BP) medications and (ii) significant association between reduced sleep-time BP decline of non-dippers and their heightened risk of cardiovascular disease (CVD). The Syst-Eur and HOPE outcome trials showed evening administration of nitrendipine and ramipril in these respective studies impacts sleep-time BP, converting the 24-h BP pattern to a more dipper one and in the HOPE study decreasing CVD risk. The CONVINCE study intended to compare BP control and CVD protection afforded by conventional β-blocker and diuretic medications versus a special drug- delivery verapamil formulation as a bedtime hypertension chronotherapy; however, the trial was terminated prematurely, not based on inadequate performance of the chronotherapy but on a corporate business decision. The just completed MAPEC study is the first trial specifically designed to prospectively test the hypothesis that bedtime administration of ≥1 conventional medications exerts better BP control and CVD risk reduction than the traditional approach of scheduling all medications in the morning. The results of this 5.6-yr median follow-up study establish that bedtime chronotherapy more effectively improves BP control, better decreases prevalence of non-dipping, and, most importantly, best reduces CVD morbidity and mortality. This chronotherapeutic approach to hypertension is justified by the fact that BP is usually lowest at night as is sodium excretion, but when sodium intake is excessive or its daytime excretion hampered, nocturnal BP is adjusted higher, to a level required for compensation overnight, via the pressure/natriuresis mechanism, resulting in non-dipping 24-h BP patterning. In diurnally active persons, the entire circadian BP pattern may be reset to a lower mean level and to a "more normal" day-night variation, simply by enhancing natriuresis during the night-the time-of-day when it can be most effective. A modification as simple and inexpensive as switching ≥1 hypertension medications from morning to evening may be all that is needed to normalize nighttime BP, exerting an effect exactly like sodium restriction. Current clinical concepts such as "normotensive non- dipper" (with higher CVD risk than a hypertensive dipper), broad recommendation of pharmacotherapy with exclusively high "smoothness index" medications (without attention to individual patient needs defined by the features of the 24-h BP pattern), and reliance upon static daytime diagnostic BP thresholds based solely on single office cuff assessment necessitate urgent reconsideration.
13. Fès, le 20 Juillet 2013
Pr KHABBAL YoussefCancer chronotherapeutics: experimental, theoretical, and clinical aspects. Ortiz-TudelaE,MteyrekA,BallestaA,InnominatoPF,LéviF.HandbExp Pharmacol.2013;(217):261-88. AbstractThe circadian timing system controls cell cycle, apoptosis, drug bioactivation, and transport and detoxification mechanisms in healthy tissues. As a consequence, the tolerability of cancer chemotherapy varies up to several folds as a function of circadian timing of drug administration in experimental models. Best antitumor efficacy of single- agent or combination chemotherapy usually corresponds to the delivery of anticancer drugs near their respective times of best tolerability. Mathematical models reveal that such coincidence between chronotolerance and chronoefficacy is best explained by differences in the circadian and cell cycle dynamics of host and cancer cells, especially with regard circadian entrainment and cell cycle variability. In the clinic, a large improvement in tolerability was shown in international randomized trials where cancer patients received the same sinusoidal chronotherapy schedule over 24h as compared to constant-rate infusion or wrongly timed chronotherapy. However, sex, genetic background, and lifestyle were found to influence optimal chronotherapy scheduling. These findings support systems biology approaches to cancer chronotherapeutics. They involve the systematic experimental mapping and modeling of chronopharmacology pathways in synchronized cell cultures and their adjustment to mouse models of both sexes and distinct genetic background, as recently shown for irinotecan. Model-based personalized circadian drug delivery aims at jointly improving tolerability and efficacy of anticancer drugs based on the circadian timing system of individual patients, using dedicated circadian biomarker and drug delivery technologies.
14. Fès, le 20 Juillet 2013
Pr KHABBAL YoussefChronopharmacology of anti-convulsive therapy. Ramgopal S,Thome-Souza S,Loddenkemper T.Curr Neurol Neurosci Rep.2013 Apr;13(4):339. AbstractApproximately one-third of patients with epilepsy continue to have seizures despite antiepileptic therapy. Many seizures occur in diurnal, sleep/wake, circadian, or even monthly patterns. The relationship between biomarkers and state changes is still being investigated, but early results suggest that some of these patterns may be related to endogenous circadian patterns whereas others may be related to wakefulness and sleep or both. Chronotherapy, the application of treatment at times of greatest seizure susceptibility, is a technique that may optimize seizure control in selected patients. It may be used in the form of differential dosing, as preparations designed to deliver sustained or pulsatiledrug delivery or in the form of 'zeitgebers' that shift endogenous rhythms. Early trials in epilepsy suggest that chronopharmacologymay provide improved seizure control compared with conventional treatment in some patients. The present article reviews chronopharmacologyin the treatment of epilepsy as well as future treatment avenues.
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Points communsUn médicament consommé avec la même dose et dans des conditions identiques présente un profil cinétique et dynamique différent entre le jour et la nuitPharmacologie phénomène circadien phase dépendant
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Pr KHABBAL YoussefFONDEMENT SCIENTIFIQUE
17. Fès, le 20 Juillet 2013
Pr KHABBAL YoussefApproche chronobiologique de la pharmacologie
18. Fès, le 20 Juillet 2013
Pr KHABBAL YoussefReconnaitre les paramètres pharmacologiques qui peuvent être influencer par ramadanExpliquer les mécanisme auxquels ils obéissent.
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1. Absorption = RésorptionPénétration du médicament dans le sang à partir de son lieu d’absorption. Le PA dissous traverse les membranes biologiques pour pénétrer dans le circulation sanguine. Cette étape n’existe pas lorsque le médicament est introduit directement dans la circulation par voie intraveineuse
21. Fès, le 20 Juillet 2013
Pr KHABBAL YoussefVariations circadiennes de l’absorption des médicaments
Vidange gastrique et absorption intestinale
Substance dont la solubilité est faible
Indométacine, furosémide,
Autres facteurs:
Ph gastro-intestinal: délitement, ionisation
Motilité de l’intestin
Taux de perfusion d’organe: Circulation sanguine intestinale
22. Fès, le 20 Juillet 2013
Pr KHABBAL Youssef2. DistributionJuste après l’absorption, le Mdt parvient dans le plasma où il se trouve sous deux formes:
Forme liée aux protéines plasmatiques –Sorte de réserve en PA
Forme libre seule responsable de l’action pharmacologiqueLiaison aux protéines plasmatiques
M+ PMP
23. Fès, le 20 Juillet 2013
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Variations circadiennes de la distribution des médicaments
La perméabilité membranaire
Erythrocyte: lidocaine, metformine
Barriere hematomeningé: valproate
La liaison aux protéine
Rôle de transport
Fraction libre active
L’albumine; l’alpha1-glycoproteine, globuline sérique
Chute nocturne
Différence de 20 % chez le sujet âgé
Effets indésirables Diazépam
24. Fès, le 20 Juillet 2013
Pr KHABBAL Youssef3. Métabolisme
Les transformations métaboliques concernent la plupart des médicaments
Site de métabolisme:foie (+++), poumons, rein
Réactions:
M M-OHM-O-Conjugué
Élimination urinaire ou biliaire Phase IPhase II
25. Fès, le 20 Juillet 2013
Pr KHABBAL YoussefVariations circadiennes du métabolisme des médicaments
Rythme circadien des enzymes hépatique
Le Vmaxet Kmaxenzymatique sont 4 fois plus grandes le jour, ex: sulfotransférase
Le jeûne ne modifie pas ces rythmes.
La circulation sanguine hépatique est plus grande à la fin de la journée
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4. Elimination
1) Filtration glomérulaire:passage de substances du sang vers l’urine
2) Résorptionde substances de l’urine vers le sang
3) Excrétionfinale du plasma vers l’urineGloméruleArtériole AfférenteArtériole efférente
Urine définitive
1
23
NEPHRON
27. Fès, le 20 Juillet 2013
Pr KHABBAL YoussefVariations circadiennes de l’élimination des médicamentsPh urinaire:
basique le matinFiltration glomérulaire pdt le jour en relation la tension artérielle.
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ChronoesthésieChronoefficacité et ChronotoléranceSusceptibilité des système ciblesNombre de récepteur B max
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Circadianchangesinanticoagulanteffectofheparininfusedat a constant rate. Decousus HA,Croze M,Levi FA,Jaubert JG,Perpoint BM,De Bonadona JF,Reinberg A,Queneau PM. Six patients with venous thromboembolismwere treated withheparin, administered intravenously by a constant infusion pump. The initial daily dose ofheparinwas adjusted to keep the activated partial thromboplastintime, sampled at 0800, between 1.5 and 2.5 times the control level. Once that level was obtained, this dose was kept constant. Anticoagulation was thereafter measured, every four hours for 48 hours, by activated partial thromboplastintime, thrombin time, and coagulation factor Xainhibition assay. The results of all three coagulation tests showed acircadianvariation in the six patients. Maximum values were achieved at night and minimum values in the morning.Thesecircadianvariations were reproduced for two consecutive days. Differences between night and morning values reached almost 50% for activated partial thromboplastintime, 60% for thrombin time, and 40% for factor Xainhibition assay. Thiscircadianvariation resulted from two rhythms, acircadianrhythm lasting 24 hours and an ultradianrhythm lasting 12 hours, which were detected by cosinoranalysis for each coagulation test (p less than 0.01). Acircadianrhythm was detected individually in most of the patients for each coagulation test (p less than 0.05). All patients had a nocturnal peak in activated partial thromboplastintime on both days. In four patients this peak exceeded the upper desired limit of activated partial thromboplastintime. These rhythms should be taken into account when evaluating the dosage ofheparinto be administered.
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Comparison of once-daily evening versus morning sustained-release theophylline dosing for nocturnal asthma. Reinberg A,Pauchet F,Ruff F,Gervais A,Smolensky MH,Levi F,Gervais P,Chaouat D,Abella ML,Zidani R.
Eight diurnally active (approximately 0730-1100 hr) adults (41-61 yr) suffering from nocturnal asthma volunteered for a double-blind, cross-over randomized study of a once-daily dosing (600-900 mg/24 hr) of Armophylline (Rorer s.a., France), a sustained-release theophylline given either at 0800 hr or 2000 hr for 8-day durations. Study variables monitored daily were: (a) self-measured peak expiratory flow (PEF), heart rate, oral temperature and self-rated fatigue checked every 2 hr during the waking span as well as upon spontaneous nocturnal awakenings and (b) duration and subjective characteristics of sleep rated every morning. In addition, serum theophylline concentration (STC) plus the variables in (a) were sampled every 2 hr during the 24 hr of the eighth day of each timed treatment span. Rx at 0800 hr was associated with a nocturnal dip in PEF of 20 +/-2.8% (X +/- S.E.M.) from the level achieved at the time of the diurnal crest; Rx at 2000 hr moderated the nocturnal fall; it was only 10 +/-2.1% and within the physiologic limits of non-asthmatic persons. The STC peak height (Cmax) was greater (P less than 0.05) and time-to-peak (Tmax) shorter (P less than 0.005) with Rx at 0800 hr than at 2000 hr. With Rx at 2000 hr an STC plateau of approximately 12 hr resulted. A statistically significant correlation (r = 0.86; P less than 0.01) between PEF and the corresponding-in-time STC was observed with Rx at 2000 hr but not with Rx at 0800 hr. A small, but statistically significant, higher heart rate resulted from 2000 hr dosings in five out of eight subjects relative to the 0800 hr dosing. There were no differences in the sleep characteristics nor in oral temperature between dosing times. Once-daily (600-900 mg) SRT dosing at 2000 hr controlled the nocturnal dip of bronchial patency with no major side-effects in diurnally active adult patients with nocturnal allergic asthma.
33. Fès, le 20 Juillet 2013
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Circadianchangesof thedurationof action of local anaesthetic agents. ReinbergA,ReinbergMA. Abstract
A statistically significantcircadianrhythm of thedurationof local anaesthesiaproduced by lidocaineand betoxycainewas found in both human skin and teeth. In adult subjects with diurnal activity and nocturnal rest the longestdurationwas found around 15.00 (3 p.m.) with a large peak-trough difference amounting to more than 100% of the 24 h mean. Such chronopharmacologicrhythm might be related tocircadianrhythms in catecholamine secretion and/or incircadianchangesof cell membrane properties.
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Heure de l’injection
Durée de l’anesthésie
8 h
12 min
15h
30 min
18h
17 min
Méthodologie:
35 sujet
Anesthésie para apicale d’une dent
Intervention sur dent vivante
Ampoule de 2ml de lidocaine 2p100Résultats:
35. Fès, le 20 Juillet 2013
Pr KHABBAL YoussefTable des heures d’administration
molécule
effet
antihistaminique
Efficacité maximale le soir
Tolérance excellentequelque soit l’heure d’administration
Anesthésiqueslocaux
À15H dure 2 à FOIS Vs 7H
cancérologie
Adriamycine
Meilleure tolérance et meilleure efficacité en perfusion avec un maximum à 6H
Cisplatine
Meilleure tolérance et meilleure efficacité en perfusion avec un maximum à 18H
Antihypertenseurs:
•Bétabloquant
•Diurétique
•Inhibiteur du canal calcique
Meilleur activitédiurne que nocturne
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Conclusion
•Lareconnaissancedelastructuretemporelledel’organisme
•Impactduramadansurlesmédicamentsestimpactchronopharmacologique
•L’heuredelajournéedoitêtreinclusdanslastratégiethérapeutiquepouradapterlaposologie