This document summarizes information on two newer drugs for cardiovascular conditions - ivabradine and aliskiren. Ivabradine is a drug that reduces heart rate by binding to "funny channels" and is used to treat chronic stable angina and heart failure. Clinical trials have shown it reduces cardiovascular events when added to standard treatments. Aliskiren is a direct renin inhibitor used for hypertension by blocking renin from converting angiotensinogen to angiotensin I. It provides renin inhibition as an alternative to blocking downstream effects of the renin-angiotensin-aldosterone system. The document reviews the mechanisms, pharmacokinetics, clinical uses, trials and guidelines for use of these two
ACE inhibitors block the angiotensin-converting enzyme found throughout vascular tissue that converts angiotensin I to angiotensin II. Let us know how do ACE Inhibitors work?
This presentation consists of various approaches to treat hypertension depending on severity. It also include treatment according to international guidelines. Classification and brief description of each antihypertensive agent has been mentioned.
ACE inhibitors block the angiotensin-converting enzyme found throughout vascular tissue that converts angiotensin I to angiotensin II. Let us know how do ACE Inhibitors work?
This presentation consists of various approaches to treat hypertension depending on severity. It also include treatment according to international guidelines. Classification and brief description of each antihypertensive agent has been mentioned.
ARBs (Angiotensin receptor blockers) are the most widely used anti hypertensive throughout the world. A solid knowledge related to ARB will make our practice more patients friendly & benefit will be maximum.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
4. Atherosclerosis
Endothelial dysfunction↑
Oxidative stress↑
Plaque stability↓
Arterial stiffness↑
Ischemia
Oxygen consumption↑
Duration of diastole↓
Coronary perfusion↓
Remodeling
Cardiac hypertrophy↑
Chronic heart failure
Oxygen demand↑
Ventricular efficiency ↓
Ventricular relaxation↑
Elevated heart rate
+
+ +
+
The role of heart rate in cardiovascular disease
5. If Current
The funny current a inward mixed sodium
potassium current is highly expressed in :
1. SA node
2. AV node
3. Purkinje fibres
These are activated at voltages of diastolic range.
At the end of a sinoatrial action potential the
membrane repolarizes below the If threshold (about
-40/-50 mV), the funny current is activated and
supplies inward current, which is responsible for
starting the diastolic depolarization phase (DD);
9. It dose not alter:
1. Ventricular repolarisation
2. Myocardial Contractility
3. Blood Pressure.
B-Blockers may not be tolerated in high
doses to attain heart rate of 70.
In acute settings the negative inotropic
effect could be deleterious.
Advantages over B-Blockers
10. Pharmacokinetics
Route: Oral
Bioavailability: 40%
Protein Binding: 70%
Metabolism: Hepatic ( First- Pass) more than
50% CYP 3A4 mediated
Elimination: Renal and Fecal
Half Life: 2 hours.
11. Clinical Uses:
Chronic Stable Angina in patients with sinus
rhytm who cannot take B-blocker.
In combination with B-blockers when heart
rate is poorly controlled with b-blockers.
Off-label in treatment of inappropriate sinus
tachycardia.
Heart failure
13. Morbidity-mortality Evaluation of
The If inhibitor Ivabradine in
patients with coronary disease and
left ventricular dysfunction.
Beautiful
14. Clinical objective
To examine the effects of elevated HR (>70 bpm) on
cardiovascular events in these coronary patients
Pathophysiological objective
To examine the effects of ivabradine on cardiovascular
events in coronary patients with left ventricular
dysfunction
16. Heart rate above 70 bpm increases risk of MI by
46%
Prospective data from the BEAUTIFUL placebo arm
Years
P=0.0066
Hazard ratio = 1.46 (1.11 – 1.91)
0 0.5 1 1.5 2
0
Heart rate <70 bpm
Heart rate ≥70 bpm
8
%withhospitalizationfor
fatalandnonfatalMI
0
4
6
2
17. Ivabradine reduces fatal and nonfatal
myocardial infarction (HR ≥70 bpm)
Hospitalizationfor
fatalornonfatalMI(%)
Placebo
(HR >70 bpm)
Ivabradine
P=0.001
Hazard ratio = 0.64 (0.49 – 0.84)
Years
0 0.5 1 1.5 2
0
4
8
RRR 36%
RRR: relative risk reduction
Fox K et al. Lancet. 2008;372:807-816.
18. Summary of observed cardiovascular risk reduction in
angina patients
24%0.76Primary composite end point
12%0.88CV death
42%0.58
16%0.84Hospitalization for HF
13%0.87All-cause mortality
Risk
reduction
Hazard
ratio
Predefined end point
30%0.70Coronary revascularization
Hospitalization for MI
(n=1507)
Fox K, Ford I, et al; BEAUTIFUL Investigators. Effect of ivabradine on cardiovascular outcomes in patients with stable coronary artery
diseaseand left-ventricular systolic dysfunction with limiting angina: a subgroup analysis of the randomized, controlled BEAUTIFUL trial.
Eur heart Jour On line.
19. SHIFT (Systolic Heart Failure Treatment
with the If Inhibitor Ivabradine Trial)
In HF in sinus rhythm with HR ≥75 bpm heart rate reduction
with ivabradine improves outcomes, including all-cause
death and cardiovascular death reduces .
Ivabradine-associated risk reductions are related to both
HR achieved and magnitude of HR reduction.
Patients achieving <60 bpm or with >10 bpm reduction
have the best prognosis.
20. Reduction in the total hospitalizations for worsening HF
Reduction in the incidence of recurrent HF hospitalizations
Increase in time to first and subsequent hospitalizations
21. Secondary endpoint: change in LVEDVI
from baseline to 8 months
0
75
100
95
90
85
80
mL/m2
93.9 32.8 85.9 30.9 90.8 33.1 89.0 31.6
-7.9 18.9 -1.8 19.0
Ivabradine (n=204) Placebo (n=199)
Baseline 8 months Baseline 8 months
∆ -5.5, P=0.0019
Left ventricular end-diastolic
volume index
24. Other ongoing trials:
SIGNIFY in patients with coronary artery
disease without heart failure – results are
expected in 2013.
VIVIFY 1st trial assessing safety of
intravenous ivabradine in patients with ST-
segment elevation myocardial infarction.
Clarify : International Registry.
25. The new ESC guidelines emphasize the goals when
treating patients with established heart failure “to
relieve symptoms and signs (e.g.
oedema), prevent hospital admission, and
improve survival”.
Also Resting heart rate is established as a
routine parameter guiding the choice of therapy.
Hence guidelines recommend the addition of
ivabradine in patients with heart failure in sinus
rhythm who have a HR ≥70 bpm and an ejection
fraction ≤35%, and who are already treated with β-
blockers, ACEIs, and MRAs (mineralocorticoid
receptor antagonists).
26. Dose
5mg twice daily and may be increased upto
7.5mg twice daily
Dose may be increased or decreased
according to heart rate
If bradycardia persists then it may be stopped
27. Adverse Effects:
Luminous Phenomenon (Enhanced
brightness in a fully maintained visual field).
Bradycardia
Headaches
First DegreeAV block,Ventricular extra
systoles
Dizziness and/ or blurred vision
28. Contraindications
Sick Sinus Syndrome
Hypersenstivity
Cardiogenic shock
Severe hypotension
Pacemaker dependent
H R <60 prior to treatment
Acute myocardial infarction
Sino atrial block
Unstable or acute heart failure
Concomitantly with inhibitors of CYP3A 4 such as azole
antifungals (ketoconazole), macrolide
antibiotics, nefazodone and the anti-HIV drugs nelfinavir
and ritonavir.
29. Take home message
Ivabradine should used in all cases of heart
failure and coronary artery disease rate with
heart rate more than 75.
32. RENIN AND HYPERTENSION
Overactivity of the RAAS with high renin,
Angiotensin, and aldosterone levels causes
fatal malignant hypertension and renovascular
hypertension, whereas overactivity of the
RAAS with milder elevations of renin levels has
been associated with up to 70% of cases of
essential hypertension.
34. Inhibition of Ang II formation or action via ACEIs or
ARBs leads to compensatory increase in renin .
Ang II can also be formed using pathways that do not
involveACE.
Circulating renin can be taken up by cardiac and
coronary tissues, leading to the long-lasting
generation of Ang II via ACE and non-ACE activity
that is only partially suppressed by an ACEI.
Therefore Inhibition of renin would favor more
complete blockade of the system.
35. Direct Renin Inhibitors
Aliskiren is the first of these new nonpeptide
DRIs to be approved by the FDA for the
treatment of hypertension. It is administered
once daily per orally, either as monotherapy or
in combination with other antihyper- tensive
agents also in Europe, aliskiren received
approval for the treatment of hypertension.
36. Aliskiren:Mechanism
Aliskiren is a highly potent inhibitor of renin
with a high affinity for renin and a high
species specificity for primate renin.
It binds to S3bp binding site of renin essential
for its activity.
Binding to this pocket prevents the
conversion of angiotensinogen to
angiotensin1.
37. Aliskiren Pharmacokinetics
Peak plasma concentration – 1- 2 hrs
Steady state after –5-8 days .
Pathway of elimination:-
1. Mainly via biliary excretion as unmetabolised
drug
2. Less than 1% of an orally administered dose is
excreted in urine.
Aliskiren is not metabolized by, and does not
induce or inhibit, cytochrome P450 enzymes and
shows no clinically relevant pharmaco- kinetic
interactions.
38. Aliskiren dosage
DOSE-
150 mg once daily
May increse upto 300mg if B P is not
controlled after two weeks .
Dose more than 300 did not provide
additional blood pressure control rather
causes diarrhea.
39. INDICATIONS AND USAGE
Hypertension
•Aliskiren is indicated for the treatment of
hypertension.
• Lowering blood pressure reduces the risk of
fatal and nonfatal cardiovascular
events, primarily strokes and myocardial
infarctions.
•There are no controlled trials
demonstrating risk reduction with Aliskiren.
40. Containdications:
1) Pregnancy
Pregnancy: Category D
Reduces fetal renal function and increases fetal
and neonatal morbidity and death.
Resulting oligohydramnios can be associated
with fetal lung hypoplasia and skeletal
deformations. Potential neonatal adverse effects
include skull hypoplasia, anuria,hypotension,
renal failure, and death.
When pregnancy is detected, discontinue it as
soon as possible
41. 2)Diabetic receiving ARBs or ACEIs
(GFR<60ml/min)
Because of the increased risk of
Renal impairment
hyperkalemia
hypotension
42. 3) Anaphylactic Reactions and Head
and Neck Angioedema
Hypersensitivity reactions such as
anaphylactic reactions and angioedema of
the face, extremities, lips, tongue, glottis.
DiscontinueAliskiren immediately in patients
who develop anaphylactic reactions or
angioedema, and do not readminister.
43. 4) Hypotension
In patients with an activated renin-angiotensin
system, such as volume- and/or salt-depleted
patients symptomatic hypotension may occur
after initiation of treatment with Aliskiren.
This condition should be corrected prior to
administration of Aliskiren, or the treatment
should start under close medical supervision.
A transient hypotensive response is not a
contraindication to further treatment, which
usually can be continued without difficulty once
the blood pressure has stabilized.
44. 5) Impaired Renal Function
Monitor renal function periodically in patients
treated with Aliskiren whose renal function
may depend in part on the activity of the renin-
angiotensin system (e.g., patients with renal
artery stenosis, severe heart
failure, postmyocardial infarction or volume
depletion) or patients receiving ARB,ACEI or
non-steroidal anti-inflammatory (NSAID).
45. 6)Hyperkalemia
Risk factors for the development of
hyperkalemia include renal
insufficiency, diabetes, combination use with
ARBs or ACEIs NSAIDs, or potassium
supplements or potassium sparing diuretics.
7) Cyclosporine or Itraconazole
When aliskiren was given with cyclosporine or
itraconazole, the blood concentrations of
aliskiren were significantly increased. Avoid
concomitant use of aliskiren with cyclosporine or
itraconazole .
46. Adverse Effects
Angioedema
Hyerkalemia ( Particularly when used with ACE
inhibitors in diabetic patients)
Hypotension (Particularly in volume depleted
persons)
Diarrhoea and other GI symptoms.
Headache
Dizziness
Cough
Rash
Elevated uric acid, gout and renal stones.
47. OVERDOSAGE
Limited data are available related to
overdosage in humans.The most likely
manifestation of overdosage would be
hypotension. If symptomatic hypotension
occurs, supportive treatment should be
initiated.
Aliskiren is poorly dialyzed.Therefore,
hemodialysis is not adequate to treat
aliskiren overexposure .
49. As Monotherapy
The antihypertensive effects of Aliskiren have
been demonstrated in six randomized, double-
blind, placebo-controlled 8-week clinical trials in
patients with mild-to-moderate hypertension.
A substantial proportion (85%-90%) of the blood
pressure lowering effect was observed within 2
weeks of treatment .With cessationof
treatment, blood pressure gradually returned
toward baseline levels over a period of several
weeks.
There was no evidence of rebound hypertension
after abrupt cessation of therapy.
50. In Combinations:
With Hydrochlorthiazide : Additive
WithValsartan: Additive
With Amlodipine: Additive
51. Aliskiren in Patients with
Diabetes treated with ARB or
ACEI (ALTITUDE study)
Patients with diabetes with renal disease
(defined either by the presence of albuminuria or
reduced GFR) were randomized to aliskiren 300
mg daily and placebo . All patients were
receiving background therapy with an ARB or
ACEI.Trial was halted due to increased incidence
of nonfatal stroke, renal complications,
Hyperkalemia and hypotension in patients with
diabetes and renal impairment.
52. Relating to cardiac diseases
ALLAY and ASPIRE trials show that
there is no positive impact on LV
hypertrophy or LV remodeling with
combined
1. Aliskiren and ARB or
2. Aliskiren and ACE inhibitor therapy.
53. ALOFT Trial
Addition of Aliskiren in heart failure patients
shows reduction of neurohumoral activation
–(BNP and NT-pro-BNP which were
previously linked to adverse outcome in
patients with heart failure) .
These data are encouraging but not
definitive.
54. Results of two trials ATMOSPHERE and
ASTRONAUT regarding its beneficial role in
heart failure patients are underway.
Finally the Aliskiren in Prevention of Later
Life Outcomes (APOLLO) trial will address
elderly patients with a systolic BP 130 to 159
mm Hg, no overt cardiovascular disease, and
a high cardiovascular risk profile, in order to
test the efficacy of the drug in reducing the
risk of major cardiovascular end points.
55. Take Home Message
1. Can be used as alternative to various
antihypertensive as monotherapy or as
combination therapy .
2. Regarding beneficial role in cardiovascular
diseases and renal diseases ?