p.68
Migraine: Pathogenesis and Treatment
What type of medication is Pizotifen?
An antihistamine with antiserotonin effects.
p.10
Inflammatory Pathway and Mediators
Are eicosanoids preformed in tissues?
No, they are not preformed in tissues.
p.46
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
When may DMARDs be initiated?
On definite diagnosis of the condition.
p.17
Inflammatory Pathway and Mediators
What is inflammation?
A normal protective response to tissue injury caused by physical trauma, noxious chemicals, or microbiological agents.
p.46
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What are synthetic disease-modifying anti-rheumatoid drugs (DMARDs) often referred to as?
Second-line drugs after NSAIDs.
p.10
Inflammatory Pathway and Mediators
From what are prostaglandins generated?
From arachidonic acid in many tissues.
p.64
Migraine: Pathogenesis and Treatment
What is Phase II of a migraine characterized by?
Vasodilation due to rapid metabolism of 5HT.
p.13
Inflammatory Pathway and Mediators
What are the primary functions of prostaglandins?
Pain, fever, inflammation, uterine contraction, mucous production, gastric juice secretion, and renal flow auto regulation.
p.18
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What are the pharmacological effects of NSAIDs?
Anti-inflammatory, analgesic, antipyretic, and anti-platelet.
p.62
Migraine: Pathogenesis and Treatment
What are common accompanying symptoms of a migraine?
Nausea and distorted vision.
p.20
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What do COX-1 and COX-2 enzymes catalyze the conversion of?
Arachidonic acid to prostaglandins and thromboxanes.
p.62
Migraine: Pathogenesis and Treatment
What type of headache is characteristic of migraines?
Recurrent throbbing headache, usually affecting one side of the head but may become bilateral.
p.11
Inflammatory Pathway and Mediators
What can trigger the production of eicosanoids?
Membrane disturbance, tissue injury, thrombin, bradykinin, epinephrine, and angiotensin II.
p.62
Migraine: Pathogenesis and Treatment
How can migraines affect individuals?
They can be debilitating.
p.57
Gout: Causes and Treatment
What is the goal of therapy for gout?
To treat acute attacks and maintain therapy for hyperuricaemia.
p.5
Pain Mechanisms and Nociception
What is nociception?
The perception of noxious stimuli.
p.64
Migraine: Pathogenesis and Treatment
What type of headache is associated with Phase II of a migraine?
Throbbing headache starting in the eye or diffused/unilateral.
p.54
Gout: Causes and Treatment
What are two reasons for enhanced production of uric acid?
Metabolic aberration and oncotherapeutics.
p.49
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What are Disease-Modifying Anti-Rheumatic Drugs (DMARDs)?
Medications used to slow the progression of rheumatoid arthritis.
p.36
Corticosteroids: Mechanism and Therapeutic Uses
What are the main anti-inflammatory effects of glucocorticoids?
Reduction of prostaglandin production.
p.11
Inflammatory Pathway and Mediators
What are examples of eicosanoids?
Prostaglandins, thromboxanes, prostacycline (PGI), and leukotrienes.
p.51
Inflammatory Pathway and Mediators
What is Anakinra?
A naturally occurring anti-inflammatory cytokine.
p.45
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Do NSAIDs prevent the progression of disease?
No, they do not prevent progression of disease.
p.15
Inflammatory Pathway and Mediators
What is the primary function of COX-1?
Production of prostaglandins involved in gastric cytoprotection, renal flow autoregulation, and platelet aggregation.
p.60
Gout: Causes and Treatment
How does Probenecid assist in the treatment of gout?
It accelerates excretion of uric acid by competing for reabsorption carriers.
p.53
Gout: Causes and Treatment
What is the definition of gout?
A metabolic disease characterized by high levels of sodium urate crystals in synovial tissues, leading to an inflammatory response.
p.13
Inflammatory Pathway and Mediators
What role do thromboxanes play in the body?
They are involved in platelet aggregation and vasoconstriction.
p.6
Pain Mechanisms and Nociception
What is pain usually a response to?
An untoward event associated with tissue damage.
p.44
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What are DMARDs used for?
Disease-Modifying Anti-Rheumatic Drugs are used to treat rheumatoid arthritis.
p.30
Analgesics: Paracetamol and Its Toxicity
Name a common type of analgesic agent.
Paracetamol (acetaminophen).
p.23
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Who is particularly susceptible to NSAID-induced asthma?
Individuals with nasal polyps.
p.37
Corticosteroids: Mechanism and Therapeutic Uses
What is the recommended method for withdrawing high dose corticosteroids after long-term use?
Withdraw gradually, using alternate days or dose tapering.
p.23
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What is inhibited by NSAIDs that can affect bronchodilation?
The synthesis of bronchodilator prostaglandins (PGs).
p.68
Migraine: Pathogenesis and Treatment
What is the mechanism of action of Propranolol in migraine treatment?
It is a β-blocker that inhibits extracranial vasodilation.
p.20
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What is the mechanism of action (MOA) of NSAIDs?
NSAIDs reversibly block cyclo-oxygenase (COX-1 and COX-2) enzymes.
p.60
Gout: Causes and Treatment
What is the purpose of maintenance therapy in acute gout treatment?
To manage frequent or repeated attacks.
p.51
Inflammatory Pathway and Mediators
How does Anakinra function?
By binding to IL-1 receptors, preventing interaction with the cell.
p.61
Migraine: Pathogenesis and Treatment
What are common symptoms of a migraine?
Intense headache, nausea, vomiting, and sensitivity to light and sound.
p.39
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What type of condition is rheumatoid arthritis (RA)?
A chronic inflammatory condition affecting joints.
p.57
Gout: Causes and Treatment
Which drugs are commonly used for treating acute gout attacks?
Most NSAIDs, but not aspirin.
p.31
Analgesics: Paracetamol and Its Toxicity
Where do analgesic agents act in the body?
On the peripheral nervous system (PNS) and central nervous system (CNS).
p.38
Corticosteroids: Mechanism and Therapeutic Uses
Which skin disorders can be treated with corticosteroids?
Contact dermatitis and atopic dermatitis.
p.36
Corticosteroids: Mechanism and Therapeutic Uses
How do glucocorticoids affect allergic responses?
They suppress antibody production, especially at large doses.
p.36
Corticosteroids: Mechanism and Therapeutic Uses
What immunosuppressive effect do glucocorticoids have?
Lysis of lymphoid tissue and decreased eosinophil numbers.
p.67
Migraine: Pathogenesis and Treatment
What is the primary use of ergot alkaloids like ergotamine tartrate?
As a potent extracranial vasoconstrictor for short-term treatment when analgesics are not relieving.
p.18
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What is the mechanism of action (MOA) of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?
Reversible blockade of cyclooxygenase (COX) enzyme, which catalyzes the conversion of arachidonic acid to prostaglandins and thromboxanes.
p.17
Inflammatory Pathway and Mediators
What do anti-inflammatory agents do?
They decrease pain, inflammation, and have other therapeutic uses.
p.62
Migraine: Pathogenesis and Treatment
What factors are implicated in the treatment of migraines?
Both genetic and environmental factors.
p.10
Inflammatory Pathway and Mediators
What are eicosanoids derived from?
Polyunsaturated fatty acids, specifically arachidonic acid.
p.10
Inflammatory Pathway and Mediators
How are eicosanoids generated?
De novo from phospholipids.
p.45
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What are the primary effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?
They are analgesic and anti-inflammatory, reducing pain and joint stiffness.
p.42
Pain Mechanisms and Nociception
What is the typical onset of symptoms for this condition?
Insidious; usually developing over weeks or months.
p.15
Inflammatory Pathway and Mediators
What role does COX-2 play in the body?
Responsible for the production of prostanoid mediators of inflammation, renal function, and uterine contraction.
p.60
Gout: Causes and Treatment
What should be used as prophylactic coverage when using Probenecid?
Colchicine or NSAIDs for 3 months.
p.64
Migraine: Pathogenesis and Treatment
What are some symptoms accompanying a migraine in Phase II?
Anorexia, irritability, photophobia, cold, cyanotic extremities.
p.46
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What is a common issue with DMARDs?
Many serious adverse effects lead to poor compliance.
p.13
Inflammatory Pathway and Mediators
What is the function of prostacycline (PGI2)?
It promotes platelet disaggregation and vasodilation.
p.42
Pain Mechanisms and Nociception
Which joints are most affected by this condition?
Small joints of hands, wrists, and feet.
p.13
Inflammatory Pathway and Mediators
What are leukotrienes primarily associated with?
Inflammation and bronchoconstriction.
p.59
Gout: Causes and Treatment
What is the primary mechanism of action of Allopurinol in treating gout?
It inhibits the synthesis of uric acid by inhibiting xanthine oxidase via substrate competition.
p.16
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
How do NSAIDs work?
By inhibiting enzymes involved in the inflammatory process.
p.9
Pain Mechanisms and Nociception
What is the nociceptive pathway?
The neural pathway that transmits pain signals from the site of injury to the brain.
p.16
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What are common side effects of NSAIDs?
Gastrointestinal issues, cardiovascular risks, and kidney problems.
p.67
Migraine: Pathogenesis and Treatment
What are common side effects (SE) of ergotamine?
Nausea, vomiting, diarrhea, hallucinations, and angina pain.
p.16
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Can NSAIDs be used for chronic conditions?
Yes, they are often used for conditions like arthritis.
p.22
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What symptoms can arise from inhibition of gastric prostaglandins?
Abdominal pain, ulcer formation, nausea, vomiting.
p.58
Gout: Causes and Treatment
How does colchicine affect lactic acid production?
It decreases lactic acid production by leucocytes, which reduces uric acid deposition.
p.9
Pain Mechanisms and Nociception
What role do nociceptors play in the nociceptive pathway?
They detect harmful stimuli and initiate the pain signal.
p.27
Analgesics: Paracetamol and Its Toxicity
What severe symptoms can occur with aspirin poisoning at 300 - 500 mg/kg?
Metabolic acidosis in children and respiratory acidosis in adults.
p.12
Inflammatory Pathway and Mediators
What role do cyclooxygenase and lipoxygenase play in the body?
They are enzymes that convert arachidonic acid into eicosanoids.
p.24
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What is the effect of NSAIDs on preterm labor?
They can suppress preterm labor by relaxing uterine muscles and prolonging gestation.
p.50
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What type of DMARD is Rituximab?
An anti-CD20 monoclonal antibody.
p.9
Pain Mechanisms and Nociception
What is the significance of the spinal cord in the nociceptive pathway?
It acts as a relay station for pain signals before they reach the brain.
p.21
COX-2 Inhibitors: Advantages and Disadvantages
Which NSAIDs are considered selective?
Celecoxib, Eterocoxib, Rofecoxib, Parecoxib.
p.35
Corticosteroids: Mechanism and Therapeutic Uses
What mechanism suppresses the secretion of ACTH?
Negative feedback mechanism by glucocorticoids.
p.38
Corticosteroids: Mechanism and Therapeutic Uses
What are some therapeutic uses of corticosteroids?
Bronchial asthma, emphysema, rheumatic and collagen diseases, inflammatory diseases of GIT/kidney/liver, brain edema, and skin disorders.
p.46
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What is a key benefit of DMARDs?
They can halt or reverse underlying disease bone and joint damage.
p.62
Migraine: Pathogenesis and Treatment
How often do migraineurs typically experience attacks?
More than one episode per month.
p.57
Gout: Causes and Treatment
What is the primary focus during an acute gout attack?
Relief of inflammation and pain, not reduction of uric acid levels.
p.46
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What is a characteristic of the onset of action for DMARDs?
They have a slow onset of action.
p.23
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What type of allergies can NSAIDs trigger?
Allergies such as asthma in susceptible individuals.
p.29
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) used for?
To reduce inflammation, pain, and fever.
p.5
Pain Mechanisms and Nociception
Where do nociceptors send electrical signals?
To the CNS at the dorsal root ganglion.
p.60
Gout: Causes and Treatment
What types of medications does Probenecid compete with for elimination?
NSAIDs, Methotrexate, and sulphonamides.
p.30
Analgesics: Paracetamol and Its Toxicity
What are non-opioid analgesics?
Analgesics that do not contain opioids, such as NSAIDs and paracetamol.
p.28
COX-2 Inhibitors: Advantages and Disadvantages
Name three examples of COXIBs.
Celecoxib, Etoricoxib, Parecoxib.
p.30
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What is the mechanism of action of NSAIDs?
Inhibition of cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis.
p.23
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What CNS side effects can high doses of Indomethacin cause?
Headache, dizziness, drowsiness, mental depression, and confusion.
p.24
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What common ailments can NSAIDs help relieve?
Toothache, dysmenorrhea, headaches, and muscular injury.
p.48
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What are two examples of antimalarial agents used as DMARDs?
Chloroquine and hydroxychloroquine.
p.50
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
Name a type of DMARD that is a TNF α-antagonist.
Etanercept or Infliximab.
p.26
Mechanism of Action of Aspirin
How does aspirin affect thromboxane production?
It inhibits thromboxane production, resulting in anticoagulation.
p.2
COX-2 Inhibitors: Advantages and Disadvantages
What are the advantages of COX-2 inhibitors?
They provide pain relief with a lower risk of gastrointestinal side effects compared to traditional NSAIDs.
p.12
Inflammatory Pathway and Mediators
Name two types of eicosanoids.
Prostaglandins and leukotrienes.
p.24
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
How does Indomethacin affect the patent ductus arteriosus?
It inhibits prostaglandins that maintain the patency of the ductus arteriosus.
p.22
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
How does NSAID use affect renal function?
It disturbs fluid and electrolyte balance through inhibition of renal prostaglandins.
p.2
Mechanism of Action of Aspirin
What are the potential adverse effects (A/E) of aspirin?
Gastrointestinal bleeding, ulcers, and allergic reactions.
p.3
Analgesics: Paracetamol and Its Toxicity
How do paracetamol and NSAIDs differ in their mechanisms of action?
Paracetamol primarily acts in the central nervous system, while NSAIDs inhibit cyclooxygenase enzymes peripherally.
p.2
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What are the two types of DMARDs?
Synthetic and biological DMARDs.
p.8
Inflammatory Pathway and Mediators
What role does serotonin play in pain mediation?
Serotonin can modulate pain perception and is involved in the pain pathway.
p.63
Migraine: Pathogenesis and Treatment
What is a common preceding symptom in classic migraine?
Aura, although not all patients experience it.
p.38
Corticosteroids: Mechanism and Therapeutic Uses
What condition is treated with corticosteroids related to respiratory issues?
Bronchial asthma and status asthmaticus.
p.68
Migraine: Pathogenesis and Treatment
How does Flunarazine help in migraine treatment?
It is a calcium channel antagonist that dilates intracranial blood vessels.
p.6
Pain Mechanisms and Nociception
How is pain typically defined?
As a subjective experience that is hard to define.
p.44
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What does NSAIDs stand for?
Non-Steroidal Anti-Inflammatory Drugs.
p.5
Pain Mechanisms and Nociception
What are nociceptors?
Specialised sensory receptors responsible for detecting noxious stimuli.
p.63
Migraine: Pathogenesis and Treatment
What are some prodromal symptoms of a migraine?
Visual disturbances, mood changes, depression, irritability, anorexia, and nausea.
p.16
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What does NSAIDs stand for?
Non-Steroidal Anti-Inflammatory Drugs.
p.57
Gout: Causes and Treatment
What is the next step if NSAIDs do not provide relief during a gout attack?
Corticosteroids or colchicine.
p.44
Corticosteroids: Mechanism and Therapeutic Uses
What is the purpose of immunosuppressants?
To suppress the immune system.
p.64
Migraine: Pathogenesis and Treatment
What causes the increased amplitude of pulsation during a migraine?
Stimulation of β-adrenoceptors by adrenaline.
p.58
Gout: Causes and Treatment
What is colchicine used for in the treatment of acute gout?
It is an effective anti-inflammatory agent specifically for gouty arthritis.
p.66
Migraine: Pathogenesis and Treatment
What types of analgesics are mentioned for acute attack treatment?
Antipyretic + opioid, aspirin, paracetamol, codeine, or propoxyphene.
p.29
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What is the primary difference between COX-1 and COX-2?
COX-1 is involved in normal physiological functions, while COX-2 is induced during inflammation.
p.26
Mechanism of Action of Aspirin
What type of blockade does aspirin cause?
Irreversible blockade of cyclooxygenase (COX) enzyme.
p.29
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What are some common side effects of NSAIDs?
Gastrointestinal issues, cardiovascular risks, and kidney problems.
p.28
COX-2 Inhibitors: Advantages and Disadvantages
Why does the risk of cardiovascular issues increase with COXIB use?
Due to inhibition of prostacyclin (PGI2), leading to dominant thromboxane effects.
p.47
Disease Modifying Anti-Rheumatic Drugs (DMARDs
What are potential side effects of Methotrexate?
Suppression of bone marrow or hepatitis.
p.25
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What NSAID is effective for moderate to severe post-operative pain?
Ketorolac provides synergistic activity, reducing the dose of opioid analgesics.
p.22
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What is Misoprostol used for?
To protect gastric mucosa as a prostaglandin analogue.
p.26
Mechanism of Action of Aspirin
What effect does aspirin have on platelet adhesiveness?
It diminishes platelet adhesiveness, leading to hypothrombi anemia.
p.12
Inflammatory Pathway and Mediators
What are eicosanoids?
Signaling molecules derived from arachidonic acid, including prostaglandins and leukotrienes.
p.3
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What are the reasons behind the adverse effects of NSAIDs?
They can cause gastrointestinal issues, renal impairment, and cardiovascular risks due to their mechanism of action.
p.66
Migraine: Pathogenesis and Treatment
Can you name some examples of triptans?
Sumatriptan, eletriptan, naratriptan.
p.48
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What is the typical dosing regimen for DMARDs?
150-300 mg daily, then 150 mg daily for 10 days, then 2.4 mg/kg 5 days a week.
p.66
Migraine: Pathogenesis and Treatment
How are triptans tolerated in patients?
They are well tolerated and effective.
p.2
Analgesics: Paracetamol and Its Toxicity
What are the adverse effects of paracetamol?
Liver toxicity, especially in overdose situations.
p.61
Migraine: Pathogenesis and Treatment
What is a migraine?
A type of headache characterized by intense, debilitating pain, often accompanied by nausea and sensitivity to light and sound.
p.63
Migraine: Pathogenesis and Treatment
How is migraine classified in terms of phases?
It is divided into two phases.
p.10
Inflammatory Pathway and Mediators
What triggers the generation of eicosanoids?
Membrane disturbance, tissue injury, thrombin, bradykinin, epinephrine, and angiotensin II.
p.63
Migraine: Pathogenesis and Treatment
What occurs during Phase 1 of a migraine?
Vasoconstriction of intracranial blood vessels due to the release of serotonin and other mediators.
p.20
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What are the main pharmacological effects of NSAIDs?
Anti-inflammatory, analgesic, antipyretic, and anti-platelet.
p.38
Corticosteroids: Mechanism and Therapeutic Uses
What are some symptoms of Cushing's disease caused by corticosteroids?
Fat deposition, increased appetite, weight gain, diabetes, anti-growth hormone effect, salt water retention, and easy bruising of the skin.
p.54
Gout: Causes and Treatment
What can lead to delayed excretion of uric acid by the kidneys?
Impaired kidney function or certain drugs like aspirin.
p.61
Migraine: Pathogenesis and Treatment
How can migraines be treated?
Treatment options include medications for pain relief, preventive medications, and lifestyle changes.
p.61
Migraine: Pathogenesis and Treatment
What role do hormones play in migraines?
Hormonal changes, particularly in women, can trigger migraines.
p.6
Pain Mechanisms and Nociception
Can pain be associated with inflammation?
Yes, it may be associated with inflammation (anti-inflammatory agents) or not (analgesic agents).
p.1
Analgesics: Paracetamol and Its Toxicity
What are the potential risks associated with analgesics?
Toxicity and side effects.
p.32
Analgesics: Paracetamol and Its Toxicity
Does Paracetamol have gastrointestinal side effects?
No, it has no gastrointestinal side effects.
p.23
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What can occur when the COX pathway is blocked by NSAIDs?
The production of leukotrienes from the lipo-oxygenase pathway.
p.67
Migraine: Pathogenesis and Treatment
What are some serious adverse effects (AEs) of ergotamine tartrate?
Intense vasoconstriction leading to retroperitoneal fibrosis and gangrene of the extremities.
p.19
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What is the difference between COX-1 and COX-2?
COX-1 is involved in normal physiological functions, while COX-2 is induced during inflammation.
p.67
Migraine: Pathogenesis and Treatment
What are more serious side effects associated with ergotamine?
Angina pain, tachycardia/bradycardia, and blood pressure changes.
p.25
COX-2 Inhibitors: Advantages and Disadvantages
Why does Meloxicam have fewer side effects compared to other non-selective NSAIDs?
It has a higher degree of selectivity for the COX-2 isoenzyme.
p.67
Migraine: Pathogenesis and Treatment
What combination is found in Cafergot?
Ergotamine tartrate, caffeine, and cyclizine.
p.21
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
How do NSAIDs affect platelets?
They can cause platelet aggregation.
p.14
Analgesics: Paracetamol and Its Toxicity
What can result from inhibiting prostaglandins in the gastrointestinal tract?
It can lead to peptic ulcers.
p.2
Gout: Causes and Treatment
What are the treatment options for acute gout?
Non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, and corticosteroids.
p.8
Inflammatory Pathway and Mediators
What is Substance P known for in the context of pain?
Substance P is a neuropeptide that transmits pain signals and is involved in the inflammatory response.
p.54
Gout: Causes and Treatment
What can cause hyperuricemia?
Enhanced production of uric acid or delayed excretion by the kidneys.
p.45
COX-2 Inhibitors: Advantages and Disadvantages
What is a key advantage of COX-2 specific NSAIDs?
They have an improved gastrointestinal safety profile.
p.68
Migraine: Pathogenesis and Treatment
What is the role of Clonidine in migraine treatment?
Clonidine is used as a treatment option, though its specific mechanism is not detailed.
p.32
Analgesics: Paracetamol and Its Toxicity
What type of medication is Paracetamol?
An OTC analgesic and antipyretic.
p.15
Inflammatory Pathway and Mediators
Where is COX-3 primarily found?
In the central nervous system (CNS), with inconclusive results regarding its function.
p.43
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What is the primary goal of therapy for joint diseases?
To improve or maintain functional status.
p.49
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What is Sulfasalazine split into in the gastrointestinal tract?
Sulphapyridine and 5-amino salicylic acid.
p.43
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What are two key objectives of therapy besides improving functional status?
Control disease activity and joint pain; slow destructive joint changes.
p.5
Pain Mechanisms and Nociception
What role do mediators play in nociception?
They facilitate the transmission of nociception from primary afferent neurons.
p.4
Pain Mechanisms and Nociception
What is the primary distinction between pain and nociception?
Nociception is the sensory process that detects harmful stimuli, while pain is the emotional and psychological experience associated with that detection.
p.19
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What is a common mechanism of action for NSAIDs?
Inhibition of cyclooxygenase (COX) enzymes.
p.24
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
In which inflammatory conditions are NSAIDs useful?
Rheumatoid arthritis (RA), osteoarthritis, psoriatic arthritis, juvenile arthritis, and gout.
p.50
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What is a significant risk associated with DMARDs?
Risk of serious infections due to immunosuppression.
p.66
Migraine: Pathogenesis and Treatment
What is the role of antiemetics in treating acute attacks?
To prevent nausea and vomiting, with examples like cyclizine and prochlorperazine.
p.1
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What is a common side effect of NSAIDs?
Gastrointestinal irritation.
p.4
Pain Mechanisms and Nociception
Can nociception occur without pain?
Yes, nociception can occur without the conscious experience of pain, such as in cases of nerve damage.
p.19
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What are some common side effects of NSAIDs?
Gastrointestinal issues, cardiovascular risks, and kidney problems.
p.14
Inflammatory Pathway and Mediators
What effect do leucocytic pyrogens have on prostaglandins?
They induce PG release in the temperature center of the hypothalamus, increasing body temperature.
p.50
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What is tocilizumab classified as?
An Interleukin-6 inhibitor.
p.14
Inflammatory Pathway and Mediators
How do prostaglandins contribute to inflammation?
They enhance capillary permeability, allowing proteins and fluid to pass through extracellular spaces.
p.12
Inflammatory Pathway and Mediators
What is the function of thromboxane?
It promotes platelet aggregation and vasoconstriction.
p.14
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What is the effect of inhibiting prostaglandins on inflammation?
It results in a decrease in inflammation.
p.14
Inflammatory Pathway and Mediators
What role do prostaglandins play in the uterus?
They induce uterine contractions and are used for therapeutic abortions.
p.26
Mechanism of Action of Aspirin
How does aspirin affect uric acid secretion at low doses?
It competes with secretion carriers of uric acid.
p.3
Gout: Causes and Treatment
What is gout and what drugs are used for its management?
Gout is a form of arthritis caused by uric acid crystals; drugs include NSAIDs for acute attacks and allopurinol for long-term management.
p.42
Pain Mechanisms and Nociception
What are common symptoms associated with this condition?
Fatigue, low-grade fever, appetite loss, joint pain.
p.65
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What are common symptoms of acute attacks?
Pain, nausea and vomiting, irritability, anxiety.
p.42
Pain Mechanisms and Nociception
What symptoms precede synovitis?
Stiffness and muscle aches.
p.60
Gout: Causes and Treatment
What risk is associated with using Probenecid?
It may precipitate an acute gout attack.
p.53
Gout: Causes and Treatment
What are the symptoms of gout?
Extremely painful intermittent attacks of acute arthritis, often in the big toe.
p.29
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What is a common mechanism of action for NSAIDs?
Inhibition of cyclooxygenase (COX) enzymes.
p.16
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What is the primary use of NSAIDs?
To reduce inflammation and relieve pain.
p.30
Analgesics: Paracetamol and Its Toxicity
What is a potential risk associated with paracetamol?
Hepatotoxicity (liver damage) in high doses.
p.44
Corticosteroids: Mechanism and Therapeutic Uses
What are biologic agents?
Medications derived from living organisms used to treat various diseases.
p.24
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What are the primary therapeutic effects of NSAIDs?
Analgesic and anti-inflammatory action.
p.64
Migraine: Pathogenesis and Treatment
What are some precipitating factors for migraines?
Anxiety & tension, starvation, exhaustion, flashing lights, certain foods (chocolates, tyramine-containing foods).
p.47
Disease Modifying Anti-Rheumatic Drugs (DMARDs
What type of drug is Methotrexate?
A folic acid antagonist with potent anti-rheumatoid action.
p.32
Analgesics: Paracetamol and Its Toxicity
Can Paracetamol be combined with other medications?
Yes, it can be combined with an NSAID or an opioid analgesic.
p.43
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
How can weight reduction benefit joint health?
It can reduce stress on the joints.
p.9
Pain Mechanisms and Nociception
What are the main components of the nociceptive pathway?
Nociceptors, peripheral nerves, spinal cord, and brain.
p.32
Analgesics: Paracetamol and Its Toxicity
What is the effect of Paracetamol on COX-2?
It mildly inhibits COX-2.
p.27
Analgesics: Paracetamol and Its Toxicity
What are common symptoms of mild to moderate aspirin poisoning?
Tinnitus, light headedness, excessive perspiration, nausea, gastric hemorrhage.
p.25
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Which NSAIDs are preferred for long-term treatment in RA and osteoarthritis due to lower GIT effects?
Ibuprofen and diclofenac are preferred over indomethacin, piroxicam, and naproxen.
p.28
COX-2 Inhibitors: Advantages and Disadvantages
What rare skin reactions can be caused by COXIBs?
Stevens-Johnson syndrome and toxic epidermal necrolysis.
p.26
Mechanism of Action of Aspirin
What is one use of aspirin in postoperative care?
Prophylaxis of thrombus formation after hip surgery.
p.47
Disease Modifying Anti-Rheumatic Drugs (DMARDs
What is the role of Ciclosporin in DMARD therapy?
Useful for patients who don’t respond to conventional therapy.
p.3
Mechanism of Action of Aspirin
What is the pharmacological profile of aspirin?
Aspirin has analgesic, anti-inflammatory, and antipyretic effects, but can cause gastrointestinal bleeding and has contraindications in certain conditions.
p.21
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What are some examples of non-selective NSAIDs?
Aspirin, Diclofenac, Indomethacin, Ibuprofen, Mefenamic acid.
p.22
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What can long-term use of NSAIDs lead to in terms of renal health?
Renal damage, worsening hypertension, cardiac failure, and angina pectoris.
p.12
Inflammatory Pathway and Mediators
What is the role of prostacyclin?
It inhibits platelet aggregation and promotes vasodilation.
p.61
Migraine: Pathogenesis and Treatment
What triggers migraines in some individuals?
Triggers can include stress, certain foods, hormonal changes, and environmental factors.
p.53
Gout: Causes and Treatment
What causes the inflammatory response in gout?
Local infiltration of leucocytes and phagocytes producing lactic acid, which lowers the pH and facilitates further crystallization of uric acid.
p.32
Analgesics: Paracetamol and Its Toxicity
What is the primary action of Paracetamol?
Pain reliever and fever reducer.
p.39
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What are the key components of the pathophysiology of rheumatoid arthritis?
Inflammatory component, synovium proliferation (T and B cells and inflammatory cytokines), erosion of cartilage and bone.
p.57
Gout: Causes and Treatment
What type of therapy is used for maintenance in gout treatment?
Maintenance therapy for hyperuricaemia.
p.53
Gout: Causes and Treatment
Which foods can precipitate a gout attack?
Red meat, liver, yeast, sardines, and alcohol.
p.39
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What is a common outcome of rheumatoid arthritis?
Loss of cartilage, ankylosis, chronic deformation.
p.66
Migraine: Pathogenesis and Treatment
What are the main types of medications used for the treatment of acute attacks?
Analgesics, antiemetics, sedatives, and triptans.
p.4
Pain Mechanisms and Nociception
What triggers nociception?
Nociception is triggered by harmful stimuli such as extreme temperatures, pressure, or chemical irritants.
p.59
Gout: Causes and Treatment
What happens to uric acid levels when Allopurinol is administered?
There is a sudden decrease in uric acid levels, which may lead to acute attacks.
p.64
Migraine: Pathogenesis and Treatment
Which foods are known to precipitate migraines?
Chocolates, cheese, meat, yeast extracts, red wine, herring.
p.28
COX-2 Inhibitors: Advantages and Disadvantages
What is a significant risk associated with long-term use of COXIBs?
Increased risk of cardiovascular and cerebrovascular disease.
p.12
Inflammatory Pathway and Mediators
What is arachidonic acid?
A polyunsaturated fatty acid that is a precursor to eicosanoids.
p.37
Corticosteroids: Mechanism and Therapeutic Uses
Name a long-acting corticosteroid.
Betamethasone or Dexamethasone.
p.48
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What is the mechanism of action of chloroquine and hydroxychloroquine?
The anti-inflammatory effect is not clear, but they induce remission without reducing bone erosion.
p.3
Inflammatory Pathway and Mediators
What is the role of prostaglandins and thromboxane in the body?
They are involved in various physiological processes including inflammation and blood clotting.
p.67
Migraine: Pathogenesis and Treatment
In which conditions is the use of ergotamine contraindicated?
Peripheral, coronary, cerebrovascular, renal, hepatic disease, pregnancy, and uncontrolled hypertension.
p.58
Gout: Causes and Treatment
What are the common side effects of colchicine?
Largely gastrointestinal issues like nausea, vomiting, and abdominal pain.
p.48
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
How do DMARDs affect T lymphocytes?
They suppress the responsiveness of T lymphocytes to mitogens.
p.58
Gout: Causes and Treatment
What other side effects can colchicine cause?
Liver and renal damage, and bone marrow suppression.
p.59
Gout: Causes and Treatment
How does Allopurinol affect kidney disease progression?
It slows the progression of kidney disease.
p.14
Inflammatory Pathway and Mediators
What happens when PG synthesis and release are inhibited in relation to fever?
It leads to a decrease in fever.
p.67
Migraine: Pathogenesis and Treatment
What combination is found in Migril?
Ergotamine tartrate and caffeine.
p.27
Analgesics: Paracetamol and Its Toxicity
What is a treatment to restore acid-base balance in aspirin toxicity?
Fluid electrolyte therapy.
p.26
Mechanism of Action of Aspirin
How does aspirin help in coronary bypass procedures?
It prevents occlusion in coronary bypass.
p.64
Migraine: Pathogenesis and Treatment
What physical signs may be prominent during a migraine?
Prominent extracranial arteries and increased amplitude of pulsation.
p.19
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) primarily used for?
To reduce inflammation and relieve pain.
p.32
Analgesics: Paracetamol and Its Toxicity
How does Paracetamol work in the body?
It inhibits the synthesis of prostaglandins in the brain.
p.60
Gout: Causes and Treatment
Why can Probenecid cause toxicity?
Because it competes with the elimination of weak acids.
p.36
Corticosteroids: Mechanism and Therapeutic Uses
What metabolic processes are influenced by glucocorticoids?
Gluconeogenesis, glycogen, protein, lipid, and calcium deposition.
p.12
Inflammatory Pathway and Mediators
What are phospholipids?
Molecules that form the structural basis of cell membranes.
p.1
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
How do NSAIDs work?
By inhibiting cyclooxygenase (COX) enzymes.
p.35
Corticosteroids: Mechanism and Therapeutic Uses
What are the two main types of corticosteroids?
Mineralocorticoids and glucocorticoids.
p.59
Gout: Causes and Treatment
What should be used for prophylactic coverage when starting Allopurinol?
Colchicine or NSAIDs for 3 months.
p.14
Inflammatory Pathway and Mediators
What role do prostaglandins (PGs) play in pain sensation?
PGs sensitize pain receptors to cytokines and bradykinin.
p.59
Gout: Causes and Treatment
Is Allopurinol effective in treating acute gout attacks?
No, it is ineffective and may even exacerbate acute attacks.
p.35
Corticosteroids: Mechanism and Therapeutic Uses
What do mineralocorticoids regulate?
Electrolyte and water metabolism.
p.14
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
How do drugs relieve pain related to prostaglandins?
By inhibiting the synthesis and release of PGs.
p.47
Disease Modifying Anti-Rheumatic Drugs (DMARDs
Why should folic acid be co-administered with Methotrexate?
To mitigate side effects caused by folic acid deficiency.
p.48
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What additional effects do DMARDs have?
They decrease chemotaxis, inhibit DNA and RNA synthesis, and trap free radicals.
p.66
Migraine: Pathogenesis and Treatment
What effects do triptans have on sensory neuropeptides?
They inhibit the release of sensory neuropeptides.
p.27
Analgesics: Paracetamol and Its Toxicity
What is urine alkalinization used for in aspirin toxicity?
To enhance the elimination of aspirin.
p.2
Analgesics: Paracetamol and Its Toxicity
What is the mechanism of action of paracetamol?
It inhibits prostaglandin synthesis in the central nervous system.
p.47
Disease Modifying Anti-Rheumatic Drugs (DMARDs
What is a drug interaction concern with Methotrexate?
Risk of toxicity increases with NSAIDs.
p.14
Analgesics: Paracetamol and Its Toxicity
What protective role do prostaglandins have in the gastrointestinal tract?
They inhibit acid and pepsin in gastric juice and stimulate mucus production to protect the mucosa.
p.8
Inflammatory Pathway and Mediators
How does potassium (K+) relate to pain mediation?
Increased extracellular potassium can activate pain receptors and contribute to pain signaling.
p.50
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What are Disease-Modifying Anti-Rheumatic Drugs (DMARDs) used for?
They are used in combination with methotrexate to improve clinical outcomes.
p.58
Gout: Causes and Treatment
Why should colchicine be used in low doses?
Due to its toxic profile and only if NSAIDs are inactive.
p.48
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What are Disease-Modifying Anti-Rheumatic Drugs (DMARDs)?
Medications used to treat rheumatoid arthritis and other autoimmune diseases.
p.58
Gout: Causes and Treatment
What is one mechanism of action of colchicine?
It reduces the phagocytic action of leucocytes, decreasing the inflammatory response.
p.24
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
How do NSAIDs reduce fever?
By blocking prostaglandin synthesis in the hypothalamus.
p.4
Pain Mechanisms and Nociception
What role do emotions play in the experience of pain?
Emotions can significantly influence the perception of pain, often amplifying or diminishing the experience.
p.3
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
How do NSAIDs relieve pain, fever, and inflammation?
By inhibiting the production of prostaglandins.
p.67
Migraine: Pathogenesis and Treatment
Is ergotamine suitable for prophylaxis?
No, it is not suitable for prophylaxis.
p.22
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What adverse effect can NSAIDs have related to bleeding?
Haemorrhage due to antiplatelet effect.
p.9
Pain Mechanisms and Nociception
What happens in the brain during the nociceptive process?
The brain interprets the pain signals and generates the perception of pain.
p.50
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What type of DMARD is abatacept?
A T-cell activation modulator.
p.35
Corticosteroids: Mechanism and Therapeutic Uses
What happens when glucocorticoid plasma concentration exceeds certain limits?
It suppresses the secretion of ACTH.
p.3
Corticosteroids: Mechanism and Therapeutic Uses
How do corticosteroids exert their mechanism of action?
By modulating gene expression and reducing inflammation through inhibition of inflammatory mediators.
p.26
Mechanism of Action of Aspirin
What is a potential side effect of high doses of aspirin?
Facilitates excretion but can lead to side effects.
p.14
Inflammatory Pathway and Mediators
What is the role of prostaglandins in the kidneys?
They control renal blood flow and aid in salt and water extraction.
p.2
Gout: Causes and Treatment
What is a common prophylactic treatment for gout?
Allopurinol, which reduces uric acid levels.
p.8
Inflammatory Pathway and Mediators
What is the function of nerve growth factor (NGF) in pain mediation?
NGF promotes the survival and growth of neurons and is involved in the sensitization of pain pathways.
p.35
Corticosteroids: Mechanism and Therapeutic Uses
What are corticosteroids classified as?
Steroidal anti-inflammatory agents.
p.4
Pain Mechanisms and Nociception
How does the brain interpret nociceptive signals?
The brain processes nociceptive signals and can modulate the perception of pain based on context, emotions, and past experiences.
p.25
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Are all NSAIDs therapeutically equally effective?
No, their effectiveness depends on pharmacokinetic profile, side effects, and anti-inflammatory response.
p.23
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What should be exercised when prescribing Indomethacin?
Caution due to potential CNS side effects.
p.66
Migraine: Pathogenesis and Treatment
What drugs are used to improve the absorption of analgesics?
Domperidone and metoclopramide.
p.2
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What is the mechanism of action (MOA) of non-steroidal anti-inflammatory agents?
They inhibit cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis.
p.9
Pain Mechanisms and Nociception
How do pain signals travel from the periphery to the brain?
Through peripheral nerves to the spinal cord and then to the brain.
p.35
Corticosteroids: Mechanism and Therapeutic Uses
What stimulates the adrenal cortex to synthesize glucocorticoids?
Corticotrophin/adrenocorticotrophin (ACTH) hormone.
p.28
COX-2 Inhibitors: Advantages and Disadvantages
What are the therapeutic uses of COXIBs?
Rheumatoid arthritis, osteoarthritis, and postoperative pain.
p.66
Migraine: Pathogenesis and Treatment
What are triptans and why are they significant in migraine treatment?
They are the treatment of choice, having high affinity for serotonin receptors and causing vessel constriction.
p.58
Gout: Causes and Treatment
What is the recommended dosage of colchicine for acute gout?
6 mg over 4 days, given every 6 hours.
p.2
Mechanism of Action of Aspirin
What is the mechanism of action of aspirin?
Aspirin irreversibly inhibits COX-1 and COX-2 enzymes, leading to decreased production of prostaglandins.
p.48
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
Why is the use of DMARDs limited?
Due to their toxic effects.
p.25
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What should be avoided when using NSAIDs?
Combining more than one NSAID due to the risk of serious toxicity.
p.3
COX-2 Inhibitors: Advantages and Disadvantages
What are the advantages and disadvantages of selective COX-2 inhibitors (COXIBS)?
Advantages include reduced gastrointestinal side effects; disadvantages may include increased cardiovascular risks.
p.26
Mechanism of Action of Aspirin
What is the effect of high doses of aspirin?
It has anti-inflammatory activity.
p.12
Inflammatory Pathway and Mediators
What physiological processes are influenced by eicosanoids?
Pain, fever, inflammation, and bronchoconstriction.
p.2
Disease Modifying Anti-Rheumatic Drugs (DMARDs)
What are Disease Modifying Anti-Rheumatic Drugs (DMARDs)?
Medications that slow the progression of rheumatoid arthritis and other autoimmune diseases.
p.3
Corticosteroids: Mechanism and Therapeutic Uses
What are the therapeutic effects of corticosteroids?
They include anti-inflammatory effects, immunosuppression, and management of various autoimmune conditions.
p.2
Gout: Causes and Treatment
What causes gout?
The accumulation of uric acid crystals in the joints.
p.58
Gout: Causes and Treatment
What is the effectiveness of colchicine in gout treatment?
It is effective in preventing attacks and relieving gouty arthritis.
p.47
Disease Modifying Anti-Rheumatic Drugs (DMARDs
How does Ciclosporin work?
It inhibits cytokines involved in T-cell activation.
p.21
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
What are the primary actions of NSAIDs?
Anti-inflammatory, Antipyretic, Analgesic, Vasoconstriction, Platelet aggregation.
p.12
Inflammatory Pathway and Mediators
What is the effect of leukotrienes?
They are involved in bronchoconstriction and inflammation.
p.14
Inflammatory Pathway and Mediators
What are the consequences of inhibiting prostaglandins in the kidneys?
It can lead to decreased renal blood flow, sodium retention, and renal failure.
p.14
Inflammatory Pathway and Mediators
How can inhibiting prostaglandins affect pregnancy?
It can prevent threatening abortion.
p.3
Corticosteroids: Mechanism and Therapeutic Uses
What are the therapeutic uses and adverse effects of corticosteroids?
Used for conditions like asthma and arthritis; adverse effects include weight gain, osteoporosis, and increased infection risk.
p.2
Migraine: Pathogenesis and Treatment
What are the acute treatment options for migraines?
Triptans, NSAIDs, and anti-nausea medications.
p.2
Migraine: Pathogenesis and Treatment
What are prophylactic treatments for migraines?
Beta-blockers, antidepressants, and anticonvulsants.
p.8
Inflammatory Pathway and Mediators
What is a key role of histamine in pain mediation?
Histamine acts as a mediator in inflammatory responses and can contribute to pain sensation.
p.26
Mechanism of Action of Aspirin
What is a risk associated with aspirin displacing other highly protein-bound drugs?
It can lead to toxicity of such drugs, e.g., warfarin, methotrexate, glipizide.
p.3
Migraine: Pathogenesis and Treatment
What is the pathogenesis of migraine and its management?
Migraine involves neurovascular changes; management includes acute treatments like triptans and prophylactic medications.
p.2
Migraine: Pathogenesis and Treatment
What are the causes of migraines?
Genetic factors, environmental triggers, and neurovascular changes.
p.3
Corticosteroids: Mechanism and Therapeutic Uses
Why must the dose of corticosteroids be gradually reduced after long-term therapy?
To prevent adrenal insufficiency and allow the body to adjust.
