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NUR2125: Pharmaco: Drugs for pain management - Coggle Diagram

- - - - MoA: inhibit uric acid synthesis (competitive inhibitor of xanthine oxidase)
      - NOT during acute attacks
      - Side effect: Severe cutaneous adverse reaction (SCAR)
        Risk factor: HLA-B 58:01 genotype (Han Chinese, Thai, Korean), renal impaired creatine clearance
        
        Change to febuxostat
        
        Other side effects: skin rash, nausea & vomiting, diarrhoea, fever
        
        Chocolate, caffeine, tea: broken down by xanthine oxidase --> Drug-drug interaction
      - Allopurinol first line
    - - MoA: increase uric acid excretion
      - NOT during acute attacks
      - Side effects
        
        Nausea & vomiting, painful urination, lower back pain, allergic reactions, rash
        
        Kidney stones
      - Precaution: take plenty of fluid to minimze renal stone formation
        Keep urine pH >6.0
        Start 2-3 weeks after acute attack
    - - PHAGOCYTES
        Monocytes effective
        Neutrophils not effective
        -rupture when attacking crystals and release more neutrophils
        -release lysosomal enzymes which damage tissue + inflammation
        Rapidly drop uric acid in blood = causes crystals moving out of joint because of concentration gradient
      - For acute gouty arthritis
      - MoA: Reduces leucocyte migration into joints + anti-cancer effect (24-36 hours) Delayed before it works
        binds to tubulin, preventing proliferation of cells
        Inhibits luekotriene B4 and prostaglandin production
      - Side effects: nausea, vomiting, diarrhoea, abdominal pain
    - - Corticosteroids = started early as anti-inflammatory (faster onset than other drugs) Bridging function
  - - - Add on to make it more potent, by themselves not that strong
        
        Do not combine with biological DMARD (too much additive effects)
      - MoA: Janus kinase pathway inhibitor
        
        Blocks cytokine production
      - Side effects
        
        Anaemia
        
        Hyperlipidemia
        
        Depletion of immune cells --> Immunosuppression --> opportunistic infections
    - - TNFalpha blockers Infliximab
        
        MoA: TNF signalling blocker by binding to TNFalpha
        
        Side effects
        
        Respiratory infection
        
        Skin infection
        
        Leukopenia
        
        Aplastic anaemia
      - IL-1R Anakinra
        
        MoA: binds to IL-1 receptor and blocks signalling
        
        Side effects
        
        Infections
        
        Injection site reactions
      - IL-6 Tocilizumab
        
        MoA: humanized monoclonal antibody directed at IL-6 receptor (blocks it, preventing IL-6 from binding to it)
        
        Side effects
        
        Infections
        
        Skin eruptions
        
        Fever
        
        Neutropenia
        
        Do not get metabolised by CYP450 enzyme but changes expression of CYP450
      - Most specific but not most potent. BUT most specific = less adverse effects
    - - (First line) alone or in combination
      - May switch to Hydroxycholoroquine (best tolerated)
      - MoA: increase adenosine levels via ATIC inhibition
        (Inhibits dihydrofolate reductase and thymidylate synthetase)
        
        Activation of adenosine A2a receptor
        
        (Anti-proliferative effect on T cell and inhibition of macrophage functions)
        
        Decrease in pro-inflammatory cytokines
      - Side effects
        
        Nausea & vomiting
        
        Hairloss
        
        To keep at minimum Folic acid/folinic acid 12-24 hrs after methotrexate
        
        Folinic acid more effective (downstream) but more expensive
        
        Folate acid cheaper, give in large amounts to overcome (upstream)
      - Other examples
        
        Leflunomide
        
        Extremely long half life in medicine
        
        Sulfasalazine
        
        Hydroxycholoroquine
  - - - Evidence of efficacy controversial
      - Injected directly into the joint --> replacing natural component of synovial fluid
        
        Provide shock absorption, lubrication of cartilage
        
        Induces biosynthesis of HA and extracellular matrix
- - - - Inhibit PGI2 (prostacyclin)
        
        Block vasodilation
      - Inhbiit PGE2 (classical prostaglandins)
        
        Block vascular permeability
        
        Inhibit pain
        
        Reduce sensitisation of nociceptive fibres to stimulation by other inflammatory mediators
        
        Take note of 'analgelsic ceiling'
        Maximal turning down of volume = no more analgelsia
        
        Typical NSAIDs also have additional analgelsic actions in central nervous system
      - Antipyretic
        Inhibit cyclooxygenase in brain, preventing production of PGE2 which will cause the body's 'thermostat' to reset in the hypothalamus
      - Antiplatelet
        IRREVERSIBLE inhibitor of cyclooxygenase
        
        Platelet
        
        Cannot make more cyclooygenase (need new platelet)
        
        Takes 1-2 wweeks
        
        COX produces TXA2 thromboxane (platelet aggregration)
        
        Endothelial cells
        
        COX produces PGI2 prostacyclin (inhibits platelet aggregration)
        
        Can make more COX
        
        Takes a few hours
    - - Mild
        Tinnitus, central hyperventilation, metabolic acidosis
      - High
        Renal and respiratory failure
      - Low
        Gastric intolerance, bleeding, hypersensitivity
      - Contraindication for aspirin
        
        Children
        May cause Reye's syndrome
        Swelling of brain (encephalitis) and liver
        
        Increased risk if aspirin taken by children with viral infections
  - - - Sodium retention
        Water retention
        Peripheral oedema
        Hypertension
    - - Suppression of renin and aldosterone secretion
        Hyperkalaemia
        Acute renal failure
    - - Dyspepsia, nausea, vomiting
      - Ulcer formation and potential haemorrhage risk in chronic users
    - - Cause Acute Kidney injury
        
        Risk factors
        
        Pre existing glomerular disease/renal insufficiency
        
        Volume depletion -> lowers afferent glomerular arteriolar pressure
        
        Increasing age -> narrowing of renal arterioles
        
        Use of ACE inhibitors/ARBs -> prevent efferent arteriole vasoconstriction which is also important in maintenance of GFR
    - - Due to overaccumulation of leukotrienes
  - - - COX-1 constitutive:
        always on for 'housekeeping' functions
        
        Clinical effects
        
        Anti-platelet
        
        Adverse effects
        
        Gi disturbance
        
        Renal
        
        Bleeding
      - COX-2 inducible:
        stimulated by inflammatory responses
        
        Clinical effects
        
        Safer for GI tract
        
        Anti-inflammatory + analgesic
        Block the production of PGI2 and PGE2 for more inflammation + pain
        
        block sensitisation of nociceptive factors by blocking production of prostlaglandins
        
        Adverse effects
        
        COX-2 inhibitors may impair wound healing and hence may exacerbate ulcers
        
        COX-2 dependent for wound healing
        E.g. think of post-surgery analgesia
        Non-union repair of bone
      - COX-2 constitutive
        also present in
        CNS, kidneys, female reproductive system, synovium
        
        Adverse effects
        
        COX-2 inhibitors: contraindicated in third trimester of pregnancy
        
        Premature closure of ductus arteriosus (fetal lung bypass) in late pregnancy
        
        Effect on ovulation, including delayed follicular rupture
        
        Renal toxicity due to constitutive expression of both COX-1 and COX-2 in kidney
        
        Clinical effects
      - COX-1:
        Produces TXA2, PGI2, PGE2
        COX-2:
        Produces PGI2, PGE2
        
        Overflow to COX-1 since COX-2 blocked
        Relative increase in TXA2 favours platelet aggregation increasing risk of thrombosis
        
        Renal effects causing hypertension + risk of prothrombotic effects = risk of heart attack and stroke
        
        Greater caution using NSAIDs in elderly + history of cerebrovascular or cardiovascular disease
  - - - CNS selective COX inhibition
    - - Contraindicated for liver damage
    - - Antipyretic
      - Analgesic
    - - Studies show renal/reproductive (?)
- - - - Dietary restriction of potassium
        Potassium binder: sodium polystyrene sulfonate, sodium zirconium cyclosilicate
        
        Oedema, hypokalaemia, constipation, diarrhoea, fecal impaction, nausea, vomiting, low calcium
        
        Abdominal discomfort, bloating
    - - Hyperphosphatemia
        
        Dietary restriction of phosphate
        
        Phosphate binders: calcium carbonate, calcium acetate, sevelamer, lanthanum
        
        Oedema, hypophosphatemia, constipation, abdominal discomfort, bloating
      - Hyperparathyroidism: calcitriol, cinacalet
        
        BUN and creatinine increase, cardiac arrhythmias
    - - erythropoiesis stimulating agents: Epoetin alfa
        
        Hypertension, seizures, heart failure MI, stroke
    - - Loop diuretic: furosemide
        
        Significant hypokalaemia, blood dyscrasias, dehydration, ototoxicity, electrolytee imbalance, circulatory collapse
      - Dietary restriction of sodium: loop diuretics in acute, thiazide diuretics in mild conditions
    - - Corrected by reversing hyperphosphatemia
      - Additional calcium supplements
    - - Sodium bicarbonate/sodium citrate
  - - - DNA/RNA
        (usually broad spectrum)
        
        Fluroquinolones
        
        Examples
        
        2nd gen: Ciprofloxacin, Norfloxacin, Ofloxacin
        3rd gen: Levofloxacin
        
        MoA: DNA synthesis inhibitor
        (Stops twisting of DNA, does not allow it to break apart --> cannot replicate)
        
        Side effects
        
        Hypersensitivity/allergic reactions
        
        Central nervous systems
        
        Headache, agitation, insomniiia, dizziness
        
        Gastrointestinal
        
        Nausea, vomiting, diarrhoea, dyspepsia
        
        Contraindication in pregnancy and elderly
        
        Elderly: Tendoniitis and tendon rupture (black box warning)
        
        Articular damage
        
        Arthopathy: articular cartilage damage, arthralgias, joint swelling
        
        Black box warning
        
        Cardiac
        
        QT prolongation
        
        Alteration in blood glucose
        
        **1. UTI
        
        Gastroenteritis
        
        Osteomyelitiis
        
        Antrhax
        
        2nd line TB drugs: Levo, Moxi**
        
        Nitrofurantoin
        (very specific drug: gram-ve/+ve)
        
        MoA: DNA synthesis inhibitor
        (Reduced drug structure, it becomes anti-oxidant, causing oxidative stress on bacterial DNA)
        
        Side effects
        
        Hypersensitivity./allergic reactions
        
        (Ocassional and reversible) rash
        pneumonitis
        chills
        fever
        
        Contraindication in pregnancy and elderly
        
        Elderly: cause interstiitiial fibrosis with chronic use, especially in elderly
        
        Gastrointestinal
        
        Nausea, vomiting, diarrhoea, dyspepsiia
        
        Blood dyscrasias
        
        Neutropenia, hemolysis in infants and G6PD deficiient subjects
        
        Colours urine brown
        
        Acute UTI
        
        Prophylaxis of lower UTI
        
        Keep urine pH below 5.5
      - Folic acid synthesisinhibitors
        
        Trimethoprim
        
        MoA: inhibit dihydrofolate reductase
        
        Cotrimoxazole (sulfonamide + trimethopriim)
        
        Synergistic activity to inhibit folate acid
        
        Sulphonamides
        
        MoA: inhibit dihydropteroate synthase
        
        Side effects
        
        Hypersensitivity/allergic reactions
        
        due to products of sulpha
        
        Phototoxicity: A condition in which the skin or eyes become very sensitive to sunlight or other forms of light
        
        Gastrointestinal
        
        Nausea, vomiting, diarrhoea
        
        Hyperkalemia (with higher doses may have renal impairment)
        
        Renal
        
        False increase in creatinine levels, nephrotoxic, crystalluria
        
        Bone marrow suppression
        
        Megaloblastiic anemia (Give folinic acid supplementation in special cases- pregnant, malnourished)
        
        May cause hemolytic reactiions in G6PD patients
      - Cell wall synthesis inhibitors
        
        Examples
        
        Beta lactam
        Target both gram +ve and -ve
        
        Penicilins (penams)
        
        Cephalosporins
        
        Cephamycins
        
        Monobactams
        
        Carbapenems
        
        Carbacephems
        
        Side effects of beta-lactams
        
        Generally well tolerated
        
        Hypersensitivity/allergic reactions
        
        From mminor rash, to Stevens-Johnsons syndrome/toxic epidermal necrolysis
        
        Life threatening anaphylaxis
        
        Non-beta lactams: Fosfomycin (vancomycin)
        
        MoA: stops transglycosylation --> stops bacterial cell wall synthesis
        (stops the horizontal building/foundation of bacterial cell wall)
        
        Side effects
        
        Thrombophlebitis, fever, chills
        
        Red neck, or Red man syndrome
        
        Antibiotic choice for pregnant
        
        MoA: cell wall synthesis inhibitors
      - Protein synthesis inhibitors
        
        MoA: inhibit protein synthesis
        
        Examples
        
        Site of action: 30S subunit
        Aminoglycosides
      - Take note of minimum inhibitory concentration as some are concentration dependent antibiotics
        
        Even after dropping below MIC, post antibiotic effect present
        
        Concentration dependent antibiotics: Fluroquinolones and aminoglycosides
        (+carbapenems = too strong!!)
        NEPHROTOXIC
        
        PATIENT MUST HAVE GOOD KIDNEY FUNCTION
        
        Aminoglycosides examples: gentamicin, amikacin, tobramycin, neomycin, and streptomycin
      - For ESBLs: Carbapenems
  - - - Particularly nephrotoxic
        Antibiotics: aminoglycosides: bacteria protein synthesis
        Systemic Antifungal: Amphotericin B
        Cancer drugs, immunosuppressant drugs, contrast dyes
    - - Dysrhythmias
      - Hemorrhage
      - Heart failure
      - Dehydration
- - - - MoA: blocks receptor, inhibiting involuntary contractions --> delayed voiding
    - - MoA: activates receptor, increases relaxation --> increased storage capacity + inter-void interval
      - Side effects:
        Urinary retention
        Headache
        Hypertension
        Diarrhoea
        Constipation
        Upper respiratory tract infection
  - - - MoA: relax the muscles
    - - MoA: reduce the size of the prostrate
- - - - Grp A strep, get into body through opening in skin (like injury or surgical wound)
    - - Antibiotics
        
        Cephalexin (PO)
        
        MoA: inhibit bacterial cell wall synthesis
        
        Side effects
        
        (Well tolerated); Rash and diarrhoea most common
        
        1-4%: allergic reaction: severe hypersensitivity
        
        Thrombophlebitis (inflammation at infection site)
        
        Class: Beta-lactam anbitiotic
        1st generation cephalosporin
        
        Clindamycin (PO/IV)
        
        MoA: protein synthesis inhibition
        
        Side effects
        
        Anaphylaxis
        
        Superinfection
        
        Nausea, diarrhoea, vomiting, headache, constipation
        
        Myopathy
        
        Pseudomembraneous colitis
        
        Class: Lincosamide protein synthesis inhibitor (specifically 50S)
        
        When less toxic alternatives not effective + Effective against MRSA
    - - May develop fever and chills
      - Most common on feet and legs (if not, anywhere else)
        
        If infection on armm or leg, elevating that limb can help decrease swelling and speed up recovery
      - Skin may look pitted (peel of orange) or blisters may appear
  - - - Prolonged pressure on skin and unable to change position due to medical condition
    - - Antibiotics used to treat infection
        
        Vancomycin (PO/IV)
        
        MoA: bacterial cell wall synthesis inhibitor
        
        Adverse effects: nausea, vomiting, anaphylaxis, superinfections, nephrotoxicity, otoxicity, Red Man's syndrome
        
        Class: non-beta lactam, glycopeptide
        
        Ciprofloxacin (PO)
        
        MoA: DNA synthesis inhibitor
        
        Adverse effects: tendon rupture, black box warning, photosentivity, pseudomembraneous colitis, seizure
        
        Class: fluroquinolones
        
        Piperacillin-tazobactam (IV)
        
        MoA: inhibit bacterial cell wall
        
        Adverse effect: rash, diarrhoea, hypersensitivity
        
        Class: beta lactam + oxapenam
        
        Clindamycin (PO/IV)
        
        MoA: protein synthesis inhibition
        
        Adverse effects: anaphylaxis, superinfection, myopathy, membraneous colitis
        nausea, diarrhoea, vomiting, headache, constipation
        
        Class: Lincosamide protein synthesis inhibitor (50S subunit of bacterial ribosome)
    - - Commmonly in bony areas such as heels, ankles, hips and tailbone
      - Medical conditions that limit their ability to change position
      - Most heal, but some never heal
  - - - Heat
      - Allergens
      - Infections
      - Immune system diisorders
      - Medications
    - - Antihistamine
        
        MoA: competitive antagonism of histamine binding to cellular receptors --> block histamine from binding to its receptor, reducing histamine receptor activity
        
        Suppress histamine-induced wheal response (swelling) and flare response (vasodilation)
        
        1st gen: potentially impairing and sedating
        
        Side effects
        
        Increased appetite and weiight gain
        
        Anticholinergic: dry mouth, urinary retention, sinus tachycardia
        
        Dizziness and postural hypotension
        
        Increased QT interval + increased ventricular arrhythmias
        
        Alertness cognition, learning and memory affected
        
        2nd gen: less sedating and impairing
        
        Examples: loratadine and fexofenadine
      - Corticosteroid (topical)
        
        MoA: reducing production of certain chemicals --> lower inflammation (higher doses may lower immune system activity)
        
        Side effects
        
        Long term use: immunosuppression
        
        (resemble cortisol, hormone naturally produced --> major player in a lot biological processes such as metabolism, immune response and stress)
    - - Chronic rash, skin become thickened, itchy and dry
        On brown/black skin = small bumps around hair follicles that look like goose bumps
      - Where skiin flexes, tend to flare up periodically
- - - - Adverse effects: Nausea, vomiting, heartburt, epigastric pain, anorexia
        Pseudomembrane colitis, acute renal failure, hepatotoxicity, hyperuricaemia, blood dyscrasias
        
        Skin eruptions, fever, GIT disturbances are most common side effects
        
        Hepatitis (occasional) hyperbilirubinaemia
        
        Hepatotoxicity
        
        Immunologically mediated reactions: thrombocytopenia, flu-like syndrome
      - MoA: Inhibit RNA synthesis
      - Rifambutyin: effective but expensive. Use for patient intolerant to rifampycin (also good for HIV, hepatotoxic)
      - May cause orange color urine/sweat
    - - Adverse effects: nauseau vomiting, epigastric pian
        anaphylaxis, peripheral neuropathy, optic neuritis, hepatotoxicity, blood dyscrasias
        
        Allergic skin reactions
        
        Hepatotoxicity
        
        Neurotoxic effects
        
        Can cause pellagra
        
        Haemolysis in G6PD patients
      - MoA: inhibit mycolic acid
    - - Adverse effects: anaphylaxis, hepatotoxicity, fatal haemoptysis, haemolytic anaemia
        
        hepatotoxic
        
        GIT - nausea vomiting
        
        rashes, photosensitivity
        
        arthralgia
        
        hyperuricaemia: interferes with tubular secretion of uric acid, mostly asymptomatic. can cause acute gouty arthritis
      - MoA: inhibit bacteria cell membrane
      - Pyrazinamide most hepatotoxic
    - - Adverse effectsL anaphylaxis, optic, neuritis
        
        optic neuritis with visual abnormality
        
        allergic rash
        
        asymptomatic hyperuricaemia, occasional gouty arthritis
      - MoA: inhibit cell wall synthesis
      - Need t o check visual acuity to assess toxicity. Patient unable to perform eye test = substituted with streptomycin (aminoglycosides)
        
        watch for visual changes
    - - Muscuskeletal TB treatment: 9months
        
        (Also for those unable to tolerate pyrazinamide) R+I+E for 2 months, then R+I for 7 months
      - If hepatotoxicity develops, stop everything
      - alternative regimen (start with rifampicin and isoniazid then pyrazinamide) should be used for those with ALT elevation more than three times the upper limit of normal (ULN) in the presence of hepatitis symptoms and/or jaundice, or five times the ULN in the absence of symptoms.
        
        ALT > 3x upper limit of normal ULN with symptoms OR ALT >5x ULN without symptoms
  - - - Broad spectrum for +ve and -ve gram
      - Rash and diarrhoea. And severe hypersensitivity (Steven Johnsons syndrome)
      - MoA: transpeptidation inhibition
    - - Reserved for serious infection/MRSA
      - Nausea, vomiting, anaphylaxis, Red-neck/Red-man syndrome
        
        Vancomycin + amiinoglycosides = inccreased nephrotoxicity and ototoxicity
      - MoA: transglycosylation inhibiton