Pharmacology for chiros

GORD, bleeding tendency, driving machinery.

diet, CRF/ARF(SLE, DM),NSAID use potassium supplements, diuretics eg: spironolactone. ACE-i.

an unpleasant sensory or emotional experience associated with actual or potential tissue damage, or described in terms of such damage.

• -Acute pain: usually has a trigger, lasts for a short duration approx up to 3/52 (variable). Inflammation is the causative process.
• -Chronic pain: present after injury has healed, usually assoc with an emotional aspect (depression, anxiety, hopelessness) and physical compensatory effects (hypertonicity, LOE, LOA).
• -Neuropathic pain: complex, usually seen with diseases that damage neurological systems eg MS, shingles, phantom limb etc. Can be intense shooting, burning, P&N.

higher cortical areas; at a minimum the thalamic areas.

This occurs at the microscopic level where damage occurs, starting a cascade of events

The pathways that lead finally to processing of pain signals at the cortical level. Invloves the spinothalamic tracts, somato-sensory area (S1) and its projections to the amygdala, hippocampal, frontal areas of the brain which result in the experimental component of pain and suffering. Chemical changes at each juncture

Redness, Swelling, Heat, Pain and loss of function.

• Phospholipids realease Arachidonic acid (Aa) via Phospholipase C and A2
• Increase in intracellular Aa
• Free Aa the undergoes metabolism by 2 pathways - COX & LOX

Cyclo-oxygenase

COX - Prostaglandins (PGE₂, PGI_{2 (prostacyclin)}), thromboxanes(TXA₂)

Lipo-oxygenase

Two - COX1 and COX2

Present in normal cell homeostasis (kidney, gastric mucosa, airways and platlets)

Is supposed to be more pro-inflammatory and selective COX2 inhibitors like Celebrex and Vioxx (withdrawn) were supposed to have less COX1 effects. Vioxx was PRO-thrombotic and gastric SE were not much different in either.

End up with formation of LTB₄ & LTE₄. High concentrations in mast cells, marcophages, neuts etc. Seem to be involved in asthma.

GORD

The use of NSAIDs as they decrease GFR and in the elderly this is already decreased.

• Arteriolar smooth muscle vasodilation
• GIT smooth muscle contraction-coliky pain
• Inhibition of platelets
• Induction of labour, Dysmenorrhoea
• Pyrexia
• Maintains Patent ductus arteriosus in utero
• Increases GFR / Gastric mucosal secretion

Promotes thrombosis, greatly increases platelet adhesion

Histamine, substance P, serotonin, bradykinin and prostaglandins

A-delta and C-fibres

Stimulation of A-beta fibres resulting in inhibition at the subs gelatinosa

Serotonin, prostaglandins, thromboxane and leucotrienes

Increased sensitivity of normal pain fibres

Allodynia

Neuroplasticity

Threshold for firing decreases. NMDA and AMPA receptors are added to cell membranes at subs gelatinosa. Glutamate (excitatory) is released.

Convergance allows for other areas to be regarded as painful

Synthesis of new proteins which inhances synaptic transmission

• ^{Identify the type - acute, chronic, neuropathic}
• Treat accordingly, early and individually
• Watch for side effects of both OTC and prescribed meds

Morphine, Pethidine, Oxynorm, Oxycodone, Fentanyl

Fludrocortisone, Hydrocortisone, prednisolone, betamethasone, triamcinolone, dexamethasone, methylprednisone

Tramadol, codeine

Panadeine, pandadeine forte, mersyndol

Voltaren, Ponstan, aspirin, nurofen, indocid, colchicine

Paracetamol (panadol)

Eczema, hay fever. Prelevance of 1/4

Yes reversibility is a key component.

Common triggers: EIA, Infective, Stress, Cold etc.

• Beta-agonists: Salbutamol/Ventolin/terbutaline, salmeterol - Activates beta 2 receptors on smooth muscles - bronchodilation.
• Steroids: Prednisolone , Inhaled Steroids: beclomethasone (becotide), fluticasone (flixotide)
• Other therapies for Asthma include: Montelukast – leukotriene receptor antagonist. Useful in EIA but still hardly used.
• Ipratropium. Anticholinergic. Mainly used as nebs in COPD.

Characterised on spirometry or forced expiration time >7sec.

Rarely genetic links. Usually with a history of smoking

Emphysema is the classic example

Inhibits COX pathway but lacks the anti-inflammatory effects of NSAIDs

Regualarly, max dose of 4 grams daily

• Toxic: 8 grams
• Fatal: >15 grams

Yes

• CLF: Hepatitis B/C, Haemochromatosis, biliary cirrhosis,alcoholics.
• CRF: Diabetics, Elderly

• Inhibits COX pathway - decreases PG synthesis
• Strongly inhibits TXA₂ in platelets and increases clotting time after 1/52 dosing. Irreversible till platelets regenerate.

• Thinning blood in cardic and stroke patients.
• Good for viral illnesses

8 Days

Neurological disturbance (ataxia, lethargy, nystagmus, fits), diarrhoea +/- vomiting, hypoglycaemia, elevated LFT’s.

Decreases synthesis of TXA₂ anti-inflammatory effects and mild anti-platelet effect

2.7 grams/day (14 tablets!)

Increased cholesterol and Vit A toxicity

Bad in gall bladder removal, flatulence, stincky breath, farts, reflux, bleeding

Float oil on 30ml of juice. Drink quickly avoid lips, then follow with another 30ml of juice. Take before meals (with no liquid during meal)

Acute inflammation, injury, dysmenorrhoea, headaches

3rd trimester pregnant women!!!

Mild blood thinning effect and GORD can be severe if long term

Treatment of various inflammatory and allergic conditions such as gout, RA, OA, COPD, Asthma, SLE, Eczema, ALL and premature fetal lung development (surfactant)

• Transported into cytoplasm and bound to a protein complex which enters nucleus.
• Causes gene up-regulation and down-regulation for others. Depends on tissue type.

NF-kB, Phospholipase_A2, COX pathway and stops the inflammatory process on a number of levels

• Suppresses TSH/FSH.
• Increases GH.
• Increases insulin (d/t BSL).
• Net effect weight gain centrally.

Increases BSL's (gluconeogenesis) by breaking fat, protein and carbs down.

• Connective tissue (eg skin), decrease muscle mass, osteoporosis.
• Reduction in growth in kids despite GH.

• Decreased PG, leukotiene.
• Short term increase in neuts but impotent.
• Decreased healing.

• Euphoria, sometimes depression or psychotic symptoms.
• Buffalo hump, Hypertension, Thinning of skin, Cataracts, Moon Face, Increased abdominal fat, Easy bruising, Poor wound healing, thin arms and legs due to muscle wasting, osteoporosis, hyperglycaemia, increased appetite and obesity

Hypotension, vomiting, nausea, fatigue, dizziness, muscle weakness, anxiety, diarrhoea

Euphoria, dysphoria (10%), restlessness, skin itch, constipation (no tolerance), sedation, resp. depression, cough suppression, Miosis (no tolerance), N/V, urinary retention.

Usually occurs after a significant insult to the nervous system.

Chronic

Parethesias, radiculopathy, dull aching

• Tricyclics - Amitriptline. Given at low doses. Can be quite effective.
• SSRI's - Prozac, lexapro. Not as bad with side effects
• Opiates - Fentanyl patch, oxynorm for break through. Oxycontin for long acting effect.
• AED's - Sodium valproate, gabapentin. Stabilises nerve membranes. SE -dizzy, drowsy, oedema

• Anti HTN - mechanism unknown
• TCA's - Reinforces serotonin dysfunction theory
• Pizotifen - 5-HT Antagonist
• AEDs
• Botulinum toxin - BOTOX to neck muscles

• NSAIDS
• Triptan
• Ergots
• Opiates

Tapping the facial nerve - twitching

• GABA agonist
• Benzodiazepines
• Valium
• Side effects - risk of falls, memory affected, drowsy

Short

GABA agonist - works by hyperpolarising the cell membranes. Casues much less sedation than benzos

• Interferes with excitation-contraction coupling of muscle fibres by inhibiting the release of Ca from the sarcoplasmic reticulum.
• Causes generalised muscle stiffness and sedation

BOTOX injections - inhibits muscle completely

• AS
• RS
• EA
• OA
• PA

• RA
• SLE
• Antiphospholipid syndrome
• Scleroderma
• Polymyositis
• Sjogrens syndrome

• Fibromyalgia
• Polymyalgia Rheumatica

• Gout
• CPPD

• Inflammation and auto-immunity
• Failure of T-supressor cells - production of auto-antibodies by B-lymphocytes
• Antibodies attach to antigens - cell death or immune complex deposits

Chronic pain, loss of function, systemic decline/impairment, finacial burden, social burden, genetic repercussions, SE of meds

• Chiropractic! and the like
• Analgesics
• Fish oil
• Steroids

Reduce synovial inflammation and prevent joint damage - lots of SE!

eg. Methotrexate, hydroxychloroquine, leflunomide, azathioprine, cyclophosphamide, sulphasalazine

• Folic acid analogue - antagonises it and reduces available amount. Folic acid needed for DNA synthesis - impairs cell division
• Mechanism - increases adenosine - decreases inflammation cell activation and cytokine release

Alcohol abuse, hepatitis, pregnancy

Nausea, mouth ulcers, pancytopenia, fibrosis and cirrhosis of the liver

Blocks synthesis of pyridoxines and inhibits activated lymphocytes

Liver dysfunction, diarrhoea, alopecia, rash

In pregnant women - teratogenic

Inhibits T-cells and phagocytes

SE: Itch, eczema, gold deposits, aplastic anaemia

• Supresses inflammatory response
• Used previously to treat malaria
• Nausea, rash, dizziness

Immune suppressants. Used in post-transplant patients or with sever rheumatologic disease

Renal toxicity is common

• Tumour Necrosis Factor is released in inflammation. TNF inhibitors like etanercept and infliximab are monoclonal antibodies which bind and inactivate it
• SE: Hypersensitivity and infections
• Cost: $847 per infusion

• Clinical monitoring: Pain, function, synovitis
• Lab monitoring: CRP, ESR, antibody titre eg. rheumatic factor, ANA titre
• SE

NSAIDS esp - colchicine - inhibits mirotubule formation and decreases phagocytosis. Prednisolone can me used

Prevention is dependant on cause

• Increasing bone turn over
• Reabsorbing renal and GIT
• Ca at the expense of Phos
• Increases Vit D activation to 1,25 dihydroxy-vitamin D

Prions, Viruses, Bacteria, Fungi, Parasites

A prion . Human variant of mad cow disease aka Bovine Spongiform encephalopathy which causes neuro-degenerative disease in the brain and spinal cord. No known cure

• Consists of nucleic acid (RNA or DNA) surrounded by a protective protein coat (capsid). It attaches itself to the cell wall and inserts its nucleic acid which incorporates into the host DNA to form more virions.
• Rhinovirus, to the exotic viruses like Herpes Simplex or HIV

• 1) Absorption and penetration of host cell
• 2) Synthesis of early non structural proteins. Eg. nucleic acid polymerases.
• 3) Synthesis of RNA or DNA.
• 4) Synthesis of late structural proteins.
• 5) Assembly and maturation with release of virions.

• Retrovirus with long incubation period. RNA is converted to DNA by reverse transcriptase. High genetic variability due to high replication rate with new variants of protein structure- which allow evasion from host immune system.
• Infects CD4 T-helper cells- loss of cell-mediated immunity & subsequent rise in opportunistic infections

• NARTI’s – nucleoside analogue reverse transcriptase inhibitors, Protease inhibitors
• NNRTI’s- non nucleoside reverse transcriptase inhibitors

• Gram stain: either gram + or gram –
• Then they are mainly cocci or rods. Some are strange eg. spirochetes

• Staphylo-coccus or Strepto-coccus
• Staphylococcus Aureus: causes cellulitis, toxic shock syndrome…golden staph?
• Staphylococcus Epidermidis: commensal on skin but can cause endocarditis in susceptible individuals.
• Streptococcus Pyogenes: strep sore throat, pneumonia or necrotising fascitis.

• 1)Clostridium eg. Clostridium tetani, Clostridium perfringens – gas gangarene.
• 2) Bacillus Anthracis - Anthrax
• 3) Cornybacterium Diptheriae

Neisseria Meningitidis, Neisseria Gonorrhea

E coli, Salmonella Typhi, Shigella, Legionella, Helicobacter Pylori, Pseudomonas, Vibrio cholera

Bactera. good for strep's, most staphs have resistance. Not bad for certain G- like E-coli. Beta lactamase breaks Abx down- resistance

Bacteria. eg keflex. Usually given when allergic to penicillin's. 10% cross over reactivity. Better G- cover

Bacteria. usually combined with penicillin to give augmentin which overcomes beta-lactamase.

Bacteria. Erythromycin (rulide) - covers atypical resp infx eg Legionella, mycoplasma.

Bacteria. Affects folic acid synthesis.

• Wrong diagnosis: could be a viral infection.
• Antibiotic resistance- more common esp in community as opposed to classically nosocomial
• Delayed Initiation
• Inability to get to target site eg: abscess Co-morbidities: DM, steroid use, HIV, oedema, poor oxygenation or vascular supply etc

• Candida Albicans: causes vaginal thrush, oral thrush.
• Tinea: affects different areas.itchy. easily managed
• Pneumocystis Jiroveci: found mostly in HIV patients. Can cause fatal pneumonia. Difficult to treat.

• The –azoles: eg clotrimazole,, ketoconazole. Blocks synthesis of fungal biolipids
• Nystatin: binds to ergosterol and disturbs membrane permeability.
• Amphotericin-B: mother of all anti-fungals… binds to ergosterol and increases permeability of membranes.

Malaria, Worms (helminths), scabies (mites), lice (pediculosis)

• A number of life cycle stages. Parasites reside in RBC’s and cause haemolysis.
• Biggest issue is increasing drug resistance. Recommended treatment includes prophylaxis and preventative measures

• Chloroquine: Now not used due to drug resistance.
• Mefloquine: very effective. Needs to be trialed 1 month before leaving for potential SE - neuro-psychiatric disturbance inc epilepsy.
• Primaquine: active against late stages. Good at terminating attacks.
• Proguanil: folic acid antagonist. Good for primary stage. Combined with
• Atovaquone: to give good prophylaxis against falciparum

• Renal: Decreases Ca and Phos excretion
• Bone: Increases Ca and Phos resorption
• Serum: Increases Ca, decreases Phos

• GIT: Increases absorption of Ca and Phos
• Renal: Decreases Ca and Phos excretion
• Bone:Increases resorption of Ca and Phos
• Serum: Increases Ca and Phos

• From parafollicular cells in thyroid
• Inhibits osteoclasts - blocks bone resorption
• Useful in Paget's, hypercalaemia and osteoporosis

• Blocks collagen synthesis
• Increases PTH stimulation
• Increases renal Ca excretion
• Can be used for hypercalaemia

Vaginal dryness, itchy. prolapse. Hot flushes and sweats, decreased concentration, memory loss, fatigue and mood liability

• Hypercalaemia: can be a medical emergency - cancer, hyperparathyroidism and Vit D overdose
• Hypocalaemia: Tetany, paresthesias, muscle cramps, convulsions - causes - Hypoparathyroidism, vit D deficiency, renal failure and malabsorption
• Vit D deficiency: Cultural predispositions, lack in diet

• Ca supplements
• Vit D supplements
• Bisphosphonates
• Strontium Ranelate
• E2 supplements
• SERMs

• Troponin is th primary marker
• Blood test: FBE, UEC, CMP, TFT's, glucose, lipids
• Triple screen: History, Troponin, ECG

Plaque rupture and thrombosis leading to acute myocardinal infarction

Demand ischaemia due to stenosis of coronary arteries. No death of tissue.

• 1) stabilisation of plaque
• 2) restoring blood flow to critical organs
• 3) Decrease myocardial demand
• 4) Prevention of complications
• 5) Decrease long term complications and recurrence
• 6) Minimise systemic illness esp respiratory

• Slow the heart
• Decrease load on the heart
• Decrease force of pump/contractility
• Fix oxygenation issues eg anaemia
• Fix plumbing - stent vs bypass
• Minimise risk factors

• Beta blockers: slow the heart down. Anti-arrythmia. Decreases contractility. Also has a role in preventing pathological re-modelling of the heart
• Calcium Channel blockers: Same mechanism as above but less chronotropicity
• Nitrates: acute treatment
• Nicorandil: opens K+ channels
• ACE-i: decreases BP

Asthma, postural hypotension, cold limbs, erectile dysfunction, lethargy

SOA, oedema

headaches, light headed, oedema

• Gastro-oesophageal jx
• Oesophageal-diaphragm jx
• natural innate tone (LES)

mucus, acid production (ZES), blood supply, smoking, regenerative capability, dietary factors eg caffeine, chocolates, alcohol, NSAIDS, onions, high fat, stomach motility

Helicobacter Pylori infection- 80-90% of ulcers

• Diet modification: reduce caffeine, fatty foods
• Weight Loss
• Decrease Smoking
• Avoid supine or lifting after meals
• Drug Rationalisation: decrease NSAIDs, anticholinergics, calcium channel blockers ( nifedipine, verapamil), Bisphosphonates, doxycycline, progesterone (pregnancy/ pill)
• Decrease alcohol intake
• H. Pylori eradication

• 1st line- Antacids: Mylanta, Gaviscon
• 2nd line- Proton Pump Inhibitors (PPI’s) eg somac, nexium.
• Excellent response. Good protection. Minimal SE: headache, diarrhoea, nausea, constipation.
• 3rd line- H2 receptor antagonist eg: zantac, ranitidine SE- liver toxicity, blood dyscrasias,skin rashes etc Motility agents eg domperidone increase rate of stomach emptying. Surgical therapy- vagotomy, Nissen fundoplication

Jaundice, regurgitation…bad signs

Cholesterol is a sterol derived mainly from organic diet. precursor of steroid hormones. Transported as a lipo-protein eg: HDL, LDL, VLDL, chylomicrons

the good stuff. High density of protein to lipid. Found in fish oil. Helps to remove cholesterol from periphery back to liver for excretion via bile acids

The bad stuff. High concentration of cholesterol. Transported away from liver to cells which uptake via endocytosis through a LDL-receptor.

It is the enzyme involved in a rate controlling step in formation of cholesterol. Mild anti-inflammatory action.

• Treat reversible causes of dyslidaemia: hypothyroidism, nephrotic syndrome, cholestasis, NIDDM, obesity, alcohol use, oestrogen use.
• Diet Modification: decrease saturated fat, increase unsaturated fat, increase fibre, decrease salt, increase plant sterols
• Risk factor modification eg: OSA , HTN, Smoking, Obesity, NIDDM.

• 1st line- statins- inhibit HMG-CoA reductase. SE- myalgias, myositis,
• 2nd line- Ezetimibe- decreases absorption of chol from intestines. SE: diarrhoea, myalgias.
• Bile-acid resins- cholestyramine binds bile salts in the GIT-> decreasing available acids which trick liver to produce more bile acids->utilising cholesterol in the process. SE- nausea, GORD.
• Nicotinic acid- SE: flushing, itch, hypotension, myositis, hepatic toxicity
• Fibrates- Fenofibrate and Gemfibrozil enhance triglyceride clearance. SE: increase risk of gall stones. Phototoxic in some cases. Myositis

• 275 new cases / day.
• Estimated 1.7 million patients but only ½ diagnosed
• In 20 years, 3.3 million will have DM
• Cost to the health care system is $10.3 billion
• Australia’s fastest growing chronic disease
• 60% are preventable with good lifestyle choices
• 10-15% of DM are Type 1 in nature.

• Absolute lack of insulin either through physical destruction of pancreas or autoimmune destruction of beta cells
• Usually occurs < 30 y.o., Symptoms include thirst, polyuria, weight loss.

• Treatment requires lifelong insulin replacement and monitoring for complications
• Combination of long acting and short acting insulin to give basal levels eg: Novomix 30/70
• Note increased requirements in times of stress, illness etc

• Genetic predispositions. RF include: fam hx, HTN, > 55 y.o. , overweight, Aboriginal / Torres Strait, Pacific Islander, Chinese, Indian, PCOS & gestational DM.
• Characterised by insulin RESISTANCE or relative decreased insulin production

• Treatment is both conservative initially and with medications if poor glycaemic control
• Insulin may be needed as a last resort

• Weight loss via Diet and Exercise: decrease fat = decrease IL-1, IL-6, FFA’s , adiponectin, leptin -> decreased insulin resistance.
• Correction of other risk factors: HTN, Smoking, Renal failure, Foot care, Eye care, Prevention of PVD.
• Drug Therapy - Glycaemic Control: BSL’s, HbA1c

• 1st line. Insulin sensitizers - Biguanide (Metformin) and Glitazones (Thiazolidinediones/ TZD)
• 2nd line. Insulin Secretogogues-Sulfonylurea's & Glitinides
• 3rd line. Acarbose- inhibits alpha-glucosidase (breaks down complex carb’s).
• 30% of NIDDM’s will go onto requiring insulin. Usually after 10-15 years of oral therapy

• - Hypercoagulability: composition of blood, Anti-thrombin III deficiency, polycythaemia, thrombocytosis, leukaemia, Protein C deficiency, Factor V Leiden mutation.
• - Quality of vessel wall: endothelial cell wall injury – plaques, stents,
• - Nature of Blood Flow: Turbulence, stagnation

• Aspirin: inhibits COX pathway which decreases TXA2. prevents platelet binding. Platelet regeneration in 10/7.
• Adenosine Diphosphate Receptor inhibitors: Clopidogrel (Plavix). The “dog” of surgeons, irreversible for 7 days.
• Glycoprotein IIB/IIIA inhibitors: Abciximab, Tirofiban
• Adenosine Re-uptake inhibitors: Dipyrimidole (Persantin)

• Heparin: binds to Anti thrombin (IIa) and increases potency by x 1000.
• Derivatives like enoxaparin (clexane) inhibit anti-Factor Xa activity.
• SE: osteoporosis, thrombocytopaenia, haemorrhage,

• Commonly used for Atrial Fibrillation and DVT prevention.
• Impairs utilisation of Vit K and stops formation of F2,7,9,10 (TV channels)
• Needs to be monitored with INR INR easily affected by other drugs eg amiodarone, panadol etc
• Signs of overdose: Haematemesis/malena, haemoptysis, spont nose bleeds, gum bleeds, bruising

Elderly, pregnancy, retinal disease, recent surgery or stroke

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