Pharmacology

Indications: iron overload

Route: SC infusion

Notes: expensive, iron excreted in urine and stool

Indications: iron overload

• Contraindications: hepatotoxicity, extreme overload
• Route: PO TDS

• Notes:
• - cardio-protective 
• - less effective than desferrioxamine?
• - iron excreted in urine

Route: PO OD

Notes: iron excreted in stool

• Class: corticosteroid (no mineralocorticoid activity)
• Dose: 5 - 7.5mg is equivalent to endogenous secretion

• MoA:
• - decrease prostaglandin synthesis
• - decrease phagocyte trafficking and proteolytic enzyme release
• - sequestration of lymphocytes in lyphoid tissue
• - induction of lymphocyte apoptosis
• - inhibition of cytokine gene expression
• - decreased antibody production

Adverse Effects: diabetes, obesity, lipid abnormalities, osteoporosis


USA give prednisone, which is metabolised to prednisolone by the liver.

metabolic: diabetes, central obesity, lipid abnormalities, osteoporosis, adrenal suppression

visible: bruising, striae, moon face, buffalo hump, hirsuitism

glaucoma, peptic ulcers, immunosuppression, cataracts,  pancreatitis, avascular necrosis, psychosis

• Notes:
• - patients taking steroids for more than 3 weeks need to be tapered off gradually 
• - patients are at risk if exposed to VZV

• Indications: severe connective tissue disease with end-organ damage (SLE, Wegener's) or Cancer

Class: anti-proliferative

Mechanism: alkylates guanine  DNA damage therefore blokcs cell division

Adverse Effects: bone marrow suppression, hair loss, sterility (M > F), haemorrhagic cystitis, immunosuppression,  infection, teratogenesis 

• Indications: transplantation, auto-immune and auto-inflammatory diseases (Crohn’s, UC)

Class: anti-proliferatives

• ˜Mechanism: liver metabolises to 6-mercaptopurine which blocks de novo purine (G & A) synthesis.
• (Suppresses Tc activation and proliferation in particular)

Adverse Effects: bone marrow suppression (esp Tc and plt), hepatotoxicity (idiosyncratic), immunosppression,  infection, teratogenesis

• 1:300 people have a Thiopurine methyltransferase
• (TPMT) polymorphism meaning they cannot metabolise azathioprine and get severe bone marrow suppression

Indications: transplantation, auto-immune disease with end-organ damage

Class: anti-proliferatives˜

Mechanism: blocks de novo nucleotide synthesis

Adverse Effects: bone marrow suppression (espTc and plt), immunosppression, infection, teratogenesis, reactivation of viruses including herpes and JC (no test available for JC virus)


JC reactivation  progressive multifocal  leukoencephalopathy (PML)

• Indications: transplantation, severe auto-immune disease

Class: calcineurin inhibitors, immunosuppressants

Mechanism: blocks intracellular signalling in Tc, therefore inhibiting IL-2 mediated proliferation and activation

Adverse effects: nephrotoxicity, neurotoxicity, hypertension, dysmorphism (gingival hypertrophy, hirsuitism)

Indications: transplantation, topical for skin disease

Class: calcineurin inhibitors, immunosuppressants

Mechanism: blocks intracellular signalling in Tc, therefore inhibiting IL-2 mediated proliferation and activation

Adverse effects: nephrotoxicity, neurotoxicity, hypertension, diabetes mellitus

Class: bisphosphonate

Mechanism: Inhibit osteoclasts to reduce bone resorption

Indications: osteoporosis, hypercalcaemia

• Class: bisphosphonate

Mechanism: Inhibit osteoclasts to reduce bone resorption

Indications: osteoporosis, hypercalcaemia

• Class: SERM

Mechanism: Agonist of oestrogen ?at bone decreases rate of bone resorption

Indications: osteoporosis

• Mechanism: Makes collecting duct less responsive to ADH therefore decrease water retention

Indications: SIADH, euvolaemic hyponatraemia

Class: V2 receptor blocker

Mechanism: Blocks ADH therefore collecting duct less permeable, more water excreted

Indications: SIADH, euvolaemic hyponatraemia

Expensive

• Indications: high potassium

Mechanism: protects the myocardium

Route: IV 10ml 10% asap

Class: Beta 2 agonist

Mechanism: Bronchodilation, movement of potassium into cells

Indications: acute asthma, hyperkalaemia

• Class: Anti inflammatory

Indications: acute gout

Class: Xathine oxidase inhibitor

Mechanism: decreases synthesis of uric acid, halts pathway at xanthine which is excreted in urine? 

Indications: after an acute episode of gout, before starting chemo for haematological malignancies (avoiding tumour lysis syndrome)

Notes: extends the mercaptopurine from azathioprine metabolism, so increases bone marrow toxicity

Oxidation byt cytochrome P450

• * arrhythmia - particularly ventricular extrasystoles, bigeminy/trigeminy, atrial tachy + complete heart block
• * anorexia, nausea and vomiting
• * xanthopsia, blurred vision, photophobia

Symptoms of under-treatment and toxicity may be similar... 

Adverse effects: ototoxicity, nephrotoxicity

monitor peak and trough levels

if given with thiazides  decreased excretion, raised plasma level, increased risk of toxicity

4 for BUGS: Griseofulvin (antifungal), Rifampicin, Rifabutin, Rifapentine

4 for BAD DAYS: Barbituates (phenobarbitone, phenobarbitol, meprobamate, primidone), Alcohol (chronic use - CYP 2E1), Smoking, St John's Wort (Hypericum perforatum)

4 for FITS: Phenytoin, Carbamazepine > Oxcarbazepine, Topiramate (induces OCP)

3 for HIV: Nevirapine (substrate and inducer), Efavirenz (substrate, inducer, inhibitor = the 'triple'), Ritonavir (substrate, inducer, inhibitor = the 'triple')

and a handful for SUGAR: Sulfonylureas (tolbutamide, glipizide, gliclazide, glibenclamide)

• Sodium valproate
• Isoniazid (especially in slow acetylators)
• Cimetidine (not ranitidine)
• Ketoconazole (> itraconazole > fluconazole)

• Ciprofloxacin (esp. w. Warfarin and theophylline),
• Omperazole (not lansoprazole)
• Phenylbutazone

• Metronidazole
• Allopurinol
• Disulfiram

• Fluconazole
• Alcohol (binge drinking)
• Chloramphenicol
• Erythromycin, clarithromycin, telithromycin (not Azithromycin)

• Verapamil
• Sulfinpyrazone

• Synerdic (Quinuprustin-Dalfopristin)
• Amiodarone
• Diltiazem

• Grapefruit juice
• Protease inhibitors (Ritonavir is "triple")

Anti-depressants: MAOI, duoloxetine, fluoxetine, fluvoxamine, sertraline, paroxetine (not citalopram)