Cancer Flashcards
NSAIDs
E.g. ibuprofen, naproxen
Uses: PRN mild-moderate pain as an alternative or in addition to paracetamol, regular treatment for pain related to inflammation (RA, severe OA, gout)
MOA: inhibit COX enzymes, inhibiting PG synthesis from arachidonic acid. COX-1 is the constitutive form; COX-2 is the inducible form (expressed in response to inflammation). COX-1 stimulates PG synthesis required to maintain gastric mucosa integrity, maintains renal perfusion (alters afferent arterioles) and inhibits thrombus formation expressed in vascular endothelium. Therapeutic effects of NSAIDs are predominantly due to COX-2 inhibition; adverse effects of NSAIDs are due to COX-1 inhibition.
Adverse effects: GI toxicity, renal impairment, increased risk of CV events (MI, stroke). Ibuprofen has the lowest risk of GI toxicity; naproxen and low-dose ibuprofen have the lowest risk of CV events; COX-2 inhibitors are assoc. with increased risk of CV events; all NSAIDs cause renal impairment. Can also cause hypersensitivity reactions and fluid retention.
Cautions: avoid in severe renal impairment, HF, liver failure and known NSAID hypersensitivity.
Interactions: many drugs increase the risk of NSAID-toxicity e.g. peptic ulceration (low dose aspirin, corticosteroids), GI bleeding (anticoagulants, SSRIs, venlafaxine), renal impairment (ACEi, diuretics).
Paracetamol
Uses: first-line analgesic for acute or chronic pain (first step on WHO ladder), antipyretic (reduces fever)
MOA: weak inhibitor of COX. In the brain, inhibition of COX increases the pain threshold and reduces PGE2 conc. in the thermoregulatory region of the hypothalamus (controlling fever).
Adverse effects: in OD it causes liver failure (the elimination pathway becomes saturated with its toxic metabolite, causing hepatic necrosis)
Cautions: dose reduction in those at risk of hepatic toxicity due to increased NAPQI production (chronic excessive alcohol use) or reduced glutathione (malnutrition, low body weight, severe hepatic impairment)
Interactions: CYP inducers (phenytoin, carbamazepine) increase rate of NAPQI production and risk of liver toxicity after OD
Weak opioids
E.g. codeine phosphate, dihydromorphine
Uses: mild-moderate pain (e.g. post-op) when paracetamol is insufficient (step 2 of the WHO ladder)
MOA: metabolised in the liver to produce small amounts of morphine (codeine) or dihydromorphine. These metabolites are agonists of opioid u receptors.
Adverse effects: nausea, constipation, dizziness and drowsiness. Neurological and respiratory depression in OD. Never give IV as this can cause anaphylactic-type reaction.
Cautions: significant respiratory disease, dose reduction in renal or hepatic impairment and the elderly.
Interactions: do not use with other sedating drugs (antipsychotics, Benzos, TCAs)
Strong opioids
E.g. Morphine sulfate, oxycodone
Uses: rapid relief in acute severe pain (post-op, acute MI), relief of chronic pain (when paracetamol/NSAIDs/weak-moderate opioids are insufficient; rung 3 of WHO ladder), relief of breathlessness at EoL, relief of breathlessness and anxiety in acute pulmonary oedema (with oxygen, furosemide and nitrates)
MOA: activation of opioid u receptors in the CNS which reduces neuronal excitability and pain transmission. Blunt the response to hypoxia and hypercapnoea in the medulla, reducing respiratory drive and breathlessness. By relieving breathlessness and assoc. anxiety, they reduce sympathetic NS activity.
Adverse effects: respiratory depression (by reducing respiratory drive), euphoria and detachment, neurological depression (higher doses), N&V (activation of the CTZ), pupillary restriction (stimulation of Edinger-Westphal nucleus), constipation (activation of u receptors increases SM tone and reduces motility), itching/urticaria/vasodilation/sweating, tolerance and dependence, withdrawal reaction
Cautions: dose reduction in hepatic failure, renal impairment and the elderly. Do not give in respiratory failure, avoid in biliary colic (worsens pain).
Interactions: do not use with other sedating drugs (antipsychotics, Benzos, TCAs)
Amitriptyline
Uses: second-line for moderate-severe depression, neuropathic pain
MOA: inhibit neuronal reuptake of 5-HT and NA from the synaptic cleft, increasing their availability for neurotransmission. Also block muscarinic, histamine-1, alpha-1 and -2 adrenergic, and D2 receptors (accounting for side effects)
Adverse effects: antimuscarinic effects (dry mouth, constipation, urinary retention, blurred vision), sedation and hypotension (blockade of H1 and a1 receptors), arrhythmias and ECG changes (QT and QRS prolongation), convulsions, hallucinations, mania, breast changes and sexual dysfunction (DA blockade). Cause severe hypotension, arrhythmias, convulsions, coma and respiratory depression in OD. Sudden withdrawal results in GI upset, neurological and influenza-like symptoms.
Cautions: those at risk of adverse effects (elderly, epilepsy, CVD), those with BPH/glaucoma/constipation (may worsen symptoms due to antimuscarinic effects)
Interactions: do not give with MAOi (both drugs have same MOA resulting in HTN and hyperthermia or serotonin syndrome). May augment antimuscarinic, sedative or hypotensive effects of other drugs.
Duloxetine
Uses: major depressive disorder, GAD, diabetic neuropathy, moderate-severe stress urinary incontinence
MOA: inhibits the reuptake of NA and 5-HT
Adverse effects: anxiety, decreased appetite, constipation, diarrhoea, dizziness, drowsiness, dry mouth, fall, fatigue, flushing, GI discomfort, headache, muscle complaints, nausea, pain, palpitations, paraesthesia, sexual dysfunction, skin reaction
Cautions: bleeding disorder, cardiac disease, elderly, hx of mania, hx of seizures, HTN, raised intra-ocular pressure, susceptibility to angle-closure glaucoma. Avoid in hepatic impairment and if GFR <30.
Interactions: with drugs that increase risk of bleeding,
Gabapentin
Uses: add-on for treatment of focal epilepsy, first-line for neuropathic pain
MOA: bind pre-synaptic voltage-sensitive Ca2+ channels, inhibiting release of excitatory NTMs, reducing neuronal excitability.
Adverse effects: drowsiness, dizziness, ataxia
Cautions: dose reduction in renal impairment (renal elimination)
Interactions: sedative effects are enhanced with other sedating drugs (Benzos)
Carbamazepine
Uses: generalised tonic-clonic seizures and focal seizures, trigeminal neuralgia
MOA: inhibits neuronal Na+ channels, stabilising resting membrane potentials and reducing neuronal excitability
Adverse effects: GI upset, neurological effects (dizziness, ataxia), hypersensitivity (mild maculopapular skin rash), anti epileptic hypersensitivity syndrome (severe skin reactions, fever, lymphadenopathy within 2 months of starting), oedema, hyponatraemia
Cautions: assoc. with NTDs/cardia and urinary tract abnormalities in utero. Do not use if prior anti-epileptic hypersensitivity syndrome. Caution in hepatic, renal or cardiac disease (increased risk of toxicity).
Interactions: it is a cytochrome P450 inducer reducing the conc. and efficacy of drugs metabolised by this enzyme (warfarin, oestrogen, progestogens). Conc. and adverse effects of the drug is increased by CYP inhibitors (macrolide). Efficacy reduced by drugs which lower the seizure threshold (antipsychotics, tramadol).
Capsaicin
Uses: localised neuropathic pain, OA symptomatic relief, peripheral neuropathic pain, diabetic neuropathy
Adverse effects: sneezing, watering eye
Cautions: avoid contact with broken or inflamed skin, eyes/face/scalp.
H1 receptor antagonists
E.g. cyclizine, cinnarizine, promethazine
Uses: prophylaxis and treatment of N&V (motion sickness, vertigo)
MOA: block H1 and ACh receptors in the vomiting centre and its communication with the vestibular system.
Adverse effects: drowsiness, dry mouth and throat, transient tachycardia (IV injection)
Cautions: avoid in patients at risk hepatic encephalopathy and those susceptible to anticholinergic side effects (BPH)
Interactions: sedation increased when combined with other sedative drugs (Benzos, opioids), enhanced anticholinergic effects with ipratropium or tiotropium
Hyoscine
Uses: vomiting, reducing copious respiratory secretions, IBS
MOA: antimuscarinic; competitive inhibitor of ACh. Increase HR and conduction, reduce SM tone and peristaltic contraction, reduce secretions.
Adverse effects: tachycardia, dry mouth, constipation, urinary retention in BPH (reduce detrusor muscle activity), blurred vision, drowsiness, confusion (elderly)
Cautions: patients susceptible to angle-closure glaucoma, patients at risk of arrhythmias
Interactions: adverse effects enhanced with other antimuscarinic drugs (TCAs)
D-2 receptor antagonist
E.g. metoclopramide, prochlorperazine, domperidone
Uses: prophylaxis and treatment of N&V, particularly in context of reduced gut motility
MOA: block D2 receptors which are the main receptors in the CTZ (the area responsible for sensing emetogenic substances in the blood) and has a prokinetic effect in the gut (promoting gastric emptying)
Adverse effects: diarrhoea, extrapyramidal syndromes (metoclopramide), increased risk of QT prolongation and arrhythmias (domperidone)
Cautions: metoclopramide should be prescribed <5 days (reduce risk of EPSEs) and avoided in neonates/children/young adults. Domperidone is CI in patients with cardiac conduction abnormalities and severe hepatic impariment. Both are CI in intestinal obstruction and perforation. Metoclopramide should be avoided in PD (crosses the BBB).
Interactions: increased risk of EPSEs when prescribed with antipsychotics, do not combine with DA agents for PD, avoid in drugs that prolong QT interval (antipsychotics, quinine, SSRIs) or those which inhibit CYP450 inhibitors (amiodarone, diltiazem, macrolide, fluconazole, protease inhibitors)
Ondansetron
Uses: prophylaxis and treatment of N&V, particularly in context of GA and chemotherapy
MOA: 5-HT3 receptor antagonist which are in high density in the CTZ (the area responsible for sensing emetogenic substances in the blood) and this is the key NTM released by the gut in response to emetogenic stimuli. Acting on 5-HT3 receptors stimulates the vagus nerve which activates the vomiting centre via the solitary tract nucleus.
Adverse effects: constipation, headache, diarrhoea
Cautions: small risk of QT interval prolongation (avoid if patient already has this)
Interactions: drugs that prolong QT interval (antipsychotics, quinine, SSRIs)
Aprepitant
Uses: adjunct treatment to prevent N&V assoc. with chemotherapy
MOA: NK1 antagonist (GPCR in the central and peripheral NS)
Adverse effects: decreased appetite, asthenia, constipation, GI discomfort, headache, hiccups
Cautions: CI in acute porphyria. Avoid in pregnancy, breast feeding, hepatic impairment.
Nabilone
Uses: N&V due to chemotherapy unresponsive to conventional antiemetics
MOA: synthetic cannabinoid, acts as an agonist at endogenous cannabinoid receptors.
Adverse effects: drowsiness and dizziness
Cautions: mental state effects 48-72 hours after stopping. Caution in elderly, heart disease, hx of psych disorder, HTN. Avoid in pregnancy, breast feeding, severe hepatic impairment.
