Medications Flashcards
Platinum compounds e.g. cisplatin, carboplatin
Activated within cell by displacement of chloride, leaving positively charged molecules that react with DNA
Inhibits replication/transcription/division, leading to apoptosis
Chemotherapeutic agent, e.g. neuroblastoma
Adverse effects: myelosuppression (cumulative and dose related, ~3 weeks after dose and recover within 6 weeks), nephrotoxic, ototoxic
Dinutuximab
Monoclonal antibody against disialoganglioside GD2 (ubiquitous expression on neuroblastoma cells)
Topotecan
Topoisomerase I inhibitor, inhibits nucleic acid synthesis
Indications: Cancers
A/E: myelosuppression (1 week and recover in 3)
Doxorubicin/danorubicin
AKA Hydroxydaunorubicin
Inhibits DNA/RNA synthesis by intercalation of DNA base pairs, prevents repair by inhibiting topisomerase II
Indications: Cancers
A/E: Infusion reactions, myelosuppression, cardiac toxicity, extravasation, secondary malignancy (AML)
AE: N/V, cardiomyopathy, red urine, tissue necrosis on extravasation, myelosuppression, conjunctivitis, radiation dermatitis, arrhythmia
Dexrazoxane reduces risk of cardiotoxicity
Etoposide
AKA VP-16
Inhibits topoisomerase II, therefore DNA strand breaks and inhibits cell division
I: Cancers
A/E: Myelosuppression (1-2 weeks, recover by 3), hypersensitivity, secondary malignancy (AML)
Cyclophosphamide
Immunosuppressant/chemotherapeutic due to cytotoxic effect of lymphocytes
Interferes with all replication by forming cross-linkages between DNA - alkylates guanine -> inhibits DNA synthesis
I: Cancers, autoimmune
A/E: Myelosuppression (1-2 weeks, 3-4 recovery), haemorrhagic cystitis (chemotherapy man), pulmonary fibrosis, SIADH, infertility
Eculizumab
Anti-C5 antibodiy
Inhibits complement activation
I: Atypical haemolytic uraemic syndrome, paroxysmal nocturnal haemoglobinuria
Diazoxide
Opens K-ATP channels (in beta-cells of pancreas this prevents depolarisation of the cell, thereby preventing insulin secretion
Used for some causes of hypoglycaemia
Octreotide
Somatostatin analogue (mimics somatostatin)
Inhibits release of growth hormone, insulin, others
Reduces splanchnic blood flow
I: Acromegaly, ?hyperinsulinaemic hypoglycaemia…
Sumatriptan
MOA: Constrict cranial vessels by acting selectively at 5HT1B/1D receptors; also thought to inhibit the abnormal activation of trigeminal nociceptors.
I: Migraine, cluster headache
S/E: Tightness in jaw, chest, fingers d/t vascular constriction, subsequent feeling of grogginess and fatigue from central serotonin effect, transient burning sensation in the nose or throat, taste disturbance (nasal spray); dyspnoea, dystonia (rare)
Prochlorperazine
MOA: Dopamine antagonist (D2)
I: Nausea, vomiting, vertigo, migraine
A/E: Common: constipation, dry mouth, drowsiness, akathisia, parkinsonism, blurred vision, EPSE (especially in children), hypotension, hyperprolactinaemia; Rare: prolonged QT interval, tardive dyskinesia
Amitriptyline
MOA: TCAs inhibit reuptake of noradrenaline and serotonin into presynaptic terminals. Although unrelated to the therapeutic effects of the TCAs, they also block cholinergic, histaminergic, alpha1-adrenergic and serotonergic receptors.
S/E: Drowsiness, anticholinergic effects, prolong QT
Indications Major depression Nocturnal enuresis, seek specialist advice Accepted Adjuvant in pain management Migraine prophylaxis
Sodium channel blockers
Class 1 anti-arrhythmic (NAB-KC)
Block sodium channel, inhibit depolarisation
Quinidine, lignocaine, flecainide
Beta blockers (anti-arrhythmic)
Class 2 (NAB-KC) Act at SA/AV node to inhibit sympathetic activity
Potassium channel blockers
Class3 antiarrhythmic (NAB-KC) Prolonged repolarisation Amiodarone, sotalol (also beta blocker action)
Calcium channel blockers
Class 4 anti-arrhythmic
Block L-type Ca channels, inhibit AV node conduction
Digoxin
Cardiac glycoside
Mechanism
Stimulate vagal activity, inhibit Na/K/ATPase
AMH: Slows heart rate and reduces AV nodal conduction by an increase in vagal tone and a reduction in sympathetic activity. Increases the force of myocardial contraction by increasing the release and availability of stored intracellular calcium.
I: AF, atrial flutter, heart failure
b. Side effects:
i. Risk of arrhythmias
ii. Not to be given in WPW
AMH: Narrow therapeutic window
Digoxin usually has an effect on the ECG and may result in prolonged PR interval, ST depression or T wave inversion (these changes do not necessarily indicate digoxin toxicity or myocardial ischaemia).
In children, arrhythmias (including sinus bradycardia) are the earliest and most frequent indicators that digoxin dosage is too high.
Atropine
a. Anticholinergic (a group of substances that blocks the action of the neurotransmitter called acetylcholine at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous system by selectively blocking the binding of ACh to its receptor in nerve cells.)
b. Inhibits vagal stimulation
Indications Premedication for anaesthetic procedures Prevention of muscarinic effects of neostigmine when used to reverse neuromuscular blockade Bradycardia with haemodynamic compromise Organophosphate poisoning
Adenosine
a. Naturally occurring nucleotide (not adenine)
Mechanism (AMH)
Depresses sinus node activity and slows conduction through the atrioventricular node; also produces peripheral and coronary vasodilation.
Adenosine has a rapid onset and short duration of action.
c. Useful to terminate SVT
d. Very short half life (10 seconds)
e. Side effects: Headache, Dyspnoea, Bronchospasm, Can trigger atrial fibrillation
ACE inhibitor
- Action
a. Inhibit production of angiotensin II reduce afterload +/- have some effect on venodilation , reduction of preload
b. Decrease afterload by reducing peripheral vascular resistance
c. Increase myocardial contractility
d. Remodeling benefits likely - Side effects
a. Hypotension
b. Hyperkalemia
c. Rash (often disappears spontaneously)
d. Chronic cough - Contraindications
a. Stenotic lesions of LV outflow tract ( may compromise coronary perfusion)
AMH:
Mechanism:
ACE inhibitors block conversion of angiotensin I to angiotensin II and also inhibit the breakdown of bradykinin. They reduce the effects of angiotensin II-induced vasoconstriction, sodium retention and aldosterone release. They also reduce the effect of angiotensin II on sympathetic nervous activity and growth factors.
Indications
Hypertension
Chronic heart failure with reduced ejection fraction
Diabetic nephropathy
Prevention of progressive renal failure in patients with persistent proteinuria (>1 g daily)
Post MI
Cyclosporin
Calcineurin inhibitor. AMH: Ciclosporin and tacrolimus form complexes with cytoplasmic immunophilins (cyclophilin and FKBP‑12 respectively), which block the action of calcineurin in activated T cells. This prevents production of interleukin‑2 and other cytokines, which normally stimulate T cell proliferation and differentiation.
Indications Prevention of transplant rejection Nephrotic syndrome Severe rheumatoid arthritis unresponsive to other antirheumatics Atopic dermatitis, severe refractory Psoriasis, severe refractory
AE (Common): gingival hyperplasia, hirsuitism
Azathioprine
Purine antimetabolite. Azathioprine is metabolised, via mercaptopurine, to thioguanine nucleotides which interfere with purine synthesis, impairing lymphocyte proliferation, cellular immunity and antibody responses.
Indications Prevention of organ transplant rejection Used for its immunosuppressant effects in a number of immune and inflammatory diseases including: Severe rheumatoid arthritis Inflammatory bowel disease Autoimmune hepatitis Systemic lupus erythematosus Pemphigus
AE: dose dependent myelosuppression, pancreatitis
Thiopurine methyltransferase (TPMT) activity—where possible, determine TPMT phenotype (enzyme activity) or genotype before starting treatment. 1 in 300 people have low or no detectable TPMT activity and are at risk of severe myelosuppression; avoid use in these people if possible or reduce the dose (to one-tenth of normal or less). As TPMT testing does not identify all patients at risk of severe myelosuppression, regular blood count monitoring is still required.
Interaction with allopurinol or febuxostat
Both allopurinol and febuxostat reduce azathioprine metabolism, increasing the risk of severe bone marrow toxicity
Mycophenolate mofetil (MMF)
Depletes guanosine nucleotides.
Mycophenolate mofetil and mycophenolate sodium are both converted to mycophenolic acid, which selectively suppresses lymphocyte proliferation and antibody formation by inhibiting inosine monophosphate dehydrogenase. Depletion of guanosine nucleotides (required for de novo purine synthesis in lymphocytes) results.
Acts on the immune system at a similar level to azathioprine but by a distinct and more lymphocyte-selective mode of action.
i. Antimetabolite: affects denovo purine synthesis – noncompetitive inhibitor of de novo guanine nucleotide synthesis
ii. Selectively inhibits lymphocyte proliferation (with less myelosuppression than AZA)
iii. More potent than azathioprine
iv. Side effects
1. Opportunistic infections more common
2. Main side effects: GI – N+V+D
Prostaglandin E1 / Alprostadil
Alprostadil is a synthetic PG used to relax the ductus arteriosus in the early post-natal life. Preserves ductal patency if administered before anatomical closure occurs. Over time ductus arteriosus rapidly loses its responsiveness – MOST effective within 96 hours of birth
Actions
a. Maintain patency of ductus arteriosus
b. Vasodilation of all arterioles
c. Inhibition of platelet aggregation
d. Stimulation of intestinal and uterine smooth muscle
Metabolism
a. Rapidly cleared by metabolism in the lungs and excreted by kidneys – therefore given as continuous infusion
b. Maximal effect in 30 minutes
Dose
a. 5-100 nanongrams/kg/min
Side effects
a. Apnoea usually occurs in neonates <2kg within the first hour of administration
b. Fever
c. Irritability
d. Cutaneous flushing – secondary to vasodilation
e. Bradycardia or tachycardia
f. Hypotension
g. Seizures
h. Decreased platelet aggregation, thrombocytopaenia
i. Edema
j. May require ventilation for transport + caffeine
k. With-holding can kill patient
Palivizumab
a. Palivizumab = humanized monoclonal antibody against RSV
i. Provides passive immunity against RSV
ii. Decreases hospitalisation for RSV related illness
iii. Dose = 15 mg/kg IM any time from birth; dose 2 given 3 weeks after dose 1 and then 4 weekly for duration of RSV season
iv. Indications
- Preterm infants with or without chronic lung disease of prematurity or congenital heart disease
- Infants with haemodynamically significant congenital heart disease
- Children with anatomic pulmonary abnormalities or neuromuscular disorder
- Immunocompromised children assessed on an individual basis
v. Adverse effects
- Common: fever, rash, rhinitis, wheeze, cough, diarrhoea, injection site reaction
- Infrequent: anaemia, elevated liver enzymes
- Rare: hypersensitivity
Salbutamol
Mechanism of action
● Simulates beta 2 receptors 🡪 increased adenlylate cyclase 🡪 increase cAMP levels 🡪 diminishes Ca2+ available for contraction 🡪 bronchodilation
● B2 selective at lower doses
● In high doses, loses its selectivity 🡪 B1 agonist to heart 🡪 tachycardia
AE ● Tremor ● Palpitations ● Headache ● Hyperglycaemia (high dose) ● Tachycardia (high dose) ● Hyperactivity in children ● Lactic acidosis – with high doses
Ipratropium bromide
Mechanism
● Relax smooth muscles by inhibiting cholinergic bronchomotor tone
● Block muscarinic action of acetylcholine ●
AE
Headache, nausea, taste disturbance
● Anti-cholinergic AE = blurred vision, dizziness, urinary retention, constipation, palpitations
Magnesium sulphate
Mechanism
● Relaxation of bronchial smooth muscles
AE
● Related to hypermagnesaemia
Aminophylline
Mechanism
● Not entirely understood
● Possible effects include bronchial smooth muscle relaxation, anti-inflammatory effects, increase in diaphragm contractility and CNS stimulation
AE
● Nausea, vomiting, diarrhoea, GERD, headache, insomnia, irritability, anxiety, tremor plapitations
● Seizures
● Arrythmias (continue cardiac monitoring)
● Tachycardia
Montelukast
Mechanism
● Inhibits Cysteinyl leukotriene receptor
● Antagonises smooth muscle contraction and inflammation caused by leukotrienes
AE
● Headache, abdominal pain, diarrhoea
● Neuropsychiatric effects = nightmares, hallucinations, mood or behavior changes
Inhaled corticosteroid
Mechanism
● Reduce airway inflammation and bronchial hyper-reactivity
● Decreases activation of eosinophils, production of cytokines, generation of prostaglandins/leukotrienes, histamine release, production of IgE, and production of mast cells.
AE
● Local = dysphonia, oral candidiasis
● Systemic = adrenal suppression, loss of bone density, cataract, skin thinning and bruising, poor growth (contentious)
Omalizumab
Mechanism
● Humanised monoclonal Ab directed against IgE
● Reduces the immune system’s response to allergen exposure
AE ● Injection site reactions ● Rash, bleeding, headache, MSK pain ● Mild thrombocytopenia ● Anaphylaxis ● Angioedema, urticaria, serum sickness, Churg-Strauss
Loop diuretics
- Act in the thick ascending LOH
- Sodium entry primarily mediated by the Na-K-2Cl carrier in the luminal membrane
- Loop diuretics compete for the chloride site – therefore reducing net reabsorption
• Key AE o Hypokalaemia (due to tubal Na) o Hypercalciuria + hypocalcaemia o Alkalosis (due to tubal Cl) o Hypotension/hypovolemia o Hyponatremia o Hypochloraemia o Hypomagnesaemia
Thiazide diuretics
- Act in the distal tubule
- Sodium entry is mediated by Na-Cl co-transporter
- Thiazides inhibit NaCl reabsorption in these segments by competing for chloride site on the transporter
• Key AE
o Hypokalaemia (Na-K antiporter Na absorb distally)
o Hyponatremia
o Hypochloraemic alkalosis (Cl- lost, Na-H+ antiporter Na absorb distally)
o Hypercalcaemia + hypocalciuria
o Hyperuricaemia
Potassium sparing diuretics
• Act in the collecting duct
• Sodium entry mediated by aldosterone-sensitive sodium channels
o Reabsorption of cationic sodium without an anion creates a lumen-negative electrical gradient that favours the secretion of potassium (through selective potassium channels) and hydrogen ions
o Inhibition of sodium reabsorption results in hyperkalaemia + metabolic acidosis due to the reduction in potassium and hydrogen ion excretion
• Two classes
o Amiloride
Act on principle cells (ENaC)
Inhibits Na+ reabsorption – therefore inhibiting K+ secretion
o Aldosterone inhibitors = spironolactone
Act on intercalated cells
Aldosterone normally stimulates Na/K/ATPase pump on basolateral side of cortical collecting tubule AND increases sodium permeability on luminal side of the membrane (activates ENAC)
Blocks BOTH these actions - reducing resorption of Na+ and excretion of K+
• Key AE
o Hyperkalaemia
Calcineurin inhibitors
Ciclosporin, tacrolimus
Mode of action
Ciclosporin and tacrolimus form complexes with cytoplasmic immunophilins (cyclophilin and FKBP‑12 respectively), which block the action of calcineurin in activated T cells. This prevents production of interleukin‑2 and other cytokines, which normally stimulate T cell proliferation and differentiation.
Indications
Prevention and treatment of transplant rejection
Prevention and treatment of graft-versus-host disease in stem cell transplants
Induction or maintenance of remission in immune and inflammatory diseases
Adverse effects
Commonly dose-related. Major dose-limiting toxicity is acute nephrotoxicity.
Common (>1%)
nephrotoxicity (below), hypertension, hypercholesterolaemia, neurotoxicity (below), raised bilirubin, raised aminotransferases, hypomagnesaemia, hyperkalaemia, opportunistic infection, diarrhoea, hyperglycaemia, diabetes
Nephrotoxicity
Acute nephrotoxicity is dose-related and reversible with dose reduction or withdrawal. Chronic nephrotoxicity occurs with long-term use, is unrelated to dosage, potentially irreversible and involves permanent renal structural changes (eg interstitial fibrosis).
Neurotoxicity
Tremor and headache are most frequent; other effects include paraesthesia, confusion, seizures, coma, psychosis. Reversible posterior leucoencephalopathy syndrome has also been reported.
Basiliximab
Mode of action
Chimeric monoclonal antibody against interleukin‑2 receptors expressed on activated human T lymphocytes; blocks binding of interleukin‑2, inhibiting T lymphocyte proliferation.
Indications
Prevention of acute kidney transplant rejection
Adverse effects
Studies indicate a possible increase in surgical wound complications but otherwise no increase in adverse effects, incidence of opportunistic infection or lymphoproliferative disease, compared with baseline immunosuppression.
Rare (<0.1%) hypersensitivity reactions (below), cytokine release syndrome
Rituximab
Mode of action
Chimeric monoclonal antibody that binds to CD20 on B lymphocytes.
In cancer, it starts an immune response that lyses normal and malignant B cells. In chronic inflammatory diseases (eg rheumatoid arthritis), it suppresses immune response and inflammation by reducing T cell activation and resulting cytokine production.
Adverse effects
Generally the frequency and severity of adverse effects are greater with rituximab for antineoplastic indications than when used for other conditions.
Common (>1%)
infusion-related reactions (below), SC injection site reactions (eg erythema, pain, swelling), infections, neutropenia (may be delayed onset), lymphopenia (see below), decreased immunoglobulin levels, arrhythmias, musculoskeletal pain
Infusion-related reactions
Most common with first infusion and may be indistinguishable from hypersensitivity reactions, cytokine release syndrome or tumour lysis syndrome. Reactions usually occur 30–120 minutes after starting infusion and include fever, chills and/or rigors, nausea, vomiting, urticaria, itch, headache, bronchospasm, dyspnoea, angioedema, rhinitis, hypotension.
Stop the infusion if symptoms occur and treat symptomatically. If appropriate, restart the infusion at half the previous rate when symptoms resolve.
Lymphopenia
Rituximab induces a rapid loss of B lymphocytes. In patients with cancer, recovery usually begins about 6 months after stopping treatment; full recovery often occurs within 12 months but may take longer. In rheumatoid arthritis, time to recovery is variable (>2 years after last dose in about 8% of patients).
Sirolimus
Also known as rapamycin.
Mode of action
(Mode of action from mTOR inhibitors)
Bind to the same intracellular protein (FKBP‑12) as tacrolimus; however, the protein-drug complex blocks the activity of mTOR kinase, preventing cell cycle progression and cytokine-induced T and B cell proliferation.
Indications
Prevention of kidney transplant rejection
Alkylating agents (oncology)
Disrupt double helix of DNA by adding alkyl groups DNA breakage and cell death
Most active in resting phase of cell cycle
Can cause infertility and secondary cancers
Examples: cyclophosphamide, ifosfamide
Ifosfamide
Alkylating agent. Alkylates guanine -> inhibits DNA synthesis.
I: NHL, Wilms, soft tissue sarcoma
AE: N/V, myelosuppression, haemorrhagic cystitis (less common), pulmonary fibrosis, SIADH, Renal tubular acidosis, Ifosfamide encephalitis, infertility
Mesna
Mode of action
Contains free sulfhydryl (thiol) groups that interact with urotoxic metabolites, including acrolein, of ifosfamide and cyclophosphamide and reduce the incidence of haemorrhagic cystitis and haematuria. Enhances urinary excretion of cysteine, which may increase uroprotective effect.
Indications
Reduction and prevention of haemorrhagic cystitis and haematuria caused by cyclophosphamide or ifosfamide
