t100 summaries

Question 1

Aminoglycosides

Class:
Examples:
Indications:
Mode of action:
Spectrum of action:
Adverse effects:
Cautions
Contraindications:
Interactions:
Administration
Monitoring:
Prescribing:
Specific scenarios:

Answer 1

Examples: gentamicin, neomycin
Spectrum of action: gram negative aerobes, staphylococcus and mycobacteria
Indications: severe sepsis, pyelonephritis, biliary and intra-abdominal sepsis, endocarditis
Mode of action: inhibit protein synthesis 30S
Adverse effects: nephrotoxicity (worse if CP w ciclosporin, platinum chemo, cephalosporins and vancomycin) ototoxicity (worse if CP w diuretics or vancomycin)
Cautions: renal impairment, obesity, CF - always calculate dose properly
Contraindications: by inj: myasthenia gravis. In ear: patent grommet, perforated tympanic membrane
Interactions: ciclosporin, platinum chemo, cephalosporins, vancomycin, diuretics
Administration: IV, otic, opthalmic
Monitoring: measure plasma drug concentration at 18-24 hours, next dose only given if fallen to safe level eg <1 mg/ml.
Prescribing: combine with penicillin and or metronidazole when organism unknown (to cover streptococci and anaerobic bacteria)
Specific scenarios NICE/BNF: moderate otitis externa - otomize spray (neomycin, dexamethasone and acetic acid)

Question 2

cephalosporins and carbapenems

Class:
Examples:
Indications:
Mode of action:
Spectrum of action:
Adverse effects:
Cautions:
Contraindications:
Interactions:
Administration
Monitoring:
Prescribing:
Specific scenarios:

Answer 2

Examples: cephalosporins - cefalexin, cefotaxime. Carbapenems - meropenem
Indications: oral cephalosporins - 2nd and 3rd line for urinary and resp. IV ceph and carb - very severe or complicated or resistant organisms
Mode of action: inhibit cell wall synthesis B lactam
Spectrum of action: broad spectrum
Adverse effects: common - GI upset. Uncommon - c.diff. Hypersensitivity. Carbapenems - CNS toxicity causing seizures esp if high dose or renal impairment
Cautions: cephalosporins and carbapenems used with caution if history of B lactam delayed sensitivity eg a rash, renal impairment (dose adjust), caution if epilepsy
Contraindications: cephalosporins and meropenem contraindicated in patients with immediate hypersensitivity to b lactams. Cross-sensitivity with 1st and 2nd generation cephalosporins is 10%. With 3rd gen its 2-3%.
Interactions: avoid meropenem + valproate (reduces conc of valproate). Enhances anticoag of warfarin (INR increases),
Administration: cefalexin oral. Rest mostly IV.
Monitoring:
Prescribing:

Question 3

Macrolides

Class:
Examples:
Indications:
Mode of action:
Spectrum of action:
Adverse effects:
Cautions:
Contraindications:
Interactions:
Administration
Monitoring:
Prescribing:
Specific scenarios:

Answer 3

Examples: clarithromycin, azithromycin, erythromycin
Indications: resp and soft tissue when pen contraindicated by allergy. In severe pneumonia added to amoxicillin to cover atypical, eradication of h.pylori (with amoxicillin/metro and PPI)
Mode of action: inhibit protein synthesis 50S
Spectrum of action: broad spectrum, better for gram positive, atypical
Adverse effects: adverse effects more common with erythromycin. Irritant = N&V, abdo pain, diarrhoea, thrombophlebitis when IV. antibiotic associated colitis and c.diff. Liver abnormalities including cholestatic jaundice, prolongation of QT, ototox in high doses = tinnitus
Cautions: caution in patients taking drugs which prolong QT such as amiadarone, antipsychotics, quinine, quinolone abx, SSRIS. Cuation in hepatic impairment as hepatic processed. Caution in renal impairment (dose reduce). May aggravate myasthenia gravis
Contraindications:
Interactions: E and C inhibit cytochrome P450 and therefore increase plasma conc of drugs such as warfarin and statins
Administration: oral and IV infusion
Monitoring:
Prescribing:
Specific scenarios: most commonly [prescribed is claruthromycin as fewer side effects than E and cheaper than A.

Question 4

metronidazole

Class:
Examples:
Indications:
Mode of action:
Spectrum of action:
Adverse effects:
Cautions:
Contraindications:
Interactions:
Administration
Monitoring:
Prescribing:
Specific scenarios:

Answer 4

Examples: metronidazole

Indications: antibiotic associated colitis caused by c.diff (gram positive bacilli), oral infections (such as dental abscess), aspiration pneumonia caused by gram negative anaerobes from the mouth, surgical and gynaecological infections caused by gram negative anaerobes from the colon, protozoal infections including trichomonal vaginal infection, amoebic dysentery, giardiasis

Mode of action: DNA degradation and cell death - mechanism only works in anaerobic bacteria

Spectrum of action: anaerobic bacteria only, protozoa

Adverse effects: GI upset, immediate and delayed hypersensitivity, when used in high doses can cause peripheral and optic neuropathy, seizures and encephalopathy

Cautions: metabolised by cytochrome p450 so dose reduce in severe liver disease

Contraindications: alcohol- disulfiram like reaction. Don’t drink for the duration of treatment and for 48 horus after.
Interactions: p450 inhibitor so can increase plasma conc of drugs such as warfarin
Administration: oral, IV, rectal,
Monitoring:
Prescribing:
Specific scenarios:

Question 5

Class: Penicillins

Class:
Examples:
Indications:
Mode of action:
Spectrum of action:
Adverse effects:
Cautions:
Contraindications:
Interactions:
Administration
Monitoring:
Prescribing:
Specific scenarios:

Answer 5

Examples: benzylpenicillin, phenoxymethylpenicillin (pen V)

Indications: strep infection including tonsillitis, pneumonia, endocarditis skin and soft tissue

Mode of action: inhibit bacterial cell wall synthesis. B lactam
Spectrum of action:

Adverse effects: delayed IgG hypersensitivity (7-10 days rash), immediate IgE anaphylactic hypersensitivity (hypotension, bronchial and laryngeal spasm/oedema and angioedema. CNS toxicity with high doses/renal imapirment

Cautions: dose reduce renal impairment

Contraindications: penicillin hypersensitivity

Interactions: reduces renal excretion of methotrexate, increasing risk of toxicity

Administration: ben pen (IV or IM), pen V (oral)
Monitoring:
Prescribing:
Specific scenarios:

Question 6

Class: Penicillins, antipseudomonal

Examples:
Indications:
Mode of action:
Spectrum of action:
Adverse effects:
Cautions:
Contraindications:
Interactions:
Administration
Monitoring:
Prescribing:
Specific scenarios:

Answer 6

Examples: piperacillin with tazobactam

Indications: severe infections particularly where there is a broad spectrum of potential pathogens (including pseudomonas aeruginosa) where abx resis is likely eg hospital aq, or patients are immunocompromised eg neutropenia. Resp, urine, intra-abdo, skin and soft tissue

Mode of action: CWS b lactam. Side chain of piperacillin increases activity against pseudomonas. Tazobactam is a b lactamase inhibitor

Spectrum of action: broad spectrum

Adverse effects: delayed/immediate hypersensitivity. Antibiotic associated colitis

Cautions: in people at risk of c.diff. Dose reduce in mod/severe renal impairment

Contraindications:
Interactions: reduces renal excretion of methotrexate, increasing risk of toxicity. Antipseudomonal penicillins increase anticoagulant effect of warfarin as it kills flora that produce vit K

Administration: IV infusion
Monitoring:
Prescribing:
Specific scenarios:

Question 7

Class: Penicillins, broad spectrum

Examples:
Indications:
Mode of action:
Spectrum of action:
Adverse effects:
Cautions:
Contraindications:
Interactions:
Administration
Monitoring:
Prescribing:
Specific scenarios:

Answer 7

Examples: amoxicillin, co-amoxiclav

Indications: empirical treatment of penumonia, UTI, combination treatment for hospital aquired and h.pylori

Mode of action: CWS B lactam. Amoxicillin amino group side chain increases activity against aerobic gram negative bacteria. Addition of clavulanic acid increases spectrum to include b lactam producing bacteria eg s aureus, gram negative anaerobes

Spectrum of action:
Adverse effects: delayed/immediate hypersensitivity. Antibiotic associated colitis

Cautions: in people at risk of c.diff. Dose reduce in mod/severe renal impairment

Contraindications:
Interactions: reduces renal excretion of methotrexate, increasing risk of toxicity. Broad spectrum penicillins increase anticoagulant effect of warfarin as it kills flora that produce vit K

Administration: amoxicllin IV and oral. Co-amox IV and oral
Monitoring:
Prescribing:
Specific scenarios:

Question 8

Class: Penicillin, penicillinase resistant

Examples:
Indications:
Mode of action:
Spectrum of action:
Adverse effects:
unique adverse effect:
Cautions:
Contraindications:
Interactions:
Administration
Monitoring:
Prescribing:
Specific scenarios:

Answer 8

Examples: flucloxacillin

Indications: skin and soft tissue, osteomyelitis, septic arthritis,

Mode of action: acyl side chain protects b lactam ring against b lactamases
Spectrum of action:

Adverse effects: mild GI disturbance, delayed IgG hypersensitivity (7-10 days rash), immediate IgE anaphylactic hypersensitivity (hypotension, bronchial and laryngeal spasm/oedema and angioedema. CNS toxicity with high doses/renal imapirment

Unique adverse effect: liver toxicity including cholestasis and hepatitis

Cautions: dose reduce renal failure
Contraindications:

Interactions: reduces renal excretion of methotrexate, increasing risk of toxicity
Administration: IV and oral
Monitoring:
Prescribing:
Specific scenarios:

Question 9

Class: nitrofurantoin

Examples:
Indications:
Mode of action:
Spectrum of action:
Adverse effects:
Unique adverse effects:
Cautions:
Contraindications:
Interactions:
Administration
Monitoring:
Prescribing:
Specific scenarios:

Answer 9

Indications: uncomplicated lower UTI

Mode of action: damages bacterial dna and causes cell death (bactericidal)

Spectrum of action: effective against the common causative organisms of UTI eg e.coli (gram negative) and staphylococcus saprophyticus (gram positive). Some bacteria that cause UTI eg klebsiella and proteus have natural resistance to nitrofurantoin

Adverse effects: GI upset, immediate and delayed hypersensitivity

Unique adverse effect: can turn urine dark yellow/brown. May cause chronic pulmonary reactions (including pneumonitis and fibrosis), hepatitis and peripheral neuropathy. In neonates can cause haemolytic anaemia

Cautions: caution using as long term prevention of UTI as chronic use increases risk of AE

Contraindications: pregnant women near term, babies under 3 months. Contraindicated in renal impairment as it increases toxicity and reduces efficacy due to lower urinary drug concs.
Interactions:

Administration: oral tablets, capsules, suspecnsion. Take with food/milk
Monitoring:
Prescribing:
Specific scenarios:

Question 10

Class: quinolones

Examples:
Indications:
Mode of action:
Spectrum of action:
Adverse effects:
Unique adverse effects:
Cautions:
Contraindications:
Interactions:
Administration
Monitoring:
Prescribing:
Specific scenarios:

Answer 10

Examples: ciprofloxacin, moxifloxacin, levofloxacin

Indications: reserved as second and third line treatment due to possibility of rapid resistance and c.diff risk. UTI, GI, LRTI

Mode of action: inhibit DNA synthesis

Spectrum of action: ciprofloxacin is the only oral antibiotic with activity against pseudomonas aeruginosa

Adverse effects: GI upset and delayed and immediate hypersensitivity. Promotes c.diff colitis

Unique adverse effects: lowering seizure threshold, hallucinations, inflammation and rupture of muscle tendons. Quinolones (particularly moxifloxacin) prolong the QT interval and therefore increase risk of arrhythmias.

Cautions: ppl at risk of seizures, who are growing (risk of arthropathy) and risk factors for QT prolongation

Contraindications:
Interactions:
Drugs containing divalent actions (eg calcium, antacids) reduce absorption and efficacy of quinolones
Ciprofloxacin inhibits certain P450 enzymes increasing risk of toxicity with some drugs, notably theophylline
Co-prescription of NSAIDs increases the risk of seizures
Co-prescription of prednisolone increases the risk of tendon rupture
Caution with drugs that prolong QT interval

Administration: oral - still gets high plasma concs
Monitoring:
Prescribing:
Specific scenarios:

Question 11

Class: tetracyclines

Class:
Examples:
Indications:
Mode of action:
Spectrum of action:
Adverse effects:
Cautions:
Contraindications:
Interactions:
Administration
Monitoring:
Prescribing:
Specific scenarios:

Answer 11

Examples: doxycycline, lymecycline

Indications: acne vulgaris, LRTI inc atypical organisms, chlamydial infection inc PID, other infections such as typhoid, anthrax, malaria, lyme disease

Mode of action: inhibit bacterial protein synthesis 30S

Spectrum of action: relatively broad spectrum

Adverse effects: GI disturbance, hypersensitivity

Unique adverse effects: oesophageal irritation, ulceration and dysphagia, photosensitivity, discoloration and/or hypoplasia of tooth enamel if prescribed for children. Intracranial hypertension is a rare adverse effect
Cautions:

Contraindications: tetracyclines bind to teeth and bones during fetal development infants and childhood so DO NOT prescribe during pregnancy, breastfeeding or for children under 12. Avoid in ppl with renal impairment
Interactions: tetracyclines bind to divalent cations so shouldnt be given within two hours of calcium, antacids or iron which will prevent antibiotic absorption, enhances anticoagulant effect of warfarin by killing gut flora

Administration: oral
Monitoring:
Prescribing:
Specific scenarios:

Question 12

Class: antifolates

Class:
Examples:
Indications:
Mode of action:
Spectrum of action:
Adverse effects:
Unique adverse efects:
Cautions:
Contraindications:
Interactions:
Administration
Monitoring:
Prescribing:
Specific scenarios:

Answer 12

Examples: Trimethoprim, co-trimoxazole,

Indications: trimethoprim is used for uncomplicated UTI (alternatives include nitrofurantoin and amoxicillin), co-trimoxazole (trimethoprim combined with sulfamethoxazole) is used for treatment and prevention of pneumocystis pneumonia

Mode of action: inhibit bacterial folate synthesis,

Spectrum of action: broad spectrum but widespread bacterial resistance

Adverse effects: GI upset, hypersensitivity,
Unique adverse effects: haematological disorders such as megaloblastic anaemia, leukopenia and thrombocytopenia due to inhibition of folate synthesis. Can cause hyperkalemia

Cautions: caution in folate deficiency, dose reduce in renal impairment. Neonates, elderly and ppl with HIV are most susceptible to adverse effects
Contraindications: contraindicated in first trimester of pregnancy,
Interactions:
use with potassium elevating drugs ef aldosterone antagonists, ACE inhibitorsm ARBs predisposes to hyperkalaemia.
Use with other folate antagonists eg methotrexate) and drugs that increase folate metabolism eg phenytoin, increases risk of haematological effects, trimethoprim can enhance the anticoagulant effect of warfarin by killing normal gut flora

Administration: trimethoprim oral. Septrin oral or IV

Monitoring: for long term treatment FBC monitor
Prescribing:
Specific scenarios:

Question 13

Class: Glycopeptides

Examples:
Indications:
Mode of action:
Spectrum of action:
Adverse effects:
Cautions:
Contraindications:
Interactions:
Administration
Monitoring:
Prescribing:
Specific scenarios:

Answer 13

Examples: vancomycin, dalbavancin, teicoplanin

Indications: treatment of gram positive infection e.g. endocarditis, where infection is severe and/or penicillins cannot be used due to resistance e.g. MRSA. Treatment of antibiotic-associated colitis caused by c.diff infection

Mode of action: inhibits growth and cross-linking of peptidoglycan chains - inhibiting synthesis of cell wall of gram positive bacteria.
Spectrum of action:

Adverse effects:
Unique adverse effects: pain and inflammation of the vein (thrombophlebitis) at the infusion site, if infused rapidly- anaphylactoid ‘red man syndrome’ - generalised erythema and may be associated with hypotension and bronchospasm. Anaphylactoid reactions are not true allergy - not antigen mediated. NOT seen with teicoplanin

However, true allergy can also occur. IV can cause nephrotoxicity - including renal failure and interstitial nephritis, ototoxicity with tinnitus and hearing loss and blood disorders including neutropenia and thrombocytopenia.

Cautions: requires careful monitoring of plasma concentrations and dose adjustment to avoid toxicity.

Contraindications:
Interactions: increases risk of nephrotoxicity and ototoxicity when prescribed with aminoglycosides, loop diuretics, or ciclosporin

Administration: oral or slow infusion

Monitoring: need to keep between 10-15 mg/L. Daily renal function and regular RFB during prolonged therapy.

Prescribing: warn them to report ringing in ears and change in hearing - only reversible if stopped promptly
Specific scenarios:

Question 14

Aspirin
mechanism
adverse effects
overdose
preventing adverse effects
contraindicatons
interactions
administration
specific scenarios

Answer 14

Mechanism: irreversibly binds to COX-1 enzyme within platelets, this prevents the release of thromboxane A2, which in turn prevents the stimulation of other platelets and platelet aggregation thereby preventing clot formation

Adverse effects: gastritis and peptic ulcers, hypersensitivity including bronchospasm, tinnitus in high doses, can trigger gout attack

Overdose: hyperventilation, metabolic acidosis, confusion, convulsions, cardiovascular collapse and rep arrest

Preventing adverse effects: prescribe PPI if risk of gastric complications eg >65, previous peptic ulcer disease, comorbidities, taking other gastric damaging drugs eg NSAIDs and steroids

Contraindications: children under 16 (risk of reyes syndrome- brain swelling and liver damage), allergy to aspirin or another NSAID, avoid in 3rd trimester as prostaglandin inhibition may prematurely close ductus arteriosus,

Interactions: works synergistically with other antiplatelets and anticoagulants - can be good but also increased risk of bleeding - caution

Administration: oral - after food

Specific scenarios: ischemic stroke 300 mg for 2 weeks then 75mg. Acute coronary syndrome 300mg once-only dose then 75 mg daily

Question 15

P2Y12 inhibitors
examples
differences
mechanism
adverse effects
contraindications
caution
interactions
administration
specific scenarios

Answer 15

Examples: clopidogrel, ticagrelor, ticlopidine, Prasugrel

Differences: clopidogrel was associated with a significantly lower risk of major bleeding than ticagrelor.
Prasugrel provides greater and more consistent platelet inhibition than clopidogrel
A 2019 randomized trial suggested that prasugrel is superior to ticagrelor.

Mechanism: Block ADP P2Y12 receptor on platelet which prevents the binding of ADP and therefore prevents the formation of GPIIb/IIa which is required for fibrinogen cross-linking of platelets thereby preventing aggregation

Adverse effects: bleeding (GI, intracranial, following surgery), GI upset inc dyspepsia, abdo pain, diarrhoea, rarely can affect platelet numbers - thrombocytopenia

Contraindications: don’t prescribe for active bleeding. May need to be stopped 7 days before elective surgery

Caution: caution in patients with renal and hepatic impairment, especially where otherwise patient has increased risk of bleeding

Interactions: clopidogrel is a pro-drug that is metabolised by cytochrome P450. cytochrome p450 inhibitors may reduce efficacy of clopidogrel. Notably omeprazole, ciprofloxacin, erythromycin, some SSRIs, antifungals. If gastroprotection is required, use lansoprazole instead - less likely to inhibit clopidogrel activation. Co-prescription with other antiplatelets/anticoagulants increases bleeding risk

Administration: oral, low doses take 7 days to reach full effect - if need rapid - may req a loading dose 300mg once only then 75mg a day after

Specific scenarios: 75mg clopidogrel for secondary prevention of isc stroke (from post 2 weeks for life). Dual antiplatelet therapy for acute management of ACS. 1. Aspirin + ticagrelor 2. Aspirin + clopidogrel if high bleeding risk, if PCI indicated 1. Aspirin + prasugrel 2. Aspirin + clopidogrel if already taking anticoagulant. Dual antiplatelet therapy for 12 months following ACS

Question 16

phosphodiesterase inhibitors
examples
mechanism
adverse effects
caution
interactions
specific scenarios

Answer 16

Examples: dipyridamole, cilostazol

Mechanism: inhibit phosphodiesterase which is responsible for breaking down cAMP to AMP. This decreases intracellular levels of calcium and in turn prevents platelet aggregation. Also inhibits phosphodiesterase in the vascular wall, as well as adenosine, which leads to vasodilation.

Adverse effects: headache, flushing, dizziness, GI symptoms due to vasodilation. These tend to settle - can slowly titrate dose to try to avoid these. Increased risk of bleeding, can cause thrombocytopenia

Caution: caution in IHD, aortic stenosis and heart failure - vasodilation and tachycardia can exacerbate these conditions.

Interactions: dipyridamole inhibits cellular uptake of adenosine - this prolongs adenosine action on the heart increasing risk of cardiac arrest - reduce dose of adenosine in these pts. Increased risk of bleeding when co-prescribed with other antiplatelets/anticoagulants
Administration: oral modified release

Specific scenarios: secondary prevention of TIA/ischaemic stroke: 1. Clopidogrel 75 mg od 2. Aspirin 75 mg daily with modified-release dipyridamole 200 mg twice daily 3. Dipyridamole 200 mg twice daily

Question 17

Alpha blockers
examples
indications
mehcanism of action
adverse effects
cuation
interactions
administration
specific scenarios

Answer 17

Examples: doxazosin, tamsulosin, alfuzosin

Indications: first line BPH, add on treatment in resistant HTN, acute urinary retention

Mechanism of action: block alpha-1-adrenoceptors found on smooth muscle - including in blood vessels and urinary tract. Blockade induces relaxation.

Adverse effects: postural hypotension, dizziness, syncope

Caution: caution in ppl with postural hypotension

Interactions: may be combined therapeutically with other antihypertensives, however to avoid pronounced first dose hypotension, omit other drugs on first day of alpha blocker - particularly beta blockers which inhibit reflex tachycardia that is compensatory for vasodilation

Administration: oral, take at bedtime due to blood pressure lowering effect

Specific scenarios:
Doxazosin - initially 1mg od for 1-2 weeks then increased by doubling - up to max 16mg for HTN and up to 8mg for BPH. if modified release start 4mg, can be increased to 8mg for both HTN and BPH

Tamsulosin 400mcg for BPH

Question 18

Unfractionated heparin, low molecular weight heparin and fondaparinux

Answer 18

Differences: LMWH is more predictable than UFH. This means UFH needs monitoring whereas LMWH doesn’t. Bleeding is less of a risk with fondaparinux.

Examples:
LMWH: dalteparin, enoxaparin
UFH
Fondaparinux

Mechanism: binds to naturally circulating anticoagulants called antithrombin III and accelerates its activity. Antithrombin III inactivates thrombin and factor Xa. Heparin inactivates both. Low molecular weight heparin selectively accelerates inhibition of factor Xa. As does fondaparinux.

Contraindications:Acute bacterial endocarditis; after major trauma; avoid injections containing benzyl alcohol in neonates; epidural anaesthesia with treatment doses; haemophilia or other haemorrhagic disorders; peptic ulcer; recent cerebral haemorrhage; recent surgery to eye; recent surgery to nervous system; spinal anaesthesia with treatment doses; thrombocytopenia (including history of heparin-induced thrombocytopenia). For dalteparin sodium - Mechanical prosthetic heart valve

Cautions: Elderly; risk of bleeding; severe hypertension

Side effects: bleeding, heparin induced thrombocytopenia (HIT) - this is where antibodies are produced against heparin when binded to platelet factor 4. This activates platelets forming clots and thrombocytopenia

Reversal agent for excessive bleeding: protamine sulphate - binds to heparin and forms a stable inactive complex. Fondaparinux doesn’t have a reversal agent

Administration: SC injection or IV infusion

Monitoring: renal and FBC beforehand. In UFH, activated partial thromboplastin ratio needs monitoring every 6 hours initially.

Question 19

Direct inhibitors of factor Xa

Answer 19

Examples:
Parenteral: otamixaban
Oral: (NOACs) apixaban, rivaroxaban, edoxaban

Mechanism: bind to factor Xa, thus preventing conversion of prothrombin to thrombin

Benefit: available in oral formulation

Contraindications: avoid in conditions with significant risk factors for major bleeding, avoid concomitant use with any other anticoagulant is contra-indicated, except when switching therapy, or when unfractionated heparin is given at doses necessary to maintain an open central venous or arterial catheter or for catheter ablation

Caution: use STOPP criteria in the elderly, Anaesthesia with postoperative indwelling epidural catheter
Renal impairment: avoid if creatinine clearance less than 15 mL/minute
Hepatic impairment: caution in mild to moderate impairment (or if hepatic transaminases greater than 2 times the upper limit of normal, or if bilirubin is equal or greater than 1.5 times the upper limit of normal); avoid in severe impairment or impairment associated with coagulopathy and clinically relevant bleeding risk.

Pregnancy and BF: avoid in pregnancy and BF

Side effects: common: Anaemia; haemorrhage; nausea; skin reactions.
Uncommon: CNS haemorrhage; hypotension; post procedural haematoma; thrombocytopenia; wound complications
No reversal agent for bleeding

Question 20

Direct thrombin inhibitors (thrombin = factor II)

Answer 20

Oral: dabigatran
Parenteral: argatroban, bivalirudin, hirudin
Benefit: Good for heparin induced thrombocytopenia as don’t bind to platelet factor 4

Mechanism: bind directly to thrombin and do not require a cofactor such as antithrombin to exert their effect. DTIs can inhibit both soluble thrombin and fibrin-bound thrombin

Contraindications: avoid in conditions with significant risk factors for major bleeding, avoid concomitant use with any other anticoagulant is contra-indicated, except when switching therapy, or when unfractionated heparin is given at doses necessary to maintain an open central venous or arterial catheter or for catheter ablation

Caution: Anaesthesia with postoperative indwelling epidural catheter, elderly use STOPP criteria

Adverse effects: common: Anaemia; diarrhoea; gastrointestinal discomfort; haemorrhage; hepatic function abnormal; nausea. Uncommon: Dysphagia; gastrointestinal disorders; hyperbilirubinaemia; intracranial haemorrhage; post procedural complications; skin reactions; thrombocytopenia; vomiting; wound complications

Pregnancy and BF: avoid in both

Renal impairment: Avoid if creatinine clearance less than 30 mL/minute. Dose adjust above this

Hepatic impairment: Manufacturer advises avoid in severe impairment; consider avoiding in those with liver enzymes greater than 2 times the upper limit of normal

Question 21

Vitamin K antagonists

Answer 21

Warfarin
Mechanism: inhibit hepatic production of vitamin K dependent coagulation factors (10,9,7,2) by inhibiting the enzyme that activates vitamin K for coagulation factor synthesis.

Adverse effects: bleeding

Contraindications: Avoid use within 48 hours postpartum; haemorrhagic stroke; significant bleeding

Cautions: Bacterial endocarditis (use only if warfarin otherwise indicated) (Anticoagulation is a controversial issue in Staphylococcus aureus infective endocarditis (IE) because these patients are believed to be particularly susceptible to hemorrhagic transformation of embolic lesions.); conditions in which risk of bleeding is increased; history of gastrointestinal bleeding; hyperthyroidism; hypothyroidism; peptic ulcer; recent ischaemic stroke; recent surgery; uncontrolled hypertension, elderly use STOPP criteria.

Interactions: interacts with lots of medications which inhibit or induce cytochrome p450 enzymes. Inhibitors such as fluconazole, macrolides, protease inhibitors) decreases metabolism so increases bleeding risk. Inducers such as phenytoin, carbamazepine, rifampicin increases metabolism so increases clot risk

Renal impairment: Use with caution in mild to moderate impairment. In severe renal impairment, monitor INR more frequently.

Hepatic impairment: In general, manufacturers advise caution in mild to moderate impairment; avoid in severe impairment.

Pregnancy: should not be used in first trimester as it causes foetal malformations. Near term it may cause maternal haemorrhage . Postpartum (delay warfarin until risk of haemorrhage is low—usually 5–7 days after delivery)

Specific scenarios: 5-10mg oral od on day 1, subsequent doses are guided by INR. use heparin cover whilst initiating if anticoagulation immediately necessary
Monitoring: monitor INR to keep within range 2-3

Question 22

beta blockers

Answer 22

Examples: bisoprolol, atenolol, propranolol, metoprolol

Indications:
Ischaemic heart disease
Chronic heart failure
Atrial fibrillation
Supraventricular tachycardia
Hypertension
Anxiety somatic symptoms

Mechanism of action
B1 receptors are mainly on the heart, whereas B2 receptors are found mainly in the smooth muscle of blood vessels and airways.
Beta blockers reduce the force of contraction and speed of conduction in the heart - this relieves cardiac ischaemia by reducing cardiac work and oxygen demand and increasing myocardial perfusion.
Beta blockers improve the prognosis in heart failure by protecting the heart from the effects of chronic sympathetic stimulation
Beta blockers slow ventricular rate in atrial fibrillation by prolonging the refractory period in the AV node.
Beta blockers may break the reentry circuit in SVT and restore sinus rhythm
In HTN, b blockers lower blood pressure through a variety of means, one is reducing renin secretion from the kidney since this is mediated by B1 receptors

Adverse effects: may cause impotence, fatigue, headache, cold extremities, dizziness

Warnings: In patients with asthma, beta blockers can cause life threatening bronchospasm and should be avoided. Beta blockers are usually safe in COPD but you should use a b1 selective eg bisoprolol, atenolol, metoprolol instead of non-selective eg propranolol

Interactions: DO NOT use with non-dihydropyridine calcium channel blockers eg verapamil or diltiazem - this combination can cause heart failure, bradycardia and even asystole

Specific scenarios:
Hypertension, angina - bisoprolol 5mg od. Usual maintenance 10mg od

Heart failure - initially bisoprolol 1.25mg od for 1 week, then increase if tolerated to 2.5 mg once daily for 1 week, then increased if tolerated to 3.75 mg once daily for 1 week, then increased if tolerated to 5 mg once daily for 4 weeks, then increased if tolerated to 7.5 mg once daily for 4 weeks, then increased if tolerated to 10 mg once daily.

Arrythmias atenolol 50-100 mg daily

Angina bisoprolol 5mg od

Question 23

H1 receptor antagonists

Answer 23

Examples: cyclizine, promethazine
Indication: N + V, particularly in the treatment of motion sickness and vertigo
MoA: Block H1 receptors + AcH receptors therefore widespread activity but particularly good for vestibular (motion sickness/vertigo)
Adverse effects: most common-drowsiness. Cyclizine is the least sedating. Due to anticholinergic effects they may cause dry mouth + throat (may be useful in Pts with oral secretions. After IV inj - may cause transient tachycardia + palpitations
Warnings: avoid in pts at risk of hepatic encephalopathy due to sedating effect. Also should be avoided in pts susceptible to anticholinergic effects e.g. prostatic hypertrophy (who may develop urinary retention. DRIVING
Interactions: sedation may be greater when combined with other sedating drugs e.g. benzodiazepines, opioids.
Anticholinergic effects may be greater in pts taking ipatropium or tiotropium

Standard dose cyclizine 50mg tds PO or IM or IV
FOR MOTION SICKNESS TAKE 1-2 HOURS BEFORE DEPATURTURE

Question 24

D2 antagonists

Answer 24

Examples: metoclopromide, domperidore
Indications: prophylaxis of N&V, particularly in context of reduced gut motility
MOA: D2 is main receptor in CTZ which is responsible for sensing emetogenic substances in the blood
Dopamine is important in the gut where it promotes relaxation of stomach and lower oesophageal
sphincter + inhibits gastro duodenal coordination → drugs that block D2 have a prokinetic
effect -promoting gastric emptying
They are effective in N&v due to CTZ stimulation (e.g. drugs) AND reduced gut motility e.g.
opiods or diabetic gastro paresis)
Adverse effects: Diarrhoea- most common. metoclopramide can induce extrapyramidal side effects via the same mechanisms as antipsychotics. e.g. acute dystonia reaction. Domperidone tends not tocause EPSE as it doesn’t cross the blood brain barrier
Warnings: EPSE are more common in children + young adults so avoid in this group. As pro kinetic -
contraindicated in al obstruction + perforation

If patient has Parkinson s - use domperidone.

Dose : up to 60KG = 500 mCG/Kg in 3 divided doses (PO, IM injection or slow IV infusion)
over 60kg = 10mg up to 3 times per day

Question 25

5HT3 antagonists

Answer 25

Examples: ondansetron, granisetron
Indications: nausea and vomiting, particularly in the context of general anaesthesia and chemotherapy
MoA: High density of 5HT3 receptors in CTZ which is responsible for sensing emetogenic substances in the blood (eg drugs). Secondly, seretonin is the key neurotransmitter released by the gut in reposne to emetogenic stimuli. Acting on 5HT3 receptors, it stimulates the vagus nerve which in turn activates the vomiting centre via the solitary tract nucleus. Importantly, serotonin is not involved in the communication between the vestibular system and the vomiting centre, thus 5HT3 antagonists are not useful for motion sickness
Adverse effects: rare - constipation, headaches, diarrhoea
Warnings: prolong the QT interval although usually only evident at high doses eg >16mg ondansetron. Avoid in pts with prolonged QT, if in doubt, ECG before prescribing
Interactions: avoid in pts taking drugs that prolong the QT interval eg antipsychotics, quinine, SSRIs,
Pregnancy: risk of cleft lip/palate if used in first trimester of pregnancy

Question 26

Phenothiazines

Answer 26

Examples: prochlorperazine, chlorpromazine
Indications:
Nausea and vomiting, particularly if due to vertigo, however due to SE profile other classes used first
Psychotic disorders where they are used as a first generation (typical) antipsychotic
MoA: block D2 in CTZ and gut. Also block H2 and Ach in vomiting centre and vestibular system.
Adverse effects: drowsiness, postural hypotension, EPSE eg acute dystonia (due to D2 blocking), prolong QT interval
Warnings: can cause hepatotoxicity and drowsiness = avoid in severe liver disease, avoid in pts susceptible to anticholinergic SE such as ppl w prostatic hypertrophy - may cause urinary retention
Interactions: use BNF as lots, avoid with drugs that prolong QT eg other antipsychotics, amiodarone, ciprofloxacin, macrolides, quinine, SSRIs
Administration: IM or oral

Question 27

Butyrophenone antipsychotics
for N&V

Answer 27

Examples: Haloperidol
Indications:Used in chemical causes of nausea & vomiting (N&V) e.g. opioids
MoA: Act on dopamine (D2) receptors in the chemo-receptor trigger zone
Adverse effects: extrapyramidal symptoms, sedation, QT-prolongation, Depression. At the low dose required for N&V, it causes few SE
Warnings: Avoid in Parkinson’s disease
Dosing for haloperidol: 500micrograms - 1.5mg/24 hours CSCI or PO/SC
at night &/or 4 hourly ‘PRN’. If necessary titrate to max 5mg/24 hours
(doses can be divided). If eGFR <30ml/min/1.73m2 , increase ‘when required’ frequency to every six hours.

Question 28

Antimuscarinics used in palliative care

Answer 28

Examples: Hyoscine hydrobromide and hyoscine butylbromide
MoA: bind to muscarinic receptors antagonistically- block effect of parasympathetic rest and digest
Palliative care uses: antiemetic and reducing copious respiratory secretions
Other uses:BUSCOPAN is the trade name for “hyoscine butylbromide”. This belongs to a group of medicines called “antispasmodics” - used in IBS.
Adverse effects: anticholinergic side effects : dry mouth, tachycardia, urinary retention, blurred vision, confusion, drowsiness
Warnings: use with caution in pts with ?acute angle glaucoma - can ppt a dangerous increase in intraocular pressure. Avoid in pts at risk of arrhythmias, unless indication for use is bradycardia
Interactions: adverse effects more pronounced when combined with other drugs with antimuscarinic activity eg TCAs.
Prescribing: be careful when prescribing, hyoscine hydrobromide and hyoscine butylbromide have quite different doses. Be clear to nurses which one you are prescribing

Difference between hyoscine hydrobromide and hyoscine butylbromide
Unlike hyoscine hydrobromide, hyoscine butylbromide does not cross the blood-brain barrier and therefore does not cause drowsiness or have a central anti-emetic action.

Question 29

Paracetamol

Answer 29

Indications: first-line analgesic for nociceptive pain, antipyretic

MoA: poorly understood, weak inhibitor of cyclooxygenase (COX), the enzyme involved in prostaglandin metabolism. Has specificity for COX-2

Adverse effects: few side effects due to specificity for COX-2. COX-1 inhibition can cause peptic ulceration, renal impairment and ppt cardiac events
In overdose, paracetamol can cause liver failure. Cytochrome P450 metabolises it into NAPQI (toxic metabolite) which is conjugated with glutathione before elimination. Acetylcysteine (treatment for overdose) is a glutathione precursor

Warnings: paracetamol should be reduced in ppl with liver failure (due to increased NAPQI production eg in excess alcohol intake, OR reduced glutathione stores (malnutrition, low body weight, severe hepatic impairment) - this is particularly important for IV infusion paracetamol

Interactions: cytochrome p40 inducers eg phenytoin, carbamazepine increase the rate of NAPQI production and risk of liver toxicity after paracetamol overdose

Prescribing: if you’re prescribing regular paracetamol, make sure you cross it off PRN

Dosing: 0.5-1g PO 4-6 hourly (maximum 4g/24 hours)

Question 30

NSAIDs

Answer 30

Indications: analgesic particularly for pain related to inflammation

MoA: inhibits COX

Warnings: avoid NSAIDs in severe renal impairment, heart failure, liver failure

Interactions: many drugs when combined, increase the risk of NSAID adverse effects. Eg gastric ulceration: aspirin and corticosteroids. Gastric bleeding: anticoagulants, SSRIs, venlafaxine. RENAL IMPAIR: ACEi, diuretics. NSAIDs increase the risk of bleeding with warfarin and reduce the therapeutic effects of anti-HTNs and diuretics

Administration: take with food
Adverse effects:
COX-1 inhibition
Peptic ulceration (decreased PGE2),
Bleeding (decreased TXA2), this is more prominent in selective COX-1 inhibitors
Renal impairment (decreased PGE2 and PGI1)
COX-2 inhibition
Increased risk of cardiovascular events (decreased PGI1) this is more prominent in selective COX-2 inhibitors as TXA from COX-1 is unopposed whilst PGI2 is suppressed
LOX upregulated
Importantly, if the COX system is being inhibited, there is more arachidonic acid to be directed to LOX - this makes leukotrienes and can ppt bronchospasm in asthmatics! caution!

Contraindications: active bleeding, thrombocytopenia, peptic ulcer, history of adverse effects with NSAIDs, severe heart failure, varicella infection

Prescribing: consider PPI

Dosing:
Ibuprofen 300-400mg tds-qds
Normal tablet is 200mg but check as there are many different types

Question 31

weak opioids

Answer 31

Examples: codeine, dihydrocodeine, tramadol
MoA: codeine and dihydrocodeine are metabolised in the liver to produce small amounts of morphine
10% of people have a less active enzyme meaning they can’t convert this properly making codeine/dihydrocodeine largely ineffective
Tramadol is a synthetic analogue of codeine. Tramadol, unlike other opioids, also acts on serotonergic and adrenergic pathways where it is thought to act as a serotonin and noradrenaline reuptake inhibitor- contributes to analgesic effect
Adverse effects: nausea, constipation, dizziness, drowsiness, neurological and respiratory depression when taken in overdose. Tramadol may cause less constipation and respiratory depression than other opioids.
Warnings: caution in severe resp disease. Tramadol, codeine and dihydrocodeine rely on liver and kidneys for excretion so dose reduce in renal and hepatic impairment and in the elderly. Tramadol lowers seizure threshold so avoid in epilepsy
Interactions: try to avoid other sedating drugs eg benzodiazepines, antipsychotics, TCA. don’t give tramadol with other drugs that lower seizure threshold eg SSRIs and TCAs. Tramadol can also cause serotonin syndrome especially when combined with other serotonergic drugs eg many antidepressants
Administration: codeine and dihydrocodeine MUST NOT be given IV - causes a histamine mediated severe reaction (looks similar but isn’t anaphylaxis)
Prescribing:advise the person of the risks of constipation, and prescribe a stimulant laxative (such as senna or dantron-containing laxative) at the time of first prescription. Just think that opioids turn the gut off so you need to turn it back on with a stimulant laxative

Question 32

Strong opioids

Answer 32

Examples: morphine and oxycodone
Indications:
Rapid relief of acute severe pain eg post-operative or pain associated with MI
Chronic pain where rest of WHO ladder is exhausted
Relief of breathlessness in EOLC
To relieve breathlessness and anxiety in acute pulmonary oedema , alongside oxygen, furosemide and nitrates
MoA:
Activation of opioid mu receptors in the CNS. activation of these G coupled receptors reduces neuronal excitability and pain transmission.
In the medulla they blunt the response to hypoxia and hypercapnia, reducing respiratory drive and breathlessness. By relieving pain, breathless and associated anxiety, opioids reduce sympathetic nervous system activity. The theory extends that in Mi and acute pulmonary oedema they may decrease cardiac work and oxygen demand,a s wella s relieving symptoms
Important adverse effects:
Respiratory depression
Euphoria and detachment and in higher doses neurological depression
Can activate the CTZ → nausea and vomiting
Pupillary constriction
Reduced motility in the large intestine → constipation
In the skin, opioids may cause histamine release → itching, urticaria, vasodilation, sweating
Tolerance and dependency
Overdose is exaggerated opioid effects: neurological depression and drowsiness, respiratory depression and associated cyanosis (blue lips and peripheries) , pupil constriction, flushing of the skin, itching,
Opioid withdrawal is the opposite of the opioid effects: anxiety, pain, breathlessness, pupil dilation, skin is cool and dry with piloerection pt has gone “cold turkey” and appears like a “cold turkey”

Warnings: rely on liver and kidneys for excretion so dose reduce in renal and hepatic impairment and in the elderly. Do not give in resp failure (unless expert guidance in palliative care), avoid opioids in biliary colic as they may cause spasm of sphincter of oddi and make pain worse.
Interactions: dont use with other sedating drugs eg antipsychotics, benzodiazepines, TCA
Prescribing:
Acute severe pain in high dependency areas: IV (onset about 5 minutes) initial dose of 2-10mg tailored to pain, age and other factors - prescribed in once only section
On a general ward IM or SC is preferred

Chronic pain: oral route is safest and preferred. Immediate release oral morphine (oramorph 5mg every 4 hours) is used initially. Then, having found the optimum dose, this is converted into a modified release form (every 12 hours). Alongside this ‘breakthrough’ analgesia is prescribed in the as required section (usually 1/6th of the regular daily dose)
ABC of strong opioid prescribing
Start Antiemetic (metoclopramide)
Consider Breakthrough pain
Prescribe laxatives for Constipation (stimulant - senna)

Question 33

Naloxone

Answer 33

Indications: treatment of opioid toxicity associated with respiratory and/or neurological depression
MoA: binds to opioid receptorsa s a competitive antagonist. It has little to no effect in the absence of exogenous opioids.
Adverse effects: can ppt withdrawal if given too much particularly in opioid dependence
Administration: small incremental dose 200-400 mcg IV every 2-3 minutes until satisfactory reversal has been achieved. In patients who develop[ opioid toxicity in the context of chronic use (especially in palliative care) - smaller incremental doses should be used e.g. 40-100mcg.
Monitoring: closely monitor patient fot at least an hour. This is beacuse the action of naloxone (20-60 mins) is shorter than most opioids so opioid toxicity can reoccur