Drugs for the MAU

Clive Roberts

Extract from 5th year handbookYou should have a working knowledge of therapeutics. You should know the uses, dose, side effects, contraindications and alternatives for widely used medication. For example (in rough order of exposure frequency): a) Aspirin b) Loop and other diuretics (thiazides,

amiloride etc.) c) Minor analgesics d) Antibiotics e) Treatments for bronchial asthma f) Laxatives g) Proton pump inhibitors and H2 antagonists h) ACE inhibitors i) Enteral steroids j) GTN and slow release nitrates k) Beta blockers l) Antidepressants

1. Iron, thiamin and other vitamins 2. Warfarin 3. Benzodiazepines 4. Digoxin 5. NSAIDs 6. Statins 7. Treatments for type I and type II diabetes 8. Calcium antagonists 9. Thyroxine 10.Major tranquillizers 11.Anticonvulsants 12.Amiodarone 13.The contraceptive pill

Which drugs am I expected to know about??

So what are drugs good at treating (or preventing)?

• Pain• Inflammation• Infection• Fluid retention• Heart problems• High blood pressure• Epilepsy• Parkinsonism• Asthma / COPD• Peptic ulcer disease

• Diarrhoea/constipation• Depression• Anxiety/sleeplessness• Psychosis• Metabolic /endocrine

diseases• Malignant disease• Degenerative disease• Haematological

problems• Etc Etc

• A 45 year old lady presents with increasing wheeze over the previous 6 months. No past history of asthma. She is wheezy throughout both lungs and has a tachycardia. Her peak flow is 150 l/min.

• What immediate investigations are indicated?

• What immediate measures should be taken?

Acute asthma and COPD - available approaches

• Oxygen• Bronchodilators

– Salbutamol – Ipratropium– Aminophylline

• Anti-inflammatories– Corticosteroids

• Intravenous• Oral

• Anti-biotics

Severe asthma

• Sit patient up and give high flow O2

• Check PEFR & O2 sats• Nebulised bronchodilators salbutamol 5mg

+ ipratropium 500mcg (repeat after 15 min if needed)

• Prednisolone 40-50mg po stat• Consider IV Magnesium sulphate 1.2-2g

over 20 mins• ABGs, CXR, FBC, U&Es

General rules about Oxygen therapy

• Correct hypoxia with an appropriate delivery device

• Check ABGs if SaO2 <93% or suspicion of ventilatory impairment or acidosis

• Some patients (esp. COPD) with chronic hypoxia rely on hypoxic drive and will hypoventilate on high flow O2

Oxygen delivery devices

Hudson mask: variable performance

Nasal cannulae

                                                                                                                                   

    

Venturi devices: fixed performance

Key drug features• Salbutamol – beta 2 stimulant

– Easy to administer– Watch for tremor and potassium level

• Ipratropium – muscarinic blocker– Nebuliser and inhaler– Few side effects

• Aminphylline – phosphodiesterase inhibitor– Major dosing problems– Severe adverse effects on CNS and heart– Great caution needed

Key drug features

• Corticosteroids– Safe in acute situations– IV hydrocortisone or oral prednisolone– Avoid long term or rapidly repeated courses

because lead to • BP+, fluid retention, hypokalaemia, weight gain,

Diabetes, osteoporosis, myopathy, skin fragility, gastric ulcer, reduced host defence, risk of hypocorticism

Infection Antibiotic TreatmentDuration of Treatment

Comments

Infective Exacerbation of COPD

Amoxicillin 500mg po tds 5-7 days

•Penicillin allergic •Doxycycline 100mg po bd 5 -7days

Community Acquired Pneumonia

Risk Factors in CAP(CURB-65)

C = Confusion MTS 8 or lessU = Urea > 7mmol/l

R = Resp. Rate >/= 30/minB = BP Systolic < 90 mmHg+/- Diastolic </= 60 mmHg

65 = age >/= 65 yrs3 or more of the above risk

factors (CURB-65 Score >/=3) = Severe Community

Acquired Pneumonia

Non-severe •Amoxicillin 500mg–1gram po tdsplus* Clarithromycin 500mg po bdAmoxicillin 500mg-1gram IV tds

plus* Clarithromycin 500mg IV bdcan be used if a patient is unable to

swallow or is not absorbing.

•5-7 days •*Amoxicillin monotherapy may be considered for (i) those previously untreated in the community or (ii) those admitted to hospital for non-

clinical reasons who would otherwise be treated in the community.

Non-severe Penicillin allergic

Moxifloxacin 400mg po od •5-7 days

•Severe •Co-amoxiclav 1.2grams IV tds•plus Clarithromycin 500mg IV bd

•(Switching to Co-amoxiclav 625mg po tds plus Clarithromycin 500mg po bd)

•7-10 days •If systemic sepsis add Gentamicin 5mg/kg IV stat

pending culture results

•Severe•Penicillin allergic

•Levofloxacin 500mg IV bd•(Switching to Moxifloxacin 400mg po

od)

•7-10 days

Antibiotic guidance

• A 45 year old man known to be alcoholic and addicted to Valium is admitted following three tonic clonic seizures

• What might be the possible causes?– Effect of alcohol on brain– Metabolic abnormality 2ndry to alcohol– Alcohol withdrawal– Drug withdrawal– Head injury– Overdose of something

• What specific urgent investigations are indicated?

• CT scan• Glucose and electrolytes, serum

Calcium• Toxicology

What will you prescribe?

• Correct electrolytes, dehydration, hypoglycaemia

• Oxygen

• Treat alcohol withdrawal Vit B complex (Pabrinex)

• Give anti-epileptic treatment

Urgent anti-epileptic treatment for repeated fits

• Lorazepam 4mg iv (repeat once after 10 mins if fits again)

• If no control after 30 mins Phenytoin 15mg/kg iv (1g for 70kg person over 20 mins), monitor BP & ECG, then maintenance dose of 100mg every 6-8hrs

• Consideration of ITU at 60 mins• Subsequently:-

– Consider need for maintenance treatment• Carbamazepine• Valproate• Phenytoin• Lamotrigine

• Advise not to drive

Key features of drugs

• Lorazepam – potent benzodiazepine with short half life

• Phenytoin – – highly effective in controlling status epilepticus

/ repeated fits– Low therapeutic ratio / complex

pharmacokinetics / many adverse effects / precautions / drug interactions

Key features of drugs

• Carbamazepine– Effective prophylactic in most common epilepsies– Powerful enzyme inducer– Toxicity includes hepatic and blood disorders and

hyponatraemia (SIADH)

• Valproate– Also widely effective including absence seizures– Possibly less problematic

• A 60 year old man presents with severe shortness of breath at rest and orthopnoea. He has been waking at night with frightening episodes of dyspnoea. He is distressed and sweaty. Examination reveals elevated JVP some oedema of ankles. Crepitations throughout the lungs. Gallop rhythm at 120/min. BP 140/90.

• He had suffered an anterior myocardial infarction 3 years previously and has been on tablets for blood pressure.

Heart failure - approaches• Improve oxygenation• Reduce pre-load

– Reduce blood volume – Diuretics– Increase vascular capacity – Nitrates and other

vasodilators• Reduce afterload

– ACE inhibitors / AII blockers• Reduce demands on myocardium

– Beta blockers– (calcium channel blockers)

• Increase force of contraction– Digoxin

• Reducedistress– Morphine

• Avoid fluid overload, sodium retaining drugs, negative inotropes, arrhythmogenic

`

Severe heart failure

• Acute SOB, frothy sputum, tachypnoea, course crackles, hypoxia. May be cardiac history, ECG usually abnormal.

• Is there a precipitating cause? • Need to exclude acute MI or arrhythmia• Urgent ECG, CXR, bloods (inc TnI), ABGs• Pay close attention to BP

Severe heart failure - treatment

• Sit patient up, give high flow O2 (60-100%)

• Furosemide 40-120mg iv

• Diamorphine 2.5-5mg iv

• Metaclopramide 10mg iv

• GTN spray s/l then GTN (isoket) infusion 1-10mg/hr (monitor bp)

Key drug features

• Furosemide – loop/high ceiling dose diuretic– Safe for rapid IV injection, rapid diuresis but

depends on renal function– Risk of over-diuresis, hypokalaemia, and in

longer term gout and hyponatraemia

• ACE inhibitors – Risk of early drop in BP and renal function– Minor hyperkalaemia and cough in long term

Key drug features

• Digoxin – NA/K ATPase inhibitor– Negative chronotrope/positive inotrope– Most useful in atrial fibrillation / limited in SR

(except in children)– Risk of AV block / supraventricular and

ventricular tachyarrhythmias esp if low K+– Elderly and renal impairment predispose to

toxicity which starts with nausea and progresses to CNS effects.

• Morphine – CNS effects – also venodilator

Key drug features

• Nitrates – venodilators– Reduce pre-load therefore good in LVF with

preserved cardiac output– Sublingual / iv infusion– Risk to BP

• Beta blockers– Reduce mortality in heart failure in long term

by decreasing sympathetic drive but use only when stable or if severe tachycardia

Acute Pain• Paracetamol

– Effective as aspirin, antipyretic but not anti-inflammatory, not GI adverse effect, dangerous in o/d

• Codeine– Opioid so causes drowsiness and constipation

• NSAIDs– Effective in somatic pain but risk of/in GI, renal, heart failure,

hypertension, hypersensitivity, hepatic damage, alveolitis, skin diseases, pancreatitis. Drug interactions ++

• Opiates, Morphine and diamorphine– Vary in potency for somatic and visceral pain and adverse effect

but all tend to affect mood, respiration, GI motility. Risk of addiction

• A 90 year old lady is admitted coughing up blood and with pleuritic pain in her R side

• She had had bilateral ankle swelling

• CXR clear, D dimer raised, S1Q3T3 on ECG

• Current treatment amoxycillin –just started, carbamazepine for trigeminal neuralgia, aspirin prophylactic, diclofenac for shoulder pain.

Outline of treatment regime

• Low molecular weight heparin for 5 days

• Load with warfarin

• Daily INR

• Adjust warfarin according to recommendation on chart

• Deal with over anti-coagulation according to BNF

Key features of anticoagulants

• Warfarin – suppresses synthesis of Vit K dependent

clotting factors in liver (II,VII,IX and X). Therefore slow onset and offset.

– Effect easily monitored by prothrombin time (INR)

– Dose requirement highly susceptible to pharmacokinetic and pharmacodynamic variation from disease states, drug interaction and compliance.

– Many people die from over anti-coagulation each year

WARFARIN- Indications

Long-term anti-thrombotic treatment

• Treatment of DVT or PE

• Prevention of arterial thrombosis in……– Atrial fibrillation– Mechanical or bio-prosthetic valves– Peripheral vascular disease– Cerebrovascular disease– Ischaemic heart disease

WARFARIN- Important interactions

• Assume all co-prescriptions will alter warfarin dose response

Cause over-anticoagulation

AmiodaronePPI’sStatinsFluconazoleErythromycin

Cause under-anticoagulation

BarbituratesCarbemazepineRifampicinCholestyramine

•Anti-platelet agents increase bleeding risk

Description & action- HEPARIN

• Parenteral anticoagulant

• Naturally occurring glycosaminoglycan

• Mixture of different length molecules

(UFH av. 50 LMWH av. 15-20)

How it works• Increases activity of plasma Antithrombin

• Inhibits active clotting factors esp. factors IIa and Xa

(LMWH inhibits Xa better)

PHARMACOLOGY OF HEPARINS

UF HEPARIN LMW HEPARIN

RouteRoute IV SC

BioavailabilitBioavailabilityy

Variable, poor

Predictable, good

MetabolismMetabolism Complex, mostly renal

Predictable renal

TT1/2 1/2 (hours)(hours) 1-2 4-6

Presentation- UF Heparin

• Vials containing..

25,000 IU/ml (sc)5,000 IU/ml1,000 IU/ml (flush)10 IU/ml (flush)

Typical dose5000 IU loading then 30,000 IU by iv

infusion / 24 hrs

Presentation- LMW heparin

• 4 generic preparations

eg Tinzaparin (Innohep)

Enoxaparin (Clexane)

• Pre-filled syringes

Clexane 100 mg/ml; 20, 40, 60, 80, 100, 120, 150 mg syringes

Typical doses

40mg sc once daily ‘prophylactic’

100 mg sc once daily ‘treatment’

HEPARINS- Indications

Anti-thrombotic activity with rapid onset /offset

• Initial treatment of DVT or PE LMWH

• Acute coronary syndromes LMWH

• Cardiothoracic surgery UFH

• Other extra-corporeal circuits UFH

• Warfarin unsuitable esp pregnancy LMWH

• Prophylaxis against venous thrombosis LMWH