Drugs for the MAU

(Medical Admissions Unit)

Clive Roberts

Who comes in on medical take? • 30 to 40 patients per day

• GI haemorrhage

• Acute myocardial

ischaemic episodes

• Heart failure

• Convulsions/seizures/

epilepsy

• Pneumonia

• COPD and asthma

• Supraventricular

arrhythmia / bradycardia

• Neurological events / CVA

• Acute alcohol related

• Chronic liver disease

• Falls / collapses

• DVT and PE

• Vomiting +- diarrhoea

• Urinary infection

• Diabetes

• Acute renal insufficiency

• Hypertension

• Headache ? meningitis

• Confusion on dementia

• Unwell ? Cause

• Cellulitis / infections

• Skin diseases

• New neoplasm

• Overdose – self inflicted

• Anti-coag out of control

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

• Thrombo embolism

• Anxiety/sleeplessness

• Psychosis

• Metabolic /endocrine diseases

• Malignant disease

• Degenerative disease

• Haematological problems

• Depression

So what are drugs bad for causing?

• Blood pressure

instability

• Arrhythmia

• Myocardial depression

• Fluid retention

• Electrolyte and

metabolic changes

• Haematological

problems

• GI bleeding points

• Nausea

• Diarrhoea/constipation

• Confusion

• Neurological syndromes

• convulsions

• Renal impairment

• Hepatic reactions

• Skin diseases

• Interaction (warfarin)

• Respiratory depression

• 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

• Exclude – Sedatives

– B blockers

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

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, masking f

physical signs, risk of hypocorticism

Infection Antibiotic TreatmentDuration of

TreatmentComments

Infective Exacerbation

of COPD

Amoxicillin 500mg po tds 5-7 days

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

Community Acquired

PneumoniaRisk Factors in CAP

(CURB-65)

C = Confusion MTS 8 or less

U = Urea > 7mmol/l

R = Resp. Rate >/= 30/min

B = BP Systolic < 90 mmHg

+/- Diastolic </= 60 mmHg

65 = age >/= 65 yrs

3 or more of the above risk

factors (CURB-65 Score

>/=3) = Severe Community

Acquired Pneumonia

Non-severe •Amoxicillin 500mg–1gram po tds

plus* Clarithromycin 500mg po bd

Amoxicillin 500mg-1gram IV tds

plus* Clarithromycin 500mg IV bd

can 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

– Hypoglycaemia

– Hyponatraemia

– 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

Amiodarone

PPI’s

Statins

Fluconazole

Erythromycin

Cause

under-anticoagulation

Barbiturates

Carbemazepine

Rifampicin

Cholestyramine

•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

Route IV SC

Bioavailability Variable,

poor

Predictable, good

Metabolism Complex, mostly renal

Predictable renal

T1/2 (hours) 1-2 4-6

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

Prophylaxis against venous

thromboembolic disease on the

MAU• All patients unless:

– Rapid mobilisation expected

– Bleeding source known

– Bleeding risk identified

– Uncontrolled hypertension

– Renal impairment

A 70 year old man presents with a heart rate of 124 per

min. He is sweaty and a bit SOB. ECG shows narrow

complex tachycardia possibly atrial flutter.

• Adenosine causes slowing and reveals Atrial Flibrillation

• Consider need for cardioversion – either DC or chemical

• Chemical cardioversion – Amiodarone

• If no CVS embarrassment – Digoxin and beta blockade

• Prophylaxis against PAF or SVT – beta blocker,

flecainide or amiodarone

• Anti-coagulate all stable AF unless contraindicated

• If ECG thought to show VT- lignocaine or amiodarone

or DC shock

Drugs to control heart rate

• Class 1 – membrane stabilisers – lignocaine and

flecainide

• Class 2 – beta blockade

• Class 3 – prolong action potential duration –

amiodarone and sotalol

• Class 4 – Calcium channel blocker – Verapamil

• Adenosine – blocks conduction and impulse

propogation – effective in SVT

• Digoxin – blocks conduction – controls

ventricular rate in AF

• Atropine – blocks parasympathetic – increases

rate in bradycardias.

Amiodarone

• Prolongs action potential therefore increases

refractory period probably by blocking

potassium channels

• Therefore potent antiarrhythmic effect for both

supra- and ventricular arrhythmias

• No negative inotropic effect but sometimes

hypotension

• Huge volume of distribution and so v long half

life

• Unpleasant catalogue of adverse effects –

thyroid, skin, eye, liver, lung, nervous system