Transcript Drugs for the MAU - University of Bristol

Drugs for the MAU
Clive Roberts
Which drugs am I expected to know about??
Extract from 5th year handbook
You 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
So what are drugs good at treating (or
preventing)?
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Pain
Inflammation
Infection
Fluid retention
Heart problems
High blood pressure
Epilepsy
Parkinsonism
Asthma / COPD
Peptic ulcer disease
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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
Antibiotic guidance
Infection
Antibiotic Treatment
Infective Exacerbation
of COPD
Amoxicillin 500mg po tds
5-7 days
•Doxycycline 100mg po bd
5 -7days
•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
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
•Severe
•Penicillin allergic
•Levofloxacin 500mg IV bd
•(Switching to Moxifloxacin 400mg po
od)
•7-10 days
•Penicillin allergic
Community Acquired
Pneumonia
Risk 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
Duration of
Treatment
Non-severe
Comments
•*Amoxicillin monotherapy may be
considered for (i) those previously
untreated in the community or (ii)
those admitted to hospital for nonclinical reasons who would otherwise
be treated in the community.
•If systemic sepsis add
Gentamicin 5mg/kg IV stat
pending culture results
• 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?
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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
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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
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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 (60100%)
• 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
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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
Cause
under-anticoagulation
Amiodarone
PPI’s
Statins
Fluconazole
Erythromycin
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
Route
LMW HEPARIN
IV
SC
Variable,
poor
Predictable,
good
Metabolism
Complex,
mostly renal
Predictable
renal
T1/2 (hours)
1-2
4-6
Bioavailability
Presentation- UF Heparin
• Vials containing..
25,000
5,000
1,000
10
IU/ml (sc)
IU/ml
IU/ml (flush)
IU/ml (flush)
Typical dose
5000 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