Respiratory + Pain Drugs Flashcards
What do you use paracetamol for
1) 1st line - acute and chronic pain
2) Antipyretic
How does paracetamol work
Weak inhibitor of COX
In the CNS COX Inhibition appears to increase the pain threshold and reduce prostaglandin concentration in the thermoregulatory centre of the hypothalamus
Which COX is paracetamol specific for?
COX 2 –> however it is only a weak inhibitor as its actions are inhibited by peroxides
What inhibits the action of paracetamol
peroxides
Adverse effects of paracetamol
Generally very safe
This is because lack of COX-1 inhibition prevents, GI, renal and CV implications
How is paracetamol metabolised
By CP450 enzymes in the liver
Metabolised to NAPQI that is conjugated with glutathione
In overdose NAPQI builds up causing hepatocellular necrosis
When should we reduce paracetamol dose
In those at risk of liver toxicity e.g.
Increased NAPQI production –> chornic excessive alcohol use or inducing enzymes
Decreased glutathione stores –> malnutrtion, low body weight, severe hepatic impairment
What does patacetaml interact with
CP450 Inducers e.g. carbamazepine and phenytoin
This increase the rate paracetamol is metabolised hence increased NAPQI production and risk of liver toxicity
How do we establish the efficacy of n-acetylcysteine in treating paracetamol overdose?
Test INR, ALT and creatinine
Name strong opioids
Morphine, Oxycodone
What do we use strong opioids for
Acute severe pain - rapid onset e.g. post-op and MI
Chronic pain –> step 3
Breathlessness –> relieves it in end of life care
Acute pulm oedema –> with furosemide and oxygen and nitrates
How do strong opioids work
Activation of opioud mu receptors in the CNS
Decreases neuronal excitability and pain transmission
In the medulla they blunt the response to hypoxia and hypercapnia –> hence redce breathlessness
AS they relieve pain also decrease sympathetic stimulation –> this may reduce cardiac work and oxygen demand hence relieving symptoms in MI and pulm. oedema
Adverse effects of strong opiods
1) Respiratory depression
2) Neurological symptoms
3) Nausea and vomiting –> as they activate chemoreceptor trigger zone –> usually decreases with time but offer them an anti-emetic
4) Pupillary constriction –> activate the Edinger-Westphal nucleus
5) Constipation –> decrease motility and increase smooth muscle tone
6) itching, urticaria, vasodilation and sweating –> as may cause histamine release
7) Toelrance
8) Withdrawal reaction –> anxiety, pain, breathlessness, pupils dilate, cold and dry skin
Warnings of strong opioids
Redice dose in hepatic or renal impairment
Avoid in respiratory failure
Avoid in biliary colic –> can cause smooth muscle contraction and spasm of Sphincter of Oddi –> worsens pain
Interactions of strong opioids
Dont use with other sedating drugs e.g. anti-psychotics, benzodiazepines or tricyclic antidepressants.
Name opiate compounds
Co-codamol
Co-dydamol
Indications for opiate compounds
Treatment of mild-moderate pain –> when paracetamol is insufficient
Overdose effects of opiate compounds
Hepatotoxicity - paracetamol
Neurological and respiratory depression - opiods
Warnings of opiate compounds
Extreme caustion in significant respiratory disease
Dose reductin in renal/hepatic impairment
What should we avoid prescribing opiate compounds with
Other sedating drugs (tricyclic antidepressants, benzodiazepines, antipsychotics)
Name weak opiods
Codeine, Dihydrocodeine, Tramadol
How do weak opiates work
Codeine and dihydrocodeine metabolised by the liver to produce small amounts of morphine/dihydromorphine
Why do some poeple find opiates ineffective
10% of caucasians have an enzyme CP450 2D^ that is less active hence don’t metablise it
What is tramadol
Synthetic analogue of codeine
What effects does tramadol have
As well as opiate effect also acts via adrenergic and serotonin pathways
Prevents the reuptake of noradrenaline and serotonn
Adverse effects of weak opiods
Nausea Constipation Dizziness Drowsiness Neurological and respiratory depressoin
Tramadol causes less constipation and respiratory depresssion
What route should you never give codeine/dihydrocodeine
IV - causes a severe reaction, similar to anaphylaxis but it is actually mediated by histamine
Caution in giving weak opiods in
1) Significant respiratory depression
2) renal/hepatic impairment –> need a dose reduction
3) Epilepsy and unvontrolled epilepsy –> tramadol lowers the seizure thresholds
Interactions of weak opiods
1) avoid with other sedating drugs (anti-psychotics, benzodiazepines, tricyclic antidepressants)
2) Dont use tramadol with other drugs that lower the threshold potential (SSRIs and tricyclic antidepressants)
Name inhaled corticosteroids
Beclometasone, Budesonide, fluticasone
Uses of inhaled steroids
1) Asthma –> decreases airway inflammation
2) COPD –> controls symptoms and reduces exacerbations
How do steroids work
Downregulate pro-inflammatory interleukins, cytokines and chemokines
Upregulate anti-inflammatory proteins
Reduces mucosal inflmation, widens airways and reduces exacerbations and mucus secretions
Adverse effects of inhaled steorids
Oral candidiasis
Hoarse voice
Increased risk of pneumonia in COPD
Is asthma or COPD steroid responsive?
Asthma - generally steroid responsive and stops disease progression
COPD - generally poorly responsive to steroids and dose not stop disease progression
Warnings of using inhaled steroids
1) COPD With history of pneumonia –> caution in high dose steroids
2) CHildren - high dose steroids shouldn’t be used in children unter 16
Name systemic corticosteroids
Dexamethasone
Prednisolone
Hydrocortisone
Usually oral except give IV dexamethasone for cerebral oedema due to cancer
Uses of systemic corticosteroids
1) Allery/inflammatory disorders
2) suppression of autoimmune diseases
3) Cancer
4) Hormones replacement
What metabolic effects do systemic corticosteroids have
Increase gluconeogenesis from circulationg amino acids and fatty acids
What mineracorticoid effects do systemic corticosteroids have?
Act like aldosterone
Cause sodium and water retention and potassium excretion
Adverse effects of systemic corticosteroids
Immunosuppresion
Metabolic: DM and osteoporosis
Increased catabolism causes proximal muscle weakness, skin thinning, easy brusising
Mood changes: insomonia, confusion, psychoisis
Mineracorticoid effects Lhypertension, low potassium and oedema
Adrenal atrophy
Caution of systemic steroids in who
In infection ad children
Interactions of systemic steroids
1) NSAIDS –> increased risk of pepetic ulcers and GI bleeds
2) Beta 2 agonists, theophylline, loop/thiazine diuretics - all cause low potassium
3) Cytochrome P450 inducers (carbamazepine, phenytoin, rifampicin) –> this reduces corticosteroids efficacty
4) Vaccines –> reduces immune response
What shall we consider the use of in long term systemic steroids use
Bisphosphonates –> stops osteoporosis
PPI –> prevents ulcers
In long term also monitor HbA1c and DEXA scans
Name topical corticosteroids
Hydrocortisone, betamethasone
Uses of topical steroids
Inflammatory skin conditions e.g. eczema
Adverse effects of topical steroids
Potent can cause thinning of skin, striae, telangextasia, contact dermatitis
Perioral dermatitis and acne exacerbation if on face
Contraindiciations of topical steroids
Infection present
Facial lesions
How long can you use topical steroids for
2 weeks max, 1 week if on face
Name NSAIDS
Naproxen, ibuprofen, diclofenac and etroicoxib
What is etoricoxib
A Slective COX-2 Inhibitor
What do you use NSAIDS for
As needed traetment for pain
Regular treatment of pain related inflammation
What should you take NSAIDS with
FOOD –> avoids stomach upset
How do NSAIDS work?
Inhbiit COX enzymes –> prevents the synthesis of prostaglandins from arachadonic acid
What do the 2 different types of COX do?
COX - 1, the constitutive form
Stimulates prostaglandin synthesis that is essential to rpeserve integrity of the gastic mucosa, maintain renal perfusion (as dilates the afferent glomerular arteriole) and inhibits thrombus formation at the vascular endothelium
COX-2 inducible form expressed in response to inflammatory stimuli –> stimulates production of prostaglandings that cause inflammation
Whcih COX enzyme inhbition causes therapetic effects and which causes adverse effects
COX - 1 = adverse effects
COX - 2 = therapeutic effects
Adverse Effects
GI toxicity
Renal Impairment
Cardiovascular events
Hypersensitivity Fluid retention (espesically if given with loop diuretics)
Who should we avoids NSAIDS in
Renal impairment Heart failure Peptic ulcer disaese Liver failure Hypersensitivity
Interactions of NSAIDS
GI ulceration –> low-dose aspirin, corticosteroids
GI bleeding –> anticoagulants, SSSRIS, venlafaxine
Renal Impairment –> ACEi, diuretics
Who should we consider gastroprotection in for NSAIDS?
1) OVer 65
2) Previous peptic ulcer disease
3) Other drugs with GI effects, particularly low dose aspirin and prednisolone
Name some anticholinergics/antimuscuranics
Ipratropium
Tiotropium, glycopyronium (long acting)
Uses of anticholinergives
1) COPD –> short acting used to relieve brethlessness, long acting to prevent breathelssness
2) ASthma –> short acting used as an adjuvant for breathlessness during acute exacerbations
Long acting are added at step 4 of chronic asthma treatment
How do anticholinergics work?
Competitive inhibitor of acetylcholine at the muscarinic receptor!!
Normally receptor stimulation causes parasympathetic effects
What happens when you block the anticholinergic receptor?
Decreased Heart rate
Decreased smooth muscle tone
Decreased secretions from respiratory and GI tract
ALSO CAUSES RELAXATION OF PUPILLARY CONTRICTOR AND CILIARY MUSCLES –> causes pupilllary dilation and prevents the accomodation reflect
Adverse effects of anticholinerigcs
Dry mouth
Caution of using antichlinergics
Angle-closure glaucome
Can precipitate a dangerous rise in intraoccular pressure
Caution if arrhytmias
Interactions of antibholinergics
Generally none as little systemic absoprtion as it is inhaled
Name Beta-2-agonists
Salbutamol, terbutaline (short acting)
Salmeterol, formaterol (long acting)
Indivations of beta 2 agonists
1) Asthma: Short acting PRN for step 1, long acting as step 3 (but always give in combo with a steroid)
2) COPD: - short acting to relieve breathlessness, long acting = step 2
3) Hyperkalaemia urgent tratment: give with glucose, insulin and calcium gluconate
How do beta - 2- agonists work
Stimulates the receptor fround in the GI tract, bronchus, uterus and blood vessles
Causes smooth muscle relaxation
Also stimulates the Na/K ATPase pump (like insulin) causing potassium to be moved from extracellular to intracellular
Adverse effects of beta-2-agonists
Causes sympathetic response –> tachycardia, palpitations, fine tremore
Promotes glycogenolysis
Increaess serum lactate levels
Muscle cramp –> in long acting beta - 2- agonists
Caution of using beta-2-agonists
Only give long acting with inhaled corticosteroids
Caution in patients with V –> tachycardia may provoke angina arryhythimias
Interactions of beta-2-agonists
beta blockers reduce their effectiveness
Concommitant use of high dose nebulises beta 2 agonsit with theophylline and corticosteroids can cause hypokalaemia
What is seretide
combo of long acting beta - 2 agonists and a corticosteroid
Who do we give oxygen too
Hypoxaemia
Pneumothoraw
CO Poisonin
How does oxygen treat a pneumothoraw
decreaesse the partial pressure of nitrogen in alveolar gas hence accelerates its diffusions out of the body
How does oxygen treat CO poisoning
It competes with CO to bing to Hv therefore shortens the half life of carboxyhaemoglobin
Adverse effects of oxygen
mainly due to the felivery methods e.g. discomfort from face mask
Dry throat due to lack of humidity
Warnings of giving oxygen
Type 2 respiratory failure e.g. CO2, they have a hypoxic drive to breathe not hypercapnic
Heat sources/naked falmes
Target oxygen saturations§
94-98% for normal
88-92% for COPD
Name mucolytics
Carbocysteine
Indicationsf or mucolytics
Respiratory disoders characterised by excessive, viscous mucus
mechanism of carbocysteine
Reduces the viscosits of sputum to help relieve symptoms by alllowing the sufferer to bring up the sputum more easily
Targets glutathione S-transferase P protein
Adverse effects of mucolytics e.g. carboysteine
Skin rashes
Hypersensitivity
Stomach bleeding
Contraindications of mucolytics
Cough suppressants (antitussives) Active peptic ulcer disaese Lactose/fructose intolerance as contins these
Interactions of carbocysteine
Increased risk/severity of adverse effects when combined with chloramphenicol, disulram, gliclazide, ketoconazole, metronidazole, griseofulvin
What is theophylline
A methylxanthine
What do we use theophylline to treat
Severe asthma/treat nocturnal asthma symtpoms
How does theophylline work
Raises intracellular cAMP by competitvely inhibiting phosphodisesterase –> relaxes airway smooth muscles and inhibits mediator release from mast cells
Antagonism of adenosine (a potent bronchoconstrictor) at alpha 2 receptors
Anti-inflammatory activity on T-lymphocytes by reducing release of platelet-activating factors
GI adverse effects of theophylline
Nausea, vomiting, anorexia
Cardiovascular effects of theophylline
Dilatation of vascular smooth muscle –> headaches, flushing and hypotension
Tachycardia and cardiac dysrhytmias
CNS effects of theophylline
Insomnia Hypervenitlation Anxiety Agitations Headaches Fits
Interactions of theophyliine
Many drugs inhibit the CYP1A2 hepatic enzymes that eliinate theophylline
e.g. macrolides, fluoroquinolones, interferon, cimetidine
CYP450 inducers (phenytoin, carbamazepine, rifampicin) increase the metabolism of theophylline therefore reducing its efficacy)
