PPT - Drugs Flashcards
Cyclizine
H1 Receptor Antagonist
Actions: sedative (less so than others), antiemetic
MOA: Competitive inhibition of H1 receptor in vestibular nuclei and vomiting centre.
ADE: significant first pass metabolism
Use: nausea in early pregnancy. Motion sickness and other emesis of vestibular origin
Side effects: sedation, confusion in elderly, severe respiratory depression in under 2s, dry mouth (anticholinergic)
Promethazine
H1 Receptor antagonist
Actions: sedative, antiemetic
MOA: Competitive inhibition of H1 receptors in vestibular nuclei and vomiting centre
ADE: significant first pass metabolism
Use: nausea in early pregnancy. Motion sickness. Meniere’s or other causes of emesis that is vestibular in origin.
Side effects: sedation, confusion in elderly, respiratory depression in under 2s, dry mouth (anticholinergic)
Ondansetron
5HT3 receptor antagonist
Actions: antiemetic
MOA: competitive inhibition of 5HT3 receptors in chemoreceptor trigger zone (CTZ) and at sensory endings of vagal afferents in GIT
ADE: Metabolised by cytochrome p450
Use: chemotherapy related sickness. Post-op or post-radiotherapy. Limited efficacy in motion sickness.
Side effects: well tolerated. GIT disturbance and headache.
Metoclopramide
D2 receptor antagonist
Actions: antiemetic. antipsychotic
MOA: Competitive antagonism of D2 receptors in the chemoreceptor trigger zone.
ADE: P450 metabolism
Use: N&V post chemotherapy, radiotherapy and surgery.
Side effects: EPS (Parkinsonian symptoms). Prolactin release (galactorrhoea), hypotension, antihistamine and anitmuscarinic actions.
Carbemazepine
Sodium channel blocker
Actions: anticonvulsant, relieves neuropathic pain
MOA: blocks Na channels in inhibit action potential initiation and propagation. Acts preferentially on epileptic focus (rapid firing)
ADE: P450 metabolism
Use: epilepsy (partial and generalised), NOT ABSENCE. neuropathic pain, bipolar disorder
Side effects: drowsiness, headache, mental disorientation, motor disturbance
Rare: liver damage, agranulocytosis, aplastic anaemia
P450 INDUCER
Phenytoin
Sodium channel blocker
Actions: anticonvulsant
MOA: Blocks Na channels to inhibit propagation and initiation of action potentials
ADE: P450 inducer
Use: generalised and focal seizures, not absence. bipolar, neuropathic pain
Side effects: drowsiness, headache, mental disorientation, motor disturbance
Rare: liver damage, agranulocytosis, aplastic anaemia
TERATOGEN - cleft palate
Lamotrigine
Inhibits glutamate release
Action: anticonvulsant
MOA: inhibits glutamate release and decreases post-synaptic excitation. May be due to Na channel inhibition
Use: partial and generalised seizures. Bipolar.
Side effects: dizziness, headache, double vision, sedation
Diazepam
Benzodiazepine receptor agonist
Actions: anticonvulsant. hypnotic. anxiolytic
MOA: benzodiazepine receptor agonist on GABA receptor enhancing channel opening by GABA. Increases Cl influx reducing excitability
Use: status epilepticus
Side effects: sedation, tolerance, addiction
Severe respiratory depression
Clonazepam
Benzodiazepine receptor agonist
Actions: anticonvulsant. hypnotic. anxiolytic
MOA: benzodiazepine receptor agonist on GABA receptor enhancing channel opening by GABA. Increases Cl influx reducing excitability
Use: tonic clonic and absence seizures
Side effects: sedation, tolerance, addiction
Severe respiratory depression
Phenobarbital
Barbiturate agonist
Actions: anticonvulsant
MOA: binds to barbiturate site on GABA receptor causing increased opening. Increasing Cl- influx decreasing excitability.
Use: tonic clonic and simple partial seizures.
Side effects: highly sedative. megaloblastic anaemia. hypersensitivity reactions
OD = coma, respiratory and cardiac failure
P450 INDUCER
Vigabatrin
GABA transaminase inhibitor
Actions: anticonvulsant
MOA: inhibits GABA transaminase which breaks down GABA. Increase synaptic GABA, increase Cl- influx, reduce excitability
Use: adjunct to other anticonvulsants
Side effects: sedation, fatigue, hyperactivity in children
Visual field defects if long-term use
Gabapentin
Calcium channel blocker
Actions: anticonvulsant, analgesic
MOA: Blocks voltage activated Ca channels to block calcium entry and prevent exocytosis of glutamate
Use: adjunct for partial seizures, neuropathic pain
Side effects: sedation, dizziness, unsteadiness
Pregabalin
Calcium channel blocker
Actions: anticonvulsant, analgesia
MOA: blocks voltage gated calcium channels to prevent calcium influx therefore restricting exocytosis of glutamate
Use: adjunct for partial seizures, neuropathic pain
Side effects: dizziness, sedation, unsteadiness
Sodium valproate
Na channel antagonist & inhibits GABA transaminase
Action: anticonvulsant, mood stabiliser
MOA: blocks voltage gated sodium channels to inhibit action potential initiation and propagation.
Inhibits GABA transaminase to decrease GABA breakdown, increase synaptic GABA, decreased excitation
Use: epilepsy. Manic phase of bipolar. Migraine
Side effects: nausea and vomiting, tremor, weight gain, reproductive dysfunction, hepatic and pancreatic toxicity
TERATOGEN: neural tube defects
Ethosuximide
Calcium channel blocker (neuronal)
Action: anticonvulsant
MOA: blocks T type sodium channels in thalamic neurons to counteract slow 3Hz spike and wave firing
Use: absence seizures
Side effects: anorexia, GI upset, rash, drowsiness, fatigue
Topiramate
Glutamate receptor antagonist
Actions: anticonvulsant
MOA: block AMPA receptors for glutamate and sodium channels and potentiates GABA actions
Use: generalised tonic clonic seizures, partial seizures. Migraine
Side effects: psychomotor slowing, memory impairment, paraesthesia, sedation, fatigue, confusion, decreased appetite and weight.
Rare: vision loss
Side effects of amlodipine
Postural hypotension
Peripheral oedema
Side effects of furosemide
AKI
Dehydration
Postural hypotension
Hypokalaemia
AMTS
Age DOB Place Time Year Give 42 West Street WWII Current monarch Recognise 2 people Recall 42 West Street Count 20-1
Symptoms of hyponatraemia
Off legs
Instability
Confusion
Immobility
Nausea and vomiting
Postural hypotension
Decreased appetite
Very low - seizures
Causes of hyponatraemia
Heart failure, liver failure, renal failure
Infection
Drugs - diuretics, SSRIs, PPIs, phenytoin
SIADH - lung cancer, infection
Stroke
Brain tumour
Primary aldosteronism (Addison’s)
Treatment of hyponatraemia
IV fluids
TRICKLE and check every 4 hours
Too quick an increase can cause CENTRAL PONTINE MYELINOSIS
Treatment of hypernatraemia
IV 5% dextrose
Drop slowly - check regularly
No more than 8 mmol/L drop in 24 hourss
Causes of hyperkalaemia
Sando K ACEi ARBs Potassium sparing diuretics Haemolysed blood sample Thrombocytosis
ECG changes in hyperkalaemia
Tented T waves
Broad QRS –> sine
Hyperdynamic T waves
Treatment for hyperkalaemia
Calcium carbonate/gluconate - to stabilise myocardium
Insulin and dextrose infusion
Repeat - if it fails then renal haemofiltration
Causes of hypokalaemia
Diuretics
Vomiting
Chronic diarrhoea
Bullaemia
Symptoms and ECG changes in hypokalaemia
Achy
Nausea
Fatigue
Unwell
ECG: u waves
Treatment for hypokalaemia
IV 20-40mmol/L
Sando K
Stop diuretics
Symptoms of hypercalcaemia
Headache Aches and pains Bone pain Constipation Renal stones Polyuria Polydipsia Confusion Depression
ECG changes in hypercalcaemia
shortened QT interval
Treatment of hypercalcaemia
IV fluids
Loop diuretic
Bisphosphonates
Prednisolone if due to malignancy
Causes of hypercalcaemia
Bony mets (BBKTP) Breast Bowel Kidney Thyroid Prostate
Myeloma
PTH secreting tumours
Primary hyperparathyroidism (most common)
Thiazide diuretics
Iatrogenic (Calcium supplements)
Milk alkali syndrome
Symptoms of hypocalcaemia
periorbital tingling
muscle twitching
What is the dollshead reflex?
When you roll the head
Eyes should move together in opposite direction to head movement
Aetiology of coma
Vascular - cerebral hypoperfusion (cardiac), cerebrovascular accident, hypertensive encephalopathy
Infection - meningitis, encephalitis, abscess, malaria, toxoplasmosis
Trauma - SAH, SDH, depressed skull fracture
Autoimmune - vasculitis
Metabolic - hypo/hyperglycaemia, hypercalcaemia, hyper/hyponatraemia, hypopituitarism, hypothyroid, hypoxia, hypercapnia
Neoplasm - brain tumour, SOP
Drugs - over dose sedative, alcohol
Carbon monoxide poisoning
Investigations in coma
Blood glucose ABG Bloods - FBC, U&Es, LFTs, TFTs, troponin Urine dip and pregnancy test Paracetamol and salicylate levels Blood cultures Blood films for malaria Ethanol levels ECG CXR Head CT/MRI EEG LP
Management of coma
Resuscitation - intubation and ventilation if needed IV thiamine and glucose if cause unclear Trial naloxone and flumazenil Mannitol if raised ICP Fluid rehydration Prevention of pressure sores Adequate nutrition
Drugs contraindicated in breast feeding
Almost all drugs pass into breast milk but these are contraindicated
Amiodarone Chloramphenicol Chemotherapy agents Iodine Methotrexate Lithium Tetracycline Pseudoephedrine Ergotamine Cabergoline Ergot alkaloids
Drugs that decrease milk production
progestins
oestrogens
ethanol
bromocriptine
MOA of local anaesthetics
Reversible blockade of voltage gated sodium channels
Stages of Na+ channels
Resting - closed but able to open
Open - allow rapid influx
Inactivated - rapid change at cytoplasmic end. Resistant to depolarisation.
Factors that influence local anaesthetic action
Local concentration of LA
Size of nerve fibre
Nerve myelination
Length of nerve exposed to LA
Which nerve fibres carry pain? How are they affected by LA
A delta
C fibres
Blocked quicker than motor and sensory nerves
Most rapidly affected by LA
Have longest LA effect
What determines the intrinsic and clinical potency of local anaesthetics
Intrinsic
- pH and kPa
- Lipophilic hydrophilic balance
Clinical
- vasoconstrictor use
- fibre size, type, myelination
- frequency of nerve stimulation (increase = increased potency)
- Electrolyte concentration
Describe components of local anaesthetic
Lipophilic end - allows for transfer across nerve membrane
Amide bond
Hydrophilic end - allows binding to sodium channels once across lipid membrane
- ## LAs are weak bases
Relationship between kPa and pH (onset and block)
The closer the pKa is to physiological pH then faster onset due to high concentration of non-ionised base
(when non-ionised it is lipid soluble)
The higher the kPa the slower the onset but the more effective the block
What can be added to local anaesthetic
Bicarbonate to increase speed of onset
Adrenaline to increase duration time (not in digits)
Differences between epidural and spinal
Epidural is above dura, leave in catheter for top ups, 15-30 minute onset
Spinal
- Into subarachnoid space
- much lower drug doses (especially opioids)
Both between L3 and 4
Spread depends on density of solution and posture post event
Side effects of local anaesthesia
Irritiation and inflammation
Iscahemia (if using vasoconstrictor)
CV
- myocardial depression
- vasodilation and hypotension
- arrhythmia
CNS
- agitation
- confusion
- tremor
- convulsions
What dose is in 10ml of 1% lidocaine?
1g in 100ml
100mg in 10ml
Steps in general anaesthetic?
- premedication
- induction
- muscle relaxant and intubation
- maintenance of anaesthesia
- analgesia
- reversal
Action of IV anaesthetics
Potent amnesics
Potent sedatives
Weak muscle relaxants
Enhance activity at GABA A receptors
Factors affecting inhalation anaesthesia
Absorption of alveolar membranes
Solubility
Cardiac output
Relative concentration at brain in equilibrium
What is MAC?
Minimum alveolar concentration
Measures potency
concentration of a vapour in the lungs that is needed to prevent movement (motor response) in 50% of subjects in response to surgical (pain) stimulus
