Drugs Flashcards
Sieve
C - class U - use P -presentation A - action D - dose O - onset/offset R - routes S - side effects E - everything else T - toxicity Kinetics - Absorption/Distribution/Metabolism/Excretion
Template
C - U - P - A - D - O - R - S - E - T - A - . D - . M - . E - .
Thiopentone
C - barbiturate
U - induction of anaesthesia / adjunctive management of status epilepticus
P - a hygroscopic yellow powder containing thiopental sodium and 6% sodium carbonate, stored under nitrogen gas. It is reconstituted in water to give a 2.5% solution. pH 10.8 and pKa 7.6.
A - barbiturates work by mimicking inhibitory GABAa-mediated Cl- influx at the GABAa r. also at other receptors (non-NMDA glutamate)
D - 3-7mg/kg IV for induction. 250mg boluses for status.
O - onset in 1 arm-brain circulation time. lasts for 5-15mins.
R - IV (and PR?)
S - CV-negative inotrope so decreases CO. Resp-depressant / Doesn’t suppress laryngeal reflexes so not ideal for LMA / CNS- reduces ICP and lowers cerebral metabolic rate and may improve outcomes in TBI / extravasation may lead to tissue necrosis / Inadvertent intra-arterial injection will lead to thrombosis / if mixed with acidic drugs (morphine) it will precipitate.
E - may induce porphyria crisis.
T - may induce porphyria crisis.
ADME - A? / D-highly protein bound (65-85%) + highly lipid soluble/ M- liver oxidised. short duration of action is not due to metabolism but rapid distribution into other compartments / E-in the urine as inactive metabolite.
Propofol
C - a phenol derivative - 2,6 di-isopropylphenol
U - induction of anaesthesia / maintenance of anaesthesia / sedation / status epilipticus
P - a white emulsion of propofol in soybean oil, egg phosphatide, benzyl alcohol and sodium hydroxide. At a pH of 7-8.5. Stable at RT.
A - multiple actions. potentiates GABAa / inhibits AchRs in the hippocampus / others.
D - 1-2.5mg/kg for induction. 4-12mg/kg/hr as infusion. dose reductions in elderly or unstable.
O - onset 30s. offset 5-10 mins.
R - IV
S - pain on injection / hypotension due to decreased SVR / apnoea
E - CV- marked hypotension due to decreasedSVR. attenuates response to laryngoscopy. works as antiemetic.
T - ppf infusion syndrome-prolonged infusions on ITU, esp pads. rhabdomyolysis, metabolic acidosis and MOF. Green urine and hair.
ADME - D-98% protein bound in plasma. distribution based on 3 compartment model . M-liver. rapid. conjugated into inactive metabolite. may also be some extra hepatic metabolism in the lungs. E-in urine. takes longer in RF.
Ketamine
C - a phencyclidine derivative
U - induction of anaesthesia (dissociative - between the limbic and the thalamoneocortical systems) / procedural sedation / analgesia / adjunct in rx-resistant asthma
P - clear colourless solution of racemic ketamine. equal mix of S and R enantiomers. Comes in 10/50/100mg/ml concentrations.
A - non-competitive antagonist of NMDAr. also inhibits pre-synaptic release of glutamate (probs analgesic mechanism). Also complex interaction with opioid receptors.
D - for dissociation IV 1-2mg/kg. IM 4mg/kg. 0.25mg IV for analgesia.
O - IM onset 2-8mins, lasts 10-20mins. IV onset 30s, lasts 5-10mins.
R - IV / IM / PO / PR / IN / epidural
S - CV- tachycardia and inc BP. RS-mild stimulant and relaxes bronchial smooth muscle. CNS- emergence delirium.dilated pupils and inc tone. Some ?concern over raised ICP and intra-ocular pressure. GI-hypersalivation. PONV.
E - S isomer 4x greater affinity for the NMDAr than R with twice the potency as an analgesic. S enantiomer is preservative free so can be given in epidural / Helps to prevent chronic pain and opioid tolerance.
T -
ADME - A-bioavailabilty 25% oral, 25-50% nasal, 95% IM. D- 20-50% protein bound. Vd large 3L/kg. can be given TCI with 3C model. M-liver by CYP450. E-in urine as conjugated metabolites. t1/2 2.5hours.
Etomidate
C - imidazole derivative
U - induction of anaesthesia
P - clear colourless solution of 2mg/ml etomidate in propylene glycol and water. Weak base. pH 8.1. pKa 4.2.
A - inhibits GABA type A receptors.
D - 0.3mg/kg IV.
O - onset 10-60s, offset 6-10mins. halve dose for elderly.
R - IV
S - pain on injection, PONV. safety issues - not to be used in critically ill as infusion as increases mortality. also not to be used in adrenal insufficiency as inhibits steroid production.
E - CV-relatively cardiostable. RS-resp depression. CNS-myoclonic movements. Also-inhibits platelet function.
T -
ADME - D- 75% protein bound. vd 4.5 l/kg. M- rapid by plasma and hepatic esterases. E- Approx 80% in urine. Rest in bile.
Nitric Oxide
C - anaesthetic gas
U - analgesic / sedation / to supplement anaesthesia
P - stored in french blue cylinders as a vapour over liquid.
A - inhibits NMDA receptors in the CNS
D - n/a
O - rapid onset and offset.
R - inhalational as an addition to anaesthetic gas or as a 50:50 mix O2 for Entonox.
S - N+V / hypoxic mixture (2nd gas effect) / B12 inhibition causing megaloblastic changes in BM if prolonged use / increased CBF so avoid in neurosurg / very slight rest + CVS depression.
E - MAC 103% / blood:gas coefficient 0.47 so rapid effect / Critical temp 36.5 / SVP 52000kPa
T - contraindicated in PTHX as N20 diffuses from blood into gas filled spaces / eye+middle ear surgery (same reason) /
Benzodiazepines
C - benzodiazepine. classified based on duration of action. oxazopam (short) / temaz+loraz (medium) / diaz+clonaz (long)
U - sedation / anxiolysis / anticonsulsant / muscle relaxant / amnesia
P - diaz as emulsion in intralipid / loraz in propylene glycol / midday @ ph 3 to make it water soluble.
A - GABAa agonists affecting Cl- influx. GABA is an inhibitory neurotransmitter so BZDs enhance GABA activity (hyperpolarizes cell)
D - dose depends on which BZD and desired effect.
O - onset/offset
R - IV (bolus or infusion) / PO / Buccal / PR /
S - mainly with prolonged use. sedation / memory impairment / poor coordination / dependence / withdrawal
E - zopiclone is not a BZD but acts on the same site of the GABAa.
T - common in OD. sedation / hypotension / bradycardia.
Kinetics - Highly protein bound and lipid soluble so cross BBB quickly / Metabolised in the liver by CYP450s / Excreted renal.
Aspirin
C - NSAID.
U - analgesic / antiplatelet
P - tablet form 75mg commonly
A - Irreversible inhibitor of COX1 + COX2
D - 300-900mg QDS / low dose 75g for IHD Rx.
O -
R - PO
S - GI upset / PUD / Reyes syndrome / platelet fx irreversibly affected for 7 days.
E - therapeutic benefit from COX2i…SEs from COX1i / inhibits thromboxane A2 and prostaglandins to prevent platelet aggregation.
T - hepatic+renal failure / tinnitus / hyperventilation and rest alkalosis / seizures. Rx - alkaline diuresis/CRRT.
A - from gut in unionised form. D. M - gut wall esterases + liver. first order kinetics until enzyme saturation then zero order. E - renal.
Paracetamol
C - NSAID
U - analgesic / antipyretic
P - 500mg tablets sometimes combined with a weak opiate. or liquid form for paediatrics / IV 10mg/ml.
A - selective COX3 inhibitor (mainly in the CNS)
D - 0.5-1g QDS. Decrease dose in low BMI or liver.
O -
R - PO / IV / PR
S - very few/rare.
E -
T - GI upset / liver necrosis / thrombocytopaenia. Occurs when saturation of liver enzymes and exhaustion of liver glutathione (NAC replaces this).
A - from gut bioavailability 80%. D. M - liver. E - renal.
NSAIDs
- Non-selective (ibuprofen/aspirin/naproxen/diclofenac) or Selective Cox2i (celecoxib/meloxicam).
- Selective has possibly fewer GI SEs.
- inhibits prostaglandins which reduces inflammation, temperature and pain.
- rapidly absorbed, metabolised in liver and excreted in urine/bile.
- Significant SEs…
- GI upset/PUD.
- Increased MI risk.
- Bronchospasm - leukotriene overproduction.
- Renal - decreased RBF as prostaglandins are renal vasodilators. Especially if hypovolaemic/old.
- Platelet fx - only Cox1i.
Morphine
C - Morphinan opioid
U - analgesia / sedation. Especially good for visceral pain. Less good for sharp/superficial pain.
P - clear colourless liquid in 10mg/ml vial.
A - Pure mu opioid receptor agonist.
D - 0.1-0.2mg IV / multiply dose by 4 for PO.
O - peak effect 10-20mins.
R - IV / PO / IM / SC / PR / intrathecal (preserve free)
S - resp depression / hypotension from histamine release / N+V / constipation / sedation+euphoria / pruritis / urinary retention.
E -
T -
A - bioavailability 25% due to 1st pass metabolism. pKa 8 so slow onset as ionized form in stomach. PO. D - . M - liver by glucuronidation. E - urine/bile t/12 3hours but very variable.
Diamorphine
C - Morphinan opioid but no affinity for MOPr. It is a prodrug with active metabolite.
U - analgesia
P - 10mg tablet / white powder that is easily dissolved prior to administration.
A - MOPr
D - 2.5-10mg IV / 0.1-0.4mg intrathecal.
O -
R - PO / IV / SC / epidural / intrathecal.
S - resp depression / hypotension from histamine release / N+V / constipation / sedation+euphoria / pruritis / urinary retention.
E -
T - same as morphine
A - well absorbed from gut as highly lipid soluble but low BA as 1st pass metab. D - pKa 7.6. M - liver and plasma esterases. E -
Fentanil
C - phenylpiperidine class of synthetic opioids.
U - severe pain / induction of anaesthesia
P - clear colourless liquid in 50mcg/ml vials. 100+500mcg vials.
A - MOPr
D - 1-2mcg/kg
O - rapid as very lipid soluble and crosses BBB easily.
R - IV / topical / mucosal
S - resp depression / hypotension from histamine release / N+V / constipation / sedation+euphoria / pruritis / urinary retention.
E -
T - same as morphine
A - highly lipid soluble. . D - Vd 4.0. Highly protein bound. pKa 8.4. M - .E - .
Alfentanil
C - phenylpiperidine class of synthetic opioids.
U - severe pain / induction of anaesthesia
P - clear colourless liquid in 500mcg/ml vials. 1000mcg vials.
A - MOPr
D -
O - more rapid onset than fentanyl despite being less lipid soluble…this is due to the low pKa 6.5…so 90% of drug is unionized at physiological pH…so creates a large conc gradient to cross BBB.
R - IV / intrathecal / topical
S - resp depression / hypotension from histamine release / N+V / constipation / sedation+euphoria / pruritis / urinary retention.
E -
T -
A - . D - Vd 0.6 so much smaller than fent. pKa 6.5. M - liver demethylated. E - .
Remifentanil
C - ester class of synthetic opioid
U - analgesia and as part of a balanced anaesthetic plan.
P - white powder in a glass vial containing 1,2 or 5mg. Also contains glycine so can’t be used intrathecal. Reconstitutes easily with saline.
A - MOPr
D - TCI model pump.
O - Rapid on and off.
R - IV infusion
S - resp depression / chest wall rigidity / hypotension from histamine release / sedation.
E - context sensitive half time is essentially unchanged by the duration of infusion as the elimination is dependent on the metabolism not the distribution.
T -
A - . D - Vd 0.3L/kg tiny. pKa 7.1 . M - rapidly broken down by plasma and tissue esterases. E - renal. elimination t1/2 only 5-10 mins .
Tramadol
C - phenylpiperidine analogue of codeine.
U - analgesia
P - tablets or capsules in variety of strengths / solution 100mg in 2ml.
A - has 2 stereoisomers. One is a weak agonist at all opioid receptors. Other is a SNRI/SSRI which is why it is only partially reversed by naloxone.
D - 50-100mg QDS
O -
R - IV / PO
S - less constipation and less resp depression than other opiates / Less addiction so not a CD.
E - should not be given to epileptics.
T - Concern regarding hypertensive crisis and patients on SSRIs/TCAs.
A - bioavailability 75%. D - . M - liver CYP enzymes. Metabolite mono-o-desmethyltramadol has high affinity for MOPr. E - urine.
Efficacy vs Potency
Efficacy is the measure of maximal response. Eg codeine is a full MOPr agonist so has the same efficacy as morphine.
Potency is a measure of the dose required to elicit the same response so codeine is less potent than morphine.
