neuro pharmacology Flashcards

Question

What are the toxic effects of lignocaine?

Answer 1

● CNS ○ Early: perioral or tongue numbness, metallic taste ○ Moderate: nystagmus, tinnitus, muscle twitching, nausea, vomiting ○ Severe: seizures, sedation ● CVS ○ Arrhythmias i.e. bradycardia, conduction blocks ○ Hypotension ○ Worsening of CCF ○ Cardiovascular collapse ● GIT ○ Vomiting, anorexia, nausea ● Haem: ○ Methaemoglobinaemia (most often associated with prilocaine) ● Allergy ○ Rare but not impossible

Answer 2

● Low solubility in the blood so reaches arterial tension rapidly. ● Rapid equilibrium in the brain and fast onset of action and fast recovery

Answer 3

Multiple actions ● Modulates GABA-A receptors ● Increases dynorphin release ● NMDA agonist

Answer 4

● CNS: analgesia, amnesia, increased cerebral blood flow ● Renal: decreased GFR, increased renal vascular resistance ● CVS: dose dependent myocardial depression ● Resp: reduced response to carbon dioxide ad hypoxia ● GI: Nausea and vomiting

Answer 5

● Administration: IV only - as a bolus or an infusion ● Distribution: Rapid onset and recovery is driven by redistribution of the drug from the brain to other areas. Distribution half life is 2-4 minutes, elimination half life up to 25 mins, ● Metabolism: rapidly metabolised in the liver. ● Elimination: Excreted in the urine as inactive metabolites.

Answer 6

Induction agent, maintenance of anaesthesia, procedural sedation.

Answer 7

Rapid onset and offset

Answer 8

1-2.5mg/kg in adults, 2.5- 3.5mg/kg in kids

Answer 9

● Anaesthesia/sedation (no analgesia) ● Transient apnoea ● Decreased blood pressure ● Anti-emetic properties

Answer 10

Related to the system effects ● Hypotension from vaso and veno dilation and the negative inotropic effect ● Apnoea - dose related central depression of respiratory drive ● Pain on injection ● Allergy/anaphylaxis ● Propofol infusion syndrome (a metabolic acidosis)

Answer 11

● Titration of small doses ● Not using opiates or benzos concurrently ● Using an IV fluid bolus ● Reduce dose in elderly or those with poor cardiovascular reserve

Answer 12

● NMDA receptor antagonist ● Inhibits reuptake of catecholamines and serotonin ● Potent short acting sedative, amnestic, analgesic and anaesthetic agent

Answer 13

● Absorption: Highly lipid soluble, so rapid onset ● Distribution: Effect is terminated by redistribution to inactive tissue sites. Low protein binding. ● Metabolism: Metabolised in the liver via cytochrome P450 enzymes to inactive metabolites ● Elimination: metabolites are excreted in the urine

Answer 14

● CNS: dissociative anaesthesia, profound analgesia. Cerebral vasodilation. Potential anticonvulsant properties. ● CVS: hemodynamically stable, increases HR, BP, CO and myocardial oxygen consumption ● Respiratory: Maintains airway reflexes, minimal respiratory depression, bronchodilator effects. Can cause lacrimation and laryngospasm in children, ● Ocular: nystagmus

Answer 15

● Related to the system effects ● CNS- emergence phenomenon, dysphoria, hallucinations ● GI - nausea, vomiting ● Respiratory - laryngospasm, increased salivation

Answer 16

● Induction agent ● Bronchodilator effect in asthma ● Acute behavioural disturbance

Answer 17

● Propofol causes a marked decrease in peripheral BP, whereas ketamine is hemodynamically stable on induction ● Ketamine has a slower recovery and is associated with emergence phenomena

Answer 18

● IV bolus ● Rapidly crosses BBB ● Highly lipid soluble ● Redistributes to muscle and fat ● Metabolised in the liver ● Excreted by the kidney

Answer 19

Rapid onset, amnesic, reduction in ICP, anticonvulsant properties

Answer 20

Drops BP, SV, CO due to myocardial depressant effect and increased capacitance Apnoea

Answer 21

Depolarizing neuromuscular blocker - 2 acetylcholine molecules linked end to end 2 phases ● Phase I (depolarising) ○ Reacts with nicotinic receptor to open the channel ○ Depolarises the motor endplate with spread to adjacent membranes ○ Causes fasciculation ● Phase II (desensitising) ○ Continued or repeated exposure to sux ○ End plate depolarisation increases ○ Membrane repolarizes but cannot be depolarised because it is now desensitised ○ Means it is unresponsive to subsequent impulses ○ Causes a flaccid paralysis

Answer 22

● Administration: IV ● Distribution: rapid onset (30-60 seconds) short duration (2-8 minutes) ● Metabolism: Hydrolysed rapidly by plasma pseudocholinesterase

Answer 23

● Muscle pain from fasciculations ● Bradycardia (with repeated doses) ● Release of K+, especially in burns, trauma ● Raised IOP and raised ICP ● Risk of malignant hyperthermia ● Risk of prolonged paralysis in cases of reduced or abnormal cholinesterase

Answer 24

● A nondepolarizing neuromuscular blocker ● Competitive inhibitor of acetylcholine at the nicotinic receptors ● In large doses is can enter the pore of the ion channel and cause a stronger block

Answer 25

● Absorption: Given as an IV bolus 1.2mg/kg, onset within 45-60seconds. ● Distribution: Rapid. Highly ionized, small Vd. Duration of 20-75 mins. ● Metabolised in the liver, short half life ● Eliminated in the urine

Answer 26

● Duration of action of sux is much shorter (5-10 mins) ● Different side effect profile and contraindications ● Sux is a depolarizing NMB, whereas roc is a non depolarising ● Rocuronium has an antidote ● Suxamethonium metabolised in the plasma, roc in the liver

Answer 27

● CNS: sedation, disinhibition, impaired judgement, impaired motor skills, ataxia, slurred speech, coma, respiratory depression. ● CVS: decreased contractility ● Smooth muscle vasodilation = hypothermia

Answer 28

● Absorption: rapidly absorbed from the GIT (water soluble) ● Distribution: Rapid, Vd is total body water ● Metabolism: mostly in the liver by alcohol dehydrogenase via zero order kinetics ● Excretion: Lungs, urine.

Answer 29

Elimination occurs at a constant rate, independent of the drug concentration

Answer 30

Phenytoin, theophylline, warfarin, salicylate, heparin.

Answer 31

Binds to components of the GABA- A receptor in neuronal membranes in the CNS. This receptor is a chloride ion channel. Benzodiazepines enhance GABAs effects without directly activating the channel. This causes an increased frequency of channel opening.

Answer 32

● Sedation - calming effect, anxiolysis at low doses. Can also cause psychomotor and cognitive depression, amnesia ● Hypnosis and anaesthesia at higher doses. ● Anticonvulsant effects ● Muscle relaxation ● Respiratory and cardiovascular depression - especially at high doses or in those with CCF/chronic heart disease or in hypovolemic states

Answer 33

● Anticonvulsant ● Sedation of an agitated patient ● Withdrawal states - alcohol, benzodiazepines ● Various toxidromes to prevent seizures

Answer 34

● Sodium channel blockade ● Binds to those in an inactive state and stabilises them there ● Inhibits high frequency repetitive firing neurons - so no interference with baseline or normal activity

Answer 35

● 100% oral bioavailability Peak levels 6-8 hours ● 70% protein bound ● Low clearance - 36 hour half life initially which decreases over time ● Induces its own metabolism via P450 enzyme effect so dose increase required in the first few weeks of treatment

Answer 36

● Ataxia, diplopia ● Sedation at high doses ● Blood dyscrasias - aplastic anaemia, agranulocytosis ● Skin rash ● Drug interactions with other P450 metabolised drugs i.e. phenytoin

Answer 37

● Given oral or IV, High oral bioavailability, not well absorbed IM ● Peak serum concentration at 3-12 hours ● Highly plasma protein bound with moderate volume of distribution ● Metabolised in the liver to inactive metabolites and then renal excretion ● Elimination is dose dependent - lower concentrations is first order kinetics, but enzymes become saturated at high concentrations and metabolism shifts to zero order kinetics ● As a result, the half life is variable

Answer 38

● Sodium channel blockade ● Prolongation of the inactive state of the Na channel ● Als o enhances GABA release ● These actions work to inhibit the generation of rapidly repetitive action potentials

Answer 39

● Need 4 half lives to reach steady state, which would take 5-6 days ● So to reach target concentration more rapidly, we use a loading dose.

Answer 40

● Hypotension and bradycardia with rapid infusion - can cause cardiovascular collapse ● Local necrosis if there is extravasation ● Purple glove syndrome - black discoloration distal to the IV site

Answer 41

● Nystagmus and loss of smooth pursuits is normal with therapeutic levels and not concerning ● Anyone with diplopia and ataxia needs a decrease in their dose ● Gingival hyperplasia and hirsutism can occur over long term use, as can abnormal rashes, osteomalacia and low vitamin D ● Can cause foetal abnormalities if used in pregnant people ● Sedation, coma, cerebellar toxicity are associated with toxic levels.

Answer 42

● Binds the the SV2A synaptic vessel protein ● Undergoes endocytosis and binds in the vesicle ● Prevents release of glutamate during increased frequency activity

Answer 43

● Given orally or IV, rapid oral absorption in just over an hour ● Low protein binding ● Half life 6-8 hours so BD dosing ● ⅔ excreted unchanged in the urine ● ⅓ is deaminated in the blood ● NO liver metabolism = minimal interactions when compared to other antiepileptics

Answer 44

● Mild: somnolence, ataxia, dizziness ● Worse: behavioural and mood changes - aggression/anxiety

Answer 45

● Paeds - 40mg/kg IV/IO up to 3g ● Adults 60mg/kg IV/IO up to 4.5g

Answer 46

Unknown, could be action on GABA channels, Na channels or NMDA receptors Works on a number of different epilepsy models and the clinical effect doesn't seem to be associated with serum drug levels.

Answer 47

● Mild: Can cause nausea, vomiting, abdominal pain ● Severe: cerebral oedema and coma ● Hepatic toxicity including acute liver failure (more common in patients under 2 yrs old) ● Thrombocytopaenia and bruising from bone marrow depression ● Neural tube defects if used during pregnancy ● Hyperammonaemia leading to sedation ● Lots of drug interactions - inhibits metabolism of several drug via inhibition of the P450 enzyme system. Directly displaces phenytoin from plasma proteins, increases levels of carbamazepine and decreases the clearance of lamotrigine.

Answer 48

● Excessive stimulation of serotonin receptors in the CNS due to overdose of a single drug or concurrent use of several drugs. ● Predictable rather than idiosyncratic.

Answer 49

● Inhibition of serotonin metabolism - i.e. amphetamines, moclobemide ● Prevention of serotonin reuptake in nerve terminals - fluoxetine, sertraline, venlafaxine, tramadol, TCAs ● Serotonin release or increased intake of serotonin precursors - tryptophan, lithium

Answer 50

● Inhibition of serotonin and noradrenaline reuptake ● This increases the amount of serotonin and noradrenaline in certain parts of the brain and spinal cord. ● Based on the monoamine hypothesis for depression, this leads to improved mood and can alleviate neuropathic pain ● TCAs also block sodium channels, potassium channels, muscarinic (M1) receptors, Histaminic (H1) receptors and postsynaptic alpha 1 adrenergic receptors

Answer 51

● Well absorbed orally ● Bioavailability 40-50% ● Long half life ● High first pass metabolism ● High protein binding ● High lipid solubility ● Large volume of distribution ● Metabolised in the liver with active metabolites

Answer 52

Can be divided into important systems - cardiac, CNS, and then other anticholinergic symptoms Cardiac ● Tachycardia ● Hypotension (from alpha 1 blockade) ● ECG changes - prolonged PR, wide QRS (Na block) long QT (K block) VT, VF CNS ● Drowsiness ● Delirium (from anticholinergic effects) ● Seizures ● Coma Other Anticholinergic Effects ● Agitation ● Mydriasis ● Warm, dry, flushed skin ● Urinary retention ● Ileus

Answer 53

TCAs have a large Vd and tissue concentrations are high, especially in well perfused organs such as the brain and the heart

Answer 54

Alkalinisation - bicarb or hyperventilation Increases plasma protein binding of the free drug, removing it from the tissues and reducing its toxicity

Answer 55

● Oral administration, rapid and near complete absorption. Peak concentrations at 1-2 hours but complete by 6-8 hours. ● Volume of distribution is in total body water - very slow distribution from extra to intracellular compartments ● No protein binding ● No metabolism ● Excreted unchanged in the urine - 20% of the creatinine clearance ● Plasma half life is 20 hours

Answer 56

● Renal function - slowing down of the GFR = more time in the PCT for reabsorption ● Water and sodium status - lithium can be reabsorbed in place of sodium in water/sodium depleted states ● Drug interactions that reduce or enhance clearance ● Serum concentration to begin with

Answer 57

● Thiazide diuretics - cause a reduction in lithium clearance ● Newer NSAIDs also reduce clearance ● Osmotic or loop diuretics actually increase clearance

Answer 58

● Neuro: tremor, ataxia, dysarthria, confusion ● Thyroid: reversible hypothyroidism ● Renal: polyuria, polydipsia via nephrogenic diabetes insipidus ● CVS: oedema ● Pregnancy: category D, causes Ebstein's anomaly (a congenital cardiac malformation)

Answer 59

● Measure lithium levels (10-12 hours after the last dose) ● Treatment is supportive, dialysis

Answer 60

Oral (tablet or wafer), parenteral with short acting IM or long acting depot injection

Answer 61

● Serotonin receptor antagonism ● There is also a weaker effect on dopamine receptor antagonism (D2)

Answer 62

● Sedation ● Extrapyramidal reactions - less common that with the typical antipsychotics ● Tardive dyskinesia, akathisia ● Antimuscarinic effects - dry mouth, urinary retentions ● Orthostatic hypotension ● Weight gain ● Hyperglycaemia ● Hyperprolactinaemia ● Agranulocytosis (seen with clozapine) ● Neuroleptic malignant syndrome

Answer 63

● Carbidopa is a peripheral dopa decarboxylase inhibitor ● Because it doesn't penetrate the BBB, it reduces the peripheral metabolism of levodopa which leads to increased half life and more dopa being available to enter the CNS to exert its effects

Answer 64

● GIT: anorexia, nausea, vomiting is common due to stimulation of the emetic centre in the brainstem ● CVS: arrhythmias due to increased peripheral formation of catecholamines ● Dyskinesias: can occur in 80% of people receiving this treatment long term ● Behavioural change: depression, anxiety, agitation, insomnia, nightmares ● Other miscellaneous: gout, abnormalities to taste and smell, abnormal LFTs

Answer 65

● Migraine thought to arise secondary to vasodilation of cerebral meningeal blood vessels ● Triptans are selective agonists for 5HT-1 receptors found on these vessels ● Cause vasoconstriction, preventing symptoms

Answer 66

● Bioavailability is low or varied (10-70%) ● So given subcut or intranasal more often than orally ● Half life is 2-3 hours so frequent daily dosing

Answer 67

● Pros: only usually mild side effects (tingling, weakness) usually very effective ● Cons: contraindicated in patients with IHD due to coronary spasm risk, short duration of effect so requires multiple dosing. Very expensive.

neuro pharmacology Flashcards

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