Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Pharmacology - MRCPsych A > Pharmacokinetics > Flashcards

Pharmacokinetics Flashcards

(61 cards)

Start Studying
1
Q

Name some facts about buspirone?

A
  • Causes no dependence
  • Doesn’t have street value
  • Doesn’t cause tolerance
  • Can be withdrawn easily
  • Has to be dose TDS as has a short half life
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Quetiapine has a….

A

Short half life (7 hours) compared to Olanzapine/Clozapine/Risperidone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Name some drugs which undergo very little hepatic metabolism and therefore detectable in urine?

A

Gabapentin, Lithium, Amisulpride and Sulpride

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Why can Aripiprazole be dosed at OD

A

As it has a long half life of 72 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Pethidine + BLANK can cause a fatal serotonin syndrome?

A

MAOI - tranylcypromine or phenelzine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Name some receptors that Clozapine has effects on

A

Anatgonism:
- D1
- D2 –> weak affinity - at clinically effective doses may only occupy 40-50% of striatal D2 receptors. ? reason why low propensity for EPSEs
- D4 –> strong affinity

  • Alpha 1 adrenergic receptors
  • H1
  • 5-HT2a

Agonism:
- M4 –> ? mechanism behind silaorrhoea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

If someone is presenting with alcohol withdrawal and has severe liver damage what benzodiazepines may be of choice?

A

Oxazepam or Lorazepam
- both short acting

  • These benzodiazepines (w/ temazepam) do not undergo phase 1 metabolism through cytochrome P450 enzymes and are instead proceed straight to phase 2, are conjugated (glucuronidation) and excreted.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What does a high therapeutic index mean?

A

A drug is very safe in relation to clinical effectiveness

Methods of calculating indices include:
- Medium lethal dose (LD-50) / medium effective dose (ED-50)
- Minimum toxic dose / minimum effective dose

Drugs OTC will have a higher therapeutic index i.e paracetamol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Outline the hepatic enzyme inducers or inhibitors?

A

Inducers:

Carbamazepine
Rifampicin
Alcohol (chronic)
Phenytoin

Gresofulvin
Phenobarbitone
Smoking
St Johns Wart

Topiramate

Inhibitors:

SICK ACES COM GAQ

Sodium Valproate
Isoniazid
Cimetidine
Ketokonazole / Fluconazole

Alcohol (acute)
Chlorphenicol
Erythromycin
Sulfamides

Ciprofloxacin
Omeprazole
Metronidazole

Grapefruit juice
Amiodarone
Quinidine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Broadly name some medications that undergo metabolism by the P450 system?

A

Most anti-depressants / antipsychotics

Benzodiazepines

Warfarin

Zolpidem

Sodium Valproate

Methadone

Thyroxine

Oestrogen

Steroids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Name a reversible MAOI

A

Moclobemide (rMAO-A inhibitor) - reversible MAOIs are preferable given there is less tendency for the cheese reaction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Which anti-depressants have been associated with a therapeutic window

A

Imipramine, Desipramine and Nortrptyline (although dubious benefit of the value of them)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Name some psychotropic drugs that can be given in hepatic impairment?

A

Antipsychotics - Amisulpride and Sulpride - no dosage reduction if renal function is normal. Paliperidone if depot needed

Anti-depressants - Paroxetine, Vortioxetine, Citalopram, Sertraline

Hypnotics - Lorazepam, Oxazepam and Temepezam - these have no active metabollites. Can be used cautiously starting at a low dose as sedatives may trigger hepatic encephalopathy. Zopiclone 3.75mg may be used also.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Why may Zolpidem be a good choice for hypnotic?

A

Peak level at 1.6hrs, half-life 2.6hrs
No active metabolites

These make it short acting therefore if a patient needs to do an activity in the morning and can’t be sedated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

When does a drug which does not require a loading dose reach a steady state?

A

4-5 half lives

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Name the active metabolites of imipramine and amitriptyline

A

Imipramine - Desipramine

Amitriptyline - Nortryptiline

Both through cytochrome P450 enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Outline the differences between zero order and first order kinetics?

A

1st order kinetics - the rate of drug elimination (per unit of time) is proportion to the concentration of the drug.

Zero-order kinetics - the rate of drug elimination is not

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Outline the differences between zero order and first order kinetics?

A

1st order kinetics - the rate of drug elimination (per unit of time) is proportion to the concentration of the drug.

Zero-order kinetics - the rate of drug elimination is not proportional to drug concentration - static rate of elimination. Occurs when elimination is saturated at higher doses. Present for alcohol, high dose salicylates, high dose fluoxetine and high dose omeprazole.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What does clearance depend on?

A

The half-life of a drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Define clearance

A

The volume of blood cleared of a particular drug in a unit of time.

It represents the relationship between elimination rate and drug concentration.

Rate of clearance determines the half-life of a drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is autoinduction?

A

Where a drug induces its own metabolism - this occurs for Carbamazepine therefore it takes 2 weeks for it to reach a steady state

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Name an anti-depressant that undergoes autoinhibition?

A

Paroxetine - CYP450 2D6 inhibitor

Increasing the dose by 50% may lead to double plasma concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How does Fluoxetine increase the effect of warfarin

A

Through P450 inhibition - increases warfarin levels, also haloperidol, carbamazepine, phenytoin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How does Clonidine work?

A

Through agonism of presynaptic alpha-2 adrenergic receptors.

Decreases sympathetic outflow causing vasodilation and less NAA release from presynaptic nerve terminals - lowers arousal and sympathetic tone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Which SSRIs are most specific for serotonin reputake?
Citalopram Escitalopram Have less effect on NAA, GABA and H1
25
How does pharmacokinetics differ in the elderly?
Reduced rate of absorption - lower Gastric pH - less mesenteric blood flow - less gut motility Reduced distribution but increased levels with longer half lived - Reduced plasma protein binding m- less albumin - Lower BMI with proportionally increased body fat Reduced metabolism: - Less liver breakdown from reduction in efficiency of enzymes and less liver blood flow Reduced excretion: - Less renal clearance - Drug effects are prolonged, cumulative with higher risk of toxicity
26
What are the least sedating TCA’s?
Lofepramine and Nortryptyline - Lofepramine safest in elderly as least likely to cause postural hypotension, lowest propensity for cardiac conduction abnormalities
27
How is amphetamine intoxication treated?
Urinary acidification - give ammonium chloride every 2-3 hours and the urine is acidified to help clear the amphetamine
28
Name 3 factors that affect absorption of a drug?
Form of the drug - enteric coating etc. Blood flow at the site of absorption Solubility of the drug - particle size, pH, pKa of the drug (half of the drug in ionised form)
29
Name some factors that reduce the absorption of drugs from the GI tract?
Changes to gastric pH Food - delays gastric emptying Intestinal motility changes - diarrhoea Blood flow integrity Surface area available Inhibitors of P-glycoprotein (a transporter that pumps drugs out of intestinal wall into gut) - grapefruit juice is an inhibitor - can increase absorption of benzodiazepines/carbamazepine, calcium channel blockers etc Dissolution and disintegration of drugs - takes longer for those with enteric coating/wax mixed in - slow release forms take longer to peak therefore less side effects Gut flora - some have enzymes that aid metabolism of drugs
30
Name some factors that affect distribution
Haemodynamic factors - cardiac output Lipid solubility - permeability factors Plasma protein binding Blood-brain barrier Blood-CSF barrier
31
Name a condition where protein binding reactions may be important?
Renal disease - proteinuria There may be less albumin or apha-1 acid glycoprotein therefore free fraction could increase
32
Name the properties a particle needs to have to cross the BBB
- Unionised - High lipophilic - water coefficient However those with a low lipid-water coefficient may still be able to cross through carrier transporters (Valproate or L-DOPA) or through cerebral circulation e.g. Lithium Ions
33
Subfornical organ, area postrema of the medulla and median eminence make up the...
Circumventricular organs - no BBB - useful to detect toxic substances easily so can initiate vomiting etc
34
What is bioequivalence?
The degree of comparability between two formulations of the same drug Need to have same bioavailability and rate of absorption
35
Name the four major metabollic reactions
Oxidation, reduction, hydrolysis and conjugation
36
What are the two routes of metabolism
Phase 1: oxidation, reduction, hydrolysis - generally done by CYP450 enzymes. Active/inactive metabolite then ready for conjugation Phase 2: conjugation by adding glucuronic acid. Makes a more polar - water soluble ready for excretion in bile or urine dependent on relative molecular mass. If mass < 300 in urine.
37
Name two CYP450 enzymes that psychotropics are typically broken down by?
CYP2D6 - can be inhibited by fluoxetine, amitriptyline, clomipramine & neuroleptics -drugs metabolised: - All TCAs - fluoxetine, paroxetine - trazodone, nefazodone - valproate, all neuroleptics, risperidone CYP3A4 (in gut wall) - barbiturates and carbamazepine inducer, fluoxetine can inhibit: - Clomipramine - Fluvoxamine, - Mirtazapine, - Nefazodone, - Carbamazepine - most benzodiazepines
38
How do Fluxoetine and Fluvoxamine affect metabolism of psychotropics?
Inhibitor CYP450 enzymes (2D6 and 2C19) and can increase levels - Fluvoxamine may increase level of Clozapine 10 fold
39
How do smoking and caffeine affect the metabolism of some psychotropic drugs?
Influence glucuronidation reaction via CYP1A2 or UGT enzyme Caffeine inhibits CYP1A2 - increases levels of Clozapine and Olanzapine Smoking induces CYP1A2 - lowers levels
40
What drug forms are suitable for renal excretion?
Ionised and non-lipid soluble
41
What factors affect renal excretion?
- Age - Blood flow to kidneys - Renal impairment - pH in the urine
42
Name some drugs that undergo almost all renal excretion without any hepatic breakdown
Lithium, Sulpride, Amisulpride, Gabapentin, Acamprosate, Amantadine
43
What is distribution half-life?
Time taken from initial peak (Cmax) to half i.e. the time that redistribution halves the initial peak
44
What is elimination half life?
The time taken for elimination to halve the plasma concentration - most relevant for clinicians
45
indexWhen is a steady state of a drug achieved?
When 4-5 half lives have been administered Steady state is rate in = rate out
46
Name some drugs with a narrow therapeutic index range?
Lithium, Carbamazepine, Phenytoin
47
How does therapeutic window and therapeutic index range differ?
Therapeutic window - only concerns therapeutic range i.e. above does not consider toxicity Therapeutic index range - considers effect and safety/toxicity
48
Name some careful prescribing tips for Renal impairment
Benzodiazepines with caution: - Diazepam metabolite can accumulate - Half life of Lorazepam increased from 8-25 to 32-72. If impairment consider halving dose Antipsychotics - Avoid Lithium/Amisulpride (later all renally excreted) - Haloperidol ok unless causing SE - monitor for sedation/postural hypotension - Risperidone metabolite can accumulate Anti-D: - Sertraline avoided - Amitriptilyine and Imipramine - no dose reduction needed - Dose reductions for Citalopram and Paroxetine - Fluoxetine and Fluvoxamine ok
49
How protein bound are TCAs?
Extensively bound - imipramine 80-95%
50
After 5 half lives how much of a drug is in a steady state?
97% After 7 half lives 99% of a drug is in a steady state
51
A patient's clozapine level + 1mg/L wyd?
Reduce dose +/- prescribe anticonvulsant coverage (not bone marrow due as its an enzyme inducer and can also suppress bone marrow)
52
A patient's clozapine level + 1mg/L wyd?
Likely reduce dose +/- prescribe anticonvulsant coverage (not bone marrow due as its an enzyme inducer and can also suppress bone marrow) > 2mg/L definitely reduce the dose and prescribe an anticonvulsant
53
Which clozapine complication is dose related?
Seizures - the other are idiosyncratic or allergic in nature
54
What is the optimum clozapine dose?
0.35-0.6 mg/L
55
Why may clozapine:norclozapine ratio be helpful?
Can indicate non-compliance Should be 1.33:1 (or 0.66:1 if norclozapine:clozapine) If clozapine:norclozapine is < 1 could indicate non-compliance - to be interpreted with caution given genetic factors, incorrect sampling time and the influence of other drugs e.g. fluovaxmine - inhibitor
56
Name some drugs that may cause Lithium levels to increase due to poor renal excretion?
NSAIDs Thiazide like diuretics (not loop/K+ sparing) ACEi Angiotensin-II-blockers Note hyponatraemia can also elevate lithium levels through increased reabsorption at renal tubule
57
Name some drugs which Carbamazepine reduces the concentration of?
Clozapine, risperidone, amitriptyline - through CYP1A2, CYP2C19, CYP3A enzyme induction Carbamazepine takes 2-3 weeks to reach a steady state Therapeutic drug window 4-10mg/L
58
What drugs may increase levels of Carbamazepine
Clarithromycin, Fluconazole and Diltiazem
59
Why should combination of anti-D fluoxetine/paroxetine + TCA matter?
Fluoxetine/Paroxetine are inhibitors of CYP450 system therefore the dose of TCAs will go up increasing risk of serotonin syndrome
60
If augmenting Clozapine what plasma concentration should be aimed for?
< 1mg/L

Pharmacology - MRCPsych A (5 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions