Introduction
Postmortem redistribution (PMR)
Mechanisms of PMR of drugs
Mechanisms | Consequences |
---|---|
Drug reservoirs: | Redistribution to surrounding tissues: |
- Gastrointestinal tract | Cardiac chambers, thoracic vessels, left lung, liver, inferior vena cava. |
- Lungs | Cardiac chambers, thoracic vessels, liver. |
- Myocardium | Heart blood. |
- Liver | Inferior vena cava, right cardiac chambers, pulmonary vessels, stomach, duodenum, gall bladder. |
Cadaveric changes: | |
- Cell death | Leakage of xenobiotics into the extracellular space |
- Blood coagulation and hypostasis | Modification of serum/blood ratio |
- Blood movements | Transport of xenobiotics and mixing of bloods from different origins |
- Putrefactive process (bacteria) | Degradation and/or synthesis of macromolecules |
Drug chemical and pharmacokinetic properties: | |
- Acidic/basic properties | * |
- Lipophilicity | * |
- Drug binding proteins or red cells | * |
- High volume of distribution | Leakage from tissues |
- Residual metabolic activity | * |
Passive diffusion from reservoir organs
Cadaveric changes
Drug properties
Markers of PMR of drugs
Cardiac blood to peripheral blood ratio (C/P)
Alprazolam (1.5) | Methamphetamine (2.4) |
Amantadine (2) | Methylenedioxy methamphetamine or MDMA (2.65) |
Amitriptyline (3.1) | Methyprylon (1.9) |
Amoxapine (1.8) | Metoprolol (3.8) |
Amphetamine (2.0) | Mexiletine (3.6) |
Benztropine (1.3) | Midazolam (4) |
Bupropion (1.9) | Morphine (heroin) (2.2) |
Chloroquine (3.0) | Naproxen (1.5) |
Chlorpheniramine (3.1) | N-methylbenzodioxazolybutamine MBDB (2.5) |
Chlorpromazine (4.0) | Nortriptyline (2.4) |
Clomipramine (1.9) | Orphenadrine (1.9) |
Clonazepam (2.0) | Oxazepam (1.3) |
Clozapine (2.8) | Oxycodone (3.1) |
Cocaine (1.5 to 2.3) | Paramethoxyamphetamine (1.6) |
Codeine (1.8) | Paroxetine (2.7) |
Cyanide (1.3) | Pentazocine (2) |
Cyclobenzaprine (2.2) | Pethidine or meperidine (2.1) |
D-methamphetamine (2.1) | Phencyclidine (1.8) |
Desipramine (2.4) | Phentermine (1.7) |
Dextromethorphan (2) | Phenylbutazone (2.3) |
Diazepam (1.6) | Phenylpropanolamine (2.4) |
Diltiazem (2.6) | Phenytoin (1.4) |
Diphenhydramine (2.3) | Promethazine (1.6) |
Dothiepin (3) | Propafenone (2.4) |
Doxepin (5.5) | Propoxyphene (3.5) |
Flecanide (3.6) | Propranolol (2.5) |
Flunitrazepam (3) | Pseudoephedrine (1.5) |
Fluoxetine (2.9) | Secobarbital (1.5) |
Flurazepan (3.0) | Strychnine (15) |
Fluvoxamine (1.7) | Temazepam (1.6) |
Furosemide (1.7) | Thiopental (1.9) |
Gamma hydroxybutyrate (2) | Timolol (2) |
Haloperidol (3.6) | Tranylcypromine (2.2) |
Hydrochlorthiazide (23) | Trazadone (1.6) |
Ibuprofen (1.8) | Triazolam (2.8) |
Imipramine (1.8 to 2.2) | Trichlorethanol (2.0) |
Indomethacin (1.9) | Trimipramine (1.6) |
Ketamine (1.6) | Venlafaxine (1.6) |
Maprotiline (4.7) | Venlafaxine (1.6) |
Meprobamate (1.7) | Zolpidem (2.1) |
Mesoridazine (1.3) |
Liver to peripheral blood ratio (L/P)
Drug | L/P (mean) | C/P (mean) |
---|---|---|
Tramadol | 1.6 | 1.1 |
Carisoprodol | 2.8 | 1.3 |
Venlafaxine | 5.0 | 1.3 |
Mirtazapine | 5.8 | 1.1 |
Methadone | 6.8 | 1.3 |
Lamotrigine | 8.6 | 1.0 |
Quetiapine | 9.0 | 1.4 |
Citalopram | 9.9 | 1.2 |
Paroxetine | 22 | 2.0 |
Olanzapine | 23 | 1.3 |
Amitriptyline | 25 | 3.0 |
Clomipramine | 58 | 1.9 |
Sertraline | 97 | 1.3 |
Other PMR markers
Artifacts of postmortem drug concentrations
Alcoholsa Carbon monoxide Carbamazepine Chlordiazepoxide Diflunisal Ephedrine Hydrocodone Hydroxyzine Lorazepam Lamotrigine | Mirtazapine Nitrazepam Phenelzine Pheniramine Phenobarbital Primidone Procyclidine Quinine/Quinidine Theophylline Zopiclone |