Clinical Psychopharmacology Flashcards
SNRIs
Venlafaxine
Duloxetine
SARI
Serotonin Antagonist and Re-uptake Inhibitor
Trazadone
- Blocks SERT (serotonin reuptake pump) at
5HT1A - Antagonised 5HT2A and 5HT2C
Trazadone blocks SERT and receptors responsible for side effects such as insomnia, anxiety and sexual dysfunction (5HT2A/C)
NaSSa
Noradrenaline Serotonin Specific antidepressant
Mirtazapine
- 5HT2 and 5HT3 antagonist
- H1 antagonist
- alpha 1 and 2 antagonist
- moderate muscarinic antagonist
Pharmacokinetics
ADME
What the body does to a drug:
Absorption
Distribution
Metabolism
Excretion
Pharmacodynamics
What the drug does to the body
MOA
Drug interaction
Reception binding
Biological effects
Pharmacokinetics in pregnancy
Most pronounced changes in 3rd trimester
Plasma ⬆️, albumin ⬇️ = volume of distribution increases for lipohillic drugs
Concentration of albumin-bound drug decreases
Renal blood flow and gfr increases = enhanced elimination
Delayed gastric emptying, reduced small intesting mobility
Prog and oest induce some CYP enzymes and inhibit others
Volume of distribution =
Amount of drug in body ÷ concentration in plasma (volume)
Clozapine mechanism
Antagonist D4>D1>D2>D3 Alpha 1 and Alpha 2 adrenergic antagonist 5HT2a/c antagonist H, M1-3 antagonist M4 AGONIST
Low D2 receptor affinity; weak and displacable
60-70% D2 occupancy (like Quetiapine)
Type I drug reaction
IgE binds to mast cell and releases histamine and inflammatory markers.
Anaphylaxis, urticaria, bronchospasm
Minutes to hours
Type 2 drug reaction
Thrombocytopenia and Neutropenia
IgG or IgM antibody binds to cell which haa been altered by a drug hapten
Type 3 reaction
Complement system is activated.
1-3 weeks post exposure
Rash, fever urticaria, vasculitis
Type 4 reaction
MHC presents drugs to t cells.
Allergic contact dermatitis and rash. 2-7 days post exposure
Immunological adverse drug reaction
1 = anaphylaxis
2= blood abnormalities
3=fever, rash, urticaria, vasculitis
4=allergic rash
Immunological adverse drug reaction
1 = anaphylaxis
2= blood abnormalities
3=fever, rash, urticaria, vasculitis
4=allergic rash
Autoreceptor
A presynaptic receptor on the same neuron which inhibits the release of more neurotransmitter by negative feedback
E.g. mirtazapine promotes release of NA and 5HT3 by preventing the negative feedback at the presynaptic autoreceptors which would inhibit release
Elderly pharmacology
PK
Absorption;
- reduced gastric acid secretion, surface area and motility
- reduced Absorption if b12/iron/calcium.
- Levodopa increased
Distribution:
-reduced water content to body fat.
- increased concentration in water and reduced in fat (increased VoD)
Increased t1/2 in lipid soluble
Metabolism:
Reduced hepatic Metabolism due to decrease blood flow and enzyme activity
Excretion:
Drugs which are really excreted e.g. lithium and surprise will accumulate
Elderly pharmacology
Pharmacodynamics
Therapeutic response is delayed
Receptor sensitivity tends to increase so they tend to require lower doses
Secondary amine
2nd generation
Desipramine
Nortriptyline
Protriptyline
Amoxapine
Tertiary amine
First-generation
Amitryptyline Imipramine Lofepramone Clomipramone Dosulepin Dodecanese Trimipramine Butrptyline
Cytochrome p450
- Drug metabolism
- Endoplasmic reticulum in liver/small intestine
Enzyme induction:
Carbamazepine; Phenytoin; Alcohol; Barbituates; Smoking; St John’s Work
Enzyme inhibition: Chlorpromazine, ssri, grapefruit juice (cyp2d6 and cyp3a)
CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness)
Double-blind pragmatic RCT
2005
Atypical (OLZ, QUE, RIS, ziprasidone vs perphenazine)
Real World measure of discontinuation
74% patients had discontinued treatment at 18 months. Median 4.6 months.
OLZ lowest discontinuation (64%), but highest SE burden. Most discontinued ziprasisone (79%).
Phase 2
People who stopped due to ineffectiveness of therapy were re-randomised to clozapine.
Clz has lowest discontinuation rate of all atypicals.
People who stopped due to intolerance were re-randomised to OLZ, Qu, ris, ziprasidone. (OLZ AND RISP equally effective better than Que and Zipra)
CUtLASS
Cost-Utility and Latest Antipsychotic Drugs in Schizophrenia
Unblinded RCT
Typical Vs Atypical
QoL at 12 months primary outcome, symptom measure secondary
Atypical: amisulpride, olanzapine, quetiapine, risperidone
Those on typical seemed to do slightly better in QoL and symptom burden vs typical.
Participants no clear preferences for either class.
Phase 2 = clozapine vs atypical in 136 pts who had not responded to 2 or more previous drugs. Significant advantage with clozapine in symptom improvement at 1 year and patients preferred.
STAR*D Trial
Sequenced Treatment Alternatives to Relieve Depression
Pragmatic, effectiveness study
Symptom remission main outcome.
Received citalopram for 14 weeks (remission 28%); then entered into study of sequential treatment
Switch
- Bupropion
- Venlafaxine
- Sertraline
Or augment bupropion, buspirone
Next
Then mirtazapine, nortriptyline
Or Augment
Add Lithium Or T3
4th step mirtazapine and venlafaxine or tranylcypromine
GHB intoxication
Euphoria, reduced inhibition, anxiety, loss of motor control, emotional warmth, increase libido
Reduced GCS, resp depression
Psych: amnesia, disorientation
OD - headache, n+v, hallucinations, seizure, coma
GHB withdrawal
– Medical Emergency
Tachycardic, hypertensive Anxiety/ restlessness Delirium/ confusion Nausea, vomiting, tremor Hallucinations Sweating
Withdrawal lasts around 9 days
Dependency can come on after using 3-4mls for 2-3 months
Can use diazepam and baclofen to detox
GHB t1/2 <1hr, abrupt onset
Illicit drug mechanism
Iontoropic receptors
Alcohol
Benzodiazepines
Nicotine
Ketamine
Illicit drugs: G-Coupled receptors
Opioid, GHB, Cannabinoids
Drugs that target monoamine transporter
Amphetamine, ecstasy, cocaine
Mdma (ecstasy) and cocaine increase the dopamine levels at the synaptic cleft.
