Other pharmacology Flashcards
Examples of 5-HT3 antagonists
*ondansetron
*granisetron
Common adverse effect of 5-HT3 antagonists
constipation
Most common use of 5-HT3 antagonists
Nausea and vomiting n chemotherapy
Where do 5-HT3 antagonist mainly work?
chemoreceptor trigger zone area of the medulla oblongata
Agomelatine works how?
It acts as an agonist at melatonin M1 and M2 receptors, increasing melatonin, and as an antagonist at 5HT2C receptors, leads to the release of dopamine and norepinephrine in the frontal cortex.
Does agomelatine affect serotonin levels
No
Antihistamines block what
the effects of histamine at either H1 or H2 receptors
Which are the H2 receptor blockers
Cimetidine
Ranitidine
Which are the H1 receptor blockers
Diphenhydramine
Cetirizine
Chlorpheniramine
Cyclizine
Hydroxyzine
Some first generation antihistamines have use in psychiatry such as what?
Promethazine
Contra indications to first generation antihistamines
Benign prostatic hyperplasia
Angle-closure glaucoma
Pyloric stenosis (in infants)
How do barbituates work?
facilitate GABAA action by increasing the duration of chloride channel opening
How do benzodiazepines work?
increase the frequency of chloride channels
How should benzodiazepines be withdrawn?
switch patients to the equivalent dose of diazepam
reduce dose of diazepam every 2-3 weeks in steps of 2 or 2.5 mg
time needed for withdrawal can vary from 4 weeks to a year or more
How are benzos divided?
into hypnotics (short half-life) and anxiolytics (long half-life).
Describe benzodiazepine pharmokinetics - how well do they bind to plasma protein, where metabolised and lipophilic or lipophobic
They show high plasma protein binding (95% for diazepam). They are mainly metabolised in the liver. They tend to be highly lipophilic and rapidly cross the blood brain barrier and placental barrier.
What is bioavailability?
the percentage of drug that is detected in the systemic circulation after its administration
Give examples of biogenic amines.
Catecholamines (adrenaline, noradrenaline, and dopamine)
Serotonin
Histamine
What is biotransformation?
a metabolic process that takes place mainly in the liver, in hepatocytes (but also in the kidneys, intestine, adipose, skin, and the lungs) and helps to facilitate the excretion of both exogenous and endogenous substances
What is biotransformation Phase 1?
Oxidation with cytochrome P450 (most common)
Reduction
Hydrolysis
What is biotransformation Phase 2?
Adding hydrophilic groups to the original molecule
The most common method is conjugation with glucuronic acid. (glucuronidation) but also can be by:
Methylation
Acetylation
Sulfation
Conjugation with glutathione
Conjugation with amino acids (glycine, taurine, and glutamic acid)
What is biotransformation phase 3?
A chemical substance can undergo further metabolism and excretion. It classifies into the following:
ATP-binding cassette (ABC)
Solute carrier (SLC) transporters
Phase III reactions refer to the active transport of the compound into urinary or hepatobiliary system to facilitate elimination.
What is tegretol
Carbamazepine
How does carbamazepine work?
binds to sodium channels increases their refractory period
When is carbamazepine contraindicated?
a history of bone marrow depression
combination with monoamine oxidase inhibitors (MAOIs)
What is an important warning with carbamazepine?
Serious dermatological reactions (toxic epidermal necrolysis (TEN: also known as Lyell’s syndrome) and Stevens Johnson syndrome - both rare)
What was CATIE?
Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Study was a nationwide clinical trial that compared the effectiveness of older (first available in the 1950s) and newer (available since the 1990s) antipsychotic medications used to treat schizophrenia.
What was Phase 1 CATIE
Phase I compared old and new antipsychotics.
CATIE compared four of the newer medications to one another, and to an older medication. Participants in CATIE were followed for 18 months
What was phase 2 CATIE?
Phase II sought to provide guidance on which antipsychotic to try next if the first failed (either due to ineffectiveness or intolerability).
Risk factors for Charles Bonnet
Advanced age
Peripheral visual impairment
Social isolation
Sensory deprivation
Early cognitive impairment
Prevalence of CBS in visually impaired people
thought to be between 11 and 15 percent
What was the first drug used specifically for psychosis.
Chlorpromazine
What is important side effect of chlorpromazine
photosensitivity reactions
What does hepatic clearance involve?
conversion of the parent drug into a different chemical entity by the liver enzymes
What does renal clearance involve?
emoval of the drug from the plasma into the urine.
Describe zero order kinetic reactions and give 2 examples
the clearance of a drug is constant and is not related to the concentration of drug in the plasma, ethanol and phenytoin
Describe first order reactions
Here the clearance is related to the concentration of the drug in the plasma.
What is difference between half life in zero and first order reactions
In first order reactions this is constant.
In zero order reactions it gets progressively shorter.
Steady state is usually achieved by how many half lives?
4.5
Risk factors for paradoxical reaction to Benzos
Learning disability
Extremes of age (elderly or young)
History of aggression or poor impulse control
Benzodiazepine with short half life
High dose benzodiazepine
Intravenous administration of benzodiazepine
What is a pharmokinetic drug interaction
take place when one drug interacts with another at the level of metabolism, absorption or excretion.
What is pharmodynamic drug interaction
when one drug directly alters the effect of another.
Examples of pharmokinetic interaction
Enzyme induction/ inhibition (interference with metabolism)
Changes in gastrointestinal tract motility and pH (interference with absorption)
Chelation
Competition for renal tubular transport (interference with excretion)
Changes in protein binding
Examples of pharmodynamic drug interaction
Synergism
Antagonism
Interaction at receptors (e.g. allosteric modulation)
Which drugs may be affected in terms of their stability eg by moisture/light in environment, and therefore not be suitable for compliance aids?
Sodium valproate
Zopiclone
Venlafaxine
Topiramate
Methylphenidate
Mirtazapine
Olanzapine
Amisulpride
Aripiprazole
What is V Max?
maximum rate of the catalysed-reaction
What is KM?
the concentration of substrate that leads to half-maximal velocity.
What model is used to estimate V max and kM
Michaelis-Menten
How does ethosuximide work?
blocks T-type calcium channels in thalamic neurons
Drugs with little to no first pass effect?
lithium
pregabalin
Name the phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation.
first pass effect
Where is most concentration of drug lost in first pass effect
liver and gut wall
What scale is used for discontinuation syndrome/symptoms?
The DESS (Discontinuation-emergent signs and symptoms scale), a 43-item rating scale
Which antiP is most likely to cause sedation?
clozapine
Very common side effects of carbamazepine?
leucopenia
ataxia, dizziness, somnolence
vomiting, nausea
urticaria
fatigue
Common side effects of carbamazepine?
hrombocytopenia, eosinophilia
Oedema, fluid retention, weight increase, hyponatraemia and blood osmolarity decreased due to an antidiuretic hormone (ADH)-like effect, leading in rare cases to water intoxication accompanied by lethargy, vomiting, headache, confusional state, neurological disorders
diplopia and accommodation disorders (e.g. blurred vision), headache
dry mouth
Drugs which undergo significant first pass effect?
imipramine
fluphenazine
morphine
diazepam
buprenorphine
How does flumazenil work
a selective GABAA receptor antagonist
through competitive interaction
How is flumazenil administered
IV
Half life flumazenil
1 hour
Which drug is is used for the complete or partial reversal of the sedative effects caused by benzodiazepines.
flumazenil
It takes about 5 half-lives for a drug to be roughly what percent eliminated
97%
In which type of kinetics is there a fixed half life?
1st order
Zero order there is no fixed half life
Which type of kinetics is is described as non-linear
zero order kinetics
Recommended mood stabliser in hepatic impairment?
lithium
Which antidepressants should be avoided in Hepatic impairment?
best avoid TCA and MAOI
Which antiPs are recommended in hepatic impairment
Paliperidone (if depot required)
Amisulpride
Sulpiride
Herpes simplex encephalitis typically affects where?
temporal lobes and inferior
