RECEPTORS

• Cellular component to which the drug binds and through which initiates the effect

• Ionotropic: ligand gated Ionic Channels, activation leads to rapid and transient increase in membrane permeability. Causes excitation or inhibition of the post synaptic membrane. e.g. GABA A receptors

• Quick response • Metabotropic; Produced slower response involving G protein which bind to the

intracellular portion of the receptor and activate a second messenger. This will altered the phosphorylation state of key proteins rendering them active or inactive e.g. antipsychotics, antidepressants

Potency Amount of the drug needed to produce an effect compared to another standard drug with similar effect in same receptor

Affinity Ability to bind to its receptor

Efficacy How well the drug produces the expected response

Full agonist Produce maximal response / measured against physiological neurotransmitter efficacy for a given receptor

Partial agonist Cannot elicit maximal response, it has a ceiling effect. It degree of response depends of the availability of neurotransmitters

Inverse agonist Binds to the same receptor but produces opposite response . No clinical drug act through this mechanism

antagonism Interact with receptors by interfering with their activation by neurotransmitters

TYPES OF ADVERSE REACTIONS

Type of reactions Features

Dose Related Ataxia, coarse tremors, vomitinge.g. Lithium Toxicity

Non-Dose related Idiosyncratic e.g. Malignant hyperthermia, Lamotrigine related Steven Johnson syndrome

Dose and Time Related Cumulative drug use (Long-term Lithium use and renal damage)

Delayed Effect No due to the drug but the length of time the drug has been used (Tardive Dyskinesia)

Withdrawal Related to abrupt discontinuation.

MECHANISM OF ACTION FOR SIDE EFFECTS

• Agitation ALPHA2 Blockade, 5HT 2A/2C stimulation• Akathisia D2 antagonism, 5HT2A stimulation• Delirium anticholinergic effect (muscarinics)• EPSE D2 blockades • Insomnia alpha 1 stimulation, 5HT2A Stimulation (hence

SSRIs)• Amnesia antimuscarinics and GABA stimulation • Hyperprolactinaemia D2 blockade, 5HT1A stimulation• Sweating Cholinergic effect and increases with NARIs• Anorgasmia Alpha 1 antagonism, 5HT2A/2C stimulation

(delayed ejaculation on SSRIs • Impotence alpha 2 blockade, 5HT2A/2C stimulation (also low

libido)

WEIGHT GAIN • Cannot be explained by a single mechanism of action • Antihistaminic effect • 5HT2A/2C antagonism • Insulin resistance (Valproate and Olanzapine are noted)

• Genetic factors seems to be involved - 5HT2C receptor. Drugs with strong affinity for this receptors will have a greater impact on weight increase.

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