07 - Other side effects

Other side effects

© SPMM Course Transient leucopenia can occur with typical neuroleptics. But agranulocytosis is the rare effect. Sexual dysfunction: Increased dopaminergic transmission can enhance sexual arousal and penile erection. Hyperprolactinaemia can result in loss of sexual arousal and erectile dysfunction in men; amenorrhoea, reduced sexual desire and hirsutism in women. Antipsychotics reduce sexual performance both directly by reducing dopaminergic transmission and indirectly through inducing hyperprolactinaemia. 43% of those taking antipsychotics report sexual dysfunction at some point, not all of this attributable to the drug. Neuroleptic agents commonly cause ejaculatory problems. Total inhibition of ejaculation (dryejaculation),  reduced  ejaculatory  volume  and  ‘retrograde’  ejaculation  are  the  various  effects   associated with conventional neuroleptics and also clozapine, risperidone and olanzapine. Drug-induced priapism is  related  to  simultaneous  α1-adrenergic blockade and anticholinergic activity. The most commonly reported associations are with antipsychotic drugs (20% of all reported priapisms) followed by trazodone. Antipsychotics implicated in this problem include risperidone, chlorpromazine clozapine, olanzapine and thioridazine. The risk is doseindependent and can occur at any time during the course of treatment (duration-independent). Priapism is a urological emergency and can lead to permanent impotence if untreated. Dopaminergic agonist bromocriptine is used to treat sexual dysfunction in men that is associated with hyperprolactinaemia. Other side effects Seizure threshold is lowered especially by low potency antipsychotics. Molindone may be the least epileptogenic. This is a dose-dependent effect. Chlorpromazine is the most sedating typical antipsychotic – mediated by H1 antihistaminic action – tolerance usually develops for this effect. Low potency agents can also cause anticholinergic syndrome (see TCAs). Neuroleptics can decrease cardiac contractility, increase circulating levels of catecholamines, and prolong atrial and ventricular conduction time. Low-potency drugs are more cardiotoxic than high-potency drugs. ECG shows QT and PR prolongation, blunting of the T waves, and ST depression. Thioridazine and droperidol, in particular, can cause torsade de pointes. Antipsychotic related sudden death may be due to cardiac arrhythmias or even seizures asphyxiation or malignant hyperthermia. Drugs causing QT prolongation are associated with more sudden deaths (e.g. thioridazine). Postural hypotension is most common with

© SPMM Course low-potency drugs, and tolerance develops soon. Patients should avoid all caffeine and alcohol, drink plenty of fluid and liberal salt in food. Low-potency drugs can cause weight gain but not as much as is atypical drugs. Nearly 50% of men taking antipsychotics report ejaculatory and erectile disturbances. Thioridazine is particularly associated with decreased libido and retrograde ejaculation in men. Allergic dermatitis and photosensitivity can occur with low-potency agents. Long-term chlorpromazine use can cause blue-gray discoloration of skin areas exposed to sunlight. This is reversible. Irreversible retinal pigmentation is associated with the use of high dose thioridazine (above 1000 mg a day). An early symptom of the side effect can sometimes be nocturnal confusion associatd to difficulty with night vision. This pigmentation is irreversible and can progress even after stopping thioridazine. Chlorpromazine related pigmentation of the anterior lens and the posterior cornea is seen as whitish brown stellate granular deposits noted in slit lamp – this is benign and not vision impairing. This can resolve gradually unlike thioridazine related retinal damage. Chlorpromazine is associated with cases of obstructive or cholestatic jaundice especially in the first month of treatment associated with rash and eosinophilia. Immediate discontinuation and avoidance of rechallenge are advised. Haloperidol isone of the safest typical antipsychotics in overdose. After an overdose, the electroencephalogram (EEG) shows diffuse slowing and low voltage. QT prolongation: Prolongation of the QT interval is mediated by blockade of the rapid component of the delayed rectifier potassium current (IKr) responsible for repolarisation of cardiac Purkinje cells and myocardial cells. Many drugs, including certain antipsychotics and antidepressants, bind to this potassium channel and thereby decrease the outward movement of potassium. Some antipsychotics – especially droperidol, pimozide, sertindole and thioridazine – have a greater capacity than others to cause IKr blockade. InAdvertent IntraVascular injection event (IAIV) or postinjection delirium sedation syndrome (PDSS) has been described after olanzapine pamoate (long-acting depot) injections. Within 20 min to 3 hours of injection, patients present with sedation, confusion, dizziness, altered speech/dysarthria, and somnolence, symptoms that are consistent with those reported in the case of oral olanzapine overdose. Rarely deep coma may ensue. Medical hospitalization and supportive medical care are usually sufficient to ensure full recovery (usually within 3–72 hours). This effect is linked to accidental punctures of a vessel or injections into a rich capillary bed during administration, leading to quick dissolution and release of free olanzapine. Eli Lilly has recommended a postinjection