Pharmacology Psychotherapeutic Drugs: Antidepressants And Antimanic Drugs Iiia

Front 1

What class of drugs are tricyclic antidepressants?

Back 1

Serotonin/Norepinephrine reuptake inhibitors (SNRIs)

Front 2

What are the effects of tricyclic amines on the brain

Back 2

-Competitive blockage of the 5-HT and NE uptake pumps. This potentiates monoaminergic neurotransmission and may contribute to the antidepressant activity. However, even though the blockage of amine uptake is quickly established, antidepressant effects of the drugs do not occur for several weeks. Therefore subsequent downregulation of presynaptic, inhibitory autoreceptors resulting from high levels of neurotransmitter in the synaptic clefts is probably the mechanism of the therapeutic effects

-TCAs only weakly block dopamine uptake

Front 3

What are the effects of tricyclic amines on mood?

Back 3

-TCAs do not have a mood elevating effect when given to a normal subject. They may produce sedation.
-TCAs cause an elevation of mood when given to depressed patients. Therapeutic effects require 2-3 weeks of administration

Front 4

What are the effects of tricyclic amines on adrenergic receptors? Histamine receptors?

Back 4

There is antagonism of central and peripheral alpha1-adrenergic receptors

H1 receptor block

Front 5

What are the effects of tricyclic amines on cholinergic receptors?

Back 5

These drugs block muscarinic receptors. Amitriptyline has pronounced anticholinergic activity, while desipramine has relatively weak anticholinergic effects. The anticholinergic effects produce undesirable side effects such as dry mouth and constipation.

Front 6

Which extra serotonin receptor does amitriptyline block?

Back 6

5HT2

Front 7

Describe the cardiovascular effects of TCAs

Back 7

There are significant effects on the heart and blood vessels because of their interaction with the sympathetic and parasympathetic nervous systems. They also have direct effects on the heart.

Front 8

Describe the administration and absorption of TCAs

Back 8

They are effective orally and are promptly absorbed from the GI tract

Front 9

Describe the effect of the liver on TCAs

Back 9

There is a considerable first-pass effect in the liver where the drugs are metabolized by transformation of the tricyclic nucleus and alterations of the side chain. Hydroxylation of the 2 position of the ring leads to the production of inactive metabolites.

Front 10

Describe the effect of cytochrome P450 on amitriptyline and imiparmine

Back 10

Partial demethylation of the side chain of amitriptyline and imipramine by CYP3A4 leads to the formation of the active metabolites nortripyline and desipramine (potential for drug interactions with other drugs metabolized by this isoform, such as benzodiazepines)

Front 11

Describe the effect of cytochrome P450 on desipramine and nortripyline

Back 11

Metabolism of despiramine and nortriptyline is mainly by CYP2D6 so there is a potential for drug interactions with other drugs that are metabolized by this isoform (haloperidol, thioridazine, propranolol, codeine)

Front 12

What are the adverse side effects of tricyclic amines?

Back 12

1.Peripheral anticholinergic (antimuscarinic) effects
2. Acute confusional state
3. Orthostatic hypotension
4. Cardiac
5. Sedation

Front 13

Describe the orthostatic hypotension associated with tricyclic amines

Back 13

This is the most significant and prevalent serious side effect of the tricyclic antidepressants. It results in part from peripheral alpha1 adrenergic receptor blockade. It occurs in approximately 10% of patients treated with tricyclics and can result in serious injury and fatalities.

Front 14

Which tricyclic antidepressant induces the least orthostatic hypotension

Back 14

Nortriptyline and thus it is the tricyclic of choice in older patients

Front 15

Describe the cardiac side effects of tricyclic amines

Back 15

These antidepressants ave effects on the heart that are similar to type I antiarrhythmic drugs and may increase mortality in patients with ischemic heart disease. Tricyclics cause slow conduction in the ventricular conducting system yby a direct effect to block Na channels in the cardiac cell membrane. These drugs should not be given to treat depressin in patients who have had a myocardial infarction. Patients who have had a heart attach are often depressed and this is associated with poor clinical outcome.

Front 16

What is the most dangerous result of tricyclic overdose?

Back 16

Heart block and ventricular tachycardia.

Front 17

What are the adverse drug interactions of tricyclic amines?

Back 17

-Interact with other drugs that have anticholinergic effects such as antiparkinsonian drugs
-Dangerous potentiation of administed sympathomimetic amines can precipitate hypertensive crisis since inactivation of these drugs is inhibited
-Block effects of indirectly acting amines such as tyra,mine which must be taken up by sympathetic neurons to exert their pharmacological effects. Likewise, TCAs block the effect of other drugs, such as antihypertensive drug huanethidine, which must be taken up by a nerve ending
-TCAs and MAOIs both increase levels of biogenic amines, and hence hteir combination may result in hypertension, hyperpyrexia, and convulsions