Anti-Parkinsonism Drugs

It decreases peripheral utilisation of L-dopa

Ans. is b and c i.e. Bromocriptine therapy for mother; and Ca breast

Contraindications to Breast feeding

• Mother on IV drug abuse/excess alcohol.
• Human T cell leukemia virus type 1 (HTLV – 1).
• In females undergoing treatment for breast cancer (Acog 2000)
• Mother on anticancer drugs or other teratogenic drugs.
• Active Herpes simplex lesions of the breast.
• Active pulmonary tuberculosis in mother.
• Galactosemia and congenital lactose intolerance in infant.
• HIV-positive mother if she can afford formula feeds.
• Mother with clinically infectious varicella. (Once the infant receives varicella zoster immune globulin and there are no skin lesions on the mother’s breast, she may provide expressed milk for the infant).

As far as Hepatitis B/C infections are concerned they are not contraindications to breast feeding.

Infants of seropositive hepatitis B mothers should be given He^patitis B Immunoglobulin MI within 12 hours of birth.

Also know The milk of nursing mother with cystic fibrosis, is high in sodium and places the infant at risk for hypernatremia.

Medications contraindicated during lactation.

Medication                              Reason

Bromocriptine                         Suppresses lactation; may be hazardous to the mother

Cocaine                                   Cocaine intoxication

Cyclophosphamide                 Possible immune suppression; unknown effect on growth or association with carcinogenesis; neutropenia

Cyclosporine                           Possible immune suppression; unknown effect on growth or association with carcinogenesis;

Doxorubicin                             Possible immune suppression; Unknown effect on growth or association with carcinogenesis;

Ergotamine                               Vomiting, diarrhea, convulsions (at doses used in migraine medications)

Lithium                                      Once third to one half of therapeutic blood concentration in infants

Methotrexate                           Possible immune suppression; unknown effect on growth or association with carcinogenesis;

Neutropenia Phencyclidine     Potent hallucinogen

Phenindione                             Anticoagulant; increased prothromboplastin and partial thromboplastin time in one infant; not used in United States

Radioactive iodine                   Contraindications to breast-feeding for various periods and other radiolabeled

& other radio                            elements labelled elements

Ans. is ‘a’ i.e., Inhibits prolactin release

Ans. is ‘d’ i.e., Selegiline

o Selegiline is a MAO-B inhibitor.

o Bromocriptine, ropinerole and pramipexole are dopamine agonsists.

Ans. is ‘d’ i.e., Decreased efficacy will result

“Pyridoxine abolishes the therapeutic effect of levodopa by enhancing peripheral decarboxylation of levodopa”.

Ans. is ‘c’ i.e., Vit. B complex

Interactions of levodopa

Pyridoxine abolishes the therapeutic effect by enhancing peripheral decarboxylation of levodpa. Less levodpoa is thus available to cross BBB, to be converted into dopamine in dopaminergic neurones in CNS

1. Phenothiazines, butyrophenones, and metoclopramide reverse therapeutic effect by blocking DA receptors.
2. The antidopaminergic domperidone blocks levodopa induced nausea and vomiting without abolishing its antiparkinsonian effect, because domperidone does not cross the blood brain barrier.
3. Reserpine abolishes levodopa action by preventing entry of DA into synaptic vesicles.
4. Nonselective MAO inhibitors: prevent degradation of peripherally synthesized DA and NA hypertensive crisis may occur.
5. Atropine and other anticholinergic drugs have additive antiparkinsonion action, but retard its absorption more time is available for peripheral degradation Efficacy of levodopa may be reduced.

Note : Pyridoxine is a component of vit B complex.

Ans. is ‘d’ i.e., Domperidone blocks levodopa induced emesis and it’s therapeutic potential

`When domperidone is administered with levodopa or bromocriptine, it counteracts their dose-limiting emetic action, without affecting the therapeutic effect in Parkinsonism’                                    

Levodopa is a prodrug, inactive by itself but is the immediate precursor of the transmitter dopamine.

Ans. is ‘d’ i.e., On-off phenomenon

On-off phenomenon in Parkinsonism

• In parkinsonism the motor symptoms remain stabilized 2-3 years after therapy.

o But after 2-3 years of levodopa therapy the effect of the drug gradually begins to wear offi.e., the motor symptoms begins to appear. This is also called “end of dose” deterioration.

o After some period of time, the motor symptoms begins to appear frequently. This is called ‘switches’ or ‘on-off effect.

o With time “all or none” response develops i.e., the patient is alternately well and disabled.

o This “on-off’ phenomenon is probably a reflection of the progression of the disorder. With progressive degeneration of dopamine neurones, the ability of the drug to regulate the storage and release of Dopamine may be lost. Dopamine is then synthesized in the striatum on a moment to moment basis. This results in appearance of symptoms.

Ans. is ‘d’ i.e., To make more L-Dopa available to cross the blood brain barrier

Carbidopa

• More than 95% of an orally administered levodopa is decarboxylated by dopa-decarboxylase in peripheral tissues.
• Carbidopa and benserazide are extracerebral (peripheral) dopa decarboxylase inhibitors. Prevent peripheral decarboxylation of levodopa.

o They do not penetrate BBB and do not inhibit conversion of levodopa to dopamine in the brain.. o Benefits of levodopa-carbidopa combination are ‑

1.Plasma t 1/2 of levodopa is prolonged and its dose is reduced.

2.Nausea, vomiting, cardiac complications and other peripheral side effects are reduced as peripheral dopamine production is reduced.

3.Pyridoxine reversal of levodopa effect does not occur.

4.On-off effect is minimized

o Problems not resolved or accentuated are ‑

1. Postural hypotension

2.Involuntary movement

3.Behavioral abnormalties.

About option ‘b’

o Peripheral side effects of L-dopa are reduced when given with carbidopa as peripheral dopamine production is reduced.

o But this is an additional benefit; Levadop-carbidopa combination is primarily given to reduce peripheral decarboxylation of levodopa so that more of it will be available to cross BBB.

Ans. is ‘c’ i.e., Entacapone

o When peripheral decarboxylation of levodopa is blocked by carbidopa/benserazide, it is mainly metabolized by COMT to 3-0-methyldopa.

o Blockade of this pathway by entacaptone/tolcapone further prolongs the t 1/2 of levodopa and allows a larger fraction of administered dose to cross to brain.

Ans ‘b’ i.e. Rotigotine

*  Rotigotine is intended to be delivered through transdermal patches, so as to ensure a slow and constant dosage in a 24-hour period.

Ans. is ‘d’ i.e., Pergolide & cabergoline

o Ergot-containing dopamine receptor agonists used for Parkinson’s disease (pergolide, cabergoline, bromocriptine) cause valvular heart disease that closely resembles that seen in the carcinoid syndrome.

o Metabolites of fenfluramine, as well as the dopamine receptor agonists, have high affinity for serotonin receptor subtype 5-HT_2B receptors, whose activation is known to cause fibroblast mitogenesis.

Serotonin receptor subtypes 5-HT_{I81 D2A2B} normally are expressed in human heart valve intersitial cells. o High levels of HT_2B receptors are known to occur in heart valves and occur in cardiac fibroblasts and cardiomyocytes.

Ans is ‘b’ i.e., Anticholinergic

“Central anticholinergics are the only drugs effective in drug induced parkinsonism.”

o They act by reducing unbalanced cholinergic activity in the striatum of parkinsonism patients.

• Generally, tremor is benifited more than rigidity; hypokinesia is affected the least (Levodopa resolves hypokinesia and rigidity first and later tremor).

Trihexyphenidyl (benzhexol) is the most commonly used anticholinergic in parkinsonism.

Ans. is ‘d’ i.e., Benzhexol

Ans. is ‘c’ i.e., Ropinirole

o Dopamine agonist (Ropinirole, pramipexal, rotigotine) monotherapy is the initial treatment of choice. (But levodopa remains the most effective drug for Parkinson ism).

Ans. is ‘a’ i.e., Anticholinergics

Parkisonism

o Rigidity, tremor, hypokinesia, mask like facies, shuffling gate. o Between 1-4 weeks of therapy.

o Treatment —> central anticholinergic (levodopa is ineffective).

Ans. is ‘d’ i.e., Neuroleptic malignant syndrome

o Central anticholinergics are ineffective in neuroleptic malignant syndrome.

o Central anticholinergics are not used in tardive dyskinesia and neuroleptic malignant syndrome.

Ans. C i.e. Benzhexol

Trihexyphenidyl/Benzhexol

• It is used for the symptomatic treatment of Parkinson’s disease in mono- and combination therapy.
• It is active in postencephalitic, arteriosclerotic, and idiopathic forms.
• The drug is also commonly used to treat extrapyramidal side effects occurring during antipsychotic treatment.
• It reduces the frequency and duration of oculogyric crises as well as of dyskinetic movements and spastic contractions.
• Excessive salivation may also respond.
• Trihexyphenidyl may improve psychotic depression and mental inertia frequently associated with Parkinson’s disease and symptomatic problems caused by antipsychotic treatment.
• The drug cannot cure Parkinson’s disease, but may provide substantial alleviation of symptoms.
• To increase therapeutic activity trihexyphenidyl is often given concomitantly with levodopa, other antimuscarinic or antihistaminic (e.g. diphenhydramine) agents.

Ans. is `d’ i.e., Hypoprolactinemia

Uses of Bromocriptive

• Bromocriptine is a powerful dopamine agonist. It suppresses prolactin secretion while promoting secretion of gonadotropins.
• Its therapeutic uses are:

1. Suppression of lactation in galactorrhea
2. Cyclical mastalgia
3. Induction of ovulation in anovulatory infertility caused by hyperprolactinemia
4. Parkinsonism
5. Acromegaly due to small pitutary tumours
6. Hepatic coma
7. Recently, it has been approved for treatment of type 2 DM.

Ans. is ‘a’ i.e., Levodopa

Prodru

• Few drugs are inactive as such and need conversion in the body to one or more active metabolites.
• Such a drug is called a prodrug.

Ans. is ‘a’ i.e., Dopamine agonist

Rotigotine

• Rotigotine is a dopamine agonist drug and is indicated in the treatment of parkinosonism.
• Rotigotine is intended to be delivered through transdermal patches, so as to ensure a slow and constant dosage in a 24-hour period.
• Side effects are–skin reaction at the patch site, nausea, vomiting, diziness, drowsiness, insomnia.

Ans. is A i.e., Tolcapone

• Both Entacapone and tolcapone enhance and prolong the therapeutic effect of levodopa-carbidopa in advanced and fluctuating parkinsons disease. They may be used to smoothen off the ‘wearing off’, increase ‘on’ time and decrease ‘off’ time, improve activities of daily living and allow levodopa dose to be reduced.

Tolcapone

• It is a drug used to treat Parkinson’s disease (PD).
• It is a selective, potent and reversible nitrocatechol-type inhibitor of the enzyme catechol-O-methyltransferase (COMT).
• In comparison with entacapone, another nitrocatechol COMT inhibitor, tolcapone has a longer half life (2.9 hours vs. 0.8 hours) and can better penetrate the blood–brain barrier, acting both in the central nervous system and in the periphery. However, entacapone is less toxic for the liver.
• Tolcapone improves the bioavailability and reduces the clearance of levodopa and subsequently dopamine from the CNS.
• Without administration of tolcapone, the beneficial effects of levodopa tend to wear off more quickly, resulting in motor fluctuations.

Ans. is ‘b’ i.e., Prolactin deficiency

Bromocriptine is used in :-

• Suppression of lactation in galactorrhea
• Cyclical mastalgia
• Induction of ovulation in anovulatory infertility caused by hyperprolactinemia
• Parkinsonism
• Acromegaly due to small pitutary tumours
• Hepatic coma
• Recently, it has been approved for treatment of type 2 DM.