Pharmacology: Hot Drugs !!

LIGNOCAINE 

• Dose of lignocaine for spinal anesthesia is 5%
• Maximum safe dose of lignocaine with adrenaline is 7 mg/kg wt
• Maximum safe dose of lignocaine for spinal anesthesia is 25-100 mg
• Concentration of lignocaine is used in epidural anaesthesia is 2%
• Maximum dose of lignocaine which can be given with adrenaline for ocular blocks is 7mg/kg
• Local anaesthetics acts by blocking nerve conduction.
• Small fibers and non myelinated fibers are blocked more easily than large myelinated fibers.
• Lignocaine is used as anesthetic and class IB antiarrhythmic in 2% jelly, 4% injection form
• 2-10% is the concentration of lignocaine used for topical anaesthesia
• High first pass metabolism is seen in Lignocaine
• Lignocaine is used in Ventricular tachycardia
• Best used in digoxin induced arrhythmia Lignocaine
• Drug of choice in lignocaine toxicity is Diazepam
• Lignocaine can be used in Ventricular fibrillation, Spinal anaesthesia & Epidural anaesthesia
• A patient selected for surgery was induced with Thiopentone iv through one of anti cubital vein complains of severe pain of whole hand. The next line of management IV lignocaine through same needle
• Lignocaine is a amide
• Lignocaine in high dose produces Convulsion, Respiratory depression & Hypotension
• Adrenaline is added to Lignocaine injection for Less bleeding at the site, Higher doses can be given & Prolonged duration of action
• Lignocaine can penetrate through mucous membrane
• Lignocaine can precipitate malignant hyperthermia
• Percentage of adrenaline with lignocaine for local infilteration is 1:50000

Exam Question 

• Dose of lignocaine for spinal anesthesia is 5%
• Maximum safe dose of lignocaine with adrenaline is 7 mg/kg wt
• Maximum safe dose of lignocaine for spinal anesthesia is 25-100 mg
• Concentration of lignocaine is used in epidural anaesthesia is 2%
• Maximum dose of lignocaine which can be given with adrenaline for ocular blocks is 7mg/kg
• Local anaesthetics acts by blocking nerve conduction.
• Small fibers and non myelinated fibers are blocked more easily than large myelinated fibers.
• Lignocaine is used as anesthetic and class IB antiarrhythmic in 2% jelly, 4% injection form
• 2-10% is the concentration of lignocaine used for topical anaesthesia
• High first pass metabolism is seen in Lignocaine
• Lignocaine is used in Ventricular tachycardia
• Best used in digoxin induced arrhythmia Lignocaine
• Drug of choice in lignocaine toxicity is Diazepam
• Lignocaine can be used in Ventricular fibrillation, Spinal anaesthesia & Epidural anaesthesia
• A patient selected for surgery was induced with Thiopentone iv through one of anti cubital vein complains of severe pain of whole hand. The next line of management IV lignocaine through same needle
• Lignocaine is a amide
• Lignocaine in high dose produces Convulsion, Respiratory depression & Hypotension
• Adrenaline is added to Lignocaine injection for Less bleeding at the site, Higher doses can be given & Prolonged duration of action
• Lignocaine Can penetrate through mucous membrane
• Lignocaine  can precipitate malignant hyperthermia
• Percentage of adrenaline with lignocaine for local infilteration is 1:50000

Mefloquine

---

MEFLOQUINE

USES OF MEFLOQUINE

• Indicated for the treatment of mild-to-moderate acute malaria caused by mefloquine-susceptible strains of P. falciparum (both chloroquine-susceptible and resistant strains) or by Plasmodium vivax.
• For Prevention of Malaria.
• In places with resistance to Chloroquine and Mefloquine,prophylaxis is given by medicines Doxycycline or Proguanil/Atovaquone.
• Insufficient clinical data exist to document the effect of mefloquine in malaria caused by P. ovale or P. malariae.
• Patients with acute P. vivax malaria, treated with mefloquine, are at high risk of relapse because mefloquine does not eliminate exoerythrocytic (hepatic phase) parasites; to avoid relapse, after initial treatment of the acute infection with mefloquine, patients should subsequently be treated with an 8-aminoquinoline derivative (eg, primaquine).

SIDE EFFECTS AND DRUG INTERACTIONS OF MEFLOQUINE

• May cause neuropsychiatric adverse reactions that can persist after mefloquine has been discontinued
• Should not be prescribed for prophylaxis in patients with major psychiatric disorders .
• May increase QT interval; Halofantrine or quinidine/quinine given to patients who have received mefloquine cause QTc lengthening -cardiac arrest may occur.
• Strong CYP3A4 inhibitors (eg, ketoconazole) should do not coadminister with or within 15 weeks after the last mefloquine dose.

PHARMACOLOGY OF MEFLOQUINE

Mechanism of Action

• Structural analog of quinine; exact mechanism unknown, acts as a blood schizonticide
• May increase intravesicular pH in parasites.
• Metabolism:
• Extensively metabolized in liver by CYP3A4

SAFETY OF USE OF MEFLOQUINE IN PREGNANCY AND LACTATION

• Pregnancy Category: B
• Lactation: Minimally excreted in human breast milk; low concentrations (3% to 4%) excreted; caution advised.

Exam Question 

• Chemoprophylaxis in an Englishman visiting chloroquine and mefloquine ersistant malaria region is done with Doxycycline.
• Mefloquine is contraindicated with Halofantrine/Quinine.

Drug Distribution

---

DRUG DISTRIBUTION:

• Mainly determined by Volume of distribution – 
• Volume necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma.
• Used as a measure for drug distribution.

CALCULATION:

• Calculated by dividng plasma concentration attained for a particular drug administered I.V. & Initial plasma concentration.
• Vd – Dose administrated I.V. / Plasma concentration (C0).
• Higher volume of distribution means more drug distribution into the tissues & vice-versa.
• Eg: Cholorquine – Highest Vd – 1300 L/Kg

DRUGS WITH HIGHER VOLUME OF DISTRIBUTION:

1. Lipid-soluble drugs:

• Likely to cross blood vessels – Hence, higher volume of distribution.

2. Drugs with high plasma-protein binding:

• Increased duration of stay in plasma —> Low volume of distribution –> Decreased metabolism —> Longer-acting drugs.

Drugs included:

• Benzodiazepines (Diazepam, Chlordiazepoxide, Midazolam)
• Warfarin
• Digoxin
• Calcium channel blockers – Verapamil
• Furosemide
• Imipramine
• Cyclosporin
• Tolbutamide.

DRUGS WITH LOW VOLUME OF DISTRIBUTION:

• Drugs with low Vd are restricted to plasma.
• Hence, their poisoning can be benefited by dialysis.

LOADING DOSE:

• Drugs with higher Vd needs to be administered with higher dosage to attain plasma concentration for its therapeutic response than a low Vd drug.
• This particular dosage is “Loading dose”.
• Volume of distribution is main determinant of loading dose.

Exam Important

DRUG DISTRIBUTION

• Loading dose depends on volume of distribution.
• Apparent volume of distribution of a drug exceeds total body fluid volume if a drug is sequestrated in body tissues.
• Dosage of drug is determined by volume of distribution, half-life & lipid solubility

ANTI-DYSLIPIDEMIC DRUGS

---

ANTI-DYSLIPIDEMIC DRUGS

• First line drugs:
  • Statins, bile acid binding resins & intestinal cholesterol absorption inhibitors.
• Second line drugs:
  • Fibrates & niacin.

A). STATINS

MOA:

• HMG CoA reductase catalyzes in cholesterol biosynthesis, mainly conversion of HMG CoA to mevalonate.
• This is rate limiting step.
• Statins act by inhibiting HMG CoA reductase enzyme competitively.

Effect of statins:

• Decreases cholesterol synthesis in liver:
  • By inhibiting HMG CoA reductase enzyme.
• Decreases bile acids & steroid hormones synthesis:
  • Indirectly affected due to decreased cholesterol.
• Lowers plasma LDL levels:
  • Most powerful LDL lowering agents.
  • As an aftereffect of all above steps (decreasing cholesterol, bile acids & steroid synthesis).
  • All steps are compensated by, increasing LDL receptors on its surface & thus, LDL uptake from plasma.
• Also lowers TG, IDL & VLDL & increases HDL slightly.
• No effect on lipoprotein.
• Decreases plasma fibrinogen levels – Mainly Pravastatin.
• Pleotropic effects:
  • Antioxidant properties.
  • Anti-inflammatory properties.
  • Anti-proliferative properties.
  • Clinical benefits – Helps lower risk of stroke & MI.

Drugs:

• Pitavastatin, rosuvastatin, atorvastatin, fluvastatin & lovastatin
• Pravastatin approved for children ≥ 8 years.
• Other statins approved for children ≥ 10 years.

Adverse effects:

• Myopathy & hepatotoxicity (Major).
  • Myopathy chances increase on co-administration with fibrates (maximum with gemfibrozil) or niacin.
  • Myopathy proceeds to rhabdomyolysis & then, renal shutdown.
  • Pravastatin is safer in this regard.
• Be avoided in pregnancy & lactation.

Uses:

• First line drugs for type IIa, type IIb & secondary hyperlipoproteinemia.
  • Because these conditions, cholesterol level is raised more than TG.
• In children with heterozygous familial hypercholesterolemia.

Properties of individual drugs:

1. Half-life:

• Long-acting drugs:
  • Rosuvastatin (t1/2 – 19 hours) – Longest acting statin.
  • Atorvastatin (t1/2 – 14 hours)
  • Hence can be administered at any time of day.

2. Drug administration & timing:

• Drugs administered at night:
  • Activity of HMG CoA reductase maximum at night – Hence, most drugs administered at night.
• Drugs administrated any time of day:
  • Long-acting drugs like Rosuvastatin & Atorvastatin– Due to longer half-life.

3. Metabolism:

• All statins absorbed orally (maximum fluvastatin).
  • Food increases absorption of all drugs, except pravastatin.
• Undergo first pass metabolism
  • Lovastatin & simvastatin – Extensive first-pass metabolism & administered as prodrugs
  • Pravastatin, fluvastatin, atorvastatin & rosuvastatin – Administered as active drugs.
• All drugs are metabolized extensively by hepatic microsomal enzymes, except pravastatin.
  • Pravastatin metabolized by sulfation (non-microsomal) –> Least chances of drug interactions.
  • Hence, Pravastatin confined to liver & is safer.

4. Drug potency:

• Pitavastatin (Most potent statin) > Rosuvastatin > fluvastatin > lovastatin (least potent statins).

B). INTESTINAL CHOLESTEROL ABSORPTION INHIBITOR

• Drug: Ezetimibe
• MOA: 
  • Inhibits transporter NPC1L1, involved in intestinal absorption of cholesterol.
  • Due to decreased absorption, liver cholesterol content decreases & in turn increases LDL receptor synthesis.
• Uses:
  • Type IIa & IIb hyperlipoproteinemia – Used alone or combined with statins.

C). BILE ACID BINDING RESINS

MOA:

• Binds to bile acids in intestinal lumen –> Decreases its reabsorption –> results in more excretion via feces.
• Depletes liver cholesterol pool, because it is utilized for bile acid formation.
• Liver acquires cholesterol from plasma, by increasing LDL receptors.
• Bile acids inhibit TG production in liver & their deficiency results in TGs elevation.

Uses:

• Only for type IIa disorder (TGs are normal in this condition).

Drugs:

• Cholestyramine, colestipol & colesevelam.
• Cholestyramine & colestipol –  
  • Available as sachets.
  • Mixed with water, kept for some time (to increase palatability) & then taken with meals.
• Colesevelam – 
  • Available as tablet.
  • Has better patient compliance.

Adverse effect:

• Constipation (Major).

D). FIBRIC ACID DERIVATIVES

MOA:

• Acts by activating LPL by activating nuclear receptor, PPARα (peroxisome proliferator-activated receptor alpha).

Major effects:

• Reduces TG (contained in VLDL).
• Increases HDL.
• Reduces plasma fibrinogen level.

Drugs:

• Clofibrate, gemfibrozil, fenofibrate, bezafibrate.
• Clofibrate – Not used now.
  • Due to increased mortality from malignancies, post-cholecystectomy complications & fatal MI. 
• Gemfibrozil, fenofibrate & bezafibrate – Currently available.

Fenofibrate:

• Prodrug with longest half-life.
• Has maximum LDL cholesterol-lowering action.
• Uricosuric

Uses:

• DOC in hypertriglyceridemia (type III & IV).
• In combination with other drugs in type IIb.
• For hyperuricemia (Fenofibrate – uricosuric)

Adverse effects:

• GI distress.
• Elevation of aminotransferases.
• Increased myopathy risk – On combining with statins, except bezafibrate.

NICOTINIC ACID

• Note: Niacin (not nicotinamide).
• An inexpensive drug (vitamin B)

MOA:

• Acts by inhibiting lipolysis in adipose tissue.

Effects:

• Decreases LDL cholesterol & VLDL triglycerides.
• Increases HDL cholesterol –Maximum HDL increasing property (Among all hypolipidemic drugs).
• Decreases lipoprotein (a) & fibrinogen.

Uses:

• Useful in patients having increased risk of CAD (due to maximum HDL increasing property).
• For type IIb, III & IV disorders.

Adverse effects:

• Cutaneous flushing & pruritis – Main compliance limiting feature.
  • Due to vasodilatory effect via PGs release.
  • Prevented by aspirin pretreatment.
• To minimize side effects, niacin should be started at low doses.

Other adverse effects:

• GI toxicity.
• Hyperuricemia.
• Hepatotoxicity (manifested by fall in both LDL & HDL).

MISCELLANEOUS DRUGS

1. Probucol:

• Useful for its antioxidant action.
• MOA: Inhibits LDL oxidation –> Reduces both HDL & LDL cholesterol levels.

2. Gugulipid: 

• Drug developed by Central Drug Research Institute, Lucknow.
• Causes modest LDL reduction & slight HDL increase.
• Diarrhea – Only adverse effect.

NEW DRUGS

1. Avasimibe:

• Inhibits ACAT-1 (acyl-coenzyme A: cholesterol acyltransferase-1) enzyme.
• ACAT-1 forms cholesterol ester from cholesterol.

2. Torcetrapib & anacetrapib:

• Increases HDL cholesterol byinhibiting enzyme CETP(cholesterol ester triglyceride transport protein).

3. Lomitapide:

• Acts by inhibiting MTP (microsomal triglyceride transfer protein).
• MTP necessary for VLDL assembly & secretion in liver.

Exam Important

ANTI-DYSLIPIDEMIC DRUGS

• First line anti-dyslipidemic drugs are statins, bile acid binding resins & intestinal cholesterol absorption inhibitors.
• Second line anti-dyslipidemic drugs are fibrates & niacin.
• Statins act by inhibiting HMG CoA reductase enzyme competitively.
• HMG CoA reductase catalyzes in cholesterol biosynthesis, mainly conversion of HMG CoA to mevalonate.
• Rate-limiting step in cholesterol biosynthesis is conversion of HMG CoA to mevalonate, catalyzed by HMG CoA reductase.
• Statins decrease cholesterol synthesis in liver, by inhibiting HMG CoA reductase enzyme.
• Statins decrease bile acids & steroid hormones synthesis.
• Statins are most powerful LDL lowering agents.
• Statins decrease TG, IDL & VLDL & increases HDL slightly.
• Statins have no effect on lipoprotein.
• Statins mainly pravastatin decreases plasma fibrinogen levels.
• Statins exhibit pleiotropic effectslike antioxidant, anti-inflammatory & anti-proliferative properties.
• Pitavastatin, rosuvastatin, atorvastatin, fluvastatin & lovastatin are drugs included under statins.
• Pravastatin approved for children ≥ 8 years.
• Major adverse effect of statinsincludes Myopathy & hepatotoxicity.
• Pravastatin is safer with regard to causing myopathy.
• Statins are first-line drugs for type IIa, type IIb & secondary hyperlipoproteinemia.
• Long-acting statins are Rosuvastatin (t1/2 – 19 hours) & Atorvastatin (t1/2 – 14 hours).
• Rosuvastatin with t1/2 19 hours is the longest acting statin.
• Activity of HMG CoA reductase maximum at night, hence most statins are administered at night.
• Long-acting drugs like Rosuvastatin & Atorvastatin are administrated any time of day, due to their longer half-life.
• All statins absorbed orally, maximum with fluvastatin.
• Lovastatin & simvastatinare administered as prodrugs & have extensive first-pass metabolism.
• Pravastatin, fluvastatin, atorvastatin & rosuvastatin are administered as active drugs.
• All statins are metabolized extensively by hepatic microsomal enzymes, except pravastatin.
• Pravastatin metabolized by sulfation (non-microsomal).
• Most potent statin is Pravastatin; Least potent statin is lovastatin.
• Ezetimibe is an intestinal cholesterol absorption inhibitor.
• Ezetimibe acts by inhibiting NPC1L1 transporter, involved in intestinal absorption of cholesterol. 
• Intestinal cholesterol absorption inhibitor like Ezetimibe indicated in type IIa & IIb hyperlipoproteinemia.
• Bile acid binding resins bind to bile acids in intestinal lumen –> Decreases its reabsorption –> results in more excretion via feces.
• Bile acid binding resins are indicated only for type IIa disorder.
• Drugs included under bile acid binding resins cholestyramine, colestipol & colesevelam.
• Fibric acid derivatives act by activating LPL by activating nuclear receptor, PPARα (peroxisome proliferator-activated receptor alpha).
• Fibric acid derivatives reduces TG (contained in VLDL), increases HDL & reduces plasma fibrinogen level.
• Drugs included under fibric acid derivatives are Clofibrate, gemfibrozil, fenofibrate, bezafibrate.
• Fenofibrate is prodrug with longest half-life.
• Fenofibrate has maximum LDL cholesterol-lowering action & are uricosuric.
• DOC in hypertriglyceridemia (type III & IV) is Fenofibrate.
• Nicotinic acid acts by inhibiting lipolysis in adipose tissue.
• Main effects of nicotinic acid increase HDL cholesterol, decrease LDL cholesterol, VLDL triglycerides, lipoprotein (a) & fibrinogen.
• Among all hypolipidemic drugs,nicotinic acid is maximum HDL increasing property.
• Due to maximum HDL increasing property, Nicotinic acid is useful in patients having increased risk of CAD.
• Except for type-I disorders,nicotinic acid is useful in type IIb, III & IV disorders.
• Main limiting feature of nicotinic acid is cutaneous flushing & pruritis.
• Probucol is an anti-dyslipidemic drug useful for its antioxidant action.
• Probucol inhibits LDL oxidationresulting in reducing both HDL & LDL cholesterol levels.
• Gugulipid causes modest reduction of LDL & slight increase of HDL.
• Avasimibe is a new anti-dyslipidemic drug that acts by inhibiting ACAT-1 (acyl-coenzyme A: cholesterol acyltransferase-1) enzyme.
• Torcetrapib & anacetrapib is an anti-dyslipidemic drug, which increases HDL cholesterol, by inhibiting enzyme CETP (cholesterol ester triglyceride transport protein).
• Anti-dyslipidemic drug, Lomitapide acts by inhibiting MTP (microsomal triglyceride transfer protein).

Anti-Parkinsonism Drugs

---

CLASSIFICATION:

Drugs influencing brain dopaminergic system

• Levodopa
• Bromocriptine, Pramipexole, Ropinirole 
• Amantadine 
• Selegiline 
• Tolcapone, Entacapone 
• Carbidopa, Benserazide 

Drugs affecting brain cholinergic system

• Centrally acting anticholinergics: benztropine, benzhexol, procyclidine 
• Antihistaminics (H1 blockers) with anticholinergic activity: promethazine, diphenhydramine Large amount of levodopa is converted to dopamine in the peripheral tissues by peripheral dopa decarboxylase enzyme 
• Low bioavailability in the CNS 

LEVODOPA:

• Dopamine itself does not cross the blood-brain barrier. 
• Therefore Levodopa is the immediate metabolite of dopamine, which can cross the blood-brain barrier. 
• In brain it decarboxylated back into dopamine. 
• Levodopa is the levorotary stereoisomer of DOPA.
•  DOPA is the amino acid precursor of dopamine and norepinephrine.
• Entacapone enhances the bioavailability of levodopa
• L-Dopa is combined with carbidopa in treatment of parkinsonism because Carbidopa decreases peripheral utilization of L-dopa

MOA:

• Dopaminergic neurons originating in the substantia nigra normally inhibit the GABAergic output from the striatum, whereas cholinergic neurons exert an excitatory effect.

On-off phenomenon in Parkinsonism:

• In parkinsonism, the motor symptoms remain stabilized 2-3 years after therapy.
• But after 2-3 years of levodopa therapy, the effect of the drug gradually begins to wear offi.e., the motor symptoms begin to appear. This is also called “end of dose” deterioration.
• After some period of time, the motor symptoms begin to appear frequently. This is called ‘switches’ or ‘on-off effect.
• In parkinsonism, there is a selective loss of dopaminergic neurons. 
• Therefore, dopamine/ Levodopa is covering the loss of dopamine effectiveness

Image result for levodopa

ADVERSE EFFECT:

Gastrointestinal effects: 

• Anorexia, Nausea & Vomiting (Occur about 80% patients
• Antacid 30-60 minutes before meals is also prescribed. 

Cardiovascular effects: 

• Cardiac arrhythmias 
• Tachycardia 
• Ventricular extrasystoles
• Arterial fibrillation – rarely 
• Postural hypotension 
• Hypertension

Other effects: 

• Dyskinesia 
• Depression
• Anxiety 
• Insomnia 
• Confusion 
• Hallucinations
• Euphoria 
• Mydriasis 
• Precipitation of gout 
• Brownish discoloration of saliva

DRUG INTERACTION:

• Pyridoxine (Vit B6 ) enhances the extracerebral metabolism of levodopa. Thus decreases its efficacy.
•  Levodopa should not given to patients taking MAO inhibitors or within 2 weeks of their discontinuance.
• In Parkinsonism, phenothiazines reduce the efficacy of levodopa

CONTRAINDICATION:

• Psychotic patients 
• Angle-closure glaucoma
•  Chronic open-angle glaucoma 
• Cardiac arrhythmias 
• Active peptic ulcers

DOPAMINE RECEPTOR AGONIST:

• Drugs acting directly on dopamine receptors – MoA 
• Not require enzymatic conversions. 
• No potentially toxic metabolites. 
• Not compete food or other substances. 
•  Limited adverse effects than Levodopa. 
•  First line therapy drugs for parkinsonism. 

DRA DRUGS:

• Bromocriptine: D2 receptor agonist,
• Inhibits prolactin release
• Used in  Type II DM,  Parkinsonism, Acromegaly due to small pituitary tumors, Hepatic Coma & Cyclical mastalgia
• Pergolide :D1 & D2 receptor agonists.
• Pramipexole: D3 receptor agonists. 
• Ropinirole: Pure D2 receptor agonists. (Drug of choice for the initial treatment of parkinsonism)
• Rotigotine: Delivered daily through a skin patch. 

DRA – Adverse Effects

• Anorexia 
• Nausea & Vomiting 
• Constipation
• Dyspepsia
• Postural hypotension 
• Cardiac valvular fibrosis(by Pergolide & cabergoline)
• Peripheral edema 
• Dyskinesia 
• Confusion 
• Hallucinations 
• Delusions
• Headache

DRA – Contraindications

• Psychotic illness 
• Recent myocardial infarction 
• Active peptic ulceration
• Peripheral vascular diseases
• Breast milk feeding: Bromocriptine 

MONOAMINE OXIDASE INHIBITORS:

• Monoamine oxidase A metabolizes norepinephrine, serotonin & dopamine. 
• Monoamine oxidase B metabolizes dopamine selectively.
• Combination with Levodopa should avoid as it may cause hypertensive crisis.

MOI DRUGS:

• Selegiline: Selective irreversible inhibitor of MABO at normal doses. (Higher – MAOI)
• Rasagiline: MAO B inhibitor.
• Patient on treatment on carbidopa + levodopa for 10 yrs now has weaned off effect should be given Rasagiline

CATECHOL-O- METHYL TRANSFERASE INHIBITOR :

• Inhibition of dopa decarboxylase is associated with compensatory activation of other pathways of levodopa metabolism, as COMT. 
• It increases plasma levels of 3-O- methyldopa (OMD). 
• Elevated levels of 3-OMD cause poor therapeutic response to Levodopa. 
• There are selective inhibitors of COMT such as Tolcapone & Entacapone

Adverse effects:

• Dyskinesia
• Nausea 
• Confusion 
•  Diahorrea 
• Abdominal pain
• Sleep disturbances
• Orange discoloration of the urine

Acetylcholine Blocking Drugs:

• Antimuscarinic drugs.
• Central anticholinergics are used in treatment of  Akathisia, Parkinsonism & Acute dystonia
• Improve the tremor and rigidity of parkinsonism.
• Little effect of dyskinesia.
• Started with lower doses, then gradually being increased.
• But may occur dyskinesia
• Central anticholinergics are not used in tardive dyskinesia and neuroleptic malignant syndrome.
• Drug of choice for drug-induced parkinsonism Anticholinergic

Benzhexol :

• The drug is also commonly used to treat extrapyramidal side effects occurring during antipsychotic treatment. 
•  It is active in postencephalitic, arteriosclerotic, and idiopathic forms.

Contraindication:

• Hypersensitivity to trihexyphenidyl
• Narrow-angle glaucoma
• Ileus

Exam Question 

• Carbidopa is used in the treatment of Parkinsonism because It decreases peripheral utilization of L-dopa
• Contraindication to breast milk feeding is  Bromocriptine therapy for mother
• Bromocriptine Inhibits prolactin release
• Bromocriptine, Ropinerole & Pramipexole are dopaminergic agonists used for parkinsonism 
• Pyridoxine abolishes the therapeutic effect of levodopa by enhancing peripheral decarboxylation of levodopa
• In Parkinsonism, phenothiazines reduce the efficacy of levodopa
• Levodopa is a prodrug
• Levodopa can cause On-off phenomenon
• Entacapone enhances the bioavailability of levodopa
• Rotigotine is intended to be delivered through transdermal patches, so as to ensure a slow and constant dosage in a 24-hour period.
• Antiparkinson drug known to cause cardiac valvular fibrosis is  Pergolide & cabergoline
• Drug of choice for drug-induced parkinsonism Anticholinergic
• Benzhexol is Drug of choice in drug-induced Parkinsonism
• Drug of choice for the initial treatment of parkinsonism is Ropinirole
• Central anticholinergics are used in treatment of  Akathisia, Parkinsonism & Acute dystonia
• Bromocriptine is used in  Type II DM, Parkinsonism, Hepatic Coma & Cyclical mastalgia
• Rotigotine is Dopamine agonist
• Patient on treatment on carbidopa + levodopa for 10 yrs now has weaned off effect should be given Rasagiline