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Pharmacology 2

December 9, 2010

Drugs that affect Parkinson Disease: 1817 (James Parkinson Shaking Palsy)

- Acetylcholine (increased in secretion)- Dopamine (decreased in secretion)

Extrapyramidal System:1. Motor Control2. Posture3. Muscle Tone4. Smooth muscle activity

Dopamine Release: Target receptor is D receptors (D1,D2, D3, D4)1. Mesolimbic areas Amygdala (EMOTIONS) Schizophrenia (+ symptoms)2. Mesocortical areas Cerebral cortex Schizophrenia (- symptoms)3. Nigrostriatal areas (Substancia Nigra/Putamen)4. Basal ganglia & Hypothalamus

Dopamine Hyperstimulation can be caused by:

a. Genetic or family history lineageb. Tumor or abnormal mutationsc. Drug induced (L-Dopa overdose/Dopamine Agonist)d. Tyramine Rich Foods precursor dopamine synthesis

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KINDLY CHECK the TYRAMINE entry in Presynaptic cleft pls BULAG KA!

Effects or Commonality:1. Psychosis/Schizophrenia (Positive/Negative symptoms)2. May also stimulate other adrenergic receptors (A1,A2, B1, B2)

Dopamine Hypostimulation can be caused by:a. Drug induced (Anti-psychotic agents)

b. Neurotoxin (MPTP 1-methyl 4-phenyl 1,2,3,6 -tetrahydropyridine)c. Agingd. Wear and tear (free radical damage)e. Head traumaf. Infections that may damage dopaminergic sitesg. Genetic/ inborn errors (rare)f. Metallic poisoning (Pb, Mercury, Fe+++)d. Carbon Monoxide Poisoninge. Hypoxia/Stroke survivor

Effects or Commonality if Dopamine is Reduced:

1. Parkinson like disease- Bradykinesia- Rigidity- Tremor- Postural

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Effects or Commonality if Dopamine is Increased:1. Dyskinesia

- Chorea- Dystonia

ANTI-PARKINSON ANGENTS:

1. Anticholinergics (Benztropine, Bipiriden, Procyclidine, Trihexylperidine)2. Anti-Histamine (Diphenhydramine)3. Dopamine Receptor Agonist (Bromocriptine, Levodopa, Levodopa-carbodopa,

Pergolide)4. Indirect Acting Receptor Agonist

MAO B Inhibitor (Selegiline)

1. MAO A Norepinephrine & Serotonin Metabolism2. MAO B Dopamine Metabolism

NB: AVOID Tyramine rich food Cheese, MilkMay cause RISK HYPERTENSIVE CRISIS

Tyramine DOPA NOR NOREPINEPHRINE SURGE Apha 1

COMT Inhibitor(Entacapone)

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Miscellaneous (Antiviral used for influenza virus: Prevents attachment) Amantadine

(Re-uptake)

DOPAMINE: Lipophobic or Hydrophillic in nature Fails to pass in blood brain barrier

(cell membrane)

LEVODOPA: (Can pass through the CNS but can be converted to DOPA in thePeriphery via DD )

1. Precursor for DOPAMINE production

2. Periphery converted into Dopamine that can stimulate Adrenergic Receptors:(Dopamine Decarboxylase) LEVODOPA DOPAMINEa. Alpha 2 Vasodilation (Hypotension)b. Beta 1: Tachycardia arrhythmiasc. Beta 2: Bronchodilatesd. Beta 1: Iris Mydriasis Blurring of Vision , IOP (Glaucoma)e. CTZ (CNS) Nausea & Vomiting

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ACTION:

a. Decreases Rigidity, Tremors

SIDE EFFECTS:

a. Dopaminergic Actions in Adrenergic Receptors in PeripheryHint: Dopamine targets alpha 2 VASODILATION not ConstrictionNOREPI/EPI target Alpha1 VASOCONSTRICTION

b. On/OFF phenomenon ( Short Half Life 1-2 hours) Fluctuations in the level ofconcentration of the Dopamine

INTERACTIONS:a. HighProtein Diet (Neutral Amino Acid/Leu/Isoleucine) Impede GI Absorption

- Take NPO for 45 minutes before eatingb. Vitamin B6 (Pyridoxine), Foods rich in Vitamin B6Degrades Levodopac. MAO- A Inhibitor (Phenelzine) Hypertensive Crisis Catechoamine

Productiond. Antipsychotic Agents Contraindicated because decreases Dopamine Release

Drug Holliday 10 Days method used to start treatment

CARBIDOPA: Dopamine Decarboxylase Inhibitor1. It doesnt pass in the CNS Barrier2. Inhibits the conversion of Levodopa to Dopamine in GI & Periphery3. Decreases the side-effects in the periphery due to lack of Dopamine Conversion

Changes in the URINE Color & Saliva Brown (cathecoamine production melanin)- HARMLESS

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Deprenyl (Selegiline) : MAO B-I (Metabolize Dopamine) InhibitorMAO A-I (Metabolize Nor/Serotonin) NO effect

Amantadine: Anti-viral (Influenza)Bromocriptine: Hallucinogenic, Confusion, Nausea, Hypotension

Anti-Cholinergics:

a. Benztropine (Congentin)

b. Bipiriden (Akineton)

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NURSING CONSIDERATIONS:

1. Bromocriptine Suppress the milk let down process Mothers who do not wantto breastfeed

2. Amantadine

Anti-viral agent

3. NURSES FOCUS ON:a. Enhance, Promote and Check Activity of Daily Livingb. Motor Activity & Movement (Walking, Gait, Hand Movements)c. Communicationd. DIET (constipation), Avoid tyramine Rich food if MAO-I B is used, Vit B6e. Psychological: Hallucinations, Confusion because D1 receptor activation in the

Mesolimbic or Mesocortical Areasg. Vital Signs: BP (Hypotension) Orthostatic Hypotension Risk Injury

h. Check history of Drug Allergyi. Glaucoma Patients: Mydriasisj. Nausea and Vomiting Evaluation

Drugs that reduces Intracranial Pressure:a. Mannitol (is sugar that is doesnt absorbed retention on the blood vessels

Osmotic Effect Diuresis loosing water that reduces cerebral edema.b. Reduce intraocular pressure by allowing removal of tears/aqueous humorc. Osmotic Loose Bowel Laxative

Monitor: FOR TREATMENT ICP1. Hydration: serum Hct (increase)2. LOC Improvement3. Urine output4. Serum electrolytes: Sodium Loss5. Vital Sign: BP Hypotension (Blood volume loss WATER loss)

Drugs that can cause Muscle to Relax:

- Used to relax muscles during uncontrolled muscular spasm (PAIN, RespirationEffects)a. Loss to Functionb. Pain, Parethesias (Tingling Sensation)

- Cases: Cerebral Palsy, Multiple Sclerosis, Trigeminal Neuralgiam, Stiff Neck

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Muscle Relaxant Effects:

- DIZZINESS, LIGHTHEADEDNESS, DROWSINESS, FATIGUE- Caution with highly stimulated activities (Driving, Control of Machines)

Types:

1. Centrally Acting Muscle Relaxants ACTION IS IN THE BRAINa. Baclofen: Lioresal (GABA mimetic)

2. Direct Acting Muscle Relaxants ACTION IS IN THE MUSCLEa. Dantrolene: Dantrium (Inhibits Calcium Release in the muscle sarcoplasmic

reticulum)

Other Uses: For Malignant Hyperthermia

Drugs that affects the Seizure Activity:

Seizure: Brief, 1st Timea. Metabolic hyponatrmia, metabolic acidosisb. Hyperthermia Febrile Convulsionc. Drug Induced Antibiotics * 3rd generation cephalosporin, Cocained. Hypoxiae. Infectionf. Toxic Substances: Alcohol withdrawal, Vitamin B6 Deficiency

Epilepsy: Chronic, and repeats overtime, unpredictablea. Organic or structural damage/abnormality

Convulsion: Muscular Contractions

Types:1. Primary Epilepsy (CNS cause origin)2. Secondary Epilepsy (Tumor, Head Injury, Edema, Alcohol Withdrawal, Fever)

Location: Affected part of the brain is local (1 part)Partial Seizures (FOCAL) NO LOSS OF CONSCIOUSNESSa. Simpleb. Complex

DOC: Phenytoin , Carbamazepine

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Generalized LOSS OF CONSCIOUSNESS, HALLUCINATION(Both hemisphere are damaged/affected)

a. Tonic-Clonic (Grandmal) : DOC: Phenytoin , Carbamazepineb. Absence (Petitmal) : DOC: VALPORIC ACIDc. Myoclonic: DOC: VALPORIC ACID, CLONAZEPAMd. Febrile Seizures: DOC: Phenobarbitale. Status Epilepticus: DOC Phenytoin, Diazepam

Effects of Seizure/Epilepsy1. Injury Risk fracture, head trauma2. Airway Obstruction Aspiration3. Airway Ventilation Breathing (Stop rise/fall of the chest wall)4. LOC Amnesia, confusion, hallucinations5. Brain Damage

Steps:1. Establish Safety2. Airway3. Avoid restraints4. Re-orient the patient

ANTI-EPILEPTIC AGENTS:

1. Carbamazepine2. Clonazepam3. Diazepam4. Phenytoin5. Valporic Acid

Phenytoin: DilantinTherapeutic Index of Safety:10-20mcg/ml (Narrow/risk for toxic effects)

MONITOR BLOOD SERUM LEVELS REGULARLY

1. ACTION: Decreases the flux of Na ions to reduce electrical synaptic (-90MV) activity

2. Can cause Drowsiness (Nystagmus & Ataxia)3. Do not use with Abscence Seizure (Valporic Acid)4. ORAL: Chronic Users & IV: Status Epilepticus (Diazepam)5. Gingival Hyperplasia

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6. Megaloblastic Anemia (Vitamin B12 interaction)7. Inhibits Insulin release Hyperglycemia8. Teratogenic Agent FETAL HYDRANTOIN SYNDROME (Cleft palate, Cleft lip,

CHD)

9. Drug Interactions: Chloramphenicol, Dicumarol, Cimetidine, INH10. Increases Liver Metabolizing Action cP450 Increases Metabolism Medication11. Hirsutism and Dilantin Facies12. Osteoporosis loss of calcium deposits

Risk for Skin Allergy STEVEN JOHNSONS (Carrier HLA B Allele Ch. 12)

Carbamazepine:1. DOC for Trigeminal Neuralgia2. Can cause respiratory depression and Coma, Blurring of Vision higher dosage3. Gastric Irritant: Nausea and Vomiting (Give w/meals)4. Aplastic Anemia, Agranulocytosis, Thrombocytopenia BONE DEPRESSION5. Hepatotoxic Agent6. Skin: Exfoliative, Stevens-Johnson

Check Serum levels:a. RBC, Platelets, WBCb. Liver Function Test, Renal Function

Valporic Acid:1. GABA mimetic2. DOC : Myoclonic Seizure, Absence3. Hepatotoxic and Pancreatoxic4. Transient Hairloss5. Weight Gain

AVOID MILK & CARBONATED DRINKS Affect the pH of the Valporic acid

Nursing Considerations:1. Keep Medical and Symptoms Diary Caregiver2. Skin rashes develop Stop agent inform the doctor3. Wearing an alert bracelet/ necklase with medications and type of epilepsy4. Give meals before taking agent for CARBAMAZEPINE5. Do not mix with Milk and Carbonated Drinks (Valporic Acid)6. Seizure withdrawal occur if drug is stopped abruptly (rebound seizure)7. Skin becomes Photosensitive8. Avoid Smoking, Caffeinated agents Increase seizure activity

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9. Blood serum levels are screened regularly for toxic effects10. Identify what type of Seizure that the patient has