Pharmacology Part I PDF

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Summary

These are lecture notes from the PTA 217 class involving pharmacology in the PTA career....

Description

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PHARMACOLOGY part 1

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Marie helene Mcandrew PT,DPT

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Rev. 15

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Basic Principles of pharmacology

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BASIC NOMENCLATURE

Myriad of terms that can represent the same drug. Can be bring confusion in all settings. Chemical Name Refers to the specific compound’s structure and are usually long. Generic Name (official or nonproprietary) Derived from the chemical name and usually shorter Trade Name (brand) Assigned by pharmaceutical co. and not always bear reference to the chemical or generic terminology •

Basic Principle of Pharmacology

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Basic Nomenclature

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Examples:

Chemical Name: N- Acetyl-p- aminophenol Generic Name: Acetaminophen Brand (trade)Name: Tylenol, Panadol, many others Chemical Name: 7- Chloro-1,3-dihydro-1methyl-5-phenyl-2H-1,4-benzodiazepin-2-one Generic Name: Diazepam Brand(trade) Name: Valium •

Substitution of generic drugs for brand drugs

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Common question. Can a generic drug be substituted for a brand drug?

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Generic drugs usually cheaper and can help reduced health care cost

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Generic drugs should be as safe and effective as the original brand name product following certain criteria:

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Tests should show same amount and type of active ingredients

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Same route of administration

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Same pharmacokinetic profile(plasma level, absorption, etc.

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Substitution of generic drug for brand drug

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If such testing done, the two drugs are said to be

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“bioequivalent”

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If bioequivalence is not established, we can only assume that the therapeutic effects produces by the replaced drug, will be the same. Bioequivalence must be FDA approved.

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NB: Establishing bioequivalence does not mean a patient would get a different therapeutic effects.

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Many issues needed to address by the prescribing MD

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Pharmacology terminology

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Pharmacotherapeutics: area of pharmacology that refers to the use of specific drugs to prevent treat or diagnose a disease. Divided into two functional areas.

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pharmacokinetics: study of how the body deals with drugs in terms of the way it is absorbed, distributed and eliminated.

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pharmacodynamics: analysis of what a drug does to the body, including the mechanism by which the drug exerts its effect

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Pharmacology terminolgy

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Toxicology: study of the harmful effects of chemical

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Pharmacy: deals with the preparation and dispensing of medications

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Drug approval process

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In the USA: Food and Drug Administration (FDA) -responsible for monitoring the use of existing drugs

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-responsible for development and approval of new drugs

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In Canada: Health Products & Food Branch of the Department of National Welfare

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Primary concerns for both agencies:

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1)whether or not drug is effective

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2)whether or not drug reasonably safe for human use

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Drug Approval Process

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The development of new drugs involves extensive preclinical(animal) and clinical (human) studies

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Preclinical studies: Basic pharmacokinetic and pharmacodynamic of a compound is tested. Takes between 1-2 years. If results are good the drug sponsor ($$$) will file an investigational new drug(IND) application with the FDA

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Human Clinical Testing is divided in three primary phases.

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Drug approval process **KNOW PHASES**

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Phase I

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Purpose is to obtain some initial information about the pharmacologic actions and possible toxic effects of the drug on humans

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Sample is small number of healthy volunteers (20-80)

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Duration < 1 year

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Phase II

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Purpose is to evaluate the effectiveness of the drug and to assess the side effects and other risks

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Drug approval process

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Phase II (cont)

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Sample remain small but bigger than in phase I (200-300)

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This time subjects have specific diseases or pathologic conditions

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Duration is also two years

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Phase III

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Expansion of clinical evaluation with more subjects (hundreds to several thousands)

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Duration three years

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Drug approval process

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Phase III (cont)

Additional information is gathered to research safety and effectiveness of the drug At the end of phase III, the drug sponsor ($$$) applies for a new drug application(NDA) Results are reviewed by FDA and if OK NDA is approved Only at this point is the drug marketed and prescribed for use in the general population •

Drug approval process

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Phase IV( not primary)

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AKA postmarketing surveillance

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Instituted after NDA

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Refers to all methods used to continue monitoring drug safety and effectiveness after approval for public use

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Methods can be reporting of rare side effects by MD’s

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Development of a new drug a lengthy and very expensive endeavor

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FDA

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Approved/monitor new drugs

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Can expedite the process for a rare drug for a rare condition is needed. This type of accelerated development/review AKA fast track

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Ex: cancer or HIV drugs

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Fast track also work when a drug is already approved to treat a condition but now is discovered to treat another one

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Ex: Lasix diuretic and hypertensive medication

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Drug classification and Prescribing

MD, DO, NP can prescribe drugs. PT’s in the military and PA can also under supervision of a physician. PT’s are limited to musculoskeletal drug such as NSAID Drug are marketed as prescription and non prescription drugs (OTC- over the counter). OTC drug can be purchase directly by consumers. OTC products expended over the years and more drugs that were formerly availability by prescription do not require one anymore. What could be the problem with this? •

Drug classification and prescribing

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Drugs are classified as agonists, antagonists or mixed.

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Agonist: drug will produce a change in the cell. Binds and produces effects.

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Antagonist: Binds but do not produce an effect. It blocks an effect. AKA Blockers

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Ex: Beta-Blockers on myocardium prevent Catecholamines from increasing the heart rate or contractility.

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Drug classification and prescribing

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Mixed: some agents will stimulate certain receptors subtypes but will also blocked or inhibit other receptors subtypes.

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Ex: In women some drugs will stimulate Estrogen receptors on bone to prevent Osteoporosis while blocking the effects of Estrogen on breast tissue for cancer prevention. They are called selective drug receptors.

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Controlled Substances

1970-The Comprehensive Drug Abuse Prevention and Control Act (or Controlled Substances Act)enacted Help place drugs into categories(schedules) according to their potential for abuse Schedule I: Highest potential for abuse, not typically used in a traditional medical setting. Legal use only for approved research or therapeutic use on limited number of patients Ex: Heroin, LSD, Marijuana(antiehemetic- anti-nausea) •

Controlled Substances

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Schedule II: drugs here approved for specific therapeutic purposes but still with high potential for abuse or addiction.

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Ex.: Opioids, Morphine ,fentanyl and drugs containing Methamphetamines.

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Schedule III: Lower potential for abuse still possibility of developing mild to moderate physical or psych dependence or both.

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Ex.: certain opioids like codeine combined with other nonopioids drugs like barbiturates and amphetamines

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Control substances

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Schedule IV: less and less potential but some limited possibility of dependence

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Ex: certain depresssants and stimulants ,antianxiety drugs

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Schedule V: Lowest relative abuse potential. Low dosage of opioids that are used in cough medications and antidiarrheal preparations.

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Pharmacokinetics

Absorption- >Distribution->storage-> Elimination Absorption: Administration Routes Two primary routes: alimentary canal (enteral) Non alimentary route( paraenteral). Enteral: Oral, sublingual, rectal. Easier administration but less predictable absorption Paraenteral: Injection, inhalation, topical, transdermal. -More difficult to administer but more predictable absorption. •

Pharmacokinetics

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Distribution:

Drugs typically cross cellular membranes and penetrate tissues to reach a target site. Many routes exist but does not mean all tissues receive the drug uniformly. Affected at different areas. Ex: A cardiac med given orally has to go through the GI tract before being absorbed systemically and reach the heart and be therapeutic. The extend to which a drug reaches the systemic circulation is referred to as bioavailability, a parameter express in percentage. •

Pharmacokinetics

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Bioavailability (cont)

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Ex: If 100 mg of a drug is given orally and 50 mg eventually make it into the systemic circulation, drug is said to be 50% bioavailable.

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If 100g of the same compound is injected intravenously, the drug would be 100% bioavailable.

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Bioavailability depends on the route of administration and the drug’s ability to cross membrane barriers.

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Pharmacokinetics

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Storage: after administered, absorbed, a drug gets stored in body. Sequestrated in its active form. Not at the target site.

primary storage sites: Adipose, muscles, bone, organs like liver and kidneys. Problem of storage is high concentration of drugs in local tissue can cause damage from toxic compounds and drug metabolites (less active transformed compound) Ex: high concentration of Tylenol can cause liver damage •

Pharmacokinetics

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Drug Elimination: Biotransformation: refers to chemical changes that takes place in the drug following administration.

A- Biotransformation results in altered version of the original compound and is known as metabolites. Primary site: Liver B- Excretion: drug excreted from body Primary site: Kidneys •

Pharmacokinetics

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Factors affecting normal pharmacokinetics

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Age, gender, disease, genetics, body composition, diet, other chemicals and physical factors.

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Implication for Physical Therapy

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Timing of rehab session with drugs peaks & valleys

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Effects on absorption/distribution: heat increases/cold decreases

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Help recognize improper drug responses

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Types of drugs

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Management of Pain and Inflammation

Analgesics Anti-inflammatory Opioids/nonopioids NSAID/Glucocorticoids •

Types of drugs

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Opioids (narcotic) or Analgesics:

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Alter pain perception

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Use in mod-severe pain

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Indication: post surgery, trauma, chronic pain, cancer and others

Types: •

Strong Agonists: Morphine, Demerol

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Moderate Agonists: Codeine, Roxicodone

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Antagonists: Narcan, Trexan

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Mixed Agonist/Antagonist: Stabol, Nubain

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Types of drugs

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Adverse Effects:

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Sedation, mood changes, confusion, dyspnea, postural hypotension, nausea/vomiting, constipation, tolerance & dependence.

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Potential for addiction

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Tolerance: means, need more drug to achieve same effect.

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Physical dependence: Onset of withdrawal if drug suddenly stopped

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Types of drugs

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Patient Controlled Anesthesia (PCA)

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Pt self pump small preset amounts

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Pump is programmed to prevent OD.

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Allows better pain control with fewer side effects.

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After several day on pumps and improvement, pt is d/c from pump to another opioid by injection or per oral.

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Types of drugs

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Non-Steroidal-Anti-Inflammatory Drugs (NSAID’s)

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Effects: analgesic, anti-inflammatory, antipyretic (decrease fever),anticoagulation

OTC: •

Acetaminophen

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ASA, Ibuprofen (Motrin, Advil), Naproxen (Aleve), Ketoprofen (Orudis)

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Prescription:

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Etolac (Lodin), Fenoprofen (Nalfon), Ketorolac (Toradol), Meclofenamate , Celecobid (celebrex), Nabumetone ( Relafen), Oxaprozin (Daypro)

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Types of drugs

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NSAID’s inhibit synthesis of Prostaglandins by inhibiting Cyclooxgenase enzyme ( COX).

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Acetaminophen: analgesic and antipyretic effects w/o gastric irritation but high dose or frequent can cause liver toxicity.

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NSAID’s : Adverse effect and Rehab concerns: Gastric irritation, renal toxicity, OD (hearing loss, confusion, headaches, tinnitus(ringing in ear).

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Indication: Use in mild to moderate inflammation

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Type of drugs

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Another Anti inflammatory drugs

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Glococorticoids: Powerful anti inflammatory AND Immunosuppressive effects.

Cortisone, Paramethasone, Dexamethasone, Prednisolone, Hydrocortisone, Prednisone, Betamethasone Adverse effects and Rehab concerns: Catabolic effect on bone, muscles, ligaments and tendons. Salt/Water retention, increase infection, gastric ulcers, glucose intolerance, Glaucoma, Adrenal suppression. •

Types of drugs

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Muscle relaxants

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Selective decrease of skeletal muscle excitability

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Indications: Muscle spasms, muscle injury, PNI, tonic contraction like spasticity (CNS Lesion: CVA, SCI, CP).

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Specific to muscle spasms

Carisoprodol (Soma), Metaxalon (Skelaxin), Chlorzoxazone (Parafon), Orphenadrine ( Norflex), Cyclobenzaprine ( Flexeril), Methocarbamol ( Robaxin). •

Types of drugs

Specific to treat Spasticity Diazepam (Valium) Baclofen (Lioresal): Intrathecal Baclofen can be used in severe spasticity. Injected into the sheath surrounding the spinal cord subarachnoid space. Other ms relaxors Alpha-2 Agonists, Clonidine (used for HTN also), Tizanidine, Zanaflex, Gabapenten (Neurontin), Dantrolene Sodium( Dantrium) Botulinum Toxin (Botox) •

Types of drugs

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Muscles relaxants adverse effects and rehab concerns:

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Causes sedation, addiction, dizziness, generalized weakness.

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Types of drugs

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Seizure disorder:

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Recurrent uncontrolled cerebral electrical excitation.

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Cause is still unknown for younger people.

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Goals is to select effect on hyperexcitable neurons

Primary anti seizure: Dilantin, Tegretol, Zarontin, Deparkene, Valium. Second Generation: Neurontin, Lamictal, Gamitril, Sabril •

Rehab Concerns: sedation, HA, Dizziness, GI distress, Liver toxicity, Anemia, Incoordination

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Second generation meds created to reduce side effects

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Type of drugs

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Specific to Parkinson disease

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Dz of progressive degeneration of dopaminergic neurons in Substantia Nigra. Loss of dopamine influence, causes imbalance in other neurotransmitters.

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S&S: Rigidity, Resting Tremors, mask like face, soft voice, bradykinesia & postural instability.

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Drugs: Sinemet (Combo of L –Dopa & Caridopa), Parlodel, Permax, Symmetrel & Eldepryl.

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Rehab concers: hypotension, GI distress, psycotrophic effects and confusion.

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references

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Ciccone, C.D.(2007) Pharmacology in Rehabilitation, 4th Ed. F.A.Davis: Philadelphia, PA.

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Ciccone, C.D. (2013) Drug Guide for Rehabilitation Professionals, 1st Ed. F.A.Davis: Philadelphia, PA.

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