NPTE Pharmacology
Basic Principles of Pharmacology
• Drug Nomenclature
– Chemical name
– Generic name
– Trade name
Basic Principles of Pharmacology
• Drug Development & Approval
– FDA
– Preclinical testing
– Human testing
– New drug application approval
Basic Principles of Pharmacology
• Controlled substances
– Schedule 1- (mescaline, marijuana, heroine)
• highest potential for abuse
• Restricted to approved research
– Schedule 2- (morphine, meperidine, barbiturates)
• Specific therapeutic purpose
• High potential for abuse
– Schedule 3 (opioids)
• Mild to moderate dependence
– Schedule 4 (benzodiazepines)
• Low potential for abuse
– Schedule 5 (low doses of opioids)
• Lowest relative abuse potential
Pharmacokinetics
• Routes of administration
ENTERAL
Parenteral
Oral
Inhalation
Sublingual
Intravenous
Rectal
Intra-arterial
Intramuscular
Intrathecal
Topical
Transdermal
• Drug elimination rates
– Clearance
• Blood flow to the organ
• Extraction ratio
– Half life
• Amount of time required for 50% of drug to be eliminated
Drug Receptors
• Agonist vs Antagonist
– Agonist
• Drug binds to receptor & initiates a change in function of cell
– Antagonist (Blockers)
• Drug binds to receptor but will not cause change the function of cell
CNS Pharmacology
• The Blood Brain Barrier
– Inability to pass from bloodstream to CNS
– Tight junctions between capillary endothelial cells
– Non-polar, lipid soluble drugs able to cross by passive diffusion
CNS Pharmacology
• Sedative-Hypnotic & anxioloytics
– Barbiturates
• Barb-
– Benzodiazepines
• -epam
• -olam
Problems & adverse effects
Tolerance & physical dependence
Residual effects
GI (N & V), dry mouth
Incoordination
CNS Pharmacology
• Considerations for the PT
– Patient calmer
– Benzodiazepines reach peak 2-4 hrs
• Schedule sessions during that time
• In over sedated states
– Hazardous to do gait training & exercise
DRUGS USED FOR AFFECTIVE DISORDERS
• Pathophysiology of depression
– Underactive influence of NE, serotonin, dopamine in limbic
system
– Increased sensitivity of the post-synaptic receptor for NE
• Leads to compensatory decrease in sensitivity of the receptor
• Drugs for affective disorders
– Tricyclics
• Blocks re-uptake of amine neurotransmitters into the presynaptic terminal
• -triptyline; -pramine (amitriptyline; desipramine)
– MAO inhibitors
• Enzyme located at amine synapses
• Blocking this enzyme allow released amines to remain in the cleft
• (Isocarboxazid [Marplan]; Phenelzine [Nardyl]; tranylcypromine [parnate])
– Second-generation agents
• Mechanisms similar to tricyclics
• Selective blocking of serotonin
• Bupropion [Wellbutrin]; fluoxetine [Prozac]; sertraline [Zoloft])
• Problems & adverse effects
– Tricyclics
• Sedation
• Anticholinergic effects
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Confusion, delirium
Dry mouth, constipation
Urinary retention
Tachycardia
Arrhythmias, orthostatic hypotension
Potential for fatal overdose
• Problems & adverse effects
– MAO Inhibitors
• CNS excitation
– Restlessness, irritability, agitation, sleep loss
• Central & peripheral anticholinergic
– Tremor, confusion, dry mouth, urinary retention
– *may cause ↑BP, HTN crisis
» Ingested tyramine + decreased catecholamine breakdown (MAO inhibition)→
hypertensive crisis
» Avoid fermented cheese and wine
• Manic-Depression
– Mood swings
• Overactive NE & serotonin → manic phase
• Rebound effect→ depression
• Manic-Depression
– Lithium
• Precise mechanism of action remains undetermined
• Therapeutic: 1.0 to 1.4 mEq/L
• Toxic: 2.5 mEq/L
• Special Concerns for PT
– These drugs maybe used for other reasons (SCI, burns,
amputation, pain)
– Sedation, lethargy & muscle weakness (tricyclics, lithium)
– Orthostatic hypotension (tricyclics)
– Hypertensive crisis
– Suicidal tendency
• Anti-psychotics (neuroleptics)
– Schizophrenia
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Marked disturbance in thought
Delusions
Hallucinations
? Increased dopamine????
– Severe paranoid disorders
• Problems & Adverse Effects
– EPS
– Less likely with clozapine (Clozaril) because selective for dopamine receptors that affect
behavior rather than those affecting motor function
• Tardive dyskinesia
• Pseudoparkinsonism
– Resting tremor, bradykinesia, rigidity
• Akathisia (motor restlessness)
• Dyskinesia & dystonias (torticollis, oculogyric crisis, opisthotonos)
• Neuroleptic malignant syndrome (catatonia, stupor, rigidity, tremors, fever)
– Severe
– High mortality
• Problems & Adverse Effects
– Nonmotor effects
• Sedation
• Anticholinergic effects
• Other
– Orthostatic hypotension
– Photosensitivity (chlorpromazine)
• Special Concerns for the PT
– Monitor motor involvement
• Change in posture, balance
• Involuntary movements
– **refer to health care provider
ANTIEPILEPTIC DRUGS
• Antiepileptic Drugs
– Epilepsy- recurrent seizures
– Seizures- sudden, transient disturbances in cerebral excitation
• Classification of Seizures
– Generalized, partial, or unclassified
– Partial
• Only part of the brain is involved (e.g. one cerebral hemisphere)
– Generalized
• Whole cerebral brain is involved
• Partial Seizures
Type
Classification
Simple partial
Limited (focal) motor or sensory signs
Consciousness remains intact
Complex partial
seizures
Consciousness impaired; bizarre behavior
Partial becoming
generalized
progressive
• Generalized seizures
Seizure type
Classification
Absence
(petit mal)
Sudden brief loss of consciousness
Motor signs may be absent
Myoclonic
Sudden, brief, shock-like contraction of muscles in the face &
trunk or in one or more extremities
Consciousness may be impaired
Clonic
Rhythmic, synchronized contractions throughout the body
Loss of consciousness
Tonic
Generalized, sustained contractions throughout body
Loss of consciousness
Tonic-clonic (grand Sustained contractions of all muscles (tonic phase) followed by
mal)
powerful rhythmic contractions (clonic); loss of consciousnesss
Atonic
Sudden loss of muscle tone; consciousness may be maintained
or lost briefly
• Drugs used to treat epilepsy
– Barbiturates
– Benzodiazepines
– Carboxylic acids (valproic acid [Depakene])
– Dicarbamates (felbamate [Felbatol])
– Hydantoins (phenytoin)
– Iminostilbenes (carbamezapine [Tegretol])
– Oxazolidinediones (paramethadione [Paradione])
– Succinimides (ethosuximide [Zarontin])
• Special concerns for the PT
– Frequent side effects affecting treatment
• Headache, dizziness, sedation, gastric disturbances
– Schedule when sx are mild
• Cerebellar side effects (e.g. ataxia)
– Coordination exercises
• Prevention of seizures
– Quiet setting for therapy
Pharmacology in Parkinson’s
• Pertinent facts
– Movement disorder
– Pathophysiology
• Degeneration of dopamine producing cells in substantia nigra
– Loss of dopaminergic input into corpus striatum
• Therapeutic Agents
– Levodopa
– Levodopa- Carbidopa (1:4-1:10)
• Adverse Effects
– GI
– CV
» Arrhyhtmias, postural hypotension
– Dyskinesias
– Behavioral changes
• Other Drugs
– Dopamine agonists
• Bromocriptine (Parlodel)
• Pergolide (Permax)
– Anticholinergics
• Benztropine mesylate (Cogentin); trihexyphenidyl (Artane);
diphenhydramine (Benadryl)
– Amantadine (Symmetrel)- anti-viral. Exact mechanism ??
– Selegiline (Eldepryl)- prevents breakdown of dopa
• Special considerations for PTs
– Coordinate treatment with peak effect (1 hr)
– Schedule after breakfast dose
– During drug holiday- maintain mobility
– Monitor BP
– Prevent orthostatic hypotension
Local Anesthetics
• Methods of administration
– Topical
– Transdermal
• Iontophoresis (electricity)
• Phonophoresis (ultrasound)
– Infiltration
– Peripheral nerve block
– Central neural blockage
• Epidural
• Spinal nerve block – subarachnoid
– L3-L4 or L4-L5
• Significance in Rehabilitation
– Schedule sessions immediately after injection
– When central neural blockage used
• Sensation below diminished
• Motor function affected
DRUGS AFFECTING SKELETAL MUSCLE
Skeletal Muscle Relaxants
• Centrally acting agents
– Baclofen (GABA agonist)
• Drowsiness, confusion, hallucinations
– Diazepam
• Sedation
– Others
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Carisoprodol (Soma)
Cyclobenzaprine (Flexeril)
Metaxalone (Skelaxin)
Methocarbamol (Robaxin)
– Drowsiness, dizziness
• Direct-acting Relaxants
– Dantrolene Sodium (Dantrium)- impairs Ca+ release
• Generalized muscle weakness
• Hepatotoxicity
• Other relaxants
– Botulinum Toxin (Botox)
• Symptoms return after 2 to 3 months
– Transdermal clonidine
• Useful in spasticity in SCI
• Special Concerns for PTs
– Accommodate sedation effects
– Schedule when effects are at a minimum
DRUGS USED TO TREAT PAIN &
INFLAMMATION
Opioid Analgesics
• Strong Agonists – for severe pain (mu & kappa receptors)
– Fentanyl (Sublimase)
– Hydromorphone (Dilaudid)
– Meperidine (Demerol)
– Methadone (Dolophine)
– Morphine (Duramorph)
– Oxymorphone (Numorphan)
• Mild to moderate agonists
– Codeine
– Hydrocodone (Hycodan)
– Oxycodone (Percodan)
– Propoxyphene (Darvon)
• Mixed Agonist-Antagonists (kappa & sigma receptors)
– Less tolerance & dependence
• Naloxone (Narcan)
• Naltrexone
• Special Concerns for PTs
– Schedule during peak effects
– Respiratory response to exercise blunted (↓rate)
• Nonsteroidal Anti-inflammatory Drugs
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Aspirin
Diclofenac (Voltaren)
Diflunisal (Dolobid)
Ibuprofen (Motrin)
Indomethacin (Indocin)
Ketorolac (Toradol)
Mefenamic acid (Ponstel)
Naproxen (Anaprox, Naprosyn)
Piroxicam (Feldene)
Sulindac (Clinoril)
• Mechanism of
action of NSAIDS
Inhibition of
cyclooxygenase
enzyme
Elimination of
thromboxane &
prostaglandin
• Special Concern for PTs
– Good for moderate to mild pain but not for severe pain
– GI complications
– Acetaminophen lacks anti-inflammatory effects
– High-dose of ASA can lead to hearing loss
PHARMACOLOGY IN RA OR OSTEOARTHRITIS
• Goals of treatment
– To decrease joint inflammation
• NSAIDs
• corticosteroids
– To arrest progression of disease
• DMARDs
• Corticosteroids
– Inhibits prostaglandin & leukotriene
• Betamethasone (Celestone)
• Dexamethasone (Decadron)
• Methylprednisolone (Medrol)
– Adverse side effects
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Osteoporosis
Muscle wasting, weakness
Aggravation of DM
Cataracts & glaucoma
• DMARDS
– Modifies the pathologic process
– Inhibit immune response
• Anti-malarial drugs (decreased T cells)
– Chloroquine (Aralen); hydroxychloroquine (Plaquenil)
– Adverse effects: retinal damage
• Azathioprine (Imuran)- impairs DNA
– Adverse effect: fever, chills, sore throat fatigue, loss of appetite, n&v
• Gold therapy- inhibiting phagocytes
– Aurothioglucose (Solganal); gold sodium thiomalate (Miochrysine)
– Adverse effects: GI, stomatitis, thrombocytopenia, leukopenia
• DMARDS –continued
– Methotrexate (Folex, Rheumatrex)inhibits folic acid
decreased nucleoproteins
impaired production of genetic material
• Adverse Side Effects
– GI including GI bleed
– Penicillamine (Cuprimine)- depresses T cell function
• Adverse Side Effects
– Fever, joint pain, rashes, lymph swelling
• Special Concerns for PTs
– Use ROM & strengthening exercises cautiously in those on
corticosteroids
– Prevent skin breakdown- corticosteroids
AUTONOMIC & CV PHARMACOLOGY
The Autonomic Nervous System
• Divisions
– Sympathetic NS
(thoracolumbar
division)
– Parasympathetic
or craniospinal
– (originating in
mid-brain,
brainstem & sacral
region of the
spinal cord)
Sympathetic
• Heart
– ↑contractility (beta 1)
– ↑ heart rate (beta 1)
• Arterioles
– VC -skin & viscera (alpha-1)
– VD sk. Muscle, liver (beta-2)
• Lungs
– BD (beta-2)
Parasympathetic
• Heart
– ↓ HR (musc)
– ↓ contractility-slight (musc)
• Arterioles
– No innervation
• Lungs
– BC (musc)
Sympathetic
• GI Function
– ↓ motility (alpha 1,2; beta 1,2)
• Bladder detrusor
– Relaxation (beta 2)
• Bladder Trigone & Sphincter
– Contraction (alpha 1)
• Liver
– Glycogenolysis & gluconeogenesis
(alpha 1, beta 2)
Parasympathetic
• GI Function
– ↑ motility & secretion (musc)
• Bladder detrusor
– Contraction (musc)
• Bladder Trigone & Sphincter
– Relaxation (musc)
• Liver
– Glycogen synthesis (musc)
Adrenergic Receptors
• Alpha-1
– Smooth muscle
• Alpha-2
– CNS inhibitory synapses
– GI tract, pancreatic islet cells (↓insulin secretion)
• Beta-1
– Predominate in heart & kidneys (↑ renin)
• Beta-2
– Bronchiole smooth muscle (relaxation)
– Some arterioles (vasodilation)
Cholinergic Drugs
• Bethanechol
– Post op GI & urinary atony
• Pilocarpine
– Glaucoma
Antimuscarinic Anticholinergic Drugs
• Prototype- Atropine
• Clinical applications
– GI system
• Peptic ulcer, IBS
– Parkinson’s
– Motion sickness
Adrenergic Drugs
• Alpha-1 Selective Agonists
– Primarily on vascular smooth muscle
• Vasoconstriction & increased PVR
– Phenylephrine
– Pseudoephedrine
• Alpha-2 Selective Agonists
– Inhibits sympathetic discharge
• Useful in hypertension
– Clonidine, methyldopa
• Beta-1 Selective Agonists
– Receptor primarily in myocardium
– Increased heart rate & inotropy
• Dobutamine
• Dopamine
• Beta-2 Selective Agonists
– Bronchiole smooth muscle
• Albuterol (Proventil, Ventolin)
• Isoetherine
• Metaproterenol (Alupent)
Adrenergic Antagonists
• Alpha antagonists
– Reduces peripheral vascular tone→ vasodilation
• Ergotamine, phentolamine, prazosin
• May cause reflex tachycardia
• Beta Antagonists
– Negative chronotropic, negative inotropic
• Acebutolol, Esmolol, Nadolol, Propranolol
ANTIHYPERTENSIVE DRUGS
Diuretics
– Decreases circulating volume
• Classification
– Thiazide
• Inhibits Na+ reabsorption
– Chlorothiazide
– Loop (ascending loop)
• Inhibits reabsorption of Na+ and CL– Bumetanide, Ethacrynic acid, Furosemide
– Potassium Sparing (distal tubule)
• Prevents K+ excretion
– Amiloride, Spironalactone, Triamterene (Dyrenium)
Sympatholytic Drugs
• Beta Blockers
– Lowers heart rate & force of contraction= decreased CO
• Acebutolol
• Labetalol
• Alpha Blockers
– Decreased vascular resistance
• Doxazosin, Prazosin, Terazosin
Presynaptic Adrenergic Inhibitors
• Inhibits release of norepinephrine
– Guaethidine, Reserpine
Centrally Acting Agents
• Inhibition of sympathetic discharge from the brainstem
– Clonidine, methyldopa
Vasodilators
• Decreased peripheral resistance
– Hydralazine, Diazoxide (Hyeprstat)
ACE Inhibitors
• Prevention of conversion of Angiotensin I to AII
– Benazepril
– Captopril
– Enalapril
– Fosinopril
Calcium Channel Blockers
• Inhibits contractile process
– Diltiazem
– Felodipine
– Isradipine
– Nicardipine
– Nifedipine
– Verapramil
Special Concerns for the PT
• Caution in changing postures
• Avoid widespread vasodilation
– Whirlpool, Hubbard Tank
• Exercise may cause vasodilation in skeletal musculature
• If beta blockers- exercise tolerance may be impaired
• Encourage compliance
TREATMENT OF ANGINA PECTORIS
Organic Nitrates
• Precursor, activated when converted to nitrous
oxide→vasodilation
• Dilation of systemic venous system; arterioles→ decreased
PVR
• Decreased pre-load, afterload
• Decreased myocardial O2 demand
– Nitroglycerine
– Isosorbide dinitrate
– Amyl nitrite
Beta-adrenergic blockers
• Decreased heart rate
• Negative inotropic effect
– Atenolol
– Metoprolol
Calcium Channel Blockers
• Coronary vasodilation
• Peripheral vasodilation
– Diltiazem
– Felodipine
– Nifedapine
Special Concerns for PTs
• Make sure patient has NTG available
• Angina may occur during therapy
• Patients taking these drugs may have increase tolerance to
exercise
• Some drugs may blunt ability of heart to respond to
exercise
• Adjust exercise workloads
• CaCB & nitrates- patients may experience hypotension
when systemic heat is applied
TREATMENT OF CARDIAC ARRHYTHMIAS
• Sodium channel blockers
– Procainamide, Quinidine
• Beta Blockers
• Class III- prolongs repolarization
– Bretylium; Amiodarone
• CCB
• Special Concerns for the PT
– In exercise (cardiac rehab) monitor for arrhythmias
– Watch for postural hypotension
TREATMENT OF CHF
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Digitalis glcosides
Diuretics
ACEI
Other
– Amrinone, Milrinone- + inotropic
– Dopamine, dobutamine
– vasodilators
• Special Concerns for the PT
– Monitor for signs of CHF
– Report signs of digitoxicty
– Watch for postural hypotension
COAGULATION DISORDERS &HYPERLIPIDEMIA
• Drugs to treat overactive clotting
– Anticoagulants
• Heparin, Oral anticoagulants
– Antithrombotic drugs
• ASA
– Thrombolytics
• Streptokinase, urokinase
• tPa
• Treatment of clotting deficiencies
– Vitamin K
– Antifibrinolytics
• Aminocaproic acid (Amicar)
• Agents to treat hyperlipidemia
– HMG-CoA Reductase Inhibitors
• Decreases cholesterol production (LDL, VLDL)
– Lovastatin, pravastatin, simvastatin
– Fibric acid
• Increases breakdown of triglyceride-rich lipoproteins (LDL, IDL)
• Clofibrate, gemfibrozil
– Adverse Effects
• GI, cutaneous vasodilation (niacin)
• Liver dysfunction, gallstones, pancreatitis
• Myalgia, fatigue/weakness
• Special Concerns for PTs
– Those on anticoagulants, watch for bleeding
– Caution with deep tissue massage or chest percussion
– Hemophilia-hemarthrosis
• Improve joint function after resolution
RESPIRATORY & GI PHARMACOLOGY
Respiratory Drugs
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Drugs for Respiratory Tract irritation
Antitussives
Decongestants
Antihistamines
Mucolytics & expectorants
• Drugs to maintain airway patency on Obstructive PD
– Beta adrenergic agonists
• Albuterol, epinephrine, isoetharine, metaproterenol, terbutaline
– Xanthine derivatives
• Aminophylline, theophylline
– Anticholinergic drugs
• Ipratropium (atrovent)
– Corticosteroids
• Beclomethasone, dexamethasone
– Cromolyn sodium
• Prevents bronchospasm
• Treatment of bronchial asthma
– Steroids
– Beta-2 agonists
– Leukotriene inhibitors
• Special Concerns for PTs
– Postural drainage & breathing exercises
– Chest PT more effective after 30 min-1 hr. after treatment
– Advise patients to bring medications
– Monitor side effects
• Arrhythmias, nervousness, confusion
• For those on steroids- watch for skin breakdown
GI Drugs
• Control of gastric acidity & secretion
– Antacids
– H2 receptor Blockers
• Cimetidine, Famotidine, Nizatidine, Ranitidine
– Anticholinergics
• Pirenzepine
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Metaclopramide (Reglan)
Omeprazole (Prilosec)
Sucralfate, Carafate
Prostaglandins
• Misoprostol (Cytotec)
• Special Considerations for the PT
– GI drugs well tolerated
– Generally will not interfere with therapy
ENDOCRINE PHARMACOLOGY
• Special Concerns of adrenal steroid
– Causes general breakdown (catabolic) in muscle, bone, skin, &
other collagenous structures
– Strengthening exercises help maintain muscle mass
– Weight bearing to reduce bone loss
– Avoid injury
– Prevent skin breakdown
– Na+ & water retention
– Immunosuppression
– Watch for mood changes & psychoses
• Special concerns for use of sex hormones (estrogen
progesterone, androgens)
– Monitor BP (salt & H2O retention)
– Teach about effects if androgens
• Thyroid & Parathyroid Drugs
– Hyperthyroidism
• Iodide
• Radioactive iodine
– Hypothyroidism
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Levothyroxine
Liothyronine
Liotrix
Thyroglobulin
• Parathyroid Glands
– PTH- controlled release by amount of Ca+ in plasma
• ↓ plasma calcium stimulates PTH
– Increases bone resorption,
– renal reabsorption (as renal calcium reabsorption, PTH also increase phosphate
excretion)→ rise in Ca+, ↓ plasma phosphate
– GI tract via interaction of PTH & Vitamin D
» PTH increases conversion of Vit. D to 1,25-dihydroxycholecalciferol (calcitrol)
which increases GI reabsorption of Ca+ (small intestine)
• Regulation of Bone Mineral Homeostasis
– Parathyroid Hormone
• Decreased or normal PTH encourages bone synthesis & remodeling
– Vitamin D
• Increases intestinal calcium and phosphate absorption
• Decreases renal calcium & phosphate excretion
• Enhances bone formation by increasing Ca+ & Phosphate
– Calcitonin
• Antagonist to PTH
• Lowers blood calcium by stimulating bone formation
• Increases renal excretion of calcium & phosphate
Drugs for Bone Homeostasis
• Calcium Supplements
– Calcium gluconate
• Vitamin D analogues
– Calcifediol
– Calcitriol
• Diphosphonates
– Etidronate
• Calcitonin
– Calcimar
• Special Concerns
– Do not overstress hypothyroid patients
– Calcium abnormality- watch arrhythmias
– Ultraviolet light increases endogenous Vitamin D biosynthesis
facilitating calcium absorption and bone formation
• Significance of Diabetes Mellitus for PTs
– Watch for hypoglycemia
– Ensure that patient did not skip meal before exercise
– Have sources of glucose available