Transcript PT 154 Therapeutic Exercises III Pharmacological Considerations

PT 154 Therapeutic Exercises III
Pharmacological Considerations
for Neurological and Developmental Conditions
Jay C. Rivera, PTRP
Faculty – Department of Physical Therapy
College of Allied Medical Professions
University of the Philippines Manila
Objectives
• Review the basics of pharmacokinetics
• Identify common pharmacologic management
administered to patients with neurological and
developmental conditions
• Discuss the common rehabilitation concerns
regarding the pharmacological management
of these patients
Topic Outline
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Basic pharmacokinetics
Antihypertensive drugs
Anti-spasticity drugs
Antiepileptic drugs
Anti-Parkinson drugs
Anxiolytic drugs
Antidepressant drugs
Anti-coagulants
Why do we need to consider the
pharmacological management
of patients with neurologic and
developmental conditions?
Pharmacokinetics
• pertains to the body’s response to
drugs in terms of:
• Absorption
• Distribution
• Elimination
Pharmacokinetics
• Absorption
– from site of administration to the
bloodstream
– Route of administration: enteral and
parenteral
– Passive diffusion, active transport,
facilitated diffusion
Pharmacokinetics
• Distribution
– Biotransformation – drug metabolism in
the liver (first pass effect)
– Bioavailability – the extent to which the
drug reaches the systemic circulation
– distribution may be affected by tissue
permeability, blood flow, binding with
plasma proteins
Pharmacokinetics
• Elimination
–Biotransformation in itself is a form
of elimination
–Kidneys play its role in drug excretion
–Excretion depends on the drug’s halflife
Antihypertensive Drugs
Antihypertensive Drugs
• MEDS: Diuretics, Sympatholytics
(Beta blockers, Alpha 1 blockers,
ACE inhibitors, Calcium channel
blockers)
Antihypertensive Drugs
• Diuretics – suffix “ide”
– Hydrocholothiazide (Esidrix),
Furosemide(Lasix)
– MOA: decrease in plasma fluid volume in
the body
– Side Effects: fluid depletion, electrolyte
imbalance, orthostatic hypotension
Antihypertensive Drugs
• Sympatholytic drugs
– Beta-blockers – suffix “olol” – Atenolol,
Metoprolol (Lopressor)
• MOA: decrease in HR and force myocardial
contraction
• Side Effects: orthostatic hypertension,
excessive depression of heart rate and
myocardiac contractility; generally tolerated
Antihypertensive Drugs
• Sympatholytic drugs
– Alpha 1 blockers – suffix “sin” – Prazosin
(Minipress), Doxazosin, Terazosin
– MOA: decrease in peripheral vasculature
resistance
– Side effects: reflex tachycardia,
orthostatic hypotension, increased risk
for congestive heart failure
Antihypertensive Drugs
• ACE inhibitors – suffix “pril” –
Captopril, Moexipril (Univasc)
– MOA: inhibits conversion of
angiotensin 1 to angiotensin 2 (potent
vasoconstrictor)
– Side effects: generally well tolerated;
skin allergies in rare cases
Antihypertensive Drugs
• Calcium channel blockers - suffix
“dipine” – Amlopidine (Norvasc),
Felopidine (Plendil), Nifedipine
(Procardia)
– MOA: Blocks the calcium channels in the
smooth muscles
–Side effect: reflex tachycardia,
orthostatic hypotension
Antihypertensive drugs
• PT concerns
–Orthostatic Hypotension
–Falls
–Patient Compliance!!!!!
–Emphasis of nonpharmacologic
treatment!!!!
Anti-spasticity Drugs
Anti-spasticity Drugs
• Indications: patients with CVA, MS,
TBI, SCI, CP
• MEDS: Baclofen (Lioresal),
Dantrolene Sodium (Dantrium),
Diazepam (Valium)
Anti-spasticity Drugs
• Baclofen
–Derivative of GABA
–Affinity to GABA(B) receptors in the
spinal cord inhibiting the alpha
motor neurons
–Side effects: drowsiness, confusion,
hallucination, fatigue, muscle
weakness, nausea
Anti-spasticity Drugs
• Dantrolene Sodium
–Blocks the release of Ca
–Peripherally acting
–Indicated for severe or chronic
spasticity
–Side effects: generalized body
weakness, hepatotoxicity: transient
effects of drowsiness, dizziness,
nausea, diarrhea
Anti-spasticity Drugs
• Diazepam
–Effects at the brain level (potentiates
GABA in the brain)
–Side effects: drowsiness, decreased
mental alertness, tolerance and
physical dependence
Anti-spasticity Drugs
• PT concerns:
– Synergistic and counter effects of drug
management to rehabilitation
– Absence of spasticity is not tantamount to
increase in motor function
– Feedback on the efficacy of these drugs or
their carry-over effects in therapy
– Proper scheduling to avoid peaks of
sedation
– Explain generalized body weakness
Antiepileptic Drugs
Antiepileptic Drugs
• Indication: patients with seizures and
epilepsy
• MEDS: Barbiturates, Benzodiazepines,
Hydantoin*, Iminostilbenes,
Succinimides, Valproic acid
• MOA: enhance GABA effects, block
sodium channels
Antiepileptic Drugs
• Barbiturates and Benzodiazepines
• Hydantoins – suffix “oin” – Phenytoin
(Dilantin), Mephenytoin, Ethotoin,
• Iminostilbenes – suffix “pine” –
Carbamazepine, Oxcarbazepine
• Succinimides – suffix “mide” –
Ethosuximide, Methsuximide
• Valproic Acid (Depakene)
Antiepileptic Drugs
• Side Effects:
– Barbiturates: sedation (primary
problem), nystagmus, ataxia, folate
deficiency, vitamin K deficiency, and skin
problems
– Benzodiazepines: sedation, ataxia,
behavioral changes
Antiepileptic Drugs
• Side Effects:
– Hydantoins: gastric irritation, confusion,
sedation, dizziness, headache, cerebellar
signs, (nystagmus, ataxia, dysarthria),
gingival hyperplasia, increased body and
facial hair (hirsutism), and skin disorders
Antiepileptic drugs
• Side Effects:
– Iminostilbenes: dizziness, drowsiness,
ataxia, blurred vision, anemia, water
retention (because of abnormal [ADH]
release), cardiac arrhythmias, and
congestive heart failure
Antiepileptic Drugs
• Side Effects:
– Valproic Acid: gastrointestinal distress,
temporary hair loss, weight gain or loss,
and impaired platelet function
Antiepileptic Drugs
• Side Effects:
– Succinimides: gastrointestinal distress,
headache, dizziness, fatigue, lethargy,
movement disorders (dyskinesia,
bradykinesia), and skin rashes and
itching
Antiepileptic Drugs
• PT concerns
– Thorough medical history of seizures or
intake of antiepileptic drugs
– Aid in determining the efficacy of
antiepileptic drug therapy
– Proper scheduling of treatment session
such that side effects are relatively mild
Anti-Parkinson Drugs
Antiparkinson Drugs
• MEDS: Levodopa, Dopamine agonists,
Anticholinergics, Amantadine,
Selegiline, COMT inhibitors
• MOA: increase dopamine levels,
decrease cholinergic activity, inhibit
other excitatory amino acids
neurotransmitters, prevents
deactivation of levodopa, respectively
Antiparkinson Drugs
• Dopamine agonists: Bromocriptine,
Cabergoline, Pergolide, Pramipexole,
Ropinirole
• Anticholinergics: Benztropine
mesylate, Biperiden,
Diphenhydramine, Ethopropazine,
Procyclidine, Trihexyphenidyl
Antiparkinson Drugs
• Amantadine (Symmetrel)
• Selegiline (Deprenyl, Eldepryl)
• COMT inhibitors: Entacapone,
Tolcapone
Antiparkinson drugs
Levodopa or L-Dopa
– Metabolic precursor of dopamine that crosses
the blood brain barrier
– Required in high doses because most (99%) is
metabolized before reaching the brain
– Combined with“Carbidopa” - decarboxylase
inhibitor (Sinemet) – HONEYMOON PERIOD
Antiparkinson Drugs
• SINEMET
–Deterioration of effects 10% a year
–Therapeutic window of 5 – 7 years
Antiparkinson Drugs
• SINEMET Side effects: “End of dose deterioration”
and “on and off” phenomenon
– Freezing episodes/Dyskinesias in 50% of
patients treated for more than 2 years
– Watch out for facial grimacing/twitching of the
lips/tongue protrusion progressing to trunk and
neck
– Disabling psychiatric toxicity (hallucination,
delusion, paranoia)
– Others: depression, anxiety, abnormal sleep
patterns, morning akinesia and pain
– DRUG HOLIDAY
Antiparkinson Drugs
• Side Effects:
– Dopamine agonists: GIT problems,
postural hypotension
– Anticholinergic drugs: mood change,
confusion, hallucinations, drowsiness,
and cardiac irregularity, blurred vision,
dryness of the mouth, nausea/ vomiting,
constipation, and urinary retention
Antiparkinson Drugs
• Side Effects:
– Amantadine: orthostatic hypotension,
confusion, hallucinations (milder)
– Selegiline: dizziness, sedation, headache,
GIT distress
– COMT inhibitors: nausea, diarrhea,
dizziness, and muscle pain/cramps
Anti-Parkinson drugs
• PT concerns
– Timing of the therapy session with the
peak effects of drug therapy
– Avoidance of deconditioning effects
during drug holiday
– Fall prevention
– PT as direct and positive influence on the
patient’s health and need for drug therapy
Anxiolytic Drugs
Anxiolytic / Hypnotic Drugs
• Indications: patients with insomnia,
low stress tolerance, consistently
anxious patients
• MEDS: Benzodiazipine and
Barbiturates
• MOA: GABA enhancement
Anxiolytic / Hypnotic Drugs
• Benzodiazepine: suffix “am” Lorazepam, Clonazepam, Diazepam
(Valium)
• Barbiturates: suffix “al” –
Phenobarbital, Amobarbital,
Secobarbital
Anxiolytic / Hypnotic Drugs
• Side Effects:
– “Hang-over effect”
– Anterograde amnesia
– Tolerance and physical dependence
– Gastrointestinal discomfort, dry mouth,
sore throat, muscular incoordination
(very infrequent)
– Cardiovascular and respiratory
depression (overdose)
Anxiolytic / Hypnotic Drugs
• PT concerns
– Proper timing of treatment session with
the peak effects of the drug
– Fall prevention
– Planning and implementing
nonpharmacologic interventions may
help in weaning the patient off these
drugs
Antidepressant Drugs
Antidepressant Drugs
• Indication: patients with feelings of
extreme lowliness and loneliness
• MEDS: trycyclics, MAO inhibitors,
selective serotonin reuptake inhibitors
(SSRI)
• MOA: desensitization of amine
neurotransmitters
Antidepressant Drugs
• Trycyclics - suffix “ine” – Imipramine,
Amoxapine, Clomipramine
• MAO inhibitors – Isocarboxazid
• SSRI – Fluoxetine (Prozac), Sertraline
Antidepressant Drugs
• Side Effects:
– Tricyclics : sedation, anticholinergic
effects (orthostatic hypotension), fatal
overdose
– MAO inhibitors : CNS excitation,
anticholinergic effects (lesser extent),
“hypertension crisis”
– SSRI: GIT problems, “serotonin
syndrome”
Antidepressant Drugs
• PT concerns
– Patient perception of the rehabilitation
process being positively influenced by
medications
– Active cooperation and continuity of
treatment session may be compromised
due to side effects
– Fall prevention
– HTN crisis
– Suicidal tendencies
Anticoagulation Drugs
Anticoagulation Drugs
• Indication: patients with DVT, post-MI,
post-CVA (ischemic type)
• MEDS: Warfarin (Coumadin), Heparin
(Fragmin, Lovenox, Inndhep, Arixtra)
• MOA: inhibit clotting factors
• Side-effects: hemorrhage (external or
internal)
Anticoagulant Drugs
• PT concerns
–Increased tendency for bleeding
–Care in the use of manual techniques
Main Reference
Ciccone, CD (2007). Pharmacology in Rehabilitation
(4th ed). Philadelphia, FA Davis.