PT Pharma (FINALS)

levodopa

Drug of choice for PD

resting tremor, bradykinesia, rigidity, postural instability

Characteristics of PD:

lewy bodies

Decayed proteins and intracellular inclusion bodies

levodopa

Immediate precursor to dopamine.

dopa decarboxylase

Enzyme that converts levidopa to dopamine

carbidopa

This is combined with levodopa and is a peripheral carboxylase inhibitor

1:4 or 1:10

Ratio of carbidopa and levodopa

800 mg/day

Maximum dosage of SINEMET

dopaminergic agonists

Drug for tx of bradykinesia only. It has a neuroprotective effect on the substantia nigra

bromocriptine and pergolide

Examples of Dopaminergic Agonists

dopamine agonists

Directly stimulates dopamine receptors in basal ganglia

COMT inhibitors

Help prevent breakdown of dopamine in peripheral tissues; allows more levodopa to reach the brain

anticholinergic drugs

Inhibit excessive acetylcholine influence caused by dopamine deficiency

carbidopa

Prevents peripheral conversion of levodopa to dopamine

dopaminergic agonists

Can be used alone in early stage of mild to moderate PD

anticholinergic drugs

Used to help alleviate the symptoms of Parkinson disease (tremors and rigidity)

diphenhydramine

Example of anticholinergic drugs

amantadine

It is an antiviral drug specifically for Influenza and it decreases dyskinesia. It blocks the NMDA receptor to inhibit the effect of excitatory neurotransmitter (glutamate).

selegiline

Potently and selectively inhibits the monoamine oxidase type B (MAOB) enzyme. This is to prolong the local effect of dopamine at the CNS.

normalize the muscle excitability

Goal of skeletal muscle relaxants

hyperexcitability

The skeletal muscle relaxants are used to treat __

spasticity

Exaggerated muscle stretch reflex in the CNS

muscle spasm

Increased tension in the skeletal muscle

spasticity

It is a motor sequelae to pathologies of the brain

centrally acting

The brain or CNS is the target.

spasticity

Centrally acting is for __.

baclofen and diazepam

Examples of centrally acting drugs

dantrolene sodium

Examples of direct acting drugs

polysynaptic inhibitors

Inhibits neurons in synaptic pathway. It also decreases alpha motor neuron excitability and therefore causing relaxation of skeletal muscles.

baclofen

It has an inhibitory effect (decrease firing of alpha motor) with GABA effect. This is the drug of choice for spasticity. It also reduces alcohol consumption.

intrathecal baclofen

It is more rapid and it has fewer side effects. It is used for tx of intractable spasticity in the subarachnoid space.

dantrolene sodium

It is also used to treat malignant hyperthermia.

generalized muscle weakness

Most common adverse effect of dantrolene sodium

gabapentin

This is used to decrease excitation of alpha motor neurons. It is also used for tx of SCI and MS.

tizanidine

It is used primarily to control spasticity from spinal lesions (MS, SCI). It is also used to treat chronic headaches in the SC pathway/

methocarbamol and orphenadrine

Examples of drugs used in severe spasms

diazepam and dantrolene

Examples of drugs used in severe spasticity

generalized muscle weakness

Most common side effect of dantrolene sodium

transient drowsiness

Most common side effect of baclofen

gabapentin

It is developed originally as an antiseizure drug

depression

Most prevalent mental illness in US

sadness, irritability, feeling down

general dysphoric mood

amines

This neurotransmitter controls mood and behavior.

antidepressants

This medicine prolongs the activity of amine transmission in the brain thereby causing a compensatory decrease in the sensitivity of the amine receptors.

depression

Receptor “supersensitivity” to amine neurotransmitters

antidepressants

Enhances stimulation of post-synaptic and pre-synaptic receptors

down-regulations

Receptor sensitivity decreases

antidepressant

Attempts to increase aminergic transmission in different mechanisms

tricyclics, MAO inhibitors, second generation drugs

Categories of antidepressant drugs

tricyclic

Blocks the reuptake of amine NT into the presynaptic terminal

amitriptyline and nortriptyline

Examples of tricyclic drugs

amitriptyline and nortriptyline

Most commonly used antidepressants and it is also the standard used against other antidepressants being measured.

tricyclic

Highest potential for overdosage

MAO inhibitor

Drugs that inhibit this enzyme allow more of the transmitter to remain in the synaptic cleft and continue to exert an effect

MAO inhibitor

This is not usually the drugs of choice in depression

monoamine oxidase

Enzyme that is located at amine synapses and helps remove released transmitters through enzymatic destruction

MAO inhibitors

The adverse effect of this drug includes anticholinergic effects and hypertensive crisis

hypertensive crisis

Excessive activity at the peripheral sympathetic adrenergic terminals

isocarboxazid, phenelzine, tranylcypromine

Examples of MAO inhibitor

second generation antidepressants

More effective in treating specific depressive symptoms in some. It has lower incidence of side effects (CV problem, sedation) and it is better tolerated.

selective serotonin reuptake inhibitors

Drug of choice for initial method of treatment with depression. This is helpful in long-term management of depression

fluoxetine, citalopram

Examples of second generation antidepressants

oral; liver

**Antidepressant**

administration:

elimination:

sedative hypnotic

Used to relax patient and promote sleep.

sedative hypnotic

Used to treat epilepsy or for muscle relaxation

benzodiazepenes and non-benzodiazepenes

Sedative-hypnotic agents

benzodiazepines

Exert their effects by increasing the inhibitory effects at CNS synapses that uses the neurotransmitter gamma-aminobutyric acid (GABA)

diazepam

Most commonly used benzodiazepines but is also used as an anti-anxiety drug. It is regarded as safer because there is lesser chance for lethal overdose.

estalozam, flurazepam, quazepam, temazepam, triazolam

Examples of benzodiazepines

barbiturates

Also used as an anti-seizure. It potentiates the inhibitory effect of GABA.

zolpidem and zaleplon

Examples of other non-benzodiazepines

oral; kidney

**Sedative hypnotics**

Administration:

Elimination:

anterograde amnesia

Adverse effect of sedative hypnotics

anxiety

Described as fear or apprehension over a situation or event that an individual feels it as threatening

antianxiety drugs

Helps decrease tension and nervousness temporarily

benzodiazepene

Front line drugs to treat many forms of anxiety

diazepam

The prototypical antianxiety benzodiazepine drug in treating nervousness and apprehension

buspirone

Antianxiety agent for generalized anxiety disorder. Serotonin agonist

convulsions

Involuntary, paroxysmal skeletal muscle contraction. Not always associated with epilepsy.

seizure

Synchronous burst of firing rate

generalized, partial, unclassified

Categories of seizures

simple partial seizure

**Limited** (**focal**) motor or sensory signs

complex partial seizures

Consciousness impaired; bizarre behavior; wide variety of other manifestations; specific **electroencephalography (EEG)** abnormality

partial becoming generalized

Symptoms progressively increase until seizure resembles a generalized (**tonic-clonic**) seizure

absence (petit mal)

Sudden, brief loss of consciousness; motor signs may be absent or may range from rapid **eye-blinking** to symmetrical jerking movements of entire body

myoclonic

Sudden, brief, **shocklike** contractions of muscles in the face and trunk, or in one or more extremities; contractions may be single or multiple; consciousness may be impaired

clonic

**Rhythmic**, **synchronized** contractions throughout the body; loss of consciousness

tonic

**Generalized** **sustained** muscle contractions throughout body; loss of consciousnes

tonic-clonic

**Major convulsions** of entire body; sustained contraction of all muscles (tonic phase) followed by powerful rhythmic contractions (clonic phase); loss of consciousness

atonic

**Sudden loss** of muscle tone in the head and neck, one limb, or throughout the entire body; consciousness may be maintained or lost briefly

barbiturates

Effective in generalized tonic-clonic, simple and complex partial seizures

phenobarbital

Most common barbiturates

sedation

Adverse effect of barbiturates

diazepam and lorazepam

Used in the acute treatment of status epilepticus (prolonged seizure)

clonazepam

Recommended in specific forms of **absence** seizures

clorazepate

Used as an **adjunct** in certain partial seizures

hydantoins

**Stabilizes** neural membranes and decreases neuronal excitability by decreasing sodium entry into rapidly firing neurons.

phenytoin

Example of hydantoins

carbamazepine and oxcarbazepine

Examples of iminostilbenes

carbamazepine

Effective in the treatment of **all types of epilepsy** __except for absence seizure__. Primary agent for the treatment of **partial and tonic-clonic** seizure