Drugs Block 12 Flashcards

1
Q

Chloroquine

A
  • Chloroquine is a antimalarial drug that is used off label to treat Rheumatoid Arthritis
  • The mechanism of action of antimalarials in the treatment of patients with rheumatoid arthritis is unknown but is thought to involve changes in antigen presentation or effects on the innate immune system.
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2
Q

Hydroxychloroquine

A
  • Hydroxychloroquine is an antimalarial drug which is relatively safe and well-tolerated agent for the treatment of rheumatoid arthritis.
  • The mechanism of action of antimalarials in the treatment of patients with rheumatoid arthritis is unknown but is thought to involve changes in antigen presentation or effects on the innate immune system.
  • A period of 2 to 4 months is usual. Most agree that if a patient shows no response after 5-6 months that this should be considered a drug failure.

SIDE EFFECTS:
The most important toxicities are on the eyes:
-corneal deposits
- extraocular muscular weakness
- loss of accommodation (and sensitivity to light)
- retinopathy that may progress to irreversible visual loss.

  • Patients with underlying retinopathies or risks may not be good candidates for antimalarial drugs.
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3
Q

Azathioprine

A

Drug class: immunosuppressant

Indication: used to prevent renal transplant rejection, treat rheumatoid arthritis, crohns disease and ulcerative collitis.

Mechanism:
- inhibition of purine synthesis
- inhibition of B cells and T cells

Contraindications:

Side effects:

  • Only used for severe Rheumatoid Arthritis
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4
Q

Diclofenac

A

Drug Class: NSAID

Indications:
Pain in various inflammatory conditions
- Osteoarthritis
- Rheumatoid Arthritis

MOA:
- inhibits COX-1 and COX-2 which are the enzymes responsible for the production of prostaglandin

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5
Q

Celecoxib

A

Drug Class: NSAID

Indications:
Pain in:
- treat osteoarthritis
- rheumatoid arthritis
- acute pain
- menstrual symptoms,
- reduce polyps is familial adenomatous polyposis.

MOA:
- selective noncompetitive inhibitor of cyclooxygenase-2 (COX-2) enzyme.

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6
Q

Cyclophosphamide

A

Drug class: chemotherapy drug

Indication:
- cancer and Rheumatoid Arthritis

Mechanism of action: DNA Alkylation -> DNA crosslinking -> decreased DNA replication

Side effects: - hemorrhagic cystitis (bleeding in bladder)

  • Doctors typically use this medication to treat severe RA, specifically vasculitis, which is inflammation in the blood vessels.
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7
Q

Ciclosporin

A

Drug class: immunosuppressant

Indication: organ and bone marrow transplants as well as inflammatory conditions such as ulcerative colitis, rheumatoid arthritis and atopic dermatitis.

Mechanism:
1. Calcineurin inhibitor that inhibits T -cell activation.
2. Cyclosporin binds to the receptor cyclophilin and forms a complex called cyclosporine-cyclophilin.
3. This complex inhibits calcineurin, which stops the dephosphorylation and activation of (NFAT) that produce cytokines and inflammatory reactions.

Side effects:
- hypertension
- hyperlipidemia
- hirsutism ( excessive hair growth)
- hyperuricemia ( gout)

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8
Q

Aurothiomalate

A

Sodium aurothiomalate is a disease-modifying antirheumatic drug (DMARD) indicated for the symptomatic treatment of arthritis.

Drug Class: DMARD

Indication: Arthritis

MOA:
The precise mechanism of action is unknown. It is known that sodium aurothiomalate inhibits the synthesis of prostaglandins. The predominant action appears to be a suppressive effect on the synovitis of active rheumatoid disease.

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9
Q

Methotrexate

A

Drug Class: can also be DMARD

Indication: very effective at treating Rheumatoid Arthritis

MOA:

  • Methotrexate enters tissues and is converted to a methotrexate polyglutamate by folylpolyglutamate
  • In rheumatoid arthritis, methotrexate polyglutamates inhibit AICART more than methotrexate.
  • This inhibition leads to accumulation of AICART ribonucleotide, which inhibits adenosine deaminase, leading to an accumulation of adenosine triphosphate and adenosine in the extracellular space, stimulating adenosine receptors, leading to anti-inflammatory action
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10
Q

Sulfasalazine

A

Drug Class: DMARD

Indication:
- Rheumatoid Arthritis
- It has been shown to reduce the signs and symptoms of RA and slow radiographic damage.

Indication:
- Crohns disease
- Ulcerative Colitis
- Rheumatoid Arthritis

MOA:

  • Although the exact mechanism of action of sulfasalazine is not fully understood, it is thought to be mediated through the inhibition of various inflammatory molecules
  • can inhibit leukotrienes and prostaglandins by blocking the cyclo-oxygenase and lipoxygenase pathway.
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11
Q

RA triple therapy

A
  • Sulfasalazine
  • Methotrexate
  • Hydrochloroquine
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12
Q

Prednisolone

A

Drug class: Intermediate ( medium) acting glucocorticoids

Indications: orally, intravenously and topically

treat adrenocortical insufficiency, inflammatory conditions, endocrine, rheumatic and dermatologic.
Mechanisms:
- The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation

Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.

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13
Q

Acetazolamide

A

Acetazolamide is a carbonic anhydrase inhibitor used to treat edema from heart failure or medications, certain types of epilepsy, and glaucoma.

Drug Class: Antidiuretic and Anticonvulsant

Indication:

For adjunctive treatment of: edema due to congestive heart failure; drug-induced edema; centrencephalic epilepsies; chronic simple (open-angle) glaucoma

The anticonvulsant activity of Acetazolamide may depend on a direct inhibition of carbonic anhydrase in the CNS, which decreases carbon dioxide tension in the pulmonary alveoli, thus increasing arterial oxygen tension.

The diuretic effect depends on the inhibition of carbonic anhydrase, causing a reduction in the availability of hydrogen ions for active transport in the renal tubule lumen. This leads to alkaline urine and an increase in the excretion of bicarbonate, sodium, potassium, and water.

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14
Q

Timolol

A

Drug Class: non-selective beta blocker

Indication:
- elevated intraocular pressure in occular hypertension or open angle glaucoma.

  • given as eyedrop solution also given as tablet to treat hypertension.

MOA:
TO DECREASE BP:
- competes with adrenergic neurotransmitters (epinephrine) for binding to beta-1 receptors in the heart

  • also competes with beta-2 receptors in the vascular and bronchial smooth muscle
  • This leads to diminished actions of catelcholamines, which would normally bind to adrenegic receptors and exert sympathetic effects - like increase heart rate and pressure.
  • So the beta blocker effect - decreases heart rate and cardiac output
  • Also decreases systolic and diastolic blood pressure

TO DECREASE OCCULAR PRESSURE:
- exact way timilol reduces occular pressure is unknown
- probably because it decreases the amount of aqueous humor in the eye.

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15
Q

Mannitol

A

Drug Class: Osmotic Diuretic (sugar alcohol)

Indication:
- reduce intracranial pressure and intraocular pressure

  • measure the glomerular filtration rate (GFR)
  • manage pulmonary symptoms associated with cystic fibrosis

MOA:

  • Is a osmotic diuretic which is metabolically inert in humans
  • Occurs naturally as sugar alcohol in fruits and vegetables
  • Elevates BLOOD PLASMA OSMOLALITY - resulting in enhanced flow of water from tissues, including the brain and cerebrospinal fluid into interstitial fluid and plasma.
  • As a diuretic it also causes the excretion of water.
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16
Q

Propofol

A

Drug Class: General Anesthesia

Indications:
- is an intravenous anaesthetic agent used for induction and maintenance of general anaesthesia.

MOA:

  • positive modulation of the inhibitory function of the neurotransmitter gama-aminobutyric acid (GABA) through GABA-A receptors.

Side effects:
- vasodilation
- decreased cardiac function which can lead to hypotension
- Propofol infusion syndrome

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17
Q

Donepezil

A

Drug Class: Acetylcholinesterase inhibitor

Indication:
- behavioral and cognitive effects of Alzheimers disease and other types of dementia

  • given orally or transdermal delivery system
  • It is also available as an extended-release capsule in combination with memantine for the treatment of moderate-to-severe dementia of the Alzheimer’s type in patients previously stabilized on 10mg of donepezil hydrochloride once daily

MOA:
- Donepezil selectively and reversibly inhibits the acetylcholinesterase enzyme, which normally breaks down acetylcholine.

  • The commonly accepted cholinergic hypothesis proposes that a portion of the cognitive and behavioral decline associated with Alzheimer’s are the result of decreased cholinergic transmission in the central nervous system.
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18
Q

Suxamethonium (AKA succinlycholine)

A

Drug Class: Muscle relaxant, onset one min, effects last for 10 min

Indication:

  • is a depolarizing skeletal muscle relaxant used adjunctly to anesthesia and for skeletal muscle relaxation during intubation, mechanical ventilation, and surgical procedures

MOA:

  • Succinylcholine is a depolarizing neuromuscular blocker, meaning it causes a prolonged period of membrane depolarization in order to exert its therapeutic effects.

-It binds to the post-synaptic cholinergic receptors found on motor endplates, thereby inducing first transient fasciculations followed by skeletal muscle paralysis

Side effect:
- hyperkalemia - which is find in normal patients but not fine for burn patients where it can cause asystole.

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19
Q

SUXAMETHONIUM

A

PHASE 1 block: It binds to the post-synaptic cholinergic receptors found on motor endplates, thereby inducing first transient fasciculations followed by skeletal muscle paralysis

PHASE 2 block:
- Eventually the sodium channel closes and the membrane repolarises
- however because of the continued stimulation by suxamethonium the receptor becomes desensetised to acetylcholine, therefore preventing the formation of further action potentials.

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20
Q

GENERAL ANASTHETICS

A

Used for:
- unconsciousness
- sedation
-analgesia
- amnesia

How do they work:
- general anesthetics depress the central nervous system. In other words, they diminish the total amount of action potentials that are constantly firing in the brain.

  • The generation of these action potentials depends on excitatory and inhibitory synapses
  • EXCITATORY: The main neurotransmitter involved is glutamate, which binds to postsynaptic NMDA receptors, so some general anesthetics work by blocking these receptors.
  • INHIBITORY: Inhibitory synapses, on the other side, do the opposite; they release the inhibitory neurotransmitter called GABA, which binds to the postsynaptic neuron and keep it from firing.

So certain anesthetics work by stimulating these GABA receptors or by increasing their sensitivity to GABA.

21
Q

LOCAL ANESTHETICS

A

LOCAL A: they only block pain sensation in a specific part of the body, and don’t affect consciousness.

22
Q

GENERAL ANASTHETICS

A

-There are two main phases in anesthesia: induction, which is when the patient enters the anesthetic state; and maintenance, when the anesthetic state is prolonged for as long as required.

  • some anesthetics are better for induction, while others are better for maintenance.
  • Now, depending on how they’re administered, there are two classes of general anesthetics: PARENTERAL and INHALATIONAL anesthetics
23
Q

Parenteral anesthetics

A
  • Parenteral anesthetics are given by injection into a vein.
  • They’re highly lipophilic agents that are commonly used for anesthetic induction in a single intravenous injection, although some of them, in special situations, can be used for maintenance by continuous intravenous infusion.
  • Once in the bloodstream, these medications travel through the body to highly lipophilic tissues that receive a lot of blood, like the brain and spinal cord. There, they can induce the anesthetic state.
  • After this, the medications diffuse back into the bloodstream, get metabolized by the liver, and then excreted by the kidneys.
24
Q

Inhaled general anesthetics

A

Inhaled anesthetics are gases or volatile liquids given through a mask or a tracheal tube for the patient to inhale. The anesthetic then goes from the alveoli of the lungs into the blood, and finally to different parts of the body.

When the anesthetic agent has a high lipid solubility, it accumulates over time in the body fat, increasing its potency.

On the other hand, inhaled anesthetics with high blood solubility will bind to blood proteins and tend to have slower onset and recovery.

Each one of the inhaled anesthetics is better suited for specific patients according to their side effects.

25
Q

Isoflurane

A

Isoflurane is an inhaled general anesthetic used in surgery.​

Indication: For induction and maintenance of general anesthesia.​

MOA: ​
Isoflurane induces a reduction in junctional conductance by decreasing gap junction channel opening times and increasing gap junction channel closing times.​

Isoflurane also binds to the GABA receptor,​

Isoflurane also activates calcium dependent ATPase in the sarcoplasmic reticulum by increasing the fluidity of the lipid membrane

26
Q

Neuromuscular drugs

A
  • Neuromuscular blocking drugs are mainly in surgery as an adjunct to anaesthetic agents.
  • They cause muscle paralysis which is necessary prerequisite for mechanical ventilation.
  • Competitive antagonism of post-synaptic nicotinic receptors (bind to the acetycholine/nicotinic receptors but do not depolarise only block so that acetylcholine cannot bind).
  • Stop depolarisation of the muscle membrane and therefore stop muscle contraction
27
Q

Atracurium

A

-Atracurium is a neuromuscular blocker indicated to relax muscles during mechanical ventilation under general anesthesia or intubation.​

  • Usually injected intraveneously, onset of action less than 2 mins, effects last for 40 min.

​-MOA: Competitive antagonism of post-synaptic nicotinic receptors (bind to the acetycholine/nicotinic receptors but do not depolarise only block so that acetylcholine cannot bind). Atracurium is non depolarising. ​

-Stop depolarisation of the muscle membrane and therefore stop muscle contraction​

  • paralyse small fast contracting muscles first: eyes, face, fingers then larger muscles neck, limb and trunks and lastly diaphragm. The muscles return in the reverse manner so diaphragm first.

Conditions involving the larynx are most likely to be blocked most rapidly by this drug​.

​Side effect: hypotension​

28
Q

Opiods

A
  • Normally, in the absence of endorphins, inhibitory neurons secrete a neurotransmitter called gamma-aminobutyric acid, or GABA, that prevents nearby neurons from releasing neurotransmitters like dopamine, serotonin, and norepinephrine.
  • Now, let’s say someone goes to play a rigorous game of badminton. Exercise releases endorphins which activate the three major opioid receptors located on the inhibitory neurons, called the mu, kappa, and delta receptors.
  • As endorphins bind to these receptors, they block the inhibitory neuron from releasing GABA, allowing the dopamine, serotonin, and norepinephrine secreting neurons to freely unload their neurotransmitters, which then get picked up by another neuron in the same area.
29
Q

What do all opiods do ?

A
  • inhibition of GABA release.
  • however some are full agonist and some are partial agonists
30
Q

Fentanyl

A

Indication: ​
Fentanyl is an opioid analgesic used in anesthesia, for breakthrough cancer pain, or round the clock pain management.​

100 times stronger than oral morphine​

MOA: ​
- Fentanyl binds to opioid receptors, especially the mu opioid receptor, which are coupled to G-proteins.6​

Activation of opioid receptors causes GTP to be exchanged for GDP on the G-proteins which in turn down regulates adenylate cyclase​

reducing concentrations of cAMP.​

Reduced cAMP decreases cAMP dependant influx of calcium ions into the cell.​

The exchange of GTP for GDP results in hyperpolarization of the cell and inhibition of nerve activity​

FENTANYL: Full agonist

31
Q

ANTICONVULSANTS

A
  • Barbiturates
  • Benzodiazapenes
  • Calcium channel blockers
  • Sodium channel blockers
  • Increase level of gabapentin
32
Q

ANTICONVULSANTS

A

The main excitatory neurotransmitter in our brain is glutamate which can bind to several types of receptors that are basically ligand-gated ion channels, which open up and allow Na+ and Ca2+ to flow in, and K+ to flow out.

In the end, when it’s all added up, there’s an influx of positive charge that makes the cell less negative,and the neuron becomes depolarized. This causes nearby voltage-gated Na+ channels to open on the surface of the membrane, causing more Na+ to enter. This in turn triggers other nearby voltage-gated Na+ channels to open.

33
Q

Inhibitory Neurons

A

These neurons release the main inhibitory neurotransmitter called gamma-aminobutyric acid or GABA, which binds to GABA receptors on other neurons.

These GABA receptors are also ligand-gated ion channels, but they open up to let the negatively charged Cl-, into the cell.

The influx of negative ions causes hyperpolarization where the cell’s membrane potential becomes more negative, which means it’s much more difficult for it to depolarize and fire off an action potential.

34
Q

Medications that block voltage gated sodium channels

A
35
Q

BARBITURATES

A

Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics and anticonvulsants.​

They can be physically and psychologically addictive ​

Potential to overdose​

Barbiturates have largely been replaced by benzodiazepines and nonbenzodiazepines (“Z-drugs”) in routine medical practice because there is a smaller risk of overdosing

36
Q

Phenobarbital

A

Drug Class: long lasting Barbiturate and ANTICONVULSANT ​

Indication: of all types of seizures except ABSENT SEIZURES​

MOA: ​

Phenobarbital acts on GABAA receptors, increasing synaptic inhibition. This has the effect of elevating seizure threshold and reducing the spread of seizure activity from a seizure focus.​

Phenobarbital may also inhibit calcium channels, resulting in a decrease in excitatory transmitter release.​

​This medication is also used for a short time (usually no more than 2 weeks) to help calm you or help you sleep during periods of anxiety.​

You should not suddenly stop taking this medication without consulting your docotor your seizures may worsen

37
Q

Sodium Valporate

A

Drug class: anticonvulsant

Indication:
- Epilepsy
- Bipolar disorder

  • They are useful for the prevention of seizures in those with absence seizures, partial seizures, and generalized seizures

MOA:
- Valproate is known to inhibit succinic semialdehyde dehydrogenase.

  • This inhibition results in an increase in succinic semialdehyde which acts as an inhibitor of GABA transaminase
  • GABA transaminase breaks down GABA
  • low levels of GABA transaminase means higher levels of GABA
  • As GABA is an inhibitory neurotransmitter, this increase results in increased inhibitory activity
38
Q

Sodium Valporate and pregnanacy

A

The MHRA advises that all women and girls of childbearing potential being treated with valproate medicines must be supported on a Pregnancy Prevention Programme—pregnancy should be excluded before treatment initiation and highly effective contraception must be used during treatment.

39
Q

Lithium

A

Drug Class: Lithium Cation (mood stabaliser)​

Indication: biopolar disorder, depression and mania ​

MOA: ​

It is thought that Li regulates the release of neurotransmitters, which controls a persons mood. Lithium has been found to exert a dual effect on glutamate receptors, acting to keep the amount of glutamate active between cells at a stable, healthy level, neither too much nor too little. It is postulated that too much glutamate in the space between neurons causes mania, and too little, depression.​

CANNOT BE USED BY PREGNANT WOMEN ​

Side effects: POLYURIA and HYPOTHYROIDISM

40
Q

BENZODIAZAPINES

A
  • So one way we can decrease the excitatory signals is by enhancing the effect of inhibitory neurons through medication like benzodiazepines.
  • There is short acting, intermediate acting and long acting
41
Q

Diazepam

A

Drug class: Long acting benzodiazapine ​

Indications: severe anxiety, panic disorders, alcohol withdrawal and seizures ​

​MOA:
- bind to the BZ site of GABA receptors

  • binds to GABBA receptors to a different space to which GABBA binds to which increases the inhibitory effect of GABBA​

​Side effects: DROWSINESS, LOW CONCENTRATION, LOW REACTION TIME (should not be taken before driving)

42
Q

Lamotrigine

A

Drug Class: Phenyltriazine class​

Indication: used for seizures and epilepsy (partial seizures, primary generalized tonic-clonic seizures, generalized seizures due to Lennox-Gastaut syndrome) and BIPOLAR 1 DISORDER​

MOA: not fully known thought to inhibiting sodium currents by selective binding to the inactive sodium channel, suppressing the release of the excitatory amino acid, glutamate.​

Has few side effects does not require laboratory monitoring ​

43
Q

Carbemazepine

A

Drug class: Anticonvulsant medication​

Indications: Focused seizures and tonic-clonic seizures and bipolar disorders. Is most effective against partial seizures.​

MOA: Carbamazepine stabilizes hyperexcited nerve membranes, inhibits repetitive neuronal discharges and reduces synaptic propagation of excitatory impulsess, blockade of voltage-sensitive sodium and calcium channels.

44
Q

Phenytoin

A

Drug class: Anticonvulsant drug​

Indication: treat Epilepsy seizures and prevent Epileptic Seizures​

Not used to treat absence seizures​

​MOA: Sodium channel blocker

45
Q

Gabapentin

A

Drug class: Anticonvulsant ​

Indication: in the management of peripheral neuropathic pains, postherpetic neuralgia, and partial-onset seizures.​

MOA: inhibit the action of α2δ-1 subunits, thus decreasing the density of pre-synaptic voltage-gated calcium channels and subsequent release of excitatory neurotransmitters. It is likely that this inhibition is also responsible for the anti-epileptic action of gabapentin.​

46
Q

BISPHOSPHONATES

A
47
Q
A
48
Q
A