Therapeutic profile of drugs of abuse and other CNS disorders Flashcards
D’soA that may have therapeutic uses (5)
- Cannabis
- Cocaine
- Ketamine
-Amphetamine
-Ecstacy-MDMA
Cannabis- Medical indications: (6)
THC - CB1 (+ CB2r) - class B - harm to users + others
- ↓N/V in chemotherapy patients
- Alleviates chronic pain
- Neurological problems
- ↑appetite in HIV patients
*redu PTSD
6 steps of Emesis / Vomiting (6)
Vomiting centre co-ordinates complex events
1)Vomiting centre – nucleus tractus solitarius (NTS)
NTS, nerve impulses:
- Cranial nerves (upper GI tract)
- Spinal nerves to diaphragm & abdominal muscles
2)Reverse peristalsis
- Begins at ileum → duodenum → stomach
3)Closure of epiglottis over trachea
4)Oesophagus and gastric sphincter relax
5)Abdominal muscles contract
6)Gastric contents ejected
Pathophysiology of Emesis (5)
1) chemo drugs + Chemoreceptor
Trigger Zone (CTZ)
(Outside BBB) - DAr , 5HT3, deltar, CB1, NK1
2) = Medulla - vomiting centre - Muscarinic, 5 HT3 & Histaminic H1, mu r, NK1
3) Pharynx + GIT - w/ chemo + radiotherapy = 2 -5 HT3 receptor
4) Vestibular nuclei + motion sickness = 2 -Muscarinic
Histaminic H1
5) Cerebral cortex +(smell, sight, thought) anticip emesis = 2
Chemotherapy-induced nausea/vomiting (CINV) - cannabis (2)
shown to effective - more effective than conventional anti-emetics - used in US for emesis (nabilone)
however side effects:
- LT use = hyper emesis
- Anxiety
-panic
-psychosis
- hallucinations
-loss of coordination
- ↑HR
Cannabis - Chronic Pain (5)
Benefits > Risk?
Effective? Safe?
some studies say yes (Deshpande et al 2015)
some studies say no (Andreae et al 2015)
used for MS in 10 countries
Neurological Problems - cannabis (4)
used for - MS , epilepsy , Huntington’s chorea
efficacy?
subjective relief
patient-reported relief
=PLACEBO???
Cocaine -Medical indications + side effects (3)
Class A - DA/SERT/NET blockade
Nasal surgery: Vasoconstriction by Blockade of voltage-gated Na+ channels (loss of nasal cavity/septum)
side effects:
Anxiety
panic
↑heart rate
↑BP
depression
Amino Acid Transmitters:
Glutamate - ag + antag (3)
blockade of NMDA r e.g. ion channels (glutamate) - for synp plas, LT potentiation (learning/mem)
NMDA antagonist:
Antiepileptic
Schizophrenia
Loss memory
agonists:
epilepsy
Antipsychotic
antidepressant
Cognitive enhancer
ADHD
Ketamine -Medical indications + side effects: (5)
Class C - NMDA R blockade (mostly)
- Anaesthetic-Children, but not (usually) adults (no hallo in kids)
- Treatment-resistant depression
- Pain
side effects:
Anxiety
panic
psychosis
hallucinations
↑heart rate
↑blood pressure
Ket can be a drug of choice (2)
- Ketamine does not suppress breathing
- Traumatic shock increases risk of hypotension;
ketamine stimulates the circulatory system
Current Pharmacotherapy
of anti-depressants - 3 (3)
1st line = SSRI’s - block sert r - so sert can’t get back into the neurone after being released = major surge in synp cleft
TCA’s = 2nd line: work by blocking SERT + NA transporters = inc of SET + NA in synp cleft
MOAi: 3rd line (not really used) - block the drug blocks enzyme hat breaks down SERT + NA = inc of both
Problems with current antidepressants (4)
*Side effects (especially insomnia=>relapse)
*Toxic with overdose
*Delayed effects
*Non responsive in certain people (30-40% fail to improve with drug treatment)
ket: Treatment-Resistant Depression (4)
- Given at MUCH lower doses than that used to induce analgesia
- Rapid onset (within 2 hours)
- But…cause dissociative symptoms (hallo) , abuse potential
better than electroconvulsive therapy in major depressed hospitalised patients - quicker + better lower rates
Ketamine Bladder - LT use
necrosis in the bladder = bag for their bladder
